Allogeneic Hematopoietic Stem Cell Transplantation for Peripheral T-Cell Lymphoma: Evidence of Graft-Versus-Lymphoma Effect.
Authors: Hamadani Mehdi , Awan Farrukh , Elder Patrick , Porcu Pierluigi , Lin Thomas , Blum Kristie , Scholl Diane , Devine Steven M. 
Published: October 2019

Abstract
Peripheral T-cell lymphomas (PTCL) are an uncommon and heterogeneous group of lymphoid malignancies characterized by a poor prognosis. Combination chemotherapy and autologous hematopoietic stem cell transplantation (HSCT) are not curative for majority of patients (pts) with PTCL. We evaluated the role of allogeneic (allo-) HSCT in pts with PTCL. We performed a retrospective analysis of all pts with histologically confirmed PTCL who underwent allo-HSCT between 5/1997 to 2/2007 at our institution. ALK1+ anaplastic large cell lymphoma (ALCL) were excluded from this analysis. There were 14 pts (11 male) with a median age of 43 years (range 30–52). Histology included 5 (35%) PTCL unspecified, 4 (28%) angioimmunoblastic T-cell lymphoma, 2 (14%) ALK1 negative ALCL, 2 NK/T-cell lymphoma and 1 panniculitis like T-cell lymphoma. Eight pts (57%) had chemosensitive disease (CR2=1, CR3=2, PR1=3, PR2=2); and 6 were high intermediate-high risk aaIPI. Eleven (78%) had advanced disease (stage III-IV) at transplantation. The median number of prior chemotherapy regimens was 3 (range 1–4). Two had previously undergone autologous HSCT. Median time from diagnosis to allo-HSCT was 12 months. Nine pts received graft from an HLA-identical sibling (SIB), while 5 underwent matched unrelated donor (MUD) transplantation. Stem cell source included peripheral blood (n-12) or bone marrow (n=2). Eight pts (57%) received myeloablative (MA) conditioning (BuCy=6, BuCy-VP16=2), while 6 (43%) received reduced intensity conditioning (RIC) (FluBlu). ATG was administered as part of preparative regimen in 3 RIC pts. Median number of CD34+ cells infused was 5.1× 106/Kg. GVHD prophylaxis consisted of short-course MTX with cyclosporine (n=9) or tacrolimus (n=5). Median time to neutrophil and platelet engraftment was 15 and 24 days respectively. Rates of grade II-III and III-IV acute GVHD were 42% (n=6) and 21% (n=3) respectively. 7 pts developed chronic GVHD. 2 pts died before response assessment. Among 12 evaluable pts, 8 achieved CR and 4 PR after allo-HSCT. 2 pts with refractory disease (RD) and 4 pts with PR (pre-HSCT) showed CR following allo-HSCT, while 3 pts with RD achieved PR following allo-HSCT. Day 100 TRM was 28% (n=4). Kaplan-Meier estimates of overall survival (OS) at 1 year and 2 years were 42 and 28% respectively. The corresponding estimates of progression free survival (PFS) are 28% and 28%, respectively. No patient had disease progression after 1 year. Using two-tailed Fisher’s exact test no significant difference was seen in; chemosensitive vs. chemorefractory pts, MA vs. RIC and SIB vs. MUD HSCT in terms of OS and DFS. On multiple logistic regression analysis no impact of age, LDH, stage, performance status and donor type on OS and PFS was seen. RIC had borderline significance for OS (P=0.05). Interestingly 1 patient in PR after MA allo-HSCT converted to CR with tapering immunosuppression. Immunosuppression was tapered in a second (RIC) patient at time of progression which resulted in CR. Disease relapse was heralded in two other patients with loss of full donor chimerism. In conclusion, in this limited retrospective analysis allo-HSCT provided a 28% probability of 2 year PFS in pts with advanced PTCL. Evidence of graft-versus-T-cell lymphoma effect was observed clinically. Prospective evaluation of this modality earlier in the disease course appears warranted.