Prognostic Value Of Disease Status At Time Of Allogeneic Transplant For Relapsed Non-Hodgkin’s Lymphoma
Authors: Bakhos Shams , Aleah Brubaker L , Parthasarathy Mala , Go Aileen , Rodriguez Tulio E. , Stiff Patrick J , Smith Scott E. 
Published: October 2019

Abstract

Introduction
Non-Hodgkin’s Lymphoma (NHL) is the most common hematologic malignancy in the United States with 69,700 new cases and 19,000 deaths predicted in 2013. The majority of patients diagnosed with NHL respond well to conventional chemotherapy, however, patients with relapsed or refractory NHL usually have poor long-term outcomes. While autologous stem cell transplantation (auto-SCT) is a mainstay for patients with relapsed or refractory disease that are chemotherapy-sensitive, allogeneic stem cell transplantation (allo-SCT) has been used to treat NHL in patients who have relapsed after auto-SCT, are chemotherapy-resistant, or have adverse risk factors. While some evidence has suggested that chemotherapy-resistant disease status prior to allo-SCT is associated with a poor prognosis, limited data exists to guide evidence-based transplant paradigms. We sought to determine if disease status prior to allo-SCT in patients with relapsed or refractory NHL impacts outcomes.

Methods
A retrospective chart review identified 154 patients diagnosed with relapsed or refractory NHL who underwent an allo-SCT at Loyola University Medical Center between January 1998 and January 2012. Fifteen patients were excluded for lack of data yielding 139 patients over a 14-year period. Of our patients with relapsed or refractory disease, chemotherapy-sensitive patients were defined as patients with partial or complete response to chemotherapy at time of transplant. Chemotherapy-resistant patients were defined as patients that either had progressive disease or were refractory to chemotherapy at time of transplant. Data on age, sex, type of NHL, stage at diagnosis, chemotherapy regiment, previous auto-SCT, disease status prior to allo-SCT, overall survival, and cause of death were collected.

Results
Of the 139 patients, the median age was 48 years with a male to female ratio of 1.4:1. The majority of patients had stage 3 or 4 disease (74%). Breakdown of NHL subtype revealed 31% diffuse large B-cell (DLBCL), 31% follicular, 13.7% mantle cell, 8% T-cell, 3.6% Burkitt’s, 2.1% marginal cell, and 10.7% other category that included small lymphocytic, anaplastic, natural killer cell, mixed cellularity, and unspecified NHL. A total of 44 patients (31%) underwent auto-SCT prior to allo-SCT. Subtypes of allo-SCT included matched sibling (45.3%), matched unrelated donor (MUD, 39.6%), and cord blood transplant (15.1%). Matched sibling allo-SCT had an improved 2 year overall survival of 57.1% when compared to MUD and cord allo-SCT (33% and 30%, respectively). Overall survival after allo-SCT for all patients was 41% at 3 years and 33.1% at 5 years. Disease status prior to transplant was divided into two categories: (1) chemotherapy-resistant (97 patients, 69.7%) and (2) chemotherapy-sensitive (42 patients, 30.2%). There was no statistical difference in overall survival between the chemotherapy-resistant and chemotherapy-sensitive groups at 6 months (60.8% and 78.5% respectively, p=0.066) and at 3 years (40.2% and 42.8% respectively, p=0.91). In a subgroup analysis, DLBCL patients with chemotherapy-resistant disease had similar 3 year survival as compared to patients with chemotherapy-sensitive disease (22.2% and 23%, respectively, p=0.93). Similar results were observed for both subgroups of patients with follicular lymphoma, with 55.2% survival in the chemotherapy-resistant group as compared to 64.2% in the chemotherapy-sensitive group at 3 years (p=0.81).

Conclusion
Our data suggest that disease status at the time of transplant does not impact survival outcomes in patients with relapsed or refractory NHL. This finding extended into a sub-group analysis of DLBCL, representative of an aggressive NHL subtype, and follicular cell lymphoma, representative of an indolent NHL subtype. We hypothesize that the comparable survival outcomes between chemotherapy-sensitive and chemotherapy-resistant disease states at transplant may be a result of graft versus lymphoma effect and use of a disease free graft. As no survival advantage was incurred in patients with chemotherapy sensitive disease, these data imply that the lymphoma burden at time of transplant is not prognostic. This potentially highlights the utility of earlier time to transplant in patients with chemotherapy-resistant disease, and perhaps suggest limiting the duration of attempted salvage chemotherapy after disease relapse.

Disclosures:
No relevant conflicts of interest to declare.