Salvage Therapy for Graft Rejection with Second Haploidentical Allogeneic Stem Cell Transplantion (Haplo-HCT) from a Second Related Donor

Introduction: Haplo-HCT is used increasingly as a treatment for patients with hematologic disorders lacking suitable HLA matched donors. Graft failure or rejection after myeloablative conditioning (MAC) carries high mortality. We present case of a patient with graft rejection post haplo-HCT salvaged with second haplo-HCT using second related donor.

Case Report: A 28 year old male presented with 3 week history of progressive weakness. He was severely pancytopenic with WBC of 2.4, Hb of 4g/dl and platelet count of 14k. Work-up for secondary causes of pancytopenia was negative. Complete blood count performed a year earlier was normal. Bone marrow was 70% cellular with dyserythropoiesis, decreased megakaryocytes and normal myeloid precursors. Marrow cytogenetics and Fluorescent in-situ Hybridization panel for myelodysplastic syndrome was normal. Peripheral blood flow cytometry for paroxysmal nocturnal hemoglobinuria showed a small CD59 deficient red cell clone (1.9%). His cytopenias progressed on high dose steroids. Repeat marrow 4 weeks later was similar to his original marrow. Patient had no suitable HLA matched related or unrelated donor. He underwent T cell replete peripheral blood stem cell transplantation (PBSCT) from his haplomatched sister following MAC with fludarabine (FLU), busulfan and cyclophosphamide (CY) with post transplant CY (PTC) and graft versus host disease (GVHD) prophylaxis with mycophenolate mofetil (MMF) and tacrolimus. Cell dose was CD34/kg 5 x 10⁶ and CD3/kg 4.76 x 10¹⁰. Pretransplant screening for donor specific antibodies (DSA) was negative. Four weeks after transplant, patient remained severely pancytopenic. Bone marrow exam showed an acellular marrow and peripheral chimerism studies was fully recepient. Repeat screening for DSA was again negative. Patient underwent a second T cell replete PBSCT on day 39 using his haplomatched father as the donor. The identical haplotype of the father was different from his original donor. Patient underwent reduced intensity conditioning with FLU, CY and TBI 200 cGy with standard PTC and GVHD prophylaxis with MMF and tacrolimus. Post second transplant, patient neutrophil and platelet engrafted on day 19 and day 32 respectively. Chimerism post second haplo-HCT was fully donor. During hospital course patient had multiple complications. He developed fungemia (Debaryomyces species) on day 24 post first transplant. Post second transplant he developed oliguric renal failure requiring transient hemodialysis and liver function test (LFT) abnormalities with peak bilirubin of 12.1mg/dl. Liver biopsy showed drug induced toxicity. Both his renal function and his LFT have since improved and are near normal.

Conclusion: Graft rejection in a patient undergoing haploidentical transplant could be successfully salvaged with a second transplant using a different haploidentical donor and with reduced intensity conditioning.