Non-Myeloablative Allogeneic Transplantation (NMT) with T-Cell Replete Graft for Relapsed Chemosensitive Follicular Lymphoma (FL): Donor Lymphocyte Infusion (DLI) To Convert Stable Mixed Chimerism to Full Donor Chimerism Is Not Necessary in the Absence of Disease Progression.
Authors: Khouri Issa F. , Lee Ming-Sheng , Saliba Rima M. , Acholonu Sandra A. , Valverde Rosamar , Korbling Martin J. , Champlin Ricahrd E. 
Published: April 2020

Abstract
DLI is commonly provided for mixed chimerism post NMT, even in the absence of measurable disease. This is with a high risk for graft-versus-host disease (GVHD) and a major cause of mortality and morbidity after NMT. We hypothesized that this practice may not be routinely needed in pts with indolent diseases, such as FL, and who continue to have stable mixed chimera (SMC) after NMT. We defined SMC as presence 50% to 99% donor cells by PCR analysis, and without any significant decrease of &gt; 20% on two consecutive analysis. We treated prospectively 47 pts with relapsed FL with a NMT after conditioning with fludarabine, cyclophosphamide and high-dose rituximab as previously described (Blood89:3595, 2001). ATG was added for 2 pts receiving unrelated transplants. Tacrolimus and methotrexate were used for GVHD prophylaxis. All pts received a non-manipulated graft, from peripheral blood (45 pts) or marrow (2 unrelated donors). At the time the first analysis was undertaken post NMT (median 30 days), 13 of 18 pts (72%) in clinical complete remission (CR) and 24 of 29 pts (83%) who had evidence of active disease at study entry had mixed chimera (P = 0.2). The % of donor cells were 93% and 75%, respectively. When the subsequent PCR analysis to assess engraftment was undertaken (median time, 89 days post NMT), median % donor cells were 100% and 95%, respectively, for the pts who were in CR or had active disease at study entry. All pts achieved CR post NST. Median time to achieve CR for pts who had active disease at study entry was 5.5 months after transplant. Twelve pts in CR continue to have SMC at the time of their last PCR analysis, undertaken at a median of 12 months (range, 6 to 55 months) post NMT. Nineteen pts were tested for the amplification of bcl-2 rearrangement from the marrow by PCR. They all had evidence of clonal disease prior study entry. All converted to PCR-negativity. Sixteen of these 19 pts had mixed chimera when they were first tested to be PCR (−) at a median time of 3 mos (range, 1–6 months) post NMT. At a median time follow-up time of 34 months, overall survival and disease-free survival of all 47 pts at 3-year were 88 and 85%, respectively. Only one relapse occurred. This occurred in a pt who had 60% donor at 3 months post NMT; it then decreased to 42% at 9 months. This was followed by graft failure and relapse. DLI was provided to only one pt with decreasing chimerism. This resulted to conversion to full donor after the infusion of to 1 x 105 CD3+ cells/kg, from the HLA-identical sibling donor. The incidence of acute grade II–IV and chronic (extensive and limited) GVHD in the study was 17% and 51%, respectively. These data suggest that DLI may not be needed for SMC after non-T cell depleted NMT for pts with FL who do not have evidence of progression. This strategy resulted in lower than expected acute and chronic GVHD and improved survival.