Allogeneic hematopoietic cell transplantation after failed autologous transplant for lymphoma using TLI and anti-thymocyte globulin conditioning

A R Rezvani, A S Kanate, B Efron, S Chhabra, H E Kohrt, J A Shizuru, G G Laport, D B Miklos, J E Benjamin, L J Johnston, S Arai, W-K Weng, R S Negrin, S Strober, R Lowsky, A R Rezvani, A S Kanate, B Efron, S Chhabra, H E Kohrt, J A Shizuru, G G Laport, D B Miklos, J E Benjamin, L J Johnston, S Arai, W-K Weng, R S Negrin, S Strober, R Lowsky

Abstract

We describe 47 patients with lymphoma and failed prior autologous hematopoietic cell transplantation (HCT) who received TLI-ATG (anti-thymocyte globulin) conditioning followed by allogeneic HCT. Thirty-two patients had non-Hodgkin lymphoma (NHL; diffuse large B-cell lymphoma (n=19), T-cell NHL (n=6), mantle cell lymphoma (n=4) or other B-cell subtypes (n=3)), and 15 had Hodgkin lymphoma. The median follow-up was 4.9 (range, 2.1-11.9) years. The cumulative incidence of grade II-IV acute GvHD at day +100 was 12%, and the cumulative incidence of extensive chronic GvHD at 1 year was 36%. The 3-year cumulative incidences of overall survival (OS), PFS and non-relapse mortality (NRM) were 81%, 44% and 7%, respectively. Fifteen patients died (relapse, n=10; NRM, n=5). Among the 25 patients with relapse after allogeneic HCT, 11 (44%) achieved durable (>1 year) CRs following donor lymphocyte infusion or chemoradiotherapy. The majority of surviving patients (75%; n=24) were able to discontinue all immunosuppression. For patients with relapsed lymphoma after autologous HCT, allogeneic HCT using TLI-ATG conditioning is a well-tolerated, predominantly outpatient therapy with low NRM (7% at 3 years), a low incidence of GvHD, durable disease control and excellent OS (81% at 3 years).

Conflict of interest statement

Conflict of interest disclosure: J.E.B. was a faculty member at Stanford University during the time that this research was conducted, but is now an employee of Amgen. The authors have no other conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Cumulative incidences of acute GVHD grades II–IV (red dotted line) and extensive chronic GVHD (solid line). Abbreviation: GVHD, graft-vs.-host disease.
Figure 2
Figure 2
Kaplan-Meier estimates of overall survival (solid line) and progression-free survival (dotted line). Abbreviations: HCT, hematopoietic cell transplantation; OS, overall survival; PFS, progression-free survival.
Figure 3
Figure 3
Proportion of patients requiring systemic immunosuppression over time. Abbreviations: HCT, hematopoietic cell transplantation.
Figure 4
Figure 4
Peak donor CD3+ peripheral-blood chimerism through day +180 in patients with and without disease relapse. Dark horizontal line indicates median; box indicates 25th and 75th percentile ranges; whiskers represent range with outliers shown as hollow circles. By day +180, 29 patients (62%) had achieved full donor chimerism, 16 patients (34%) had mixed chimerism, and 2 patients (4%) had primary graft failure.

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