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Use of unrelated marrow grafts compensates for reduced graft-versus-leukemia reactivity after T-cell-depleted allogeneic marrow transplantation for chronic myelogenous leukemia. Blood 1995 Nov 15;86(10):3987-96 PMID: 7579370

Pubmed ID

7579370

Abstract

The effect of donor/recipient histocompatibility on relapse in patients receiving T-cell-depleted (TCD) grafts for chronic myelogenous leukemia (CML) was evaluated. Specifically, we sought to determine whether TCD results in an attenuation of the graft-versus-leukemia (GVL) effect on recipients of unrelated marrow grafts similar to that observed in HLA-identical sibling marrow transplantations. This question was addressed by comparative analysis of the relapse rates in marrow grafts who otherwise received identical preparative regimens and graft-versus-host disease (GVHD) prophylaxis schedules (T-cell depletion with T10B9 monoclonal antibody and complement plus posttransplant cyclosporine) and by serial molecular analyses using the polymerase chain reaction (PCR) to detect the bcr/abl RNA transcript in patients transplanted with unrelated donor grafts. Patients transplanted with advanced disease (accelerated phase or blast crisis) had equally high relapse rates, regardless of whether they received HLA-identical sibling (56%;95% confidence interval [CI], 29% to 82%) or unrelated marrow grafts (8%; 95% CI, 0% to 28%) had a significantly lower incidence of relapse than did patients transplanted with HLA-identical marrow grafts (47%; 95% CI, 23% to 71%; P = .002). Because all patients were similarly treated, these data indicate that the lower relapse rate in these unrelated patients was caused by an augmented GVL effect that was most likely attributable to increased HLA disparity between donor and recipient. The probability of developing both acute and chronic GVHD was significantly increased in chronic-phase recipients of unrelated marrow grafts, suggesting that the enhanced GVL effect was at least partly GVHD-associated. The lack of such a finding in advanced disease patient receiving unrelated marrow grafts raises the possibility that clinically significant GVL effect after TCD marrow transplantation was limited and confined to patients with more indolent disease. Serial PCR analyses for the presence of the bcr/abl RNA transcript showed that the vast majority of patients transplanted in chronic phase with unrelated marrow grafts were persistently PCR-negative, indicating that the GVL effect was durable in these patients. Most of these patients were observed to become PCR negative within 1 to 2 months after transplantation, showing that early eradication of leukemia was possible with TCD marrow grafts. This study shows that the use of unrelated marrow grafts compensates for reduced GVL reactivity associated with TCD in patients transplanted for CML. Furthermore, these data indicate that, in selected patient populations with CML, TCD can be used to reduce GVHD without a commensurate compromise in the GVL effect.

Author List

Hessner MJ, Endean DJ, Casper JT, Horowitz MM, Keever-Taylor CA, Roth M, Flomenberg N, Drobyski WR

Authors

William R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of Wisconsin
Mary M. Horowitz MD, MS Center Director, Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-0028856613   56 Citations

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Bone Marrow Transplantation
Child
Child, Preschool
Disease-Free Survival
Female
Fusion Proteins, bcr-abl
Graft Survival
Graft vs Host Disease
Graft vs Host Reaction
Granulocyte-Macrophage Colony-Stimulating Factor
Histocompatibility
Humans
Immunotherapy, Adoptive
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphocyte Depletion
Male
Middle Aged
Neoplasm Recurrence, Local
Nuclear Family
Polymerase Chain Reaction
T-Lymphocytes
Tissue Donors
Transplantation, Homologous
Treatment Outcome
jenkins-FCD Prod-296 4db9d02597e0a2e889e230f853b641c12f1c3ee3