Long Term Followup of Sickle Cell Disease Post Hematopoietic Stem Cell Transplant from Uganda

Abstract Introduction: Sickle cell disease (SCD) remains associated with high risk of morbidity and early death. Many patients in sub-Saharan Africa continue to experience severe complications despite best supportive care. Hematopoietic stem cell transplant (HSCT) can be considered for a select group of patients. When successful, HSCT is economical and improves quality of life. We report the experience from our south-south partnership whereby Ugandan patients with SCD have undergone HSCT at the Bone Marrow Transplant Center in Gurgaon, India Material and methods: 23 consecutive patients suffering from SCD who underwent HSCT between June 2014 and July 2017 were included in the study. Eleven underwent matched sibling donor bone marrow transplant (BMT) using busulfan 3.2 mg/kg/day for 4 days, cyclophosphamid 50mg/kg/day for 4 days, and hATG (PfizerATGAM) 30mg/kg/day for 3 days. Two adult patients underwent matched sibling donor HSCT using reduced intensity conditioning with busulfan 3.2 mg/kg/day for 4 days, cyclophosphamid 60mg/kg/day for 2 days, and ATG (PfizerATGAM) 30mg/kg/day x 3 days. Immune suppression for for HSCT patients was cyclosporine 3mg/kg/day in 2 divided doses starting D-4 and methotrexate 10mg/m2 on D+1 followed by 7mg/m2 on day 3, 6 and 11 post HSCT. Ten patients underwent haploidentical HSCT using hypertransfusion (target Hb 11-13gm/dl), hydroxyurea (20mg/kg/day) and azathioprine (2mg/kg/day) from day -45, conditioned with Thiotepa 10mg/kg in two divided doses (D-7), fludarabine 30mg/m2 (D-6 to D-2), cyclophosphamide 14.5 mg/kg (D-5, D-4), TBI 2Gy with thymic shielding (D-1), rATG (Genzyme Thymoglobulin) 1.5 mg/kg (D-9 to D-7). GVHD prophylaxis included PTCy 50 mg/kg/day on D3 and 4, tacrolimus (target level 5-15 ng/ml) or sirolimus (target levels 10-15ng/ml) (till 6 months post HSCT) and MMF (till D35) starting from D5. Results: The median patient age was 8 years (range 10 months-31 years). Before transplantation all patients had repeated episodes of SCD complications warranting a transplant. All were non-responsive to hydroxyurea. Of the 23 patients, 18 survived without sickle cell disease with Lansky/Karnofsky scores of 100. One had a primary graft failure another secondary graft failure with recurrence of disease. At median follow up of 479 days (range 51-1204) the probabilities of survival, SCD-free survival, and transplant-related mortality after transplant were 87%, 78%, and 13%, respectively. Three children who underwent haploidentical HSCT died. One died due to PRES with intracranial hemorrhage at day 86 post BMT, another one due to primary graft failure with Klebsiella sepsis with shock. The third child died due to complicated falciparum malaria and possible invasive fungal infection at day 24 post HSCT. He had full donor chimerism. Conclusion: Outcomes of HSCT in SCD have improved significantly. With better conditioning regimens and improved supportive care, alternative donor transplant and adult HSCT have become viable therapeutic options. HSCT should be strongly considered as a curative modality for selected patients suffering from SCD. Disclosures No relevant conflicts of interest to declare.

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