CORD BLOOD AND RELATED CHILD BONE MARROW TRANSPLANTATION

Save this PDF as:
 WORD  PNG  TXT  JPG

Size: px
Start display at page:

Download "CORD BLOOD AND RELATED CHILD BONE MARROW TRANSPLANTATION"

Transcription

1 CORD BLOOD AND RELATED CHILD BONE MARROW TRANSPLANTATION Purpose of this review PGD/HLA typing can be used to create saviour siblings i.e. children who are selected to have a matching tissue type for a sibling with the intention of donating either bone marrow or cord blood. The practice of bone marrow donation is well established but the use of cord blood is newer and less well established. The purpose of this review is to outline the current uses of cord blood in terms of treatments that are reported in the literature and the potential uses of cord blood. The report is divided into three sections: the first section gives an overview of cord blood, its collection, and storage and cord blood banks. The second part of the report is brief literature review summarising some of the literature pertaining to the use of cord blood. The literature review is ordered so that the articles relating to similar issues are grouped together. The third and final part of the review comprises the abstracts and references that are summarised in the second section. Cord Blood Cord blood is the residual placenta blood collected from the cord of the newborn; it is a rich source of heamatopoetic stem cells which can be used to re-populate the bone marrow, consequently providing a source of healthy blood cells. Obtaining and storing cord blood. Cord blood can be obtained in two ways; it can be collected from the umbillical cord while the placenta remains in utero or from a placenta after delivery using sterile apparatus and a venepuncture procedure. In utero collection of cord blood is intrusive and could be disruptive to care of the mother and the child after delivery; blood collected from a post-delivery placenta has a higher chance of contamination and requires trained staff. After collection cord blood is tested for transmissible infections, cell number and HLA type for donation compatibility prior to storage. Cord blood cells are stored in liquid nitrogen for up to fifteen years in cord blood banks (no cord blood cells stored longer than fifteen years have been used).. Cord blood banks Cord blood is stored in banks that are either public, private, not for profit or for profit organisations. There are about 100 cord blood banks worldwide of which

2 75% are public and the remaining 25% are private. Most of the banks are within Europe and North America. Public cord blood banks store altruistically-donated cord blood for allogeneic transplantation. Blood is tested and typed and can be utilised by patients who require a matching haematopoetic stem cell source. There are 0.88 units of cord blood per inhabitants within the U.K compared to 7.4 units per in Belgium and 3.3 units per in Australia. Private cord blood banks are used by parents who wish to store cord blood for potential autologous or allogeneic transplantation within the family. Currently there is a very small chance of the cord blood being required within the first twenty years; in addition cord blood transplantation is most effective in children under the age of eight because of the limited number of cells obtained from each sample. The long-term storage of cord blood for treatment in adulthood is of merely hypothetical value as yet. Treatment of adults requires a larger number of cells which in turn would require stem cell population expansion. In order to achieve this, the cell population would need to be stored, before being cultured and differentiated into various cell types for the treatment of, for example, cancer, Parkinson s disease or diabetes. This requires an understanding of the control of stem cell differentiation. Current research is focussed on achieving this. It has note been demonstrated that using personal cord blood would be any more effective than using to well-matched donor cord blood. Use of cord blood Cord blood has been used to treat blood malignancies, immunodeficiency, bone marrow diseases and storage diseases. Successful treatment has been documented in related and unrelated transplants (matched cord blood from a related or unrelated donor) in both children and adults. In bone marrow transplant human leukocyte antigen (HLA) matching is essential for successful treatment. There is less requirement for absolute matches using cord blood because stem cells found in the cord blood are less immunodeveloped than stem cells from the bone marrow thus they are less likely to cause graft versus host disease than equally matched bone marrow stem cells used for transplant. Cord blood transplant versus bone marrow transplant. Cord blood transplant (CBT) is less invasive than bone marrow transplant (BMT) so there are likely to be more potential donors. The cells are rapidly available, it is not necessary to obtain the cells from a donor once a match has been made because the cells would already be banked. This also reduces the likelihood of a

3 donor refusing consent at the last minute. The cells also have a lower immunological response resulting in a lower likelihood of graft versus host disease (GVHD). There is a greater proliferative capacity of stem cells derived from cord blood compared to stem cells from bone marrow or adult circulating blood. Currently the amount of available stem cells is limiting in CBT, although there is active research into expanding the population of cord derived stem cells.

4 Literature Review: Cord blood and bone marrow transplants A literature search was carried out in order to review the field of cord blood and bone marrow transplantation. Most emphasis was placed on the use of cord blood in treatment, because treatment with bone marrow transplants is well established. PubMed was searched using key words and a selection of the literature was summarised below and abstracts collated and attached at the end of this document. The publication type is listed at the end of the abstract; all abstract were taken from peer-reviewed journals. Key words used in search in various combinations: bone marrow transplant, cord blood, treatment, children, child donors, thalassemia, matched, unmatched, leukaemia, HLA type, successful treatment, adult treatment, cord blood versus bone marrow transplant. 1. Successful treatment of diseases by use of cord blood transplantation 2. Matched cord blood transplant 3. Unmatched cord blood transplant 4. Adult treatment using cord blood 5. Technical issues of cord blood transplants 6. Potential adverse affects of cord blood transplants 7. Cord blood versus bone marrow transplants 8. Bone marrow transplant 1. Successful treatment of diseases by use of cord blood transplantation Successful treatment of acute myeloid leukaemia (AML) was seen with unmatched cord blood transplant in children with poor prognosis and no HLAmatched sibling. (1.1) Children (N=39) with haematological malignancies (acute lymphoblastic leukaemia, acute myelogenous leukaemia, chronic myelogenous leukaemia, refractory anaemia with myelodysplastic syndrome and juvenile myelomonocytic leukaemia) were treated with unmatched CBT; the study demonstrates that CBT is a feasible procedure to cure a significant proportion of children with Leukaemia if the treatment is administered in a favourable phase of the disease (1.2). Children suffering from Hurler s syndrome (causes progressive degeneration of the CNS and death in childhood) were treated with unmatched cord blood; transplant favourably altered the natural history of patients by increasing neurocognition and decreasing somatic traits of Hurler s syndrome without total body irradiation (1.3).

5 Children (N=3) suffering from X-linked immunodeficiencies (X-linked lymphoproliferative syndrome and X-linked hypoimmunoglobulin-m syndrome) were treated with CBT to reconstitute the immune system. Two years after transplantation the children all had normal immune systems (1.4). Fanconi s anemia was the first disease to be treated with cord blood cells (1.5) and there have since been many examples of treatment of this disease with CBT (1.6, 1.7, 1.8) Including an CBT from an unaffected HLA-identical sibling identified by PGD (1.9). Chronic granulomatous disease is a disease that affects neturophils resulting in a compromised immune system, a patient presenting with this disease has been successfully treated with an HLA-identical sibling CBT (1.10). Thalassemia and Sickle cell disease (common diseases affecting several million children and young adults a year) have been treated using CBT from related donors with good success rates and low incidence of graft versus host disease (1.11). 2. Matched cord blood transplant A patient suffering from Fanconi s anaemia was treated with a HLA-identical CBT from a sibling selected using PGD-HLA testing (2.1). Chronic granulomatous disease is a disease that affects neturophils resulting in a compromised immune system, a patient presenting with this disease has been successfully with an HLA-identical sibling CBT (2.2). 3. Unmatched cord blood transplant 1 or 2 HLA- mismatched cord blood transplants resulted in 42 % leukaemia free survival (3.1). 0-3 HLA-mismatched cord blood transplants (CBT) and matched bone marrow transplants (BMT) were compared and it was concluded that, despite the reduced HLA matching of the cord blood, engraftment, graft versus host disease (GVHD) and survival were comparable between unmatched CBT and matched BMT. (3.2) Children (N=3) suffering from X-linked immunodeficiencies were treated with cord blood that was matched at five out of six of the HLA loci to reconstitute the immune system. Two years after transplantation the children all had normal immune systems (3).

6 4. Adult treatment using cord blood The use of cord blood in adults is reviewed in terms of the practical applications, outcome of clinical results for haematological malignancies and the current advances in the field. The current data reviewed in this paper confirm that unmatched CBT is a reasonable alternative for patients lacking a matched bone marrow donor (4.1). Twelve adult patients suffering from myelodysplastic syndrome (loss of any or all types of blood cell) were treated by unrelated CBT, the chances of disease free survival at two years was 76.2%. A number of the patients suffered from GVHD, despite this it was concluded that advanced, adult MDS patients without suitable related or unrelated bone marrow donors should be considered for CBT treatment (4.2). Adults (N=22) with haematological malignancies were treated with 4-6 out of 6 HLA matched CBT and the outcome of treatment was analysed. Twenty patients survived 30 days after the CBT and had myeloid engraftment, one patient developed secondary graft failure. Seven patients developed acute GVHD. Disease free survival after one year was 53% but this number is increased in younger patients; for patients under 30 years the diseases free survival at one year increases to 73% (4.3). Adult patients suffering from chronic myeloid leukaemia were treated with CBT. Four of the nine patients who underwent CBT in the chronic phase of the illness remain alive and in remission 42 months after treatment, the preliminary data suggest that unrelated donor CBT in a reasonable alternative to BMT in adults with CML who lack a bone marrow donor (4.4). CBT was used to treat adults suffering from de novo acute myeloid leukaemia (AML). The probability of disease free survival at two years was 76% and the authors concluded that CBT should be considered as an alternative to BMT when there are no suitable bone marrow donors (4.5). 5. Potential adverse affects of cord blood transplants The occurrence of Hemorrhagic cystitis was compared between matched related BMT, matched unrelated BMT and unrelated CBT; it was found that there was increased incidence of hemorrhagic cystitis with matched unrelated BMT and unrelated CBT than for matched related BMT (5.1). The frequency of infection was analysed in adult patients (N=27) that underwent CBT at a single institute. All patients suffered at least one infectious episode, 66% of these were considered severe, Bacteremia occured in 55% of the

7 patients, fungal infections were detected in 11% of the patients and one patient contracted cytomegalovirus. Ten patients died within 100 days of the CBT; four as a direct result of infection and in four other patients the infection contributed to death. Infection is a major complication in adults undergoing unrelated donor CBT (5.2). The cytomegalovirus (CMV) infection is compared in 28 patients after CBT and compared to patients after BMT. It was concluded that the recovery of CMVspecific immunity is delayed following CBT when compared to the rate of recovery after BMT (5.3). 6. Technical issues of cord blood transplants The outcome of unrelated CBT were analysed in order to attempt to optimize treatment; nucleated cell dose and HLA disparities had a significant effect on outcome. The results provide information that could aid the choice of cord blood units given to a patient according to the cord blood cell content and the HLA type. (6.1) Co-infusion of low numbers of purified identical HLA-type peripheral blood stem cells with cord blood cells resulted in a shorter period of post-transplant neutropenia (reduction in neutrophils resulting in lowered immune response) due to fast engrafting of the haplo-identical cells affording immune protection until the later engrafting of the cord blood stem cells (6.2). CBT was compared to BMT in 2 groups of 12 children to analyse effective reconstitution of the haematopoietic reservoir in a clinical trial, it was shown that the CBT was more effective in restoring the haematopoietic stem cell population although there is an engraftment delay which is likely to be a result of the differentiation state of the cord blood derived cells compared to the marrow derived cells (6.3). Ex vivo expansion of cord blood derived cells has been demonstrated in order to increase the number of cells available for transplantation. There was a median of 2.4 fold increase in cell number; the expanded cell population were used in conjunction with conventional CBT. There were no significant alterations in the engraftment and the beneficial effects of this treatment are being studied further (6.4). It is possible to analyse the HLA type of an embryo in utero by amniocentesis during late pregnancy. (6.5) 7. Cord blood versus bone marrow transplants

