Haploidentical Allogeneic Hematopoietic Cell Transplantation as Salvage Therapy for Engraftment Failure After Unrelated and Autologous Cell Transplantation.

Abstract 4529

Engraftment failure is a rare but life-threatening complication of hematopoietic stem cell transplantation. The treatment of this condition is often challenging. We firstly reported haploidentical donor stem cells transplantation resulted in hematological reconstitution and long-time disease-free survival in a patient who developed engraftment failure after unrelated donor allogeneic stem cell transplantation and failure rescue treatment by re-infusion of autologous “back-up” stem cells. The 39-years-old male patient with acute myeloid leukemia(AML)-M2a achieved complete remission (CR) after one course of induction chemotherapy. He entered a lasting CR with 7 courses post-remission consolidation therapy and decided to receive unrelated donor allogeniec stem cell transplantation. In case of engraftment failure after allo-HSCT, autologous “back-up” cells were harvested after the last course chemotherapy (IDA 15 mg on days 1–2, 10 mg on day 3, Ara-c 300 mg on days 1–3, 200 mg on day 4), and mobilized with G-CSF 5 mg/kg/day for 5 days. The “back-up” cells consisting of 9.94×10⁶/kg CD34+ cells were cryopreservated in liquid nitrogen. Fifteen months after de novo AML, the patient received a myeloablative conditioning regimen of busulfan and cyclophosphamide (busulfan 3.2 mg/kg/day on days -7 to -4, and cyclophosphamide 60 mg/kg/day on days -3 to -2), and an infusion of unrelated allogeneic peripheral stem cells from the Chinese Marrow Donor Program with a HLA-Cw allele mismatch on day 0. The graft contained 11.07×10⁸/kg nucleated cells and 6.35×10⁶/kg CD34+ cells. Pancytopenia was continuously observed during 28 days after transplantation and short tandem repeat-polymerase chain reaction (STR-PCR) analysis showed no donor chimera. As a rescue attempt for graft failure, cryopreservated autologous cells were re-infused on day +28. Unfortunately, pancytopenia was still continuously observed during 23 days after re-infused of “back-up” cells(51 days after unrelated transplantation), and bone marrow examination revealed severe bone marrow hypoplasia. On day +57 and +58 after unrelated transplantation, bone marrow cells containing 2.1×10⁶/kg CD34+ stem cells and peripheral blood cells containing 2.81×10⁶/kg CD34+ stem cells from a haploidentical donor sister (HLA matched in 5/10 alleles by high-resolution genotyping) were infused respectively after reduced-intensity conditioning with fludarabine and ATG (fludarabine 30mg/m²/d on day -5 to -1, ATG 100mg/d on day -4 to -1). Absolute neutrophil count >0.5×10⁹/L was documented on day 12 after haploidentical transplantation. He achieved platelets count >20×10⁹/L on day 28 after haploidentical transplantation. Twenty-nine days after haploidentical transplantation, bone marrow examination showed reconstitution and STR-PCR analysis indicated complete donor chimera. No grades III -IV aGVHD, extensive chronic GVHD, and severe infection after transplantation were observed. Recurrent bone marrow aspiration examinations showed the patient had been in CR. The patient remained alive during a 18-month follow-up after haploidentical transplantation. Our experience suggests that combined haploidentical donor BM and PBSC transplantation after Flu- and ATG-based conditioning could provide an effective therapeutic strategy for engraftment failure after unrelated allo-HSCT in adult patients. Considering the accessibility of haploidentical donors, haploidentical transplantation has the potential to act as a first-line choice for salvage therapy.