Hematopoietic Stem Cell Transplantation in Sickle Cell Disease, Experience of a Brazilian Private Service

Introduction:

Since the enactment of the Sickle Cell Anemia Act, significant progress has been made in the screening and treatment of sickle cell disease. Despite advancements in medical therapies, sickle cell disease remains incurable for most affected individuals. Hematopoietic stem cell transplantation is currently the only available curative option for those living with the condition.

Methods:

We have collected retrospective data from a single-center, observational cohort study on all allogeneic stem cell transplantations for sickle cell disease performed at Beneficência Portuguesa of São Paulo, from 2021 to the present.

Results:

Since 2021, we have performed sixteen hematopoietic stem cell transplantation (HSCT) for sickle cell disease. Of these, ten were male and six were female, with a median age of 14 years (range: 5-23 years). Eleven patients had haploidentical HLA donors, and five had HLA-identical donors. All transplants used fresh bone marrow infusions, and none of the patients had donor-specific antibodies. In our cohort, the indications for transplantation were acute chest pain (N=8), stroke (N=5), recurrent pain crises (N=3), splenic sequestration (N=1), alloimmunization (N=1), and Moyamoya disease (N=1). The conditioning regimens used were Fludarabine/Cyclophosphamide/Tiotepa/Total Body Irradiation/Anti-Thymocyte Globulin (N=11) for haploidentical donors and Busulfan/Cyclophosphamide/Anti-Thymocyte Globulin (N=5) for HLA-identical donors. Graft-versus-host disease (GVHD) prophylaxis included post-transplant cyclophosphamide/sirolimus/mycophenolate mofetil (N=5), post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil (N=6), and cyclosporine/methotrexate (N=5). The median time to neutrophil engraftment was 17.5 days (range: 14-22 days), with HLA-identical transplants showing a shorter median of 17 days (range: 14-21 days) compared to 21 days for haploidentical transplants. The median time to platelet engraftment was 25 days (range: 19-42 days), with haploidentical transplants at 25 days (range: 19-30 days) and HLA-identical transplants at 27 days (range: 15-42 days). Two patients did not achieve platelet engraftment. Peripheral blood chimerism was evaluated on day 30, showing complete chimerism in all but one patient, who had 9% chimerism. By day 100, three patients exhibited mixed chimerism (38%-79%). During follow-up, two patients developed graft failure with autologous recovery: one primary and one secondary. Cytomegalovirus reactivation occurred in 13 cases, all of which received preemptive therapy. GVHD was common but generally mild, with skin manifestations (Grade I, N=5; Grade II, N=1). However, two cases had severe intestinal manifestations (Grade IV, N=2), with one being steroid-refractory. Currently, one patient has chronic GVHD with pulmonary manifestations. The median follow-up duration is 364 days (range: 69-904 days). One 19-year-old male patient experienced an expansive intracranial hemorrhage during transplantation and subsequently died. Two other patients died from sepsis during long-term follow-up

Conclusion

HSCT for sickle cell anemia is feasible in a lower-resourced country. Despite the benign pathophysiology of sickle cell disease, the graft failure ideally should not occur. However, given the high-risk nature of this population, mortality rates remain significant when the natural course of the disease is followed. The high cost of gene therapy for sickle cell disease limits its accessibility. Therefore, in countries like Brazil, with many sickle cell patients, HSCT will likely remain the only viable and accessible option. This small cohort study demonstrates that performing the transplant in a tertiary hospital can be done safely.

Scheinberg:Astellas: Consultancy; Novartis: Consultancy, Speakers Bureau; BMS: Consultancy; Pfizer: Consultancy, Research Funding, Speakers Bureau; Alnylam: Research Funding; Roche: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Janssen: Consultancy.