Umbilical Cord Blood Stem Cells Current Status & Future Potential

Umbilical Cord Blood Stem Cells Current Status & Future Potential Natasha Ali Assistant Professor Haematology Department of Pathology & Laboratory Medicine/Oncology The Aga Khan University Email: natasha.ali@aku.edu

Disclosure None 16-Oct-15 AATM 2015 2

Outline Stem cells, cord blood.basis Role of HLA typing Current status of cord blood transplant Future uses of cord stem cells Cord blood banking at AKUH Summary 16-Oct-15 AATM 2015 3

Stem cell What is it after all? The body's "master" cell/s Create all other tissues, organs, and systems in the body Building blocks of blood and immune system Can replicate into red blood cells, white blood cells and platelets 16-Oct-15 AATM 2015 5

Types of stem cells present in cord blood Haemopoeitic stem cells Endothelial progenitors, hemangioblasts and hemogenic endothelium Mesenchymal stem cells Revascularization of ischemic tissues Unrestricted somatic stem cells Number 10 times higher than adult blood Very small embryonic epiblast like stem cell Multipotential stem cells Treatment of GVHD CD45 negative stem cell Most primitive population Pluripotential capability 16-Oct-15 AATM 2015 6

History 1974: Discovery/ First report 1988: Gluckman 1 st sibling transplant with UCB 1993: Kurtzburg 1 st UCB transplant unrelated donor 1982:Broxmeyer suggested UCB contained HST 1992: Rubenstein Established 1 st Cord Blood bank 1998: Rubenstein published outcome of 562 recipients of UCB Tx 16-Oct-15 AATM 2015 7

First prospective study: COBLT Outcome of n=191 patients with haematological malignancies Median age: 7.7 years Enrolled between 1999-2003 16-Oct-15 AATM 2015 8

COBLT study - results Median TNC 5.1 x 10 7 /kg Acute GVHD 19.5% Chronic GvHD 20.8% CI of relapse (2 yrs) 19.9% 16-Oct-15 AATM 2015 9

HLA typing 16-Oct-15 AATM 2015 11

What has happened so far. The year 2013 marked the 25 th anniversary of the first UCBT Last 25 years the field of UCB banking and transplantation has grown exponentially More than 30,000 UCBTs have been performed (2013) Over 600,000 UCB units have been stored worldwide 16-Oct-15 AATM 2015 13

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Stem cell sources for allogeneic transplant by year * *With permission 16-Oct-15 AATM 2015 15

Allogeneic stem cell sources by recipient s age * *With permission 16-Oct-15 AATM 2015 16

Allogeneic transplants for age 20 years * *With permission 16-Oct-15 AATM 2015 17

Allogeneic transplants for age 20 years * *With permission 16-Oct-15 AATM 2015 18

Unrelated cord blood transplants by age * *With permission 16-Oct-15 AATM 2015 19

UCBT in adults Ballen et al 2013 16-Oct-15 AATM 2015 20

Related cord blood transplants 17 12 3 6 109 Acute Leukemia MDS CML LPD Solid tumour 16-Oct-15 AATM 2015 21

EuroCord registry data 16-Oct-15 AATM 2015 22

Combined data EuroCord & CIBMTR 16-Oct-15 AATM 2015 23

Current status In 1998, the foundation NETCORD was developed establish an international registry Following this, NETCORD-Foundation for accreditation of cellular therapy (FACT) was established published standards in 2008 There are now 2 international registries 1) NETCORD 2) Bone Marrow Donors Worldwide 16-Oct-15 AATM 2015 24

Current status Extensive analytical expertise in evaluating efficacy and outcome is provided by 1) EuroCord 2) Center for International Blood and Bone Marrow Transplant Research (CIBMTR) Donor selection process for Umbilical cord blood banks: 1) Carefully conducted 2) Stringent family history to minimize potential risk of transmitting unrecognized hereditary disorders 16-Oct-15 AATM 2015 25

Rationale for UCBT in Pakistan Allo SCT at AKUH (2004-2014) Despite large family sizes potential donor not identified in 30% of cases 16-Oct-15 AATM 2015 26

Future uses for cord stem cells Mainly used for the treatment of haematological disorders Novel applications in non-haematopoietic diseases as part of regenerative therapy or immune modulation 16-Oct-15 AATM 2015 28

1 1 1 1 1 1 1 1 1 1 1 16-Oct-15 AATM 2015 29

Preclinical success in animal models Newcomb et al 16-Oct-15 AATM 2015 30

Future potential Considered an accessible, less immunogenic source for Mesenchymal Unrestricted somatic Other stem cells with multipotent properties Expanding the use for non-preconditioned adult recipients regenerative purpose 16-Oct-15 AATM 2015 31

Cryopreservation at AKUH Established Laboratory Standard operating procedures Validation Reading material/brochures Consent/storage agreement forms

Stem cell storage laboratory

Summary More than 25 years; over 600,000 units stored worldwide Applicability for children and adults in malignant and nonmalignant disorders Plausible future use in the field of regenerative medicine UCBT fill the gap of a growing population of patients without matched donors for a potentially curative disease 16-Oct-15 AATM 2015 38