Outcomes of Early Relapse Following Non-Myeloablative Allogeneic Transplant for Lymphoma.
Authors: Ram Ron , Gooley Ted , Maloney David G. , Press Oliver W. , Pagel John M. , Petersdorf Stephen H. , Shustov Andrei R. , Flowers Mary E.D. , Sandmaier Brenda M. , Storb Rainer F. , Gopal Ajay K. 
Published: October 2019

Abstract
Abstract 1204
Poster Board I-226
Non-myeloablative allogeneic transplantation (NMAT) has provided the potential benefit of allogeneic hematopoietic stem cell transplantation (allo-SCT) to a broader cohort of lymphoma patients via lowered non-relapse mortality (NRM). NMAT also provides a post-transplant platform of a chemotherapy-naïve graft for both myelosuppressive and immune-mediated anti-tumor therapies, though the lack of high-dose conditioning may also heighten the risk for early relapse. Herein, we describe the survival as well as factors associated with outcomes for lymphoma patients experiencing relapse within 200 days of NMAT. Between December, 1997 and April, 2009, 267 lymphoma/CLL patients underwent NMAT at our center, of which 70 (35%) relapsed within 200 days from transplant. Histologies were categorized as aggressive (n= 36) including diffuse large-B-cell (n=22), blastic mantle cell lymphoma (n=10) and T-lymphoblastic lymphoma (n=4), and indolent (n=21) with chronic lymphocytic leukemia (n=15), follicular lymphoma (n=3) and classic mantle cell lymphoma (n=3). We also evaluated patients with Hodgkin Lymphoma (n=13). Conditioning regimens included 2 Gy total body irradiation (TBI), fludarabine 30 mg/m2 daily x 3 days + 2 Gy TBI, and Y-90-Ibritumomab-tiuxetan+ fludarabine 30 mg/m2 daily x 3 days + 2 Gy TBI in 13, 41, and 16 patients, respectively. Grafts were from HLA-matched related (n=34) or unrelated (n=31), HLA-mismatched unrelated (n=3) and HLA-haploidentical related (n=2) donors. Interventions to treat relapse included chemotherapy and/or radiation therapy in 43 (61%) patients and no therapy or withdrawal of immunosuppression in the remaining 27 (39%). Donor lymphocyte infusion (DLI) was attempted in 9 patients. Overall survival (OS) from time of relapse at 3 and 5 years among all 70 patients was 28% (95% CI 16-41%) and 19% (95% CI 9-32), respectively. Aggressive histology was associated with increased mortality relative to indolent histology (HR for death=2.57 [1.28-5.14, p=0.008]), while Hodgkin Lymphoma had similar outcome to the indolent group (HR=1.04 [0.42-2.53, p=.94]). The 3-year OS among patients with aggressive and indolent histologies was 14% (95% CI 3-33%), and 43% (95% CI 21-64%), respectively (Figure). Later relapse was associated with improved survival (p=.01) with patients relapsing between 31 and 100 days and those relapsing between 101 and 200 days having a reduced hazard of mortality relative to those relapsing less within 30 days (HR=0.36 [0.17-0.75, p=.006]; HR=0.30 [0.13-0.69, p=.005], respectively). When both histology and time to relapse were included in one model, these associations were somewhat reduced but the qualitative conclusions remained. In particular, patients with aggressive disease had a 2.16-fold (1.10-4.23, p=.03) increase in mortality compared to patients with Hodgkin or indolent lymphoma; the group that relapsed from 31 to 100 days was 0.41 (0.19-0.88, p=.02) times as likely to die compared to the group that relapsed within 30 days and the group that relapsed 101-200 days was 0.43 (0.17-1.04, p=.06) times as likely to die compared to the early-relapse group. Patients with chemoresistant disease pre-transplant were 1.46 times more likely to die than those with responding disease, but this difference was not statistically significant (95% CI, 0.82-2.62, p=.20). Fifty-nine patients relapsed with measurable disease and had a higher risk of mortality compared to 11 patients with only blood or marrow evidence of relapse, but the difference in mortality was not statistically significant (HR=1.53 [0.71-3.29, p=.28]). Pre-relapse graft-versus-host disease, bone marrow involvement, remission status at transplant, number of prior therapies, comorbidity score, and disease bulk were not statistically significantly associated with survival. These data indicate that despite early relapse of lymphoma after NMAT, some patients can experience prolonged survival with the best outcomes in patients with indolent histology and later relapse, though further improvement in disease control for patients with aggressive lymphoma and very early relapse is needed.

Disclosures:
No relevant conflicts of interest to declare.