Graft-versus-leukemia in chronic lymphocytic leukemia

Abstract

Immune-mediated anti-leukemia effects, often termed graft-versus-leukemia (GvL), operate after bone marrow or blood cell transplants for acute lymphoblastic leukemia, acute myelogenous leukemia and chronic myelogenous leukemia. Sometimes the magnitude of this antileukemia effect exceeds that of high-dose anti-leukemia drugs and radiation and can result in leukemia cure. We analyzed leukemia relapse data after transplants for chronic lymphocytic leukemia (CLL) in this context. These data support the notion of a strong GvL effect in CLL. However, as most of these data are from studies of allotransplants, it is uncertain whether GvL operates in settings where the anti-leukemia effector cells and target CLL cells are genetically identical except for leukemiarelated mutations. It is also uncertain whether GvL is distinct from GvHD. These potential limitations have important implications on whether immune therapy of CLL will work in non-allotransplant settings.

Quantitative MRD monitoring identifies distinct GVL response patterns after allogeneic stem cell transplantation for chronic lymphocytic leukemia: results from the GCLLSG CLL3X trial

“…3,4 In the setting chosen here, immunosuppression tapering was the most important element for GVL induction. As GVL was almost always observed in the context of chronic GVHD, our results strongly suggest alloreactivity rather than CLL-specific effects as principle mechanism responsible for GVL activity.…”

“…A low hematopoietic cell transplantation comorbidity index score has been shown to be a major determinant of favorable TRM and overall mortality, especially in patients with indolent lymphoid malignancies treated with RIC allo-SCT. 13,14 Apart from the pioneer Dana-Farber data obtained with TCD transplants, 15 MRD studies after allo-SCT for CLL at a sensitivity of 1 in 10 4 of patients reaching clinical CR. They observed ongoing MRD negativity paralleling complete clinical remissions in eight of nine patients at risk.…”

“…1,2 Since only small series of patients were analyzed so far, it is unknown, however, how frequently MRD negativity after RIC allo-SCT is achieved, and whether it is durable or has prognostic impact on defined high-risk CLL settings. Moreover, although there is no doubt that graft-versusleukemia (GVL) activity is the key therapeutic principle responsible for disease control after RIC allo-SCT in CLL, [3][4][5][6] time course and clinical triggers of GVL as well as resistance mechanisms to it are unclear.…”

HLA homozygosity and haplotype bias among patients with chronic lymphocytic leukemia: implications for disease control by physiological immune surveillance

“…Nonetheless, there is much evidence that the immune system can be induced to recognize CLL, including the existence of a graft versus leukemia effect after allogeneic hematopoietic stem cell transplantation, the documentation of a disease-specific antigenic profile, and the demonstration of de novo immune responses following experimental vaccination protocols. [3][4][5] In this study, we demonstrate that CLL patients with advanced disease exhibit bias toward homozygosity at human leukocyte antigen (HLA) loci, limiting the diversity of antigen presentation and potentially providing the nascent tumor with an advantage in the process of immune escape. This is the first report to correlate the clinical progression of CLL with HLA homozygosity, demonstrating that immune surveillance might have a role in the containment of non-infectious neoplasms.…”

Current strategies for the diagnosis and management of chronic lymphocytic leukemia (CLL), with a focus on poor-risk CLL: A review

“…On the basis of its capacity to induce graft-versus-leukemia (GVL) effects [60], alloHSCT has been shown to provide long-term disease control in selected CLL patients [36,[61][62][63][64][65][66][67][68]. Key outcome data from selected prospective clinical trials on reducedintensity conditioning (RIC) are summarized in Table 3.…”