8 The availability and speed of obtaining and umbilical cord blood and bone marrow were compared. The median time to receive an unrelated donor bone marrow transplant was 49 days compared to the median time of 13.5 days for unrelated cord blood transplant. For patients that received a transplant (N= 76) those receiving umbilical cord blood were transplanted a median of 25 days more rapidly than those receiving bone marrow transplants. (7.1) HLA-mismatched cord blood transplants were compared to HLA-matched transplants. 64 patients were transplanted; 36 with cord blood and 28 with bone marrow. Primary graft failure occurred in five cord blood (CB) transplanted patients compared to three bone marrow (BM) transplants, acute graft versushost disease (GVHD) in five CB patients and one BM transplant patients and chronic GVHD in no CB transplant patients and two bone marrow patients. The three-year survival was 59% in CB and 57% in BM patients. Accepting CB as a source of stem cells offers a graft to almost every child in need of an unrelated transplantation, with a probability of survival similar to that of an unrelated BM transplantation (7.2). 8. Bone marrow transplant Using unrelated bone marrow transplants for thalassemia patients was analysed by the Italian bone marrow transplant group. The main drawback was GVHD. The study shows that matching for class I, II and II haplotypes significantly improves the outcome of unrelated bone marrow transplantation in thalassemia. (8.1). A case report of a 5-year old boy with beta-thalassemia is described. The patient was treated with BMT from an HLA-matched unrelated donor. The authors suggest that BMT from an HLA-matched unrelated donor could be considered as an alternative treatment in patients with beta-thalassemia major when no HLAmatched donor is available (8.2) The outcome of allogenic bone marrow transplantation for childhood relapsed acute lymphoblastic leukaemia was compared in patients with and without a matched family donor. The authors suggest that BMT provides a clear survival advantage for children following their first relapse of ALL (8.3). The Japanese bone marrow transplantation program carried out a study of unrelated bone marrow transplantation for non-hodgkin lymphoma (NHL). Patients (N=124) underwent BMT, the overall survival was 49.7%, progressionfree survival was 42.6%, cumulative incidences of disease progression was 24.5% and nonprogression mortality at 3 years after BMT was 39.2%. The authors concluded that unrelated BMT should be considered as a treatment option for patients with high-risk NHL without an HLA-matched related donor (8.4).

9 Abstracts from a literature review of cord blood transplants 1. Successful treatment of diseases by use of cord blood transplantation 2. Matched cord blood transplant 3. Unmatched cord blood transplant 4. Adult treatment using cord blood 5. Technical issues of cord blood transplants 6. Potential adverse affects of cord blood transplants 7. Cord blood versus bone marrow 8. Bone marrow 9. Useful reviews 1. Successful treatment of diseases by use of cord blood transplantation 1.1 Blood Dec 15;102(13): Epub 2003 Aug 14. Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis. Michel G, Rocha V, Chevret S, Arcese W, Chan KW, Filipovich A, Takahashi TA, Vowels M, Ortega J, Bordigoni P, Shaw PJ, Yaniv I, Machado A, Pimentel P, Fagioli F, Verdeguer A, Jouet JP, Diez B, Ferreira E, Pasquini R, Rosenthal J, Sievers E, Messina C, Iori AP, Garnier F, Ionescu I, Locatelli F, Gluckman E; Eurocord Group. Eurocord Registry-Hospital Saint Louis AP/HP, Department of Hematology and Bone Marrow Transplantation and Clinical Research Laboratory on Cell Therapy, Paris University 7, 1 Ave Claude Vellefaux, Paris, France. Results of unrelated cord blood transplantation (UCBT) in childhood acute myeloid leukemia (AML) have not been previously reported. We analyzed 95 children receiving UCB transplants for AML (20 in first complete remission [CR1], 47 in CR2, and 28 in more advanced stage). Poor prognosis cytogenetic abnormalities were identified in 29 cases. Most patients received a 1 or 2 HLA antigens-mismatched UCB transplants. The median number of collected nucleated cells (NCs) was 5.2 x 107/kg. Cumulative incidence (CI) of neutrophil recovery was 78% +/- 4%, acute graft-versus-host disease (GVHD) was 35% +/- 5%, and 100-day transplantation-related mortality (TRM) was 20% +/- 4%. In multivariable analysis, a collected NC dose higher than 5.2 x 107/kg was associated with a lower 100-day TRM. The 2-year CI of relapse was 29% +/- 5% and was associated with disease status. The 2-year leukemia-free survival (LFS) was 42% +/- 5% (59% +/- 11% in CR1, 50% +/- 8% in CR2, and 21% +/- 9% for children not in CR). Children with poor prognosis cytogenetic features had similar LFS compared with other patients (44% +/- 11% vs 40% +/- 8%). In CR2, LFS was not influenced by the length of CR1 (53% +/- 11% in CR1 < 9.5 months compared with 50% +/- 12% in later relapses). We conclude that UCBT is a therapeutic option for children with very poor-prognosis AML and who lack an HLA-identical sibling. Publication Types: Review, Multicase

10 1.2 Br J Haematol. 2001;112: Cord blood transplantation from HLA-mismatched unrelated donors as a treatment for children with haematological malignancies. Ohnuma K, Isoyama K, Ikuta K, Toyoda Y, Nakamura J, Nakajima F, Tsuchida M, Ohira M, Suminoe A, Hara T, Nishihira H. Factors influencing the outcome for 39 children with haematological malignancy who were subjected to a cord blood transplantation (CBT) from genotypically HLAmismatched unrelated donors were analysed. This retrospective study included 21 children with acute lymphoblastic leukaemia, 15 with acute myelogenous leukaemia and one each with chronic myelogenous leukaemia, refractory anaemia with myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukaemia (JMML). Those subjected to CBT during the first or second complete remission (CR) and MDS without blasts were assigned to the standard-risk (SR) group (n = 16). Patients in third or subsequent remission, relapse or partial remission with refractory leukaemia at the time of CBT were considered to be in advanced phase, and placed in the high-risk (HR) group (n = 11). JMML and the second CR after a relapse (n = 8), or bone marrow failure after a rejection (n = 3), following haematopoietic stem cell transplantation (HSCT) in the first CR were included in the high-risk group. Kaplan-Meier estimates for neutrophil and platelet recovery were / at d 60 and /- 16.6% at d 100 respectively. The incidence of grades II-VI acute graft-versus-host disease was /- 16.8%. The Kaplan-Meier estimate for 3-year event-free survival (EFS) was / From multivariate analysis, the most important factor influencing EFS was disease status at CBT: SR patients had a 3-year EFS of /- 21.6%, compared with /- 20.6% for those with HR disease (P = 0.013, RR 4.746, 95% CI ). These data confirm that HLA-mismatched, unrelated CBT is a feasible procedure to cure a significant proportion of children with leukaemia, especially if conducted in a favourable phase of the disease. PMID: [PubMed] 1.3 N Engl J Med May 6;350(19): Cord-blood transplants from unrelated donors in patients with Hurler's syndrome. Staba SL, Escolar ML, Poe M, Kim Y, Martin PL, Szabolcs P, Allison-Thacker J, Wood S, Wenger DA, Rubinstein P, Hopwood JJ, Krivit W, Kurtzberg J. Pediatric Stem Cell Transplant Program, Duke University Medical Center, Durham, NC 27710, USA. BACKGROUND: Hurler's syndrome (the most severe form of mucopolysaccharidosis type I) causes progressive deterioration of the central nervous system and death in childhood. Allogeneic bone marrow transplantation before the age of two years halts disease progression and prolongs life, but many children lack a bone marrow donor. We investigated the feasibility of using cord-blood transplants from unrelated donors and a myeloablative preparative regimen that did not involve total-body irradiation in young children with Hurler's syndrome. METHODS: Between December 1995 and October 2002, 20 consecutive children with Hurler's syndrome received busulfan, cyclophosphamide, and antithymocyte globulin before receiving cord-blood transplants from unrelated donors. The children were subsequently evaluated for engraftment, adverse effects, and effects on disease symptoms. RESULTS: Cord-blood donors had normal alpha-l-iduronidase activity (mean number of cells, 10.53x10(7) per kilogram of body weight) and were discordant for up to three of six HLA markers. Neutrophil engraftment occurred a median of 24 days after transplantation. Five patients had grade II or grade III acute graft-versus-host disease; none had extensive chronic graft-versushost disease. Seventeen of the 20 children were alive a median of 905 days after transplantation, with complete donor chimerism and normal peripheral-blood alpha-l-

11 iduronidase activity (event-free survival rate, 85 percent). Transplantation improved neurocognitive performance and decreased somatic features of Hurler's syndrome. CONCLUSIONS: Cord blood from unrelated donors appears to be an excellent source of stem cells for transplantation in patients with Hurler's syndrome. Sustained engraftment can be achieved without total-body irradiation. Cord-blood transplantation favorably altered the natural history of Hurler's syndrome and thus may be important to consider in young children with this form of the disease. Copyright 2004 Massachusetts Medical Society PMID: [PubMed] 1.4 J Pediatr Apr;138(4): Related Articles, Books, LinkOut Unrelated umbilical cord stem cell transplantation for X-linked immunodeficiencies. Ziegner UH, Ochs HD, Schanen C, Feig SA, Seyama K, Futatani T, Gross T, Wakim M, Roberts RL, Rawlings DJ, Dovat S, Fraser JK, Stiehm ER. Division of Immunology/Allergy/Rheumatology, Mattel Children's Hospital at UCLA, Los Angeles, California , USA. Banked unrelated umbilical cord blood matched at 5 of 6 human leukocyte antigen loci was used to reconstitute the immune system in 2 brothers with X-linked lymphoproliferative syndrome and 1 boy with X-linked hyperimmunoglobulin-m syndrome. Pretransplant cytoreduction and posttransplant graft-versus-host prophylaxis were given. Hematopoietic engraftment and correction of the genetic defects were documented by molecular techniques. Two years after transplantation, all 3 patients have normal immune systems. These reports support the wider use of banked partially matched cord blood for transplantation in primary immunodeficiencies. Publication Types: Case Reports PMID: [PubMed] 1.5 N Engl J Med ;321(17): Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling. Gluckman E, Broxmeyer HA, Auerbach AD, Friedman HS, Douglas GW, Devergie A, Esperou H, Thierry D, Socie G, Lehn P, et al. Publication Types: Case Reports PMID: [PubMed] 1.6 Bone Marrow Transplant Jul;28(1): Related Articles, Books, LinkOut Unrelated cord blood transplantation in a Fanconi anemia patient using fludarabine-based conditioning. de Medeiros CR, Silva LM, Pasquini R. Publication Types: Letter.

