S114: feasibility of haploidentical allogeneic stem cell transplantation with post-transplant cyclophosphamide for patients with severe sickle cell disease with end-stage renal disease (esrd) on hemodialysis

Background: Adult patients with sickle cell disease (SCD) and ESRD have limited curative treatment options as many are deemed not to be candidates for an allogeneic transplant (SCT) or clinical trials. Furthermore, many patients lack a matched donor. Haploidentical (haplo) SCT with post-transplant cyclophosphamide (Cy) has improved the access to SCT. Mitigating the risk of graft loss for SCD patients undergoing haplo-SCT, two groups have reported successful engraftment with modified conditioning regimens - Fludarabine (Flu), Cy with augmented total body irradiation (TBI)(400 cGy) vs. Flu/Cy/TBI200cGy with additional thiotepa [1,2]. No patients with ESRD were included. Aims: To evaluate the feasibility of haplo-SCT with augmented TBI conditioning for a patient with SCD and ESRD Methods and Results: A 26-year-old male (B+, CMV-) with SCD and sickle nephropathy, on hemodialysis (HD), was referred for evaluation. The patient had a history of acute chest syndrome, priapism, and SVT. He had multiple hospitalizations in the 2 years prior to referral. His baseline Hb was 6 g/dl and he had mild liver iron overload. As there were no matched donors, his 19-yr-old, 8/12 sister (A+, CMV-), was evaluated. Due to a lack of data in ESRD, thiotepa was excluded and we opted for Flu/Cy/TBI400cGy conditioning. To avoid the risk of fludarabine neurotoxicity, dosing was decreased by 50% to 15 mg/m2 x 5 and HD was given more frequently. Rabbit-ATG was given. GvHD prophylaxis comprised of post-transplant Cy, MMF and sirolimus (fig 1). Prior to SCT, the patient underwent sperm cryopreservation, he received one dose of Rituximab for EBV prophylaxis, and he underwent exchange transfusion to target a Hb S <30%. Additional supportive therapy included: levetiracetam; ursodiol; and infection prophylaxis with posaconazole, levofloxacin, and valacyclovir. A total of 5.41 x 106/kg CD34+ PBSC were infused. No G-CSF was planned but it was added on day +15 due to slow engraftment. Neutrophil engraftment occurred at day +27. Platelets were kept above 50k and engraftment occurred at day +48. Pre-engraftment adverse events included radiation-induced parotiditis, neutropenic fever, and medication-induced rhabdomyolysis with muscle pain attributed to posaconazole (CK peaked on day +13 with levels >7800; posaconazole was switched to micafungin with adequate resolution). Upon discharge pen-VK, Valtrex and fluconazol were continued and he started SMZ-TMP. He was re-admitted twice - once for SVT, and again for pneumonia. Chimerism studies revealed a 96% donor chimerism on day +30, with subsequent sustained 100% donor chimerism from day +100. Hb electrophoresis has been normal. CD4 count at day +120 was 1795 cells/ul. Our patient has had no GVHD. Tapering of immunosuppression started at 9 months and completed at 11 months post-SCT. His new baseline Hb is 14 g/dl, his last RBC transfusion was on day +33 and monthly therapeutic phlebotomies were started at 9 months. The patient is currently 1.4 yrs post-SCT. Renal transplant evaluation is underway.Conclusion: Haploidentical transplantation with post-transplant Cy is a feasible approach for patients with severe SCD and ESRD. Patients require very close monitoring for complications by a specialized multidisciplinary team, but it can be a curative therapy with significant improvement in quality of life. References 1. Bolaños-Meade J et al. Lancet Haematol. 2019 Apr; 6(4) e183-e193 2. de la Fuente J et al. Biol Blood Marrow Transplant. 2019; 25(6) 1197–1209