Proceedings from the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse After Hematopoietic Stem Cell Transplantation: part III. Prevention and treatment of relapse after allogeneic transplantation

Abstract

In the Second Annual National Cancer Institute's Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation, the Scientific/Educational Session on the Prevention and Treatment of Relapse after Allogeneic Transplantation highlighted progress in developing new therapeutic approaches since the first relapse workshop. Recent insights that might provide a basis for the development of novel, practical clinical trials were emphasized, including utilization of newer agents, optimization of donor lymphocyte infusion (DLI), and investigation of novel cellular therapies. Dr. de Lima discussed pre-emptive and maintenance strategies to prevent relapse after transplantation, for example, recent promising results suggestive of enhanced graft-versus-tumor activity with hypomethylating agents. Dr. Schmid provided an overview of adjunctive strategies to improve cell therapy for relapse, including cytoreduction before DLI, combination of targeted agents with DLI, and considerations in use of second transplantations. Dr. Porter addressed strategies to enhance T cell function, including ex vivo activated T cells and T cell engineering, and immunomodulatory approaches to enhance T cell function in vivo, including exogenous cytokines and modulation of costimulatory pathways.

Keywords: Allogeneic; Prevention; Relapse; Stem cell transplantation; Treatment.

Figure 1. Donor-Cell Consolidation of Remission for AML Relapse after AlloSCT

Analysis of EBTR data from 38 patients in CR after first-line cytoreductive therapy for relapsed AML after AlloSCT demonstrated improved OS with use of donor cells for consolidation: 55 ± 11% vs. 20 ± 10% (p=.038); DLI and second AlloSCT were considered as time-dependent variables. Adapted from: Schmid C., et al. (Blood 2012;119:1599-1606).

Figure 2

Theoretical relative therapeutic potential of cellular therapies for relapse. The shaded quadrant represents the zone of optimal specificity with respect to tumor vs. off-target cytotoxic tissue damage, which maximizes antitumor potency and minimizes cell-mediated morbidity. Conventional DLI and second AlloSCT (depicted in red) are the currently available cell-based treatments for relapse, against which novel therapies (blue) will be judged.