12 The authors point out that patients with Fanconi anemia are natural candidates for nonmyeloablative transplantation, because of their cellular hypersensitivity to DNA crosslinking agents, such as cyclophosphamide and radiotherapy. They transplanted a 5-yearold girl with Fanconi anemia with a cord blood from an HLA-A, B and CRB1 identical unrelated donor. They used fludarabine and sublethal irradiation associated with cyclosporin and mycophenolate mofetil posttrransplant. The patient had minimal complications and no acute or chronic GVHD. 1.7 J Pediatr Hematol Oncol May-Jun;21(3): Fludarabine-based protocol for human umbilical cord blood transplantation in children with Fanconi anemia. Aker M, Varadi G, Slavin S, Nagler A. Department of Pediatrics, Hadassah University Hospital, Jerusalem, Israel. PURPOSE: A novel conditioning regimen of fludarabine monophosphate (FLM), anti-tlymphocyte globulin (ATG), and low-dose cyclophosphamide with no irradiation for human umbilical cord blood transplantation (HUCBT) for the treatment of Fanconi anemia (FA) is described. PATIENT AND METHODS: A 12-year-old girl with FA received a human umbilical cord blood transplant from a fully matched sibling donor. After the HUCBT, the patient was given granulocyte colony stimulating factor in combination with erythropoietin. Pretransplant conditioning consisted of FLM (30 mg/m2/d) from day -10 to day -5, cyclophosphamide (10 mg/kg/d) on day -7 and -6, and rabbit ATG (ATG- Frasenius, 10 mg/kg/d) from day -4 to day -1. Cyclosporin A (3 mg/kg/d) was administered from day -1 as graft-versus-host disease prophylaxis. Cord blood from a sibling donor was used as a source of hematopoietic stem cells. RESULTS: Engraftment was normal and sustained. The regimen was well tolerated with very mild toxicity and no major transplant-related complications or >grade II graft-versus-host disease. Chimerism was 100% donor origin as determined by restriction fragment length polymorphism. CONCLUSIONS: It is possible to achieve sustained engraftment and only mild toxicity in FA after HUCBT with a conditioning regimen of FLM, ATG, and cyclophosphamide with no irradiation. These preliminary results with this novel conditioning protocol are encouraging and should be evaluated in a larger group of patients with FA undergoing HUCBT. Publication Types: Case Reports PMID: [PubMed] 1.8 Bone Marrow Transplant Apr;27(7): Prompt and durable hematopoietic reconstitution by unrelated cord blood transplantation in a child with Fanconi anemia. Yoshimasu T, Tanaka R, Suenobu S, Yagasaki H, Yoshino H, Ueda T, Hisakawa H, Ishii T, Mitsui T, Ebihara Y, Manabe A, Iseki T, Maekawa T, Nakahata T, Asano S, Tsuji K. Department of Pediatric Hematology/Oncology, University of Tokyo, Japan. We describe here the case of an 8-year-old girl with Fanconi anemia (FA) whose hematopoiesis was successfully restored by unrelated umbilical cord blood (UCB) transplantation. The patient became resistant to androgen therapy, and developed intracranial hemorrhage and dyserythropoiesis. Her hematopoietic recovery after the transplantation was excellent and a complete chimerism has been durably maintained. UCB should be considered as a stem cell source for transplantation when a patient with FA does not have an HLA-identical unaffected sibling donor.

13 Publication Types: Case Reports PMID: [PubMed] 1.9 Blood Feb 1;103(3): Successful hematopoietic stem cell transplantation for Fanconi anemia from an unaffected HLA-genotype-identical sibling selected using preimplantation genetic diagnosis. Grewal SS, Kahn JP, MacMillan ML, Ramsay NK, Wagner JE. Department of Blood and Marrow Transplantation and the Center for Bioethics, University of Minnesota, Minneapolis, MN 55455, USA. The only proven cure for Fanconi anemia (FA)-associated bone marrow failure is successful allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT with donors other than HLA-identical siblings is associated with high morbidity and poor survival. Therefore, we used preimplantation genetic diagnosis (PGD) to select an embryo produced by in vitro fertilization (IVF) that was unaffected by FA and was HLAidentical to the proband. The patient was a 6-year-old girl with FA and myelodysplasia previously treated with oxymetholone and prednisone. After her parents underwent 5 cycles of IVF with intrauterine transfer of 7 embryos over a span of 4 years, successful pregnancy ensued. Twenty-eight days after delivery, the patient underwent transplantation with her newborn sibling donor's HLA-identical umbilical cord blood hematopoietic stem cells (HSCs). Neutrophil recovery occurred on day 17 without subsequent acute or chronic graft-versus-host disease. Currently, 2.5 years after transplantation, the patient is well and hematopoiesis is normal. In summary, we have described the first successful transplantation, using IVF and PGD, of HSCs from a donor selected on the basis of specific, desirable disease and HLA characteristics. The medical, legal, and ethical issues involved with this approach are discussed. Publication Types: Case Reports PMID: [PubMed] 1.10 Bone Marrow Transplant Mar;31(5): Successful umbilical cord blood stem cell transplantation for chronic granulomatous disease. Bhattacharya A, Slatter M, Curtis A, Chapman CE, Barge D, Jackson A, Flood TJ, Abinun M, Cant AJ, Gennery AR. Newcastle upon Tyne Hospitals, NHS Trust, University of New Castle upon Tyne, UK. Chronic granulomatous disease (CGD) causes growth failure, inflammatory lung damage and often early death. Prophylactic cotrimoxazole improves medium-term survival, but cannot prevent inflammatory sequelae. We report the first patient with CGD who underwent successful HLA identical sibling umbilical cord stem cell transplantation (UCSCT) after myeloablative conditioning. The patient presented with colitis, confirmed as CGD at 2 years of age. Following BU16/CY200 conditioning, he had UCSCT from his unaffected HLA identical sister. A year post- transplant, his colitis had resolved clinically and on radioisotope scan growth has improved. Neutrophil oxidative burst was 92% normal with full donor lymphocyte reconstitution. Publication Types: Case Reports PMID: [PubMed]

14 1.11 Blood ;101(6): Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease. Locatelli F, Rocha V, Reed W, Bernaudin F, Ertem M, Grafakos S, Brichard B, Li X, Nagler A, Giorgiani G, Haut PR, Brochstein JA, Nugent DJ, Blatt J, Woodard P, Kurtzberg J, Rubin CM, Miniero R, Lutz P, Raja T, Roberts I, Will AM, Yaniv I, Vermylen C, Tannoia N, Garnier F, Ionescu I, Walters MC, Lubin BH, Gluckman E; Eurocord Transplant Group. Oncoematologia Pediatrica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Universita di Pavia, Italy. Allogeneic bone marrow transplantation (BMT) from HLA-identical siblings is an accepted treatment for both thalassemia and sickle cell disease (SCD). However, it is associated with decided risk of both transplant-related mortality (TRM) and chronic graft-versus-host disease (GVHD). We analyzed 44 patients (median age, 5 years; range, 1-20 years) given an allogeneic related cord blood transplant for either thalassemia (n = 33) or SCD (n = 11). Thirty children were given cyclosporin A (CsA) alone as GVHD prophylaxis, 10 received CsA and methotrexate (MTX), and 4 patients received other combinations of immunosuppressive drugs. The median number of nucleated cells infused was 4.0 x 10(7)/kg (range, x 10(7)/kg). No patient died and 36 of 44 children remain free of disease, with a median follow-up of 24 months (range, 4-76 months). Only one patient with SCD did not have sustained donor engraftment as compared with 7 of the 33 patients with thalassemia. Three of these 8 patients had sustained donor engraftment after BMT from the same donor. Four patients experienced grade 2 acute GVHD; only 2 of the 36 patients at risk developed limited chronic GVHD. The 2-year probability of event-free survival is 79% and 90% for patients with thalassemia and SCD, respectively. Use of MTX for GVHD prophylaxis was associated with a greater risk of treatment failure. Related CBT for hemoglobinopathies offers a good probability of success and is associated with a low risk of GVHD. Optimization of transplantation strategies could further improve these results. PMID: [PubMed] 1.12 Hum Reproduction (3):700-8 Novel universal approach for preimplantation genetic diagnosis of betathalassaemia in combination with HLA matching of embryos. Van de Velde H, Georgiou I, De Rycke M, Schots R, Sermon K, Lissens W, Devroey P, Van Steirteghem A, Liebaers I. Centre for Reproductive Medicine, Brussels, Belgium. BACKGROUND: Beta-Thalassaemia results from co-inheritance of two mutant betaglobin alleles. Allogeneic cord blood cell transplantation (CBT) from an HLA-identical sibling donor is an excellent treatment option for beta-thalassaemia. In families with an affected child and willing to have another child, IVF followed by preimplantation genetic diagnosis (PGD) can be applied to exclude affected embryos. Furthermore, healthy embryos could be HLA matched with the affected child so that cord blood from the future newborn can be used to transplant the affected sibling. METHODS: We developed an indirect single-cell HLA typing technique based on the use of a bank of seven microsatellite markers within the HLA locus from which four informative and evenly distributed markers were selected. RESULTS: The methodology was validated in three beta-thalassaemia families having six ovarian stimulation cycles in view of IVF and PGD. Six PGD cycles were performed in two families. On 58 embryos tested, the combined PCR was successful in 54 (93%). Two transfers were done and one clinical pregnancy was obtained. Using confirmatory analysis on 50 embryos, the accuracy for HLA typing

15 was 100%. CONCLUSION: This strategy offers a new therapeutic option for patients with beta-thalassaemia and other monogenic diseases that can be cured with CBT. 2. Matched cord blood transplant 2.1 Blood ;103(3): Successful hematopoietic stem cell transplantation for Fanconi anemia from an unaffected HLA-genotype-identical sibling selected using preimplantation genetic diagnosis. Grewal SS, Kahn JP, MacMillan ML, Ramsay NK, Wagner JE. Department of Blood and Marrow Transplantation and the Center for Bioethics, University of Minnesota, Minneapolis, MN 55455, USA. The only proven cure for Fanconi anemia (FA)-associated bone marrow failure is successful allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT with donors other than HLA-identical siblings is associated with high morbidity and poor survival. Therefore, we used preimplantation genetic diagnosis (PGD) to select an embryo produced by in vitro fertilization (IVF) that was unaffected by FA and was HLAidentical to the proband. The patient was a 6-year-old girl with FA and myelodysplasia previously treated with oxymetholone and prednisone. After her parents underwent 5 cycles of IVF with intrauterine transfer of 7 embryos over a span of 4 years, successful pregnancy ensued. Twenty-eight days after delivery, the patient underwent transplantation with her newborn sibling donor's HLA-identical umbilical cord blood hematopoietic stem cells (HSCs). Neutrophil recovery occurred on day 17 without subsequent acute or chronic graft-versus-host disease. Currently, 2.5 years after transplantation, the patient is well and hematopoiesis is normal. In summary, we have described the first successful transplantation, using IVF and PGD, of HSCs from a donor selected on the basis of specific, desirable disease and HLA characteristics. The medical, legal, and ethical issues involved with this approach are discussed. Publication Types: Case Reports PMID: [PubMed] 2.2 Bone Marrow Transplant. 2003;31(5): Successful umbilical cord blood stem cell transplantation for chronic granulomatous disease. Bhattacharya A, Slatter M, Curtis A, Chapman CE, Barge D, Jackson A, Flood TJ, Abinun M, Cant AJ, Gennery AR. Newcastle upon Tyne Hospitals, NHS Trust, University of New Castle upon Tyne, UK. Chronic granulomatous disease (CGD) causes growth failure, inflammatory lung damage and often early death. Prophylactic cotrimoxazole improves medium-term survival, but cannot prevent inflammatory sequelae. We report the first patient with CGD who underwent successful HLA identical sibling umbilical cord stem cell transplantation (UCSCT) after myeloablative conditioning. The patient presented with colitis, confirmed as CGD at 2 years of age. Following BU16/CY200 conditioning, he had UCSCT from his unaffected HLA identical sister. A year post- transplant, his colitis had resolved clinically and on radioisotope scan growth has improved. Neutrophil oxidative burst was 92% normal with full donor lymphocyte reconstitution. Publication Types: Case Reports PMID: [PubMed] 2.3 Bone Marrow Transplant (7):

