Pediatr Blood Cancer 2015;62:1285–1287
BRIEF REPORT Allogeneic Donor Availability for Hematopoietic Stem Cell Transplantation in Children With Sickle Cell Disease David Justus, MD,1 Evelio Perez-Albuerne, MD, PhD,2 Jacqueline Dioguardi, David Jacobsohn, MD, ScM,2 and Allistair Abraham, MD2* Hematopoietic stem cell transplant is curative of sickle cell disease (SCD) but limited by donor availability. Searches for 85 patients with SCD without matched sibling donors from 2009–2013 using modern techniques (allele-level HLA matching for unrelated donors and higher total nucleated cell doses for umbilical cord blood (UCB)) showed potential match
MSHS,
2
probabilities of 20% for 8/8 HLA-matched unrelated donors, 84% for 7/8 donors, and 97% for two 4-6/6 UCBs suitable for ex-vivo expanded/double cord transplant. Searches performed by age 43 months would have a 90% chance of finding a suitable 5-6/6 UCB. Pediatr Blood Cancer 2015;62:1285–1287. # 2015 Wiley Periodicals, Inc.
Key words: BMT; transplantation; sickle cell disease
INTRODUCTION Over 300,000 patients with Sickle Cell Disease (SCD) are born annually worldwide [1]. The only available cure for SCD is hematopoietic stem cell transplant (HSCT). Using HLA-matched related donors, HSCT is successful with over 80% of recipients cured [2–5]. However, only 14% of patients have a suitable HLAidentical sibling [6]. In 2003, a study using the National Marrow Donor Program (NMDP) registry reported a 60% chance of finding a 6/6 HLA matched unrelated donor (URD) or umbilical cord blood (UCB) unit for SCD or thalassemia patients [7]. However, this study did not account for total nucleated cell (TNC) dose in UCB units, and the matching was only at the antigen level for the URD. The number of URD in the NMDP registry increased from 4 million to 10.5 million in the last decade [7,8]. Recent data demonstrate better outcomes with allele-level (compared with antigen-level) HLA matching for URDs [9,10] and higher TNC doses for UCB transplants in SCD [11]. A 2014 publication described the likelihood of an African–American finding a matched URD was 19% [8]. In that NMDP study, the TNC doses for UCB were lower than those used for SCD and more appropriate for malignant disorders. We aimed to reassess the alternative donor pool for patients with SCD, taking into account modern HLA matching criteria and UCB TNC dose targets.
MATERIALS AND METHODS Study Population Data were retrospectively collected on all patients with SCD in the Children’s National Health System in Washington, DC who underwent HLA typing from 2009 to 2013, did not have a matchedrelated donor, and met disease severity criteria for possible URD or UCB transplant (approved by Children’s National IRB).
Donor Searches URD and UCB searches were performed through the NMDP registry. Potential URD had to be less than 45 years old [12,13] and have 5% chance of being 8/8 or 7/8 allele-level HLA-matched by HapLogic NMDP search algorithm. For UCB C
2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25439 Published online 7 February 2015 in Wiley Online Library (wileyonlinelibrary.com).
units, HLA-matching was antigen- for HLA–A and B, and allele-level for DRB1.
UCB TNC Dose TNC dose for single cord transplant was based on previous data from hemoglobinopathy transplants showing that TNC dose of 5 107/kg was associated with better engraftment [11]. The cell doses for double cord transplants (two 4-6/6 HLA-matched units with TNC >2.5 107/kg but 5 107/kg. **At least two UCB units with cell dose of TNC/kg >2.5 107/kg (but 2.5 107/kg (but less
BRIEF REPORT Allogeneic Donor Availability for Hematopoietic Stem Cell Transplantation in Children With Sickle Cell Disease David Justus, MD,1 Evelio Perez-Albuerne, MD, PhD,2 Jacqueline Dioguardi, David Jacobsohn, MD, ScM,2 and Allistair Abraham, MD2* Hematopoietic stem cell transplant is curative of sickle cell disease (SCD) but limited by donor availability. Searches for 85 patients with SCD without matched sibling donors from 2009–2013 using modern techniques (allele-level HLA matching for unrelated donors and higher total nucleated cell doses for umbilical cord blood (UCB)) showed potential match
MSHS,
2
probabilities of 20% for 8/8 HLA-matched unrelated donors, 84% for 7/8 donors, and 97% for two 4-6/6 UCBs suitable for ex-vivo expanded/double cord transplant. Searches performed by age 43 months would have a 90% chance of finding a suitable 5-6/6 UCB. Pediatr Blood Cancer 2015;62:1285–1287. # 2015 Wiley Periodicals, Inc.
Key words: BMT; transplantation; sickle cell disease
INTRODUCTION Over 300,000 patients with Sickle Cell Disease (SCD) are born annually worldwide [1]. The only available cure for SCD is hematopoietic stem cell transplant (HSCT). Using HLA-matched related donors, HSCT is successful with over 80% of recipients cured [2–5]. However, only 14% of patients have a suitable HLAidentical sibling [6]. In 2003, a study using the National Marrow Donor Program (NMDP) registry reported a 60% chance of finding a 6/6 HLA matched unrelated donor (URD) or umbilical cord blood (UCB) unit for SCD or thalassemia patients [7]. However, this study did not account for total nucleated cell (TNC) dose in UCB units, and the matching was only at the antigen level for the URD. The number of URD in the NMDP registry increased from 4 million to 10.5 million in the last decade [7,8]. Recent data demonstrate better outcomes with allele-level (compared with antigen-level) HLA matching for URDs [9,10] and higher TNC doses for UCB transplants in SCD [11]. A 2014 publication described the likelihood of an African–American finding a matched URD was 19% [8]. In that NMDP study, the TNC doses for UCB were lower than those used for SCD and more appropriate for malignant disorders. We aimed to reassess the alternative donor pool for patients with SCD, taking into account modern HLA matching criteria and UCB TNC dose targets.
MATERIALS AND METHODS Study Population Data were retrospectively collected on all patients with SCD in the Children’s National Health System in Washington, DC who underwent HLA typing from 2009 to 2013, did not have a matchedrelated donor, and met disease severity criteria for possible URD or UCB transplant (approved by Children’s National IRB).
Donor Searches URD and UCB searches were performed through the NMDP registry. Potential URD had to be less than 45 years old [12,13] and have 5% chance of being 8/8 or 7/8 allele-level HLA-matched by HapLogic NMDP search algorithm. For UCB C
2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25439 Published online 7 February 2015 in Wiley Online Library (wileyonlinelibrary.com).
units, HLA-matching was antigen- for HLA–A and B, and allele-level for DRB1.
UCB TNC Dose TNC dose for single cord transplant was based on previous data from hemoglobinopathy transplants showing that TNC dose of 5 107/kg was associated with better engraftment [11]. The cell doses for double cord transplants (two 4-6/6 HLA-matched units with TNC >2.5 107/kg but 5 107/kg. **At least two UCB units with cell dose of TNC/kg >2.5 107/kg (but 2.5 107/kg (but less
