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Therapy of chronic myelogenous leukemia with allogeneic bone marrow transplantation
Insights
Allogeneic bone marrow transplantation offers significant disease-free survival for chronic phase chronic myelogenous leukemia (CML) patients. However, accelerated phase CML patients face worse survival outcomes and higher relapse rates, with graft-versus-host disease (GVHD) being a major complication.
Area of Science:
- Hematology
- Oncology
- Transplantation Medicine
Background:
- Philadelphia chromosome-positive chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm.
- Allogeneic bone marrow transplantation (BMT) is a potential curative therapy for CML.
- Assessing long-term outcomes and prognostic factors for CML patients undergoing BMT is crucial.
Purpose of the Study:
- To evaluate the efficacy and safety of allogeneic bone marrow transplantation (BMT) for Philadelphia chromosome-positive chronic myelogenous leukemia (CML).
- To identify prognostic factors influencing survival and relapse rates in CML patients post-BMT.
- To assess the incidence and impact of graft-versus-host disease (GVHD) on patient outcomes.
Main Methods:
- A cohort of 57 patients with Philadelphia chromosome-positive CML received allogeneic BMT between 1982 and 1986.
- Conditioning regimen included cyclophosphamide and fractionated total body irradiation.
- Graft-versus-host disease (GVHD) prophylaxis involved methotrexate, prednisone, and either antithymocyte globulin (ATG) or OKT3.
Main Results:
- Projected 30-month survival was 64% for chronic phase and 30% for accelerated phase CML patients (P = .005).
- Younger age (<30 years) and chronic phase disease were independent predictors of better survival.
- Acute GVHD occurred in 63% and extensive chronic GVHD in 53% of patients, contributing to morbidity and mortality.
Conclusions:
- Allogeneic BMT provides a high rate of disease-free survival for chronic phase CML patients.
- Accelerated phase CML patients have significantly worse survival, with relapse being a major concern.
- Graft-versus-host disease (GVHD) remains a significant challenge, impacting survival and quality of life in CML patients post-transplant.
Abstract:
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.