Effect of T-cell depletion as graft-versus-host disease prophylaxis on engraftment, relapse, and disease-free survival in unrelated marrow transplantation for chronic myelogenous leukemia. Blood 1994 Apr 01;83(7):1980-7
Date
04/01/1994Pubmed ID
8142664DOI
10.1182/blood.v83.7.1980.bloodjournal8371980Scopus ID
2-s2.0-0028179358 (requires institutional sign-in at Scopus site) 124 CitationsAbstract
Between January 1988 and March 1993, 48 patients received T-cell-depleted marrow grafts from unrelated donors as treatment for chronic myelogenous leukemia (CML). The median age of the population was 31.7 years (range 5.4 to 53) with 17 of 48 patients greater than 40 years of age. Twenty-seven patients were transplanted in chronic phase, 17 in accelerated phase, and 4 in blast crisis. All patients received a standardized preparative regimen of cyclophosphamide, high-dose cytosine arabinoside, methylprednisolone, and total body irradiation. Marrow grafts were depleted of mature T cells with the alpha beta T-cell receptor antibody T10B9 as graft-versus-host disease (GVHD) prophylaxis. All patients also received posttransplant cyclosporine therapy. Twenty-eight of 48 patients were mismatched with their donors for one or more HLA-A, B, DR, or DQ loci by either serology or high-resolution oligonucleotide genotyping. Nine of 28 were mismatched at multiple HLA loci. Durable engraftment was achieved in 94% (45/48) of patients. The actuarial probability of developing grades II to IV and grades III to IV acute GVHD were 39.6% (95% confidence interval (CI) 26.9 to 53.0) and 8.3% (95% CI 6.1 to 10.9) for the entire cohort. There was no difference in the incidence of grades II to IV acute GVHD between patients receiving matched (36.8%) or mismatched (41.4%) marrow grafts (P = .77). The actuarial probability of relapse at 2 years was 8.8% (95% CI 2.1 to 21.6) for the entire cohort and 18% (95% CI 4 to 41) for patients transplanted in either the accelerated or blast crisis phase (advanced disease). One cytogenetic relapse has occurred among patients transplanted in the chronic phase. The probability of disease-free survival at 2 years was 52% (95% CI 24 to 70) for patients transplanted in chronic phase and 46% (95% CI 25 to 73) for patients transplanted with advanced disease. No difference in disease-free survival was observed between patients receiving matched (49%) or mismatched (51%) marrow grafts (P = .90). This study shows that patients receiving unrelated T-cell-depleted marrow grafts for CML can achieve durable engraftment with a low incidence of severe GVHD and apparent preservation of graft-versus-leukemia reactivity. These data also suggest that T-cell depletion may allow patients who might otherwise experience unacceptable toxicity from GVHD-related complications caused by older age or increased HLA disparity to benefit from unrelated marrow grafts.
Author List
Drobyski WR, Ash RC, Casper JT, McAuliffe T, Horowitz MM, Lawton C, Keever C, Baxter-Lowe LA, Camitta B, Garbrecht FAuthors
William R. Drobyski MD Professor in the Medicine department at Medical College of WisconsinMary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
Timothy L. McAuliffe PhD Professor in the Psychiatry and Behavioral Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdolescentAdult
Bone Marrow Transplantation
Cause of Death
Child
Child, Preschool
Female
Graft vs Host Disease
Granulocyte-Macrophage Colony-Stimulating Factor
Histocompatibility Testing
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphocyte Depletion
Male
Middle Aged
Recurrence
Survival Rate
T-Lymphocytes
