Therapy of chronic myelogenous leukemia with allogeneic bone marrow transplantation.
From December 1982 to January 1986, 57 patients received allogeneic bone marrow transplantation as therapy for Philadelphia chromosome (Ph') positive chronic myelogenous leukemia (CML). All patients were prepared for transplantation with cyclophosphamide 60 mg/kg (day -6, -5) and fractionated total body irradiation, 165 cGy twice daily (day -4, -3, -2, -1) and received major histocompatibility (MHC) matched donor marrow (day 0). All patients received graft-v-host disease (GVHD) prophylaxis with methotrexate, prednisone, and either antithymocyte globulin (ATG) (55 patients) or OKT3 infusion (two patients). The projected survival of 29 chronic phase patients is 64% (95% confidence interval [Cl] 42% to 86%); and of 28 accelerated phase patients, 30% (95% Cl, 12% to 48%) at 30 months (P = .005). Multivariate regression analysis of pretransplant patient characteristics demonstrated that the presence of chronic phase and age less than 30 years were the only prognostic features studied that independently predicted survival. No evidence of persistent or recurrent disease has occurred in chronic phase patients; however, reappearance of the Ph' was observed in seven accelerated-phase patients, and hematologic relapse occurred in three of these seven patients. The incidence of grade II to IV acute GVHD is 63% (95% Cl, 50% to 76%) at 100 days, and that of extensive chronic GVHD is 53% (95% Cl, 33% to 74%) at 30 months. The median Karnofsky activity assessment of survivors is 100% (range, 60% to 100%), and all activity assessments less than 100% can be attributed to complications of GVHD. Bone marrow transplantation therapy for CML after preparation with cyclophosphamide and fractionated total body irradiation results in a high proportion of disease-free survival in chronic-phase patients. Survival in accelerated phase is significantly worse and is associated with relapse. GVHD has emerged as a significant cause of morbidity and mortality in this study.
McGlave
P
P
Arthur
D
D
Haake
R
R
Hurd
D
D
Miller
W
W
Vercellotti
G
G
Weisdorf
D
D
Kim
T
T
Ramsay
N
N
Kersey
J
J
D000954:Antigens, Surface; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D003520:Cyclophosphamide / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000517:prevention & control; D006650:Histocompatibility Testing; D006801:Humans; D007165:Immunosuppression Therapy; D007951:Leukemia, Myeloid / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D008727:Methotrexate / Q000627:therapeutic use; D010677:Philadelphia Chromosome; D011241:Prednisone / Q000627:therapeutic use; D011336:Probability; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014916:Whole-Body Irradiation
D000954:Antigens, Surface; D000961:Antilymphocyte Serum; D003520:Cyclophosphamide; D011241:Prednisone; D008727:Methotrexate