Allogeneic donor availability for hematopoietic stem cell transplantation in children with sickle cell disease

Justus, David G.; Perez-Albuerne, Evelio; Dioguardi, Jacqueline; Jacobsohn, David A.; Abraham, Allistair

doi:10.1002/pbc.25439

Cited by 37 publications

(34 citation statements)

References 15 publications

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“…However, the cumulative incidence of chronic graft-versus-host disease (GVHD) was high at 62%, including 6 patients who died from the complication, making these results less encouraging. While investigators will undoubtedly work toward decreasing this GVHD risk a major obstacle that remains is the probability of finding an HLA-matched unrelated donor who actually proceed with donation for SCD transplant is as low as 9% [32]. This likely reflects a larger issue of insufficient donors of African descent represented on donor registries given that the vast majority of patients with SCD are of African descent.…”

Section: Current State Of Hematopoietic Stem Cell Transplantation Formentioning

confidence: 99%

“…Unrelated donor transplant for SCD is still in early stages, but even when including fully matched unrelated donors and suitable single cord blood units as graft sources, over half of the patients may still not have a suitable donor option [32]. Haploidentical, or HLA half-matched, donors have also been considered as a graft source since the majority of patients should have a first degree relative who could be a potential donor.…”

Section: Current State Of Hematopoietic Stem Cell Transplantation Formentioning

confidence: 99%

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Cellular therapy for sickle cell disease

2016

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Sickle cell disease (SCD) is a monogenic red cell disorder affecting over 300,000 annual births worldwide and leading to significant organ toxicity and premature mortality. While chronic therapies such as hydroxyurea have improved outcomes, more durable therapeutic and curative options are still being investigated. Newer understanding of the disease has implicated invariant NKT (iNKT) cells as a critical immune profile that potentiates SCD. Hence, targeting this cell population may offer a new approach to disease management. Hematopoietic stem cell transplant (HSCT) is a curative option for patients with SCD, but the under-representation of minorities on the unrelated donor registry means that this is not a feasible option for >75% of patients. Work in this area has therefore focused on increasing the donor pool and decreasing transplant-related toxicities to make this a treatment option for the majority of patients with SCD. This review focuses on the currently available cell and gene therapies for patients with SCD, and acknowledges that newer gene editing approaches to improve gene therapy efficiency and safety are the next wave of potentially curative approaches.

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Section: Current State Of Hematopoietic Stem Cell Transplantation Formentioning

confidence: 99%

Section: Current State Of Hematopoietic Stem Cell Transplantation Formentioning

confidence: 99%

Cellular therapy for sickle cell disease

2016

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“…A recent study with detailed matching demonstrated that the chances of finding a potential allelic 8/8 HLA-A,-B,-C and -DRB1 MUD was only 19%. 28 Combining 5/6 and 6/6 HLA-matched cords (HLA-A,-B antigen; DRB1 potential allele) with higher cell doses as needed for hemoglobin disorders (TNC count of at least 5 × 10 7 cells/kg) could increase the alternative donor option. When this was examined, the probability of a potential 8/8 MUD, 5/6 or 6/6 unrelated cord in SCD improved the chances, but they remained relatively low at 45%.…”

Section: Alternative Donor Transplantationmentioning

confidence: 99%

“…When this was examined, the probability of a potential 8/8 MUD, 5/6 or 6/6 unrelated cord in SCD improved the chances, but they remained relatively low at 45%. 28 …”

Section: Alternative Donor Transplantationmentioning

confidence: 99%

Hematopoietic Stem Cell Transplantation for Patients with Sickle Cell Disease

Fitzhugh¹,

Abraham

Tisdale³

et al. 2014

Hematology/Oncology Clinics of North America

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Synopsis Considerable progress has been achieved in allogeneic hematopoietic stem cell transplantation (HSCT) for patients with sickle cell disease. Many studies have solidified matched sibling marrow, cord blood, or mobilized peripheral blood as the best source, with low graft rejection and graft versus host disease (GvHD), and high disease-free survival rates. For transplant eligible patients without HLA-matched sibling donors, fully allelic matched unrelated donor appears to be the next best option, though ongoing studies in sickle cell disease will provide data that are currently lacking. In general, unrelated cord transplant studies reported relatively high GvHD rates and low engraftment rates. Haploidentical transplants have emerged in the last decade to have less GvHD, but improvements are needed to increase the low engraftment rate. As there is no clear preferred choice, the decision to use unrelated cord blood units or haploidentical donors depends on the institutional expertise, and performed in the context of clinical trials. Data regarding 7/8 or lower matched unrelated donors are discouraging. Before routine use of these less matched donor sources, work is needed to improve patient selection, conditioning regimen, and/or GvHD prophylaxis.

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“…However, this matching was done at the serological level for HLA-A and-Band at the potential allele level for -DRBl. A recentlook at this scenario that incorporated more detailed matching demonstrated that the chances of a sickle cell patient finding a potential allele 8/8 HLA-A,-B,-C and -DRBl MUD was only 19% [22]. Combining 5/6 and 6/6 HLA-matched cords (HLA-A,-B antigen; DRB1 potential allele) with higher cell doses as needed for hemoglobin disorder transplants (total nucleated cell count of at least 5 × 10 6 /kg) could increase the alternative donor option.…”

Section: Introductionmentioning

confidence: 99%

Alternative Donor/Unrelated Donor Transplants for the β-Thalassemia and Sickle Cell Disease

Fitzhugh¹,

Abraham²,

Hsieh³

2017

Advances in Experimental Medicine and Biology

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Considerable progress with respect to donor source has been achieved in allogeneic stem cell transplant for patients with hemoglobin disorders, with matched sibling donors in the 1980s, matched unrelated donors and cord blood sources in the 1990s, and haploidentical donors in the 2000s. Many studies have solidified hematopoietic progenitors from matched sibling marrow, cord blood, or mobilized peripheral blood as the best source-with the lowest graft rejection and graft versus host disease (GvHD), and highest disease-free survival rates. For patients without HLA-matched sibling donors, but who are otherwise eligible for transplant, fully allelic matched unrelated donor (8/8 HLA-A, B, C, DRB1) appears to be the next best option, though an ongoing study in patients with sickle cell disease will provide data that are currently lacking. There are high GvHD rates and low engraftment rates in some of the unrelated cord transplant studies. Haploidentical donors have emerged in the last decade to have less GvHD; however, improvements are needed to increase the engraftment rate. Thus the decision to use unrelated cord blood units or haploidentical donors may depend on the institutional expertise; there is no clear preferred choice over the other. Active research is ongoing in expanding cord blood progenitor cells to overcome the limitation of cell dose, including the options of small molecule inhibitor compounds added to ex vivo culture or co-culture with supportive cell lines. There are inconsistent data from using 7/8 or lower matched unrelated donors. Before routine use of these less matched donor sources, work is needed to improve patient selection, conditioning regimen, GvHD prophylaxis, and/or other strategies.

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Allogeneic donor availability for hematopoietic stem cell transplantation in children with sickle cell disease

Cited by 37 publications

References 15 publications

Cellular therapy for sickle cell disease

Cellular therapy for sickle cell disease

Hematopoietic Stem Cell Transplantation for Patients with Sickle Cell Disease

Alternative Donor/Unrelated Donor Transplants for the β-Thalassemia and Sickle Cell Disease

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