UMBILICAL CORD BLOOD TRANSPLANTATION: KFSH EXPERIENCE

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1 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

2 INTRODUCTION Transplantation of allogeneic bone marrow used successfully treatment of high risk or recurrent hematologic malignancies Bone marrow failure Hereditary immunodeficiency Metabolic disorder Storage diseases

3 Success rates depends on: recipient age CMV status disease and disease status at time of transplant presence of pre-existing comorbidities

4 Access to suitable donor major obstacle. Limiting use potentially curative treatment. HLA-matched sibling donor Treatment itself associated with substantial risks GVHD Increased with use of volunteer adult unrelated donors

5 Novel immunoprphylactic regimens T-cell depletion GVHD prevention possible with T- cell depletion, increased high risk of graft failure, relapse, opportunistic infections

6 Alternative Treatment Strategies Umbilical Cord Blood

7 Greatest push for moving UCB forward was the inability of the adult volunteer unrelated donor registries to meet the needs of patients.

8 What is Umbilical Cord Blood? * Blood that remains in placenta after birth (40ml-100ml). * Collected no risk mother and newborn. * Stored frozen for years.

9 Cord Blood excellent source of highly proliferative stem cells Completely reconstituting the haematopoietic system

10 UCB Advantages Immunological immaturity of immune cells in UCB -Decreased frequency and severity of acute and chronic GvHD -HLA mismatched transplants for patients with uncommon HLA types Reduced risk of transmitting infections

11 UCB Advantages Cont. No risk to the donor Large donor pool with limitless supply Adequate representation of all races & ethnicities

12 UCB Advantages Cont. Can be collected safely & easily Rapid availability in frozen state particularly for patients with acute diseases for whom timely transplant is essential

13 UCB Disadvantage Lack of donor follow up (e.g. undiagnosed genetic disease) Insufficient cell dose -Delayed engraftment -Increased rates of graft failure Uncertain GVT activity

14 History of Cord Blood Transplantation First performed in year Sixteen (16) year old boy ALL, 8 different unrelated donors, untested HLA 18 days. One (1) unit engrafted. 1982, Experiment showed Cord Blood contained HSC 1988, 1 st Cord Blood transplant five (5) years old, Fanconi Anaemia

15 Umbilical Cord Blood progenitors could be cryopreserved, no loss viability & proliferative capacity Koicke, Acta Paediator Jpn-1983; 25:275

16 Umbilical Cord Blood moved from laboratory to clinical practice as a viable source of allogeneic HSCs for Transplantation. Broxmeyer. J Hematother Stem Cell Res. 2000; 9:

17 Development of Cord Blood Banks There are 54 public unrelated different parts of the world. 400,000 cord blood grafts available This development is due to the organization of international registries Eurocord BMTR NetCord NMDP CBBs in

18 INVENTORY World wide inventory 400,000 (CBs) grafts, 54 CBB 10,000 patients benefited from this curative approach

19

20 CB Collection Procedure Cord blood is collected by: Trained midwives or bank s personnel After vaginal or cesarean deliveries by a closed collection system Vaginal delivery: Collection is performed with placenta in utero or ex utero. Cesarean delivery: Collection is performed after expulsion of the placenta, which is held at its edge and suspended with the fetal aspect and the cord down

21 Umbilical Cord Blood Collection & Storage

22 First-in-Human Clinical Trial Matthew, a 6-year old boy, was the first human transplanted with cryopreserved UCB in Paris. One month later complete chimerism. Proved UCB contained pluripotent HSC Gluckman, N Engl J Med. 1989;321:

23 Clinical Experience with Related & Unrelated Umbilical Cord Blood Transplantation Comparison of GVHD in children transplanted with HLA identical sibling. Umbilical Cord Blood versus HLA identical sibling bone marrow transplant. Rocha et al,2000 Basis for Advocating the Use of Mismatched UCBT and Triggered the Development of Unrelated CBB.

24 Unrelated UCBT could used all current indications of allogeneic HSCT, malignant & non-malignant disease in children & adults.

25 In Children two studies comparing matched unrelated BMT to mismatched UCBT showed. After UCBT * Engraftment delayed * GVHD reduced * Relapse & LFS same

26 In Adult UCBT feasible CBU contain high number of cells, option for allo. stem cell, patients lacking HLA-matched BM donor Despite increasing HLA disparity, UCB unrelated donors offer sufficiently promising results to matched UBM Conclusion donor search BM & UCB unrelated donors started simultaneously.

27 Algorithm of Donor Choice Donor choice amount cells infused minimum # NC/kg 3 x 10 7 /kg CD x 10 5 /kg Using two cord units additive effect. HLA at the antigen level HLA-A & HLA-B and at the allele level for HLA-DRB1

28 Current Recommendation Cord Blood Units < 2 HLA disparities and > 3 x 10 7 nucleated cells/kg or > 2 x 10 5 CD34 + Non-malignant disease. Dose increased > 3.5 x 10 7 NC/kg & two or more HLA incompatibilities

29 New Methods for Facilitating Engraftment & Improving Results Double cord blood transplants * Cell dose CD 34+ < 2 x 10 5 /kg or NC < 3 x 10 7 /kg decrease engraftment & survival Minimum number of cells infused increases further with increasing number HLAmismatched & diagnoses of non-malignant diseases.

30 Cont Minnesota gp. Double cord, results encouraging (Barker et al, 2003) Increase rate Engraftment more graft versus-host effect less relapse One Cord Engrafts

31 Intrabone Infusions Direct Intrabone transplantation cord blood cells Better stem cell homing Improve hematological recovery Fast neutrophil and platelet engraftment

32 Autologous Cord Blood Banking Storage infant s own UCB might be useful to the child & family Biological Insurance UCB useful treatment, cancers, genetic disorders & immune deficiency states

33 Cont Several societies taken stands against private UCB Banking likelihood of autologous use remarkably low Questionnable advertising practices and low volume products, (eg < 10 ml)

34 Today only proven use UCB, conventional blood and marrow transplantation lymphohaematopoietic diseases. Other advertised uses unproven.

35 Cord Blood Transplantation Program at KFSH-RC The cord blood transplantation program at KFSH-RC started in The cryopreserved cord blood units are obtained through international registries such NMDP or directly from international cord blood banks. Each imported cord blood unit (25 ml), including the shipment, costs US$30,000 SR113,000

36 Program at KFSH-RC : 140 CBU have been imported. 180 CBU have been transplanted (40 local units). 06 JAN 2003, first CBU infused to a patient with Hemophagocytic syndrom.

37 KFSH-RC CORD BLOOD BANK The concept of establishing cord blood bank at KFSH-RC was raised after the increase in the rate of using cord blood for transplantation due to inability to find fully or closely HLA matched related donors.

38 MISSION STATEMENT The King Faisal Specialist Hospital and Research Center Cord Blood Bank is a non-profit public cord blood bank dedicated to make high quality cord blood units available to all patients in need of related and /or unrelated transplantation in the Kingdom of Saudi Arabia and in the neighboring countries through the development and maintenance of a center of excellence for the collection, storage, search and distribution of ethnically and racially diverse cord blood units.

39 MISSION STATEMENT Additionally, the mission of the cord blood bank is also to educate both the medical community and the public to the value of cord blood donation, collection and cryopreservation, and increase the awareness of the importance of cord blood banking.

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43 TRANSPLANTED CORD BLOOD UNITS International Local

44 Units Collected Total 2,932 units Contaminated Units Bacterial Viral 18 units 132 units

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