Allogeneic Hematopoietic Cell Transplantation (HCT) after Nonmyeloablative Conditioning for Relapsed or Refractory Follicular Lymphoma.
Authors: Maris Michael B. , Sandmaier Brenda M. , Storer Barry , Agura Edward , Wade James , Maziarz Richard T. , Forman Stephen , Shizuru Judy , Chauncey Thomas , Kahl Christoph , Langston Amelia A. , Niederwieser Dietger , Storb Rainer , Maloney David G. 
Published: April 2020

Abstract
Forty-five patients (pts) with relapsed or chemotherapy refractory low-grade lymphomas were treated with HLA-matched related (n=22) and unrelated (n=23) HCT after nonmyeloablative conditioning using 2 Gy total body irradiation with or without fludarabine. Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. Lymphoma histologies included follicular (n=38), small lymphocytic (n=5), and marginal zone (n=2). Seven pts had prior intermediate-grade lymphoma transformation. The median pt age was 54 (range 34–67) years and median time from diagnosis to allogeneic HCT was 4.3 (0.5–18.5) years. Twelve pts had failed and 3 received cytoreductive autologous HCT before nonmyeloablative HCT. Disease status at time of nonmyeloablative HCT included complete remission (CR, n=16), partial remission (PR, n=12), refractory (n=11) and untested relapse (n=6). Prognostic scoring at the time of HCT using the Follicular Lymphoma International Prognostic Index (FLIPI) identified 25 low-risk and 19 intermediate-risk pts and using the International Prognostic Index (IPI) identified 26 low-risk, 13 low-intermediate risk, and 5 intermediate-high risk pts. There were insufficient data to score 1 pt by the FLIPI or by the IPI. All pts received G-CSF mobilzed peripheral blood mononuclear cells. Six of the 23 unrelated donor graft recipients had human leukocyte antigen (HLA) mismatches: one at a single allele, 4 at a single antigen, and one at an antigen and an allele. The median follow up after nonmyeloblative HCT was 23.8 (range 2– 44.9) months. One pt experienced non-fatal graft rejection of a single antigen mismatched unrelated graft. The cumulative probabilities (CP) of acute grades II-IV, III-IV and chronic GVHD were 60%, 18%, and 51%, respectively. Responses [CR (n=14) and PR (n=6)] were seen in 20 of 28 (71%) pts with measurable disease at HCT while 3 had stable and 3 progressive disease, and 2 were not evaluable due to early nonrelapse death. None of the 20 pts who responded and 3 of the 17 transplanted in CR had disease relapse. At 2 years, the CPs of overall relapse/progression, and non-relapse mortality were 15% and 34%, respectively. The 2-year Kaplan-Meier estimates of overall and progression free survival were 58% and 51%, respectively. Higher IPI and FLIPI scores modeled as continuous variables were independently associated with worse PFS (HR 1.55, p=0.05 and HR 1.35, p=0.10 respectively). Use of a HLA mismatched unrelated donor was associated with a trend for worse OS and PFS (HR 3.0, p=0.08 for both). Allogeneic HCT after nonmyeloablative conditioning is a promising salvage strategy for pts with relapsed and refractory indolent lymphoma. The high response and low relapse rates with this approach suggest that relapsed indolent lymphomas are susceptible to graft-versus-tumor responses.