16 Hematopoietic stem cell transplantation using umbilical cord blood progenitors: review of current clinical results. Benito AI, Diaz MA, Gonzalez-Vicent M, Sevilla J, Madero L. Hematology/Oncology Department and Bone Marrow Transplantation Unit, Nino Jesus Children's Hospital, Autonomous University, Madrid, Spain. Summary: Umbilical cord blood (CB) has been rapidly established as an alternative source of stem cells to bone marrow for allogeneic-related and unrelated hematopoietic transplantation. To date, almost CB units are available for transplantation and more than 2000 CB transplants (CBT) have been performed, mostly in children, for the treatment of a variety of malignant and nonmalignant conditions. Considerable experience has been rapidly accumulated in this field and many aspects of CBT have been elucidated, while other questions remain unresolved. A concise review of the clinical results achieved after related and unrelated CBT is presented and discussed. PMID: [PubMed - in process] 3. Unmatched cord blood transplant 3.1 Blood Dec 15;102(13): Epub 2003 Aug 14. Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis. Michel G, Rocha V, Chevret S, Arcese W, Chan KW, Filipovich A, Takahashi TA, Vowels M, Ortega J, Bordigoni P, Shaw PJ, Yaniv I, Machado A, Pimentel P, Fagioli F, Verdeguer A, Jouet JP, Diez B, Ferreira E, Pasquini R, Rosenthal J, Sievers E, Messina C, Iori AP, Garnier F, Ionescu I, Locatelli F, Gluckman E; Eurocord Group. Eurocord Registry-Hospital Saint Louis AP/HP, Department of Hematology and Bone Marrow Transplantation and Clinical Research Laboratory on Cell Therapy, Paris University 7, 1 Ave Claude Vellefaux, Paris, France. Results of unrelated cord blood transplantation (UCBT) in childhood acute myeloid leukemia (AML) have not been previously reported. We analyzed 95 children receiving UCB transplants for AML (20 in first complete remission [CR1], 47 in CR2, and 28 in more advanced stage). Poor prognosis cytogenetic abnormalities were identified in 29 cases. Most patients received a 1 or 2 HLA antigens-mismatched UCB transplants. The median number of collected nucleated cells (NCs) was 5.2 x 107/kg. Cumulative incidence (CI) of neutrophil recovery was 78% +/- 4%, acute graft-versus-host disease (GVHD) was 35% +/- 5%, and 100-day transplantation-related mortality (TRM) was 20% +/- 4%. In multivariable analysis, a collected NC dose higher than 5.2 x 107/kg was associated with a lower 100-day TRM. The 2-year CI of relapse was 29% +/- 5% and was associated with disease status. The 2-year leukemia-free survival (LFS) was 42% +/- 5% (59% +/- 11% in CR1, 50% +/- 8% in CR2, and 21% +/- 9% for children not in CR). Children with poor prognosis cytogenetic features had similar LFS compared with other patients (44% +/- 11% vs 40% +/- 8%). In CR2, LFS was not influenced by the length of CR1 (53% +/- 11% in CR1 < 9.5 months compared with 50% +/- 12% in later relapses). We conclude that UCBT is a therapeutic option for children with very poor-prognosis AML and who lack an HLA-identical sibling. Publication Types: Review, Multicase

17 3.2 Blood.2001;97: Survival after transplantation of unrelated donor umbilical cord blood is comparable to that of human leukocyte antigen-matched unrelated donor bone marrow: results of a matched- pair analysis. Barker JN, Davies SM, DeFor T, Ramsay NK, Weisdorf DJ, Wagner JE. A matched-pair analysis compared the outcomes of recipients of hematopoietic cell transplants using 0 to 3 HLA-mismatched cord bloods vs. HLA-A, -B, and DRB1-matched bone marrow as a source of stem cells. Patients were predominantly children (median age, 5 years) undergoing transplantation for malignancy, storage diseases, BM failure and immunodeficiency syndromes between 1991 and Although neutrophil recovery was significantly slower after cord blood transplantation, the probability of engraftment at day 45 was 88% in cord blood vs. 96% in BM-MTX recipients (n = 26 pairs), and 85% in cord blood vs. 90% in BM-TCD recipients (n = 31 pairs). The authors concluded that despite increased HLA disparity, probabilities of engraftment, GVHD, and survival after cord blood transplantation are comparable to those observed after HLA-matched marrow transplantation. 3.3 J Pediatr. 2001;138(4): Unrelated umbilical cord stem cell transplantation for X-linked immunodeficiencies. Ziegner UH, Ochs HD, Schanen C, Feig SA, Seyama K, Futatani T, Gross T, Wakim M, Roberts RL, Rawlings DJ, Dovat S, Fraser JK, Stiehm ER. Division of Immunology/Allergy/Rheumatology, Mattel Children's Hospital at UCLA, Los Angeles, California , USA. Banked unrelated umbilical cord blood matched at 5 of 6 human leukocyte antigen loci was used to reconstitute the immune system in 2 brothers with X-linked lymphoproliferative syndrome and 1 boy with X-linked hyperimmunoglobulin-m syndrome. Pretransplant cytoreduction and posttransplant graft-versus-host prophylaxis were given. Hematopoietic engraftment and correction of the genetic defects were documented by molecular techniques. Two years after transplantation, all 3 patients have normal immune systems. These reports support the wider use of banked partially matched cord blood for transplantation in primary immunodeficiencies. Publication Types: Case Reports PMID: [PubMed] 3.4 Bone Marrow Transplant (7): Hematopoietic stem cell transplantation using umbilical cord blood progenitors: review of current clinical results. Benito AI, Diaz MA, Gonzalez-Vicent M, Sevilla J, Madero L. Hematology/Oncology Department and Bone Marrow Transplantation Unit, Nino Jesus Children's Hospital, Autonomous University, Madrid, Spain. Summary: Umbilical cord blood (CB) has been rapidly established as an alternative source of stem cells to bone marrow for allogeneic-related and unrelated hematopoietic transplantation. To date, almost CB units are available for transplantation and more than 2000 CB transplants (CBT) have been performed, mostly in children, for the treatment of a variety of malignant and nonmalignant conditions. Considerable experience has been rapidly accumulated in this field and many aspects of CBT have been elucidated, while other questions remain unresolved. A concise review of the clinical results achieved after related and unrelated CBT is presented and discussed. PMID: [PubMed - in process]

18 4. Adult treatment using cord blood 4.1 Leukemia Oct;16(10): Unrelated donor umbilical cord blood transplantation in adults. Sanz MA, Sanz GF. Bone Marrow Transplantation Unit, Hematology Service, Hospital Universitario La Fe, Valencia, Spain. Umbilical cord blood (UCB) has emerged as an appealing alternative source of hematopoietic stem cells for unrelated donor transplantation. Shorter time to transplant and an improved chance of finding a suitable graft are evident advantages over bone marrow transplantation from unrelated donors. The majority of UCB transplants from unrelated donors have been performed in children, but the number in adults has been growing steadily in recent years. We review herein the reported experience with that source of hematopoietic stem cells in adults with hematological malignancies. The available data support the use of UCB transplantation from unrelated donors for young adults with hematological malignancies and no appropriate bone marrow donor, especially for those requiring urgent transplantation. Publication Types: Review, Tutorial PMID: [PubMed] 4.2 Blood Jun 15;101(12): Unrelated cord blood transplantation for adult patients with advanced myelodysplastic syndrome. Ooi J, Iseki T, Takahashi S, Tomonari A, Ishii K, Takasugi K, Shimohakamada Y, Ohno N, Uchimaru K, Nagamura F, Tojo A, Asano S. Department of Hematology and Oncology, Institute of Medical Science, University of Tokyo, Japan. We report the results of unrelated cord blood transplantation (CBT) for 13 adult patients with advanced myelodysplastic syndrome (MDS). The median age was 40 years, the median weight was 51 kg, and the median number of infused nucleated cells was 2.43 x 107/kg. Twelve patients had myeloid reconstitution, and the median time to more than 0.5 x 109/L (5 x 108/L) absolute neutrophil count was 22.5 days. A self-sustained platelet count more than 50 x 109/L was achieved in 11 patients at a median time of 49 days. Acute graft versus host disease (GVHD) occurred in 9 of 12 evaluable patients and chronic GVHD in 8 of 11 evaluable patients. Ten patients are alive and free of disease at between 171 and 1558 days after transplantation. The probability of disease-free survival at 2 years was 76.2%. These results suggest that adult advanced MDS patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT. PMID: [PubMed] 4.3 Blood Oct 15;98(8): Related Articles, Links Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies. Sanz GF, Saavedra S, Planelles D, Senent L, Cervera J, Barragan E, Jimenez C, Larrea L, Martin G, Martinez J, Jarque I, Moscardo F, Plume G, Andreu R, Regadera AI, Garcia I, Molla S, Solves P, de La Rubia J, Bolufer P, Benlloch L, Soler MA, Marty ML, Sanz MA. Bone Marrow Transplantation Unit, Department of Hematology, and Laboratory of Molecular Biology, Department of Clinical Pathology, Hospital Universitario La Fe, Spain.

