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Host Lymphocyte Depletion as a Strategy to Facilitate Early Engraftment Following Reduced Intensity Allogeneic Stem Cell Transplantation

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Published:25th Mar 2020

Reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (RIC-alloHSCT) is associated with lower toxicity but higher rates of prolonged mixed chimerism than myeloablative conditioning. Decreased pre-transplant host T-cell numbers are associated with less graft rejection and early full donor chimerism. To compensate for variability in pre-transplant host lymphocyte numbers and facilitate the achievement of rapid full donor chimerism, we tested a strategy of targeted lymphocyte depletion (TLD) using chemotherapy at conventional doses to provide cytoreduction and lymphocyte depletion prior to RIC-alloHSCT. 111 patients with advanced hematologic malignancies received 1-3 cycles of conventional-dose chemotherapy to reduce circulating lymphocytes to a predetermined level. Patients then underwent RIC-alloHSCT from HLA-matched siblings. Patients received a median of 2 cycles of TLD chemotherapy resulting in a median 71% decline in CD4+ count. All patients engrafted; there were no late graft failures. By Day +14, median CD3+ chimerism was 99% donor and was significantly associated with lower post-TLD CD4+ counts (p = 0.012). One and 5-year treatment-related mortality was 15% and 21%, respectively. At one-year follow-up, 66% of patients had achieved complete remission (CR) of which 92% were not in CR at the time of transplant. Overall survival at one and five years post-transplant was 66% and 47%,

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