Outcomes among Patients with Relapsed Malignant Lymphoma after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Tanosaki Ryuji , Kim Sung-Won , Asakura Yoshitaka , Kurosawa Saiko , Yakushijin Kimikazu , Azuma Teruhisa , Mori Shin-ichiro , Fukuda Takahiro , Tobinai Kensei , Takaue Yoichi 
Published: April 2020

Abstract
Background: The management for recurrent lymphoma after allogeneic hematopoietic stem cell transplantation (HSCT) is challenging and it is not clear concerning its outcomes. Since potent graft-versus-lymphoma (GVL) effect is observed in some patients (pts) with follicular lymphoma (FL), peripheral T-cell lymphoma (PTCL) or adult T-cell leukemia/lymphoma (ATL) after allogeneic HSCT using reduced-intensity conditioning (Tanosaki et al, ASH 2006, BBMT2008;14:702), we hypothesized that it could also be exerted in relapsed patients. Hence, we retrospectively analyzed the outcomes among patients with lymphoma who relapsed after allogeneic HSCT.
Patients and Methods: Between January 1999 and December 2007, 164 patients with refractory lymphoma, who were deemed incurable with standard or high-dose chemotherapy, underwent allogeneic HSCT in our single institution. Seventy-five pts remain in CR, 33 died associated with non-relapse mortality, 4 were lost follow-up, and 52 pts relapsed after the median of 71 days (range 1–1457), including 1 graft failure. Therefore, 51 pts were analyzed in this study.
Results: Histological subtypes were diffuse large B-cell lymphoma (DLBCL) 13, ATL 12, lymphoblastic lymphoma 8, PTCL 7, FL 4, Hodgkin lymphoma (HL) 3, mantle cell lymphoma (MCL) 2, extranodal NK/T-cell lymphoma 2. Ten pts had an early relapse within 30 days, while 41 pts had a systemic (18 pts) or solitary relapse (23 pts) after the median of 98 days (range 33–1457). Relapse-oriented interventions included withdrawal of immunosuppressants (WIS), irradiation or surgical resection of localized lesion, donor lymphocyte infusion (DLI) and chemotherapy, which were used singly or in combination according to the clinical conditions; the breakdown and its outcomes were shown in Table. At the time of relapse, 46 pts (90%) had immunosuppressants, and WIS was first tried in 31 pts who didn’t have GVHD. Overall survival rate (OS) at 2 years after relapse in pts with relapse &gt;day 30 and ≤day 30 was 37±8% and 0% (p&lt;0.001). Univariate analysis revealed that histological subtypes of PTCL or ATL, relapse after day 30, relapse after day 100 and RIST favorably affected OS after relapse. Notably, 9 pts (ATL 4, enteropathy-type PTCL 2, DLBCL 1, HL 1, MCL 1) survived after relapse and currently free of disease with the median follow up of 1394 days (range 288–2035). All of them experienced RIST and relapsed at the median of day 109 (range 56–550); 5 pts who relapsed at a solitary site received local irradiation (4) followed by resection of the residual lesion in 1 pt and WIS alone (1), and 4 pts with systemic relapse had WIS alone.
Conclusions: These results suggested that some patients with chemo-refractory lymphoma with an immunogenic property could achieve a long durable disease-free survival after relapse without aggressive treatment modalities.
Interventions and Outcomes Total Interventions Response WIS Ope/RT DLI Chemo CR (CCR)* PR NC/PD *CCR; continuous complete remission after relapse. Relapse &gt;Day 30     Solitary 23 10 12 2 1 10 (5) 0 11     Systemic 18 15 0 1 1 6 (4) 1 11 Relapse ≤ Day 30 10 6 0 2 2 0 (0) 1 9 Total 51 31 12 5 4 16 (9) 2 31