19 The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults remains unclear. This study reports the results of UD-CBT in 22 adults with hematologic malignancies following conditioning with thiotepa, busulfan, cyclophosphamide, and antithymocyte globulin in 21, with thiotepa, fludarabine, and antithymocyte globulin in 1, and graft-versus-host disease (GVHD) prophylaxis with cyclosporine and prednisone. Median age was 29 years (range, years), and median weight was 69.5 kg (range, kg). HLA match was 6 of 6 in 1 case, 5 of 6 in 13 cases, and 4 of 6 in 8 cases. Median number of nucleated cells infused was 1.71 x 10(7)/kg (range, 1.01 x 10(7)/kg to 4.96 x 10(7)/kg). All 20 patients surviving more than 30 days had myeloid engraftment, and only 1, who received the lowest cell dose, developed secondary graft failure. Median time to reach an absolute neutrophil count of at least 0.5 x 10(9)/L was 22 days (range, days). Median time to platelets numbered at least 20 x 10(9)/L was 69 days (range, days). Seven patients (32%) developed acute GVHD above grade II, and 9 of 10 patients at risk developed chronic GVHD, which became extensive in 4 patients. Twelve patients remained alive and disease-free 3 to 45 months after transplantation. Diseasefree survival (DFS) at 1 year was 53%. Age strongly influenced DFS (P =.01). For patients aged 30 years or younger, the DFS at 1 year was 73%. These preliminary results suggest that UD-CBT should be considered a reasonable alternative in young adults with hematologic malignancy and no appropriate bone marrow donor. Publication Types: Clinical Trial PMID: [PubMed] 4.4 Bone Marrow Transplant. 2001;27(7): Unrelated donor cord blood transplantation in adults with chronic myelogenous leukemia: results in nine patients from a single institution. Sanz GF, Saavedra S, Jimenez C, Senent L, Cervera J, Planelles D, Bolufer P, Larrea L, Martin G, Martinez J, Jarque I, Moscardo F, Plume G, Andreu R, de la Rubia J, Barragan E, Solves P, Soler MA, Sanz MA. Bone Marrow Transplantation Unit, Department of Hematology, Hospital Universitario La Fe, Av. Campanar 21, Valencia, Spain. The potential role of unrelated donor cord blood transplantation (UD-CBT) in adults is not well established. We report the results of UD-CBT in nine adult patients with chronic myeloid leukemia (CML). The median age was 27 years (range, years), and the median weight was 62 kg (range, kg). At transplant, six patients were in chronic phase (five in first, and one in second), two in blast crisis, and one in accelerated phase. Eight had received intensive chemotherapy, and three had undergone autologous peripheral blood hematopoietic stem cell transplantation. Four had received interferon with no cytogenetic response, and only three underwent UD-CBT within 1 year of diagnosis. After serological typing for class I antigens, and high-resolution DNA typing for DRB1, the degree of HLA match between patients and cord blood (CB) units was 4/6 in six cases and 5/6 in three cases. The median number of nucleated cells infused was 1.7 x 10(7)/kg (range, 1.2 to 4.9 x 10(7)/kg), and was above 2 x 10(7)/kg in only two cases. All patients received thiotepa, busulfan, cyclophosphamide and anti-thymocyte globulin as conditioning; cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis; and G-CSF from day +7 until engraftment. All seven evaluable cases engrafted. The median time to reach an absolute neutrophil count > or =0.5 x 10(9)/l and > or =1 x 10(9)/l was 22 days (range, days) and 28 days (range, days), respectively. In the four patients evaluable for platelet recovery time to levels of > or =20 x 10(9) platelets/l, > or =50 x 10(9) platelets/l, and > or =100 x 10(9) platelets/l, these ranged from 50 to 128 days, 60 to 139 days, and 105 to 167 days, respectively. Three patients developed acute GVHD above grade II, and three of the five patients at risk developed extensive chronic GVHD. Four patients, all transplanted in chronic phase, remain alive in molecular remission more than 18, 19, 24 and 42 months after

20 transplantation. These preliminary results suggest that UD-CBT may be considered a reasonable alternative in adults with CML who lack an appropriate bone marrow donor. Publication Types: Clinical Trial PMID: [PubMed] 4.5 Blood Jan 15;103(2): Epub 2003 Aug 21. Related Articles, Links Unrelated cord blood transplantation for adult patients with de novo acute myeloid leukemia. Ooi J, Iseki T, Takahashi S, Tomonari A, Takasugi K, Shimohakamada Y, Yamada T, Ishii K, Ohno N, Nagamura F, Uchimaru K, Tojo A, Asano S. Department of Hematology and Oncology, Institute of Medical Science, University of Tokyo, , Shirokanedai, Minato-ku, Tokyo , Japan. We report the results of unrelated cord blood transplantation (CBT) for 18 adult patients with de novo acute myeloid leukemia (AML). The median age was 43 years, the median weight was 55.2 kg, and the median number of cryopreserved nucleated cells was 2.51 x 107/kg. Seventeen patients had myeloid reconstitution and the median time to more than 0.5 x 109/L absolute neutrophil count was 23 days. A self-sustained platelet count more than 50 x 109/L was achieved in 16 patients at a median time of 49 days. Acute graftversus-host disease (GVHD) above grade II occurred in 11 of 17 evaluable patients and chronic GVHD occurred in 14 of 17 evaluable patients. Fourteen patients are alive and free of disease at between 185 and 1332 days after transplantation. The probability of disease-free survival at 2 years was 76.6%. These results suggest that adult AML patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT. PMID: [PubMed] 5. Technical issues of cord blood transplants 5.1 Exp Hematol. 2004;32(4): Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Gluckman E, Rocha V, Arcese W, Michel G, Sanz G, Chan KW, Takahashi TA, Ortega J, Filipovich A, Locatelli F, Asano S, Fagioli F, Vowels M, Sirvent A, Laporte JP, Tiedemann K, Amadori S, Abecassis M, Bordigoni P, Diez B, Shaw PJ, Vora A, Caniglia M, Garnier F, Ionescu I, Garcia J, Koegler G, Rebulla P, Chevret S; Eurocord Group. Bone Marrow Transplant Unit and Eurocord Registry, Laboratory of Clinical Research on Cell Therapy, Saint Louis Hospital AP-HP University Paris VII, Paris, France. OBJECTIVE: Optimizing cord blood donor selection based mainly on cell dose and human leukocyte antigen (HLA) disparities may further improve results of unrelated cord blood transplants (UCBT). MATERIALS AND RESULTS: We analyzed 550 UCBTs for hematologic malignancies reported to the Eurocord Registry. Main outcomes and prognostic factors were analyzed in univariable and multivariable analyses incorporating center and period effects and using death and relapse as competitive risks for nonfatal endpoints. Nucleated cell (NC) dose before freezing and number of HLA disparities had a significant influence on outcome. Cumulative incidence (CI) of neutrophil and platelet recovery was associated with the number of HLA mismatches, number of NC before freezing, and use of granulocyte colony-stimulating factor. Coexistence of HLA class I and II disparities and high CD34 cell dose in the graft were associated with graft-vs-host disease grades III-IV. CI of disease relapse was higher in matched transplants showing a

UMBILICAL CORD BLOOD TRANSPLANTATION: KFSH EXPERIENCE

UMBILICAL CORD BLOOD TRANSPLANTATION: KFSH EXPERIENCE UMBILICAL CORD BLOOD TRANSPLANTATION: KFSH EXPERIENCE HIND AL HUMAIDAN, MD,FRCPA Director, Blood Bank (Donor & Transfusion Services) and Stem Cell Cord Blood Bank Consultant Hematopathologist INTRODUCTION

More information

Cord Blood Biology and Transplantation

Cord Blood Biology and Transplantation Cord Blood Biology and Transplantation Yossi Cohen MD MSc and Arnon Nagler MD Institute of Hematology, Department of Bone Marrow Transplantation and Cord Blood Bank, Sheba Medical Center, Tel Hashomer,

More information

A Cure for Sickle Cell Anemia and Thalassemia

A Cure for Sickle Cell Anemia and Thalassemia IV Simpósio Internacional de Hemoglobinopatias A Cure for Sickle Cell Anemia and Thalassemia Bertram Lubin, MD and Mark Walters, MD 4 September 2007 Topics to be covered Cord blood: Importance and biology

More information

Pr Eliane Gluckman, MD, FRCP, Disclosure of Interest: Nothing to Disclose

Pr Eliane Gluckman, MD, FRCP, Disclosure of Interest: Nothing to Disclose Pr Eliane Gluckman, MD, FRCP, Hospital Saint Louis, University Paris- Diderot, France Should Haplo-identical transplantation be preferred to cord blood in patients without a matched donor? Disclosure of

More information

Myeloablative versus Reduced Intensity Conditioning Regimen Cord Blood Transplants

Myeloablative versus Reduced Intensity Conditioning Regimen Cord Blood Transplants Educational 2 Cord Blood Transplantation Myeloablative versus Reduced Intensity Conditioning Regimen Cord Blood Transplants William Arcese University of Rome Tor Vergata Rome Transplant Network 4th April

More information

In contrast to the very high transplant-related

In contrast to the very high transplant-related Cord Blood: an Alternative Stem Cell Source or a New Standard? Juliet N. BARKER Memorial Sloan-Kettering Cancer Center, NY, ABD In contrast to the very high transplant-related mortality (TRM) associated

More information

Hematopoietic Stem Cell Transplantation. Imad A. Tabbara, M.D. Professor of Medicine

Hematopoietic Stem Cell Transplantation. Imad A. Tabbara, M.D. Professor of Medicine Hematopoietic Stem Cell Transplantation Imad A. Tabbara, M.D. Professor of Medicine Hematopoietic Stem Cells Harvested from blood, bone marrow, umbilical cord blood Positive selection of CD34 (+) cells

More information

Selecting an appropriately matched donor for hematopoietic

Selecting an appropriately matched donor for hematopoietic Transplant Outcomes in Acute Leukemia (I) Mary Eapen a and John E. Wagner b Umbilical cord blood (UCB) has gradually emerged over the last decade as an alternative source of hematopoietic cells for transplantation

More information

Selection of the Optimal Umbilical Cord Blood Unit

Selection of the Optimal Umbilical Cord Blood Unit Karen Ballen, MD Selection of the Optimal Umbilical Cord Blood Unit Massachusetts General Hospital September, 2013 OUTLINE Cell Dose HLA Match Allele Level HLA C KIR Directional Mismatch NIMA HLA Antibodies

More information

Corporate Medical Policy

Corporate Medical Policy Corporate Medical Policy Hematopoietic Stem-Cell Transplantation for CLL and SLL File Name: Origination: Last CAP Review: Next CAP Review: Last Review: hematopoietic_stem-cell_transplantation_for_cll_and_sll

More information

CHAPTER 1 BACKGROUND AND CORD BLOOD BANK (CBB) ORGANIZATION

CHAPTER 1 BACKGROUND AND CORD BLOOD BANK (CBB) ORGANIZATION CHAPTER 1 BACKGROUND AND CORD BLOOD BANK (CBB) ORGANIZATION Chapter 1 BACKGROUND AND CORD BLOOD BANK (CBB) ORGANIZATION 1.1 OVERVIEW OF THE CORD BLOOD TRANSPLANTATION STUDY Bone marrow transplantation

More information

Populations Interventions Comparators Outcomes Individuals: With an appropriate indication for allogeneic stem cell transplant.

Populations Interventions Comparators Outcomes Individuals: With an appropriate indication for allogeneic stem cell transplant. Protocol Placental and Umbilical Cord Blood as a Source of Stem Cells (70150) Medical Benefit Effective Date: 04/01/13 Next Review Date: 11/17 Preauthorization Yes Review Dates: 04/07, 05/08, 07/11, 07/12,

More information

Sibling Donor Cord Blood Transplantation for Thalassemia Major: Experience of the Sibling Donor Cord Blood Program

Sibling Donor Cord Blood Transplantation for Thalassemia Major: Experience of the Sibling Donor Cord Blood Program Sibling Donor Cord Blood Transplantation for Thalassemia Major: Experience of the Sibling Donor Cord Blood Program MARK C. WALTERS, LYNN QUIROLO, ELIZABETH T. TRACHTENBERG, SANDIE EDWARDS, LISA HALE, JOANNA

More information

Transplantation of cord blood stem cells from related or unrelated donors is considered investigational in all other situations.

