HLA-Haploidentical Stem Cell Transplant with Pre-Transplant Immunosuppression for Patients with Sickle Cell Disease

Allogeneic stem cell transplantation (HCT) is curative in patients with severe sickle cell disease (SCD) but a significant number of patients lack a HLA-identical sibling or matched unrelated donor. Mismatched related (haploidentical) HCT with post-transplant cyclophosphamide(PTCY) allows expansion of the donor pool but is complicated by high rates of graft failure. In this report, we describe a favorable haploidentical HCT approach in a limited cohort of sickle cell patients with significant co-morbidities. To reduce the risk of graft failure we administered the conditioning regimen of rabbit anti-thymocyte globulin, busulfan (BU) and fludarabine (FLU) preceded with two courses of pre-transplant immunosuppressive therapy (PTIS) with FLU and dexamethasone (DEX). Graft-versus-host disease (GVHD) prophylaxis consisted of PTCY on days +3 and +4 followed by tacrolimus and mycophenolate mofetil (MMF) starting on day +5. Four patients (ages 13, 19, 19 and 23 years) received T-cell replete haploidentical stem cell infusion. All patients engrafted with 99.9-100% donor chimerism and all patients continue with stable engraftment at the last follow up (5 - 11 months post-transplant). Time to neutrophil engraftment was 14-26 days. Two patients had high levels of donor specific anti-HLA antibodies (DSA), which required the implementation of an antibody management protocol. This facilitated neutrophil engraftment on day +16 and day +26 respectively. One patient developed grade 1 acute GVHD which resolved. 3 patients developed mild, limited skin GVHD which responded to conventional immunosuppressive therapy. Human herpes virus 6 (HHV6) viremia was detected in three patients but resolved without treatment. One patient developed asymptomatic Cytomegalovirus (CMV) viremia which responded appropriately to standard therapy with ganciclovir. The prompt, stable engraftment and low toxicity in the post-transplant period makes PTIS with haploidentical transplant a promising option for the patients with SCD.