medRxiv : the preprint server for health sciences · 2025
Nonmyeloablative Pentostatin-Cyclophosphamide Preconditioning Improves Rates of Engraftment in Adults Undergoing Haploidentical HCT for Sickle Cell Disease.
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Limerick Emily, Hsieh Matt, Queen Jackie, Grecco Mary Lacy, Varga Julia, Brooks Jennifer, Coles Wynona, Jeffries Neal, Fitzhugh Courtney
Аннотация
UNLABELLED: The morbidity and mortality of sickle cell disease (SCD) remain high. Novel nonmyeloablative haploidentical hematopoietic cell transplant (HCT) regimens are being proposed.
METHODS: This report compared the effect of adding an oral cyclophosphamide and IV pentostatin (PC) preconditioning to the nonmyeloablative NIH HCT platform of alemtuzumab and total body irradiation (TBI).
RESULTS: Thirty-nine adult SCD patients were included. The median age was 33 years, 61% were male, and 92% were HbSS genotype. The median follow-up was 6.5 years. Many patients had severe end-organ damage, including dialysis-dependent end-stage kidney disease (10%) and cirrhosis (8%).One-year overall survival was 95%. The PC regimen was associated with a reduction in acute rejection one-year post-HCT (5% vs. 44%; p=0.004) and lower graft failure rates throughout the follow-up period. After a median follow-up of 5.2 years, the disease-free survival was 71% for the PC regimen. The PC preconditioning was associated with higher rates of full donor chimerism at 2-years post-HCT (0% vs. 43%; p=0.02). Grade II-IV acute graft-versus-host disease (GVHD) rates were low; no patients developed moderate to severe chronic GVHD. There remain no cases of myeloid malignancy after PC. With the increased immunosuppression of PC, 23% of patients developed post-transplant lymphoproliferative disorder, 19% developed immune cytopenias, and 62% had viral reactivation.
SUMMARY: Further study to determine an optimal nonmyeloablative haploidentical regimen for SCD patients with compromised organ function is imperative.
METHODS: This report compared the effect of adding an oral cyclophosphamide and IV pentostatin (PC) preconditioning to the nonmyeloablative NIH HCT platform of alemtuzumab and total body irradiation (TBI).
RESULTS: Thirty-nine adult SCD patients were included. The median age was 33 years, 61% were male, and 92% were HbSS genotype. The median follow-up was 6.5 years. Many patients had severe end-organ damage, including dialysis-dependent end-stage kidney disease (10%) and cirrhosis (8%).One-year overall survival was 95%. The PC regimen was associated with a reduction in acute rejection one-year post-HCT (5% vs. 44%; p=0.004) and lower graft failure rates throughout the follow-up period. After a median follow-up of 5.2 years, the disease-free survival was 71% for the PC regimen. The PC preconditioning was associated with higher rates of full donor chimerism at 2-years post-HCT (0% vs. 43%; p=0.02). Grade II-IV acute graft-versus-host disease (GVHD) rates were low; no patients developed moderate to severe chronic GVHD. There remain no cases of myeloid malignancy after PC. With the increased immunosuppression of PC, 23% of patients developed post-transplant lymphoproliferative disorder, 19% developed immune cytopenias, and 62% had viral reactivation.
SUMMARY: Further study to determine an optimal nonmyeloablative haploidentical regimen for SCD patients with compromised organ function is imperative.