Transplantation of cord blood stem cells from related or unrelated donors is considered investigational in all other situations. MEDICAL POLICY POLICY RELATED POLICIES POLICY GUIDELINES DESCRIPTION SCOPE BENEFIT APPLICATION RATIONALE REFERENCES CODING APPENDIX HISTORY Placental and Umbilical Cord Blood as a Source of Stem Cells

More information

Placental/Umbilical Cord Blood as a Source of Stem Cells. Original Policy Date

Placental/Umbilical Cord Blood as a Source of Stem Cells. Original Policy Date MP 7.01.38 Placental/Umbilical Cord Blood as a Source of Stem Cells Medical Policy Section Surgery Issue 12:2013 Original Policy Date 12:2013 Last Review Status/Date Reviewed with literature search/12:2013

More information

Placental and Umbilical Cord Blood as a Source of Stem Cells

Placental and Umbilical Cord Blood as a Source of Stem Cells Placental and Umbilical Cord Blood as a Source of Stem Cells Policy Number: 7.01.50 Last Review: 12/2015 Origination: 12/2001 Next Review: 12/2016 Policy Blue Cross and Blue Shield of Kansas City (Blue

More information

Bone Marrow, Peripheral Blood Stem Cells or Umbilical Cord Blood transplantation? Federica Giannotti, MD Eurocord-Hôpital Saint Louis, Paris

Bone Marrow, Peripheral Blood Stem Cells or Umbilical Cord Blood transplantation? Federica Giannotti, MD Eurocord-Hôpital Saint Louis, Paris Bone Marrow, Peripheral Blood Stem Cells or Umbilical Cord Blood transplantation? Federica Giannotti, MD Eurocord-Hôpital Saint Louis, Paris Background Hematopoietic stem cell transplantation (HSCT) is

More information

Placental and Umbilical Cord Blood as a Source of Stem Cells

Placental and Umbilical Cord Blood as a Source of Stem Cells Placental and Umbilical Cord Blood as a Source of Stem Cells Policy Number: 7.01.50 Last Review: 12/2014 Origination: 12/2001 Next Review: 12/2015 Policy Blue Cross and Blue Shield of Kansas City (Blue

More information

UMBILICAL-CORD BLOOD TRANSPLANTATION FOR THE TREATMENT OF CANCER

UMBILICAL-CORD BLOOD TRANSPLANTATION FOR THE TREATMENT OF CANCER UMBILICAL-CORD BLOOD TRANSPLANTATION FOR THE TREATMENT OF CANCER Juliet N. Barker* and John E. Wagner Haematopoietic stem-cell transplantation is used to treat many haematological cancers, but is limited

More information

Umbilical Cord Blood Transplantation

Umbilical Cord Blood Transplantation Umbilical Cord Blood Transplantation V Rocha MD, PhD Hopital Saint Louis, Paris University 7 CIBMTR Milwaukee Umbilical Cord blood transplantation Background History Clinical results in children and adults

More information

The donor search: the best donor or cord blood unit

The donor search: the best donor or cord blood unit The donor search: the best donor or cord blood unit Dr Bronwen Shaw Consultant in haematopoietic cell transplantation Royal Marsden Hospital /Anthony Nolan Overview Where do we find donors/units for transplantation

More information

Disclosures. I have no disclosures.

Disclosures. I have no disclosures. Not Your Own Marrow Jenni Krajewski, MD Clinical Assistant Professor, Rutgers New Jersey Medical School Attending Physician, Pediatric Blood and Marrow Transplantation The Institute for Pediatric Cancer

More information

Umbilical cord blood transplantation

Umbilical cord blood transplantation Review article http://dx.doi.org/10.3345/kjp.2012.55.7.219 Korean J Pediatr 2012;55(7):219-223 eissn 1738-1061 pissn 2092-7258 Umbilical cord blood transplantation Hong Hoe Koo, MD 1, Hyo Seop Ahn, MD

More information

Stem Cell Transplantation in Severe Aplastic Anemia

Stem Cell Transplantation in Severe Aplastic Anemia Stem Cell Transplantation in Severe Aplastic Anemia Dr. D. Goodyear MD, FRCPC Division of Hematology and Hematological Malignancies, University of Calgary 1 of 11 Introduction Most cases of aplastic anemia

More information

Cord Blood Transplant. E. Gluckman Eurocord ESH-EBMT training course Vienna 2014

Cord Blood Transplant. E. Gluckman Eurocord ESH-EBMT training course Vienna 2014 Cord Blood Transplant E. Gluckman Eurocord ESH-EBMT training course Vienna 2014 Background Since 1988, umbilical cord blood (CB) has been successfully used to treat children and adults needing stem cell

More information

Placental and Umbilical Cord Blood as a Source of Stem Cells

Placental and Umbilical Cord Blood as a Source of Stem Cells Placental and Umbilical Cord Blood as a Source of Stem Cells Policy Number: 7.01.50 Last Review: 12/2013 Origination: 12/2001 Next Review: 12/2014 Policy Blue Cross and Blue Shield of Kansas City (Blue

More information

UMBILICAL CORD BLOOD STATISTICS

UMBILICAL CORD BLOOD STATISTICS UMBILICAL CORD BLOOD STATISTICS INTRODUCTION Stem cells are the next frontier in medicine. Stem cells are thought to have great therapeutic and biotechnological potential. This will not only to replace

More information

Cord Blood: that other stem cell source. Donna Wall, MD Director, Manitoba Blood and Marrow Transplant Program

Cord Blood: that other stem cell source. Donna Wall, MD Director, Manitoba Blood and Marrow Transplant Program Cord Blood: that other stem cell source Donna Wall, MD Director, Manitoba Blood and Marrow Transplant Program CBMTG April 2012 The problem: In order to perform a BMT from one person to another one needs

More information

POLICY PRODUCT VARIATIONS DESCRIPTION/BACKGROUND RATIONALE DEFINITIONS BENEFIT VARIATIONS DISCLAIMER CODING INFORMATION REFERENCES POLICY HISTORY

POLICY PRODUCT VARIATIONS DESCRIPTION/BACKGROUND RATIONALE DEFINITIONS BENEFIT VARIATIONS DISCLAIMER CODING INFORMATION REFERENCES POLICY HISTORY Original Issue Date (Created): 4/1/2011 Most Recent Review Date (Revised): 3/24/2015 Effective Date: 6/1/2015 POLICY PRODUCT VARIATIONS DESCRIPTION/BACKGROUND RATIONALE DEFINITIONS BENEFIT VARIATIONS DISCLAIMER

More information

PT CordLife Indonesia Premium Cordblood Bank. PT CordLife Indonesia Premium Cordblood Bank

PT CordLife Indonesia Premium Cordblood Bank. PT CordLife Indonesia Premium Cordblood Bank Cordblood Stem Cells and The Role of Cordblood Bank in Supporting Stem Cells Research Presentation Overview Company profile Haematopoietic stem cells in cordblood What we can do to help 1 2 PT CordLife

More information

Section: Transplant Last Reviewed Date: January 2015. Policy No: 45.16 Effective Date: April 1, 2015

Section: Transplant Last Reviewed Date: January 2015. Policy No: 45.16 Effective Date: April 1, 2015 Medical Policy Manual Topic: Placental and Umbilical Cord Blood as a Source of Stem Cells Date of Origin: December 2009 Section: Transplant Last Reviewed Date: January 2015 Policy No: 45.16 Effective Date:

More information

Program Co-Chairmen: Dr. John Wagner, University of Minnesota Dr. Richard Champlin, M.D. Anderson Cancer Center

Program Co-Chairmen: Dr. John Wagner, University of Minnesota Dr. Richard Champlin, M.D. Anderson Cancer Center (last updated May 13, 2004) This is an activity offered by CBBS, a CMA accredited provider. Physicians attending this course may report up to 13.25 hours of Category 1 credits toward the California Medical

More information

Pros and Cons of Stem Cell Sources and their availability in Africa. Dr Jaimendra Singh Inkosi Albert Luthuli Central Hospital Durban, South Africa

Pros and Cons of Stem Cell Sources and their availability in Africa. Dr Jaimendra Singh Inkosi Albert Luthuli Central Hospital Durban, South Africa Pros and Cons of Stem Cell Sources and their availability in Africa Dr Jaimendra Singh Inkosi Albert Luthuli Central Hospital Durban, South Africa Introduction The ability to perform a haematopoietic stem

More information

Navelstrengbloed tegen kanker

Navelstrengbloed tegen kanker Navelstrengbloed tegen kanker THERAPIEDAG 2008: "Zorgtrajecten in kanker" Zaterdag 27 september 2008 Gasthuisberg, Leuven. Hélène Schoemans, MD KUL, Stem Cell Institute Leuven Cord blood Collection and

More information

Artemisa. Hematopoietic stem-cell transplantation using umbilical-cord blood cells. medigraphic. pdf elaborado por medigraphic.

Artemisa. Hematopoietic stem-cell transplantation using umbilical-cord blood cells. medigraphic. pdf elaborado por medigraphic. medigraphic Artemisa en línea ARTÍCULO ESPECIAL Hematopoietic stem-cell transplantation using umbilical-cord blood cells Vanderson Rocha,* Federico Garnier,* Irina Ionescu,* Eliane Gluckman* * FRCP on

More information

Cord Blood Stem Cell Transplantation

Cord Blood Stem Cell Transplantation LEUKEMIA LYMPHOMA MYELOMA FACTS Cord Blood Stem Cell Transplantation No. 2 in a series providing the latest information on blood cancers Highlights Umbilical cord blood, like bone marrow and peripheral

More information

Name of Policy: Placental/Umbilical Cord Blood as a Source of Stem Cells

Name of Policy: Placental/Umbilical Cord Blood as a Source of Stem Cells Name of Policy: Placental/Umbilical Cord Blood as a Source of Stem Cells Policy #: 439 Latest Review Date: September 2014 Category: Medical Policy Grade: A Background/Definitions: As a general rule, benefits

More information

Unrelated Umbilical Cord Blood Transplantation in Children and Adults

Unrelated Umbilical Cord Blood Transplantation in Children and Adults Review Article 559 Unrelated Umbilical Cord Blood Transplantation in Children and Adults LP Koh, 1 MBBS, MRCP (UK), FAMS Abstract Umbilical cord blood (UCB) has recently been explored as an alternative

More information

Cord Blood: Research Progress and Future Promise

Cord Blood: Research Progress and Future Promise Cord Blood: Research Progress and Future Promise By Al Staropoli, AABB Contributing Writer Sue Fister found out she had leukemia when she was 50 years old. Doctors suggested a bone marrow transplant as

More information

Double cord blood transplantation

Double cord blood transplantation DCTH - 2 2013-113-121 REVIEW Double cord blood transplantation R. Angarano, I. Donnini, B. Bartolozzi, A. Bosi Ematologia, Azienda Ospedaliera Universitaria Careggi, Università di Firenze, Italy SUMMARY

More information

Cord Cor Blood Banking Scott N. Furlan, MD Ellen S. Plummer, Plummer MD

Cord Cor Blood Banking Scott N. Furlan, MD Ellen S. Plummer, Plummer MD Cord Blood Banking Scott N. Furlan, MD Ellen S.Plummer, MD Overview Background Biology of Stem Cell Transplant Opportunities i at Parkland Logistics of Banking Potential Barriers Indications for HCT Cancer

More information

Beyond Cell Dose: Selection of the Optimal Umbilical Cord Blood Unit. Karen Ballen, MD Massachusetts General Hospital June, 2012

Beyond Cell Dose: Selection of the Optimal Umbilical Cord Blood Unit. Karen Ballen, MD Massachusetts General Hospital June, 2012 Beyond Cell Dose: Selection of the Optimal Umbilical Cord Blood Unit Karen Ballen, MD Massachusetts General Hospital June, 2012 OUTLINE Cell Dose HLA Typing HLA C and KIR HLA Antibodies ABO and Racial/Ethnic

