Therapy for chronic myelogenous leukemia with unrelated donor bone marrow transplantation: results in 102 cases [published erratum appears in Blood 1990 Aug 1;76(3):654]

Abstract

From April, 1985, to February, 1989, 102 consecutive patients received unrelated donor bone marrow transplantation therapy for chronic myelogenous leukemia (CML) at four centers. Median age of the group was 31 years (range, 4.5 to 51 years). Fifty-four patients were in first chronic phase (CP) at time of transplantation, and 48 had evidence of more advanced disease (AD) (accelerated phase, 32; blast crisis, 9; second CP, 7). In 44 cases, the donor and recipient were identical at the HLA A, B, and DR loci and were nonreactive in bidirectional mixed leukocyte culture (MLC) (“matched”). In 58 cases, nonidentity between donor and recipient could be determined at at least one HLA locus or in bidirectional MLC (“mismatche”). Fifty-eight patients were prepared for transplantation with a combination of cyclophosphamide and fractionated total body irradiation (FTBI) and received acute graft- versus-host disease (GVHD) prophylaxis consisting of methotrexate alone or in combination with cyclosporine, prednisone, or antithymocyte globulin (ATG). In 44 cases, patients received preparative agents in addition to cyclophosphamide and FTBI, and marrow depleted of mature T lymphocytes by ex vivo incubation with either anti-CD3 antibody plus complement (n = 24) or Campath-1 (n = 20). Engraftment defined by a peripheral blood neutrophil count greater than 0.5 X 10(9)/L was demonstrated in 92 cases and occurred at a median of 22 days (range, 11 to 46 days). In 10 cases, peripheral blood evidence of engraftment did not occur, and in one case, engraftment was followed by aplasia. Hematologic relapse was seen in four cases. Recurrence or persistence of the Ph1 chromosome without evidence of hematologic relapse occurred in four additional cases. The incidence of grade II to IV acute GVHD is 65% (95% confidence interval [CI], +/- 10%). After adjustment for recipient age and donor matching status, recipients of T lymphocyte- depleted donor marrow had a significantly lower incidence of grade II to IV acute GVHD (P less than .01); however, T depletion was not significantly associated with improved survival (P = .34), disease-free survival (P = .51), or increased incidence of relapse (P = .39). Of 102 patients, 46 are alive, with a median survival of 12 months (range, 3 to 46 months), and the Kaplan-Meier estimate of disease-free survival is 29% (95% CI, +/- 9%) for the entire group at 2 1/2 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Unrelated donor marrow transplantation for chronic myelogenous leukaemia

“…Allogeneic BMT with a matched sibling donor marrow performed in first chronic phase (CP) results in 40–80% long‐term survival in patients with newly diagnosed CML, but is only feasible in 15–25% of cases depending on age limitations and HLA‐matched sibling availability ( Thomas et al , 1986 ; Goldman et al , 1986 ; Clift et al , 1991 ; Appelbaum et al , 1994 ). Allogeneic BMT from an HLA‐compatible unrelated donor (UD) has become a feasible and effective treatment for patients who lack a matched sibling ( Beatty et al , 1989 ; McGlave et al , 1990 , 1993; Drobyski et al , 1994 ; Spencer et al , 1995 ). The higher incidence of serious infectious complications, acute and chronic graft‐versus‐ host disease (GvHD), and unsatisfactory marrow function with respect to BMT from matched relatives resulting in a increased risk of transplant‐related mortality (TRM) is a cause of concern when using UD‐BMT as early therapy in CML ( Marks et al , 1993 ; Ochs et al , 1995 ).…”

A nested PCR‐RFLP method for high‐resolution typing of HLA‐A alleles

“…The α1 and α2 extracellular domains of the α chain are highly polymorphic and a groove to display endogenous peptides against CD8positive T cells is formed by these polymorphic domains (Bjorkman et al, 1987;Germain, 1994). The outcome of allograft transplantation, especially that of unrelated bone marrow transplantation, depends on HLA matching based polymorphism detection (Anasetti et al, 1989;McGlave et al, 1990;Spencer et al, 1995). Polymorphism detection is also useful for individual identification, analysis of genetic susceptibility to specific autoimmune diseases, and diagnosis of graft-vs.host disease (GVHD).…”

Bone marrow transplantation from partially HLA‐matched related donors in adults with leukaemia: The Experience at the University Hospital of Essen, Germany

“…A one-HLA-locus disparity (HLA-A, -B or -DR), however, appeared to have no significant effect on overall survival after BMT in patients with haematological malignancy (Anasetti et al, 1989(Anasetti et al, , 1990. Encouraging results have also been reported for BMT using fully or closely HLA-matched unrelated donor (URD) in larger retrospective series (McGlave et al, 1990Anasetti et al, 1994) and one prospective study (Hows et al, 1993).…”