Spousal Hematopoietic Stem Cell Transplantation for Post-Transplant Relapse/Rejection

Topic Significance & Study Purpose/Background/Rationale: HLA haploidentical stem cell transplantation (SCT) has expanded donor sources from family members. Nevertheless, some patients have no donor candidate and no time to a select suitable donor, especially in post-transplant relapse or rejection. In kidney or liver transplantation, on the other hand, spousal transplant has been routinely performed. In this study, we presented six cases of spousal SCT for post-transplant relapse/rejection, and discussed the possibility of spousal SCT. Methods, Intervention, & Analysis: Six patients (M/F 4/2, 25-53 years old) underwent SCT from their spouse at Hyogo College of Medicine between October 2008 and November 2013 permission of IRB. Original diseases were acute leukemia (AML 2, ALL 2, MLL 1) and one case of NHL. All patients received a third SCT for post-transplant relapse except for one undergoing SCT for graft rejection after unrelated SCT. HLA disparity in GVH/HVG directions were 2/4, 3/3, 2/2, 5/6, 2/1, and 3/3 antigens in HLA A, B, DR. The conditioning regimen consisted of FLU/MEL/ATG with or without 3 Gy of TBI for relapse cases, and ATG plus 4 Gy of TBI for the rejection case. GVHD prophylaxis consisted of the continuous infusion of tacrolimus, 1 mg/kg/day of methylprednisolone, and 15 mg/kg/day of MMF. PBSC containing 1.78-8.46 * 10e6/kg of CD34+ cells were transplanted in all cases. Findings & Interpretation: Granulocyte engraftment was achieved on days 9-11 in all cases. Complete spousal chimerism in PB was confirmed on days 3-13 by STR-PCR. Acute GVHD was controllable except in the rejection case, who died of grade IV GVHD on day 39. All five relapse cases achieved complete remission once, and three could be discharged. One patient died of VOD/SOS on day 62, and one patient was transferred to her local hospital. The remaining four patients excluding GVHD and VOD/SOS cases finally developed disease relapse (in BM 2, CNS 2) on days 106-334, and died as a direct result on days 152-548. Discussion & Implications: Since these cases are refractory and they received their third SCT, we cannot refer to the GVL effect, and GVHD would be acceptable in spousal SCT. The immune recovery remains to be elucidated over a long-term follow-up.