More information

The Infinite Potential of Stem Cell Japan s Cord Blood Bank and Transplant

The Infinite Potential of Stem Cell Japan s Cord Blood Bank and Transplant The Infinite Potential of Stem Cell Japan s Cord Blood Bank and Transplant Speech by Dr. Tsuneo A. Takahashi Translated by Stella Wang Japan and the United States are the two most experienced countries

More information

Stem Cell Transplantation In Patients with Fanconi Anemia

Stem Cell Transplantation In Patients with Fanconi Anemia Stem Cell Transplantation In Patients with Fanconi Anemia FARF Annual Family Meeting 6/28/15 Casco, ME Parinda A. Mehta, M.D. Cincinnati Children s Hospital Medical Center Improvements in Unrelated Donor

More information

Not All Stem Cells are the Same

Not All Stem Cells are the Same Cord Blood Banking and Transplantation Jennifer Willert, M.D. Hematology/Oncology Blood and Marrow Transplant Rady Children s Hospital San Diego Clinical Professor UCSD Not All Stem Cells are the Same

More information

Corporate Medical Policy Hematopoietic Stem-Cell Transplantation for Breast Cancer

Corporate Medical Policy Hematopoietic Stem-Cell Transplantation for Breast Cancer Corporate Medical Policy Hematopoietic Stem-Cell Transplantation for Breast Cancer File Name: Origination: Last CAP Review: Next CAP Review: Last Review: hematopoietic_stem_cell_transplantation_for_breast_cancer

More information

Graft Failure After HSCT

Graft Failure After HSCT Graft Failure After HSCT Vanderson Rocha, MD, PhD Professor of Haematology- Oxford University Bone Marrow Transplant Unit- Sirio Libanes Hospital- Sao Paulo Scientific Director of Eurocord-Paris Clinical

More information

Clinical Outcomes of Unrelated Donor Umbilical Cord Blood Transplantation for 30 Adults with Hematological Malignancies

Clinical Outcomes of Unrelated Donor Umbilical Cord Blood Transplantation for 30 Adults with Hematological Malignancies Clinical Outcomes of Unrelated Donor Umbilical Cord Blood Transplantation for 30 Adults with Hematological Malignancies KOICHIRO KOBAYASHI 1, YOSHINOBU MAEDA 1, YOSHITAKA HARA 1, MIYUKI NISHIE-KATAOKA

More information

Fetal Maternal Immunity and Antileukemia Activity in Cord Blood Transplant. Recipients

Fetal Maternal Immunity and Antileukemia Activity in Cord Blood Transplant. Recipients Fetal Maternal Immunity and Antileukemia Activity in Cord Blood Transplant Recipients Filippo Milano, 1 J. Lee Nelson, 1, 2 Colleen Delaney 1,3 1 Clinical Research Division, Fred Hutchinson Cancer Research

More information

INFORMATION ON STEM CELLS/BONE MARROW AND REINFUSION/TRANSPLANTATION SUR703.002

INFORMATION ON STEM CELLS/BONE MARROW AND REINFUSION/TRANSPLANTATION SUR703.002 INFORMATION ON STEM CELLS/BONE MARROW AND REINFUSION/TRANSPLANTATION SUR703.002 COVERAGE: SPECIAL COMMENT ON POLICY REVIEW: Due to the complexity of the Peripheral and Bone Marrow Stem Cell Transplantation

More information

Umbilical Cord Blood Transplantation for the Treatment of Hematologic Malignancies

Umbilical Cord Blood Transplantation for the Treatment of Hematologic Malignancies Umbilical cord blood transplantation is a useful treatment in several types of hematologic malignancies. Gene Elling. St. Lucia. Photograph. Umbilical Cord Blood Transplantation for the Treatment of Hematologic

More information

The availability of haematopoietic stem or progenitor

The availability of haematopoietic stem or progenitor Update Article Umbilical Cord Blood Transplantation: Newer Trends MB Agarwal Abstract During last ten years, over 4000 umbilical cord blood transplantations have been performed worldwide. The interest

More information

What we will discuss today

What we will discuss today Umbilical cord blood banking It s Utility? Dr. Nita Radhakrishnan Pediatric Hematology Oncology Unit, Sir Ganga Ram Hospital, New Delhi What we will discuss today What are stem cells? What are the sources

More information

SEARCHING FOR A BONE MARROW DONOR

SEARCHING FOR A BONE MARROW DONOR SEARCHING FOR A BONE MARROW DONOR Angela received a bone marrow transplant from an unrelated donor to treat her non-hodgkin s lymphoma. INFORMATION FOR PATIENTS AND THEIR FAMILIES For patients who need

More information

Corporate Medical Policy Hematopoietic Stem-Cell Transplantation for Breast Cancer

Corporate Medical Policy Hematopoietic Stem-Cell Transplantation for Breast Cancer Corporate Medical Policy Hematopoietic Stem-Cell Transplantation for Breast Cancer File Name: Origination: Last CAP Review: Next CAP Review: Last Review: hematopoietic_stem_cell_transplantation_for_breast_cancer

More information

DEPARTMENT OF BONE MARROW AND STEM CELL TRANSPLANT

DEPARTMENT OF BONE MARROW AND STEM CELL TRANSPLANT www.narayanahealth.org DEPARTMENT OF BONE MARROW AND STEM CELL TRANSPLANT About Narayana Health City Narayana Health, one of India's largest and the world's most economical healthcare service providers

More information

Challenges of Hematopoietic Stem Cell Transplantation. Robert J. Soiffer, MD Dana Farber Cancer Institute

Challenges of Hematopoietic Stem Cell Transplantation. Robert J. Soiffer, MD Dana Farber Cancer Institute Challenges of Hematopoietic Stem Cell Transplantation Robert J. Soiffer, MD Dana Farber Cancer Institute Hematopoietic Stem Cell Transplantation Objectives Deliver sufficient chemo-radio therapy to destroy

More information

One-Unit versus Two-Unit Cord-Blood Transplantation for Hematologic Cancers

One-Unit versus Two-Unit Cord-Blood Transplantation for Hematologic Cancers The new england journal of medicine Original Article One-Unit versus Two-Unit Cord-Blood Transplantation for Hematologic Cancers John E. Wagner, Jr., M.D., Mary Eapen, M.B., B.S., Shelly Carter, D.Sc.,

More information

Cord Blood Transplant Past and Future. E. Gluckman Eurocord ISCT Paris 24/04/2014

Cord Blood Transplant Past and Future. E. Gluckman Eurocord ISCT Paris 24/04/2014 Cord Blood Transplant Past and Future E. Gluckman Eurocord ISCT Paris 24/04/2014 Background Since 1988, umbilical cord blood (CB) has been successfully used to treat children and adults needing stem cell

More information

Unrelated donor umbilical cord blood transplantation for the treatment of hematologic malignancies Craig Sauter and Juliet N.

Unrelated donor umbilical cord blood transplantation for the treatment of hematologic malignancies Craig Sauter and Juliet N. Unrelated donor umbilical cord blood transplantation for the treatment of hematologic malignancies Craig Sauter and Juliet N. Barker Adult Allogeneic Bone Marrow Transplantation Service, Memorial Sloan-Kettering

More information

MEDICAL COVERAGE POLICY

MEDICAL COVERAGE POLICY Important note Even though this policy may indicate that a particular service or supply is considered covered, this conclusion is not necessarily based upon the terms of your particular benefit plan. Each

More information

On April 4, a group of physicians at the 37th annual

On April 4, a group of physicians at the 37th annual By Ronale Tucker Rhodes, MS Better gene sampling and newer transplant regimens are making stem cell transplantation possible for a host of disease states that previously were rarely considered for this

More information

Outcome of Unrelated HSCT in Patients Lacking HLA Matched Related Donors: Iranian Stem Cell Donor Program (ISCDP)

Outcome of Unrelated HSCT in Patients Lacking HLA Matched Related Donors: Iranian Stem Cell Donor Program (ISCDP) Outcome of Unrelated HSCT in Patients Lacking HLA Matched Related Donors: Iranian Stem Cell Donor Program (ISCDP) October 18, 2014 19th Congress of APBMT, Hangzhou, China AMIR ALI HAMIDIEH, MD Iranian

More information

Stem cells from Cord Blood: Myths, reality and potential. Elisabeth Semple, PhD Scientific Director Cells for Life Cord Blood Institute

Stem cells from Cord Blood: Myths, reality and potential. Elisabeth Semple, PhD Scientific Director Cells for Life Cord Blood Institute Stem cells from Cord Blood: Myths, reality and potential Elisabeth Semple, PhD Scientific Director Cells for Life Cord Blood Institute Learning objectives Understand the current usage of stem cells from

More information

4. All cord blood banks should be subject to the same standards, regulations and accreditation requirements.

4. All cord blood banks should be subject to the same standards, regulations and accreditation requirements. WMDA Policy Statement on the Utility of Autologous or Family Cord Blood Unit Storage The WMDA Board adopted this policy on 25 th of May 2006. Policy updated _April 2011 The Cord Blood Working Group and

More information

My Sister s s Keeper. Science Background Talk

My Sister s s Keeper. Science Background Talk My Sister s s Keeper Science Background Talk Outline Acute promyelocytic leukemia (APL) APL Treatment Savior Siblings In vitro fertilization (IVF) Pre-implantation Genetic Diagnosis (PGD) Risks of donating

More information

Stem Cell Background Paper

Stem Cell Background Paper Stem Cell Background Paper Introduction...2 Stem Cell Basics...3 Stem Cell Process Flow...9 Comparison of Blood, Stem Cells, Tissues and Organs Processes...10 Responsibilities for the Blood, Stem Cells,

More information

Umbilical Cord Blood: An Alternative Allogeneic Stem Cell Source for Transplantation

Umbilical Cord Blood: An Alternative Allogeneic Stem Cell Source for Transplantation Umbilical Cord Blood: An Alternative Allogeneic Stem Cell Source for Transplantation Mary J. Laughlin, MD Associate Professor of Medicine and Pathology Dr. Donald and Ruth Weber Goodman Professor of Innovative

More information

Neutrophil Recovery: The First Step in Posttransplant Recovery

Neutrophil Recovery: The First Step in Posttransplant Recovery Neutrophil Recovery: The First Step in Posttransplant Recovery is Made in the Bone Stem Cell CFU- GEMM BFU-E Pre-B CFU-E White cells B Lymphocyte T Lymphocyte Neutrophils Red cells No conflicts of interest

More information

The Value of Cord Blood Stem Cells. Mona Shafey, MD, FRCPC Medical Grand Rounds October 25 th, 2011

The Value of Cord Blood Stem Cells. Mona Shafey, MD, FRCPC Medical Grand Rounds October 25 th, 2011 The Value of Cord Blood Stem Cells Mona Shafey, MD, FRCPC Medical Grand Rounds October 25 th, 2011 Objectives To discuss umbilical cord blood as a stem cell source and the role of umbilical cord blood

More information

5. All cord blood banks should be subject to the same standards, regulations and accreditation requirements.

5. All cord blood banks should be subject to the same standards, regulations and accreditation requirements. WMDA Policy Statement for the Utility of Autologous or Family Cord Blood Unit Storage (This policy statement has been approved and adopted by the WMDA board on the 25 th of May 2006) The Cord Blood Registries

More information

Hematology, National Research Cancer Center - Istituto Tumori Giovanni Paolo II, Bari, Italy;

Hematology, National Research Cancer Center - Istituto Tumori Giovanni Paolo II, Bari, Italy; DCTH - 3 2014-125-131 CASE REPORT An alternative strategy for cord blood stem cells transplant to reduce time of neutrophils engraftment: case report of co-infusion of haploidentical and cord blood stem

More information

SAVE A LIFE... BY GIVING LIFE!

SAVE A LIFE... BY GIVING LIFE! SAVE A LIFE... BY GIVING LIFE! FOLLOW US ON: HÉMA-QUÉBEC PUBLIC CORD BLOOD BANK www.hema-quebec.qc.ca Scan this code with your smart phone to access the page Register to the Public Cord Blood Bank on the

More information

A New Beginning: Stem Cell Transplant Challenges. Dr. Wendy Lau Director, Transfusion Medicine, The Hospital for Sick Children April 8, 2016

A New Beginning: Stem Cell Transplant Challenges. Dr. Wendy Lau Director, Transfusion Medicine, The Hospital for Sick Children April 8, 2016 A New Beginning: Stem Cell Transplant Challenges Dr. Wendy Lau Director, Transfusion Medicine, The Hospital for Sick Children April 8, 2016 Objectives 1. Outline cellular therapy products and transfusion

More information

Umbilical Cord Blood (UCB) Transplantation: An Alternative to the Use of Unrelated Volunteer Donors?

Umbilical Cord Blood (UCB) Transplantation: An Alternative to the Use of Unrelated Volunteer Donors? Umbilical Cord Blood (UCB) Transplantation: An Alternative to the Use of Unrelated Volunteer Donors? Juliet N. Barker Memorial Sloan-Kettering Cancer Center, New York, NY Cryopreserved umbilical cord blood

More information

Umbilical Cord Blood Transplantation in Adults: Results of the Prospective Cord Blood Transplantation (COBLT)

Umbilical Cord Blood Transplantation in Adults: Results of the Prospective Cord Blood Transplantation (COBLT) Biology of Blood and Marrow Transplantation 11:149-160 (2005) 2005 American Society for Blood and Marrow Transplantation 1083-8791/05/1102-0010$30.00/0 doi:10.1016/j.bbmt.2004.11.020 Umbilical Cord Blood

More information

Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers. Key Points

Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation: Questions and Answers. Key Points CANCER FACTS N a t i o n a l C a n c e r I n s t i t u t e N a t i o n a l I n s t i t u t e s o f H e a l t h D e p a r t m e n t o f H e a l t h a n d H u m a n S e r v i c e s Bone Marrow Transplantation

More information

Corporate Medical Policy Cord Blood as a Source of Stem Cells

Corporate Medical Policy Cord Blood as a Source of Stem Cells Corporate Medical Policy Cord Blood as a Source of Stem Cells File Name: Origination: Last CAP Review: Next CAP Review: Last Review cord_blood_as_a_source_of_stem_cells 2/2001 3/2015 3/2016 3/2015 Description

More information

GRANIX (tbo-filgrastim)

GRANIX (tbo-filgrastim) RATIONALE FOR INCLUSION IN PA PROGRAM Background Neutropenia is a hematological disorder characterized by an abnormally low number of neutrophils. A person with severe neutropenia has an absolute neutrophil

More information

Bone Marrow, Peripheral Blood Stem Cells or Umbilical Cord Blood transplantation? E. Gluckman WBMT meeting Cape Town November 14-16, 2014

Bone Marrow, Peripheral Blood Stem Cells or Umbilical Cord Blood transplantation? E. Gluckman WBMT meeting Cape Town November 14-16, 2014 Bone Marrow, Peripheral Blood Stem Cells or Umbilical Cord Blood transplantation? E. Gluckman WBMT meeting Cape Town November 14-16, 2014 The ideal HSCs source Immediate availability Few HLA restrictions

More information

CIGNA HEALTHCARE COVERAGE POSITION

CIGNA HEALTHCARE COVERAGE POSITION CIGNA HEALTHCARE COVERAGE POSITION Subject Umbilical Cord Blood Banking Table of Contents Coverage Position... 1 General Background... 1 Coding/Billing Information... 3 References... 3 Revised Date...

More information

Saving your baby s s cord blood: Is this good insurance?

Saving your baby s s cord blood: Is this good insurance? Saving your baby s s cord blood: Is this good insurance? 32 th SEMINAR ON PERINATAL MEDICINE CONTROVERSIES IN PERINATAL MEDICINE: EVIDENCE FOR CURRENT PRACTICE Sante Fe, New Mexico Mervin C. Yoder, MD

More information

Hematopoietic Stem Cell Transplantation: Current Status and Future Directions RICHARD W. CHILDS M.D. NIH, BETHESDA MD

Hematopoietic Stem Cell Transplantation: Current Status and Future Directions RICHARD W. CHILDS M.D. NIH, BETHESDA MD Hematopoietic Stem Cell Transplantation: Current Status and Future Directions RICHARD W. CHILDS M.D. NIH, BETHESDA MD Stem cell transplantation Autologous Autologous stem cell collection Freeze Stem Cells

More information

EUROCORD. in 49 countries and 484 transplant centres* 264 EBMT 4847 (73%) cases 220 Non-EBMT 1797 (27%) cases

EUROCORD. in 49 countries and 484 transplant centres* 264 EBMT 4847 (73%) cases 220 Non-EBMT 1797 (27%) cases ! 21%! EUROCORD 6756 cord blood transplantations performed from 1988 to March 2010 in 49 countries and 484 transplant centres* 264 EBMT 4847 (73%) cases 220 Non-EBMT 1797 (27%) cases * missing center

More information

* CHAPTER 6. Choice of the donor according to HLA typing and stem cell source. Eliane Gluckman

* CHAPTER 6. Choice of the donor according to HLA typing and stem cell source. Eliane Gluckman * CHAPTER 6 Choice of the donor according to HLA typing and stem cell source Eliane Gluckman CHAPTER 6 Choice of the donor according to HLA typing and stem cell source 1. Introduction Allogeneic haematopoietic

More information

In a number of genetic, hematologic, and oncologic

In a number of genetic, hematologic, and oncologic AMERICAN ACADEMY OF PEDIATRICS Cord Blood Banking for Potential Future Transplantation: Subject Review ABSTRACT. In recent years, umbilical cord blood, which contains a large number of hematopoietic stem

More information

Umbilical Cord Blood Transplantation

Umbilical Cord Blood Transplantation Umbilical Cord Blood Transplantation Hyo Seop Ahn and Hee Young Shin Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea ABSTRACT The number of umbilical cord blood transplantation

More information

THE NEW ZEALAND MEDICAL JOURNAL

THE NEW ZEALAND MEDICAL JOURNAL THE NEW ZEALAND MEDICAL JOURNAL Vol 118 No 1208 ISSN 1175 8716 Private umbilical cord blood banking: a biological insurance of dubious future benefit! Michael Sullivan, Peter Browett, Nigel Patton In its

More information

NIH Public Access Author Manuscript Biol Blood Marrow Transplant. Author manuscript; available in PMC 2012 September 01.

NIH Public Access Author Manuscript Biol Blood Marrow Transplant. Author manuscript; available in PMC 2012 September 01. NIH Public Access Author Manuscript Published in final edited form as: Biol Blood Marrow Transplant. 2011 September ; 17(9): 1375 1382. doi:10.1016/j.bbmt.2011.01.012. Umbilical Cord Blood Transplantation

More information

Umbilical Cord Blood Banking: Implications for Perinatal Care Providers

Umbilical Cord Blood Banking: Implications for Perinatal Care Providers SOGC CLINICAL PRACTICE GUIDELINES No 156, March 2005 Umbilical Cord Blood Banking: Implications for Perinatal Care Providers This guideline has been reviewed by the Maternal/Fetal Medicine Committee and

More information

Statement of Joanne Kurtzberg, M.D.

Statement of Joanne Kurtzberg, M.D. Statement of Joanne Kurtzberg, M.D. President of the Cord Blood Association Jerome Harris Distinguished Professor of Pediatrics and Pathology Chief Scientific Officer and Medical Director, Robertson Clinical

More information

Cord Blood for Cellular Therapy: A Snapshot of this Evolving Market Landscape

Cord Blood for Cellular Therapy: A Snapshot of this Evolving Market Landscape GENReports: Market & Tech Analysis Cord Blood for Cellular Therapy: A Snapshot of this Evolving Market Landscape > Enal Razvi, Ph.D. Biotechnology Analyst, Managing Director SELECTBIO US enal@selectbio.us

More information

Introduction. About 10,500 new cases of acute myelogenous leukemia are diagnosed each

Introduction. About 10,500 new cases of acute myelogenous leukemia are diagnosed each Introduction 1.1 Introduction: About 10,500 new cases of acute myelogenous leukemia are diagnosed each year in the United States (Hope et al., 2003). Acute myelogenous leukemia has several names, including

More information

Cord Blood Transplantation from Unrelated Donors in Adults with High-Risk Acute Myeloid Leukemia

Cord Blood Transplantation from Unrelated Donors in Adults with High-Risk Acute Myeloid Leukemia Cord Blood Transplantation from Unrelated Donors in Adults with High-Risk Acute Myeloid Leukemia Jaime Sanz, 1,2 Miguel A. Sanz, 1 Silvana Saavedra, 1 Ignacio Lorenzo, 1 Pau Montesinos, 1 Leonor Senent,

More information

Blood-Forming Stem Cell Transplants

Blood-Forming Stem Cell Transplants Blood-Forming Stem Cell Transplants What are bone marrow and hematopoietic stem cells? Bone marrow is the soft, sponge-like material found inside bones. It contains immature cells known as hematopoietic

More information

Narrator: Transplants using stem cells from the blood, bone marrow or umbilical cord blood

Narrator: Transplants using stem cells from the blood, bone marrow or umbilical cord blood [Track 2: What Is a Transplant?] Narrator: Transplants using stem cells from the blood, bone marrow or umbilical cord blood can be an effective treatment for people with blood cancers such as leukemia,

More information

P R E S S K I T 2013 TABLE OF CONTENTS. About the European Group for Blood and Marrow Transplantation

P R E S S K I T 2013 TABLE OF CONTENTS. About the European Group for Blood and Marrow Transplantation TABLE OF CONTENTS About the European Group for Blood and Marrow Transplantation Haematopoietic Stem Cell Transplantation (HSCT): Key facts & figures EBMT Data - A foundation for cutting-edge research Clinical

More information

STEM CELLS : A THERAPEUTIC REVOLUTION JACQUES KADOCH ROBERT HEMMINGS MARINELA MANDRA

STEM CELLS : A THERAPEUTIC REVOLUTION JACQUES KADOCH ROBERT HEMMINGS MARINELA MANDRA STEM CELLS : A THERAPEUTIC REVOLUTION JACQUES KADOCH ROBERT HEMMINGS MARINELA MANDRA OVO CLINIC I 8000 BLVD DECARIE, MONTREAL QC H4P 2S4 I 514.798.2000 I OVOCLINIC.COM 2 a therapeutic revolution As the

More information

Infosheet. Allogeneic stem cell transplantation in myeloma. What is the principle behind stem cell transplantation?

Infosheet. Allogeneic stem cell transplantation in myeloma. What is the principle behind stem cell transplantation? Infosheet Allogeneic stem cell transplantation in myeloma High-dose therapy and autologous stem cell transplantation is currently the first-line treatment standard of care for younger/fitter myeloma patients.

More information