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Bone marrow transplantation for chronic granulocytic leukemia
Insights
Bone marrow transplants improve survival for chronic granulocytic leukemia (CGL) patients in their first chronic phase. Early intervention is key, as outcomes are significantly poorer for patients in accelerated or later disease phases.
Area of Science:
- Hematology
- Oncology
- Transplantation Immunology
Background:
- Chronic granulocytic leukemia (CGL) is a myeloproliferative neoplasm.
- Bone marrow transplantation (BMT) is a potential curative treatment for CGL.
- Disease phase at the time of BMT significantly impacts outcomes.
Purpose of the Study:
- To evaluate the efficacy and survival rates of BMT in CGL patients.
- To compare outcomes based on disease phase and duration before transplantation.
- To assess the role of post-transplant immunosuppression.
Main Methods:
- Thirty CGL patients received cyclophosphamide, total body irradiation (TBI), and HLA-identical BMT.
- Patients were stratified into first chronic phase (1CP) and accelerated/second chronic phase (CGLacc/CGL-2CP) groups.
- Actuarial survival and relapse rates were calculated.
Main Results:
- Actuarial survival was 63% for 1CP patients versus 27% for CGLacc/CGL-2CP patients.
- Patients transplanted within 24 months of CGL onset had 87% survival, compared to 45% for those transplanted later (P=0.04).
- No true hematologic-cytogenetic relapse occurred in 1CP patients; Ph' chromosome reappearance was transient in two patients.
Conclusions:
- BMT offers >60% survival for CGL patients in the first chronic phase.
- Outcomes are significantly worse (<30% survival) in accelerated or later disease phases due to relapse.
- Disease duration prior to transplant is a critical prognostic factor for CGL BMT success.
Abstract:
Thirty patients with chronic granulocytic leukemia (CGL), were given cyclophosphamide 60 mg/kg on each of 2 consecutive days, followed by total body irradiation (TBI) 10 Gy and an HLA-identical bone marrow transplant (BMT). Eleven patients were in the accelerated phase of their disease (CGLacc) or in second/secondary chronic phase (CGL-2CP), with a median age of 33 years: four patients died of transplant related complications, and four of recurrent leukemia; three patients are alive and well 19, 31, 33 months from BMT. The actuarial 33-month survival is 27%. The actuarial relapse rate is 50%. Nineteen patients were in their first chronic phase (1CP), with a median age of 32 years: three died of graft versus host disease (GvHD), two of infection, and two of acute respiratory distress syndrome (ARDS); 12 are alive and well 6 to 29 months post-BMT. The actuarial 29-month survival is 63%. The actuarial survival of patients younger than 30 years is 63%, compared to 62% for patients older than 30 (P = 0.1). The survival of patients grafted within or after 24 months from the onset of CGL is respectively 87% and 45% (P = 0.04). None of the patients grafted in 1CP had a true hematologic-cytogenetic relapse. The Ph' chromosome was detected on one occasion in two patients 12, 13 months post-BMT: they both remain hematologically normal and Ph1-negative 3 to 6 months later, after discontinuation of cyclosporin A. This study confirms that survival exceeding 60% can be obtained in CGL in the first chronic phase, whereas less than 30% of patients will survive if grafted in accelerated, second/secondary chronic phase, mainly because of leukemic relapse. The duration of the disease seems to be relevant to the outcome of the transplant. The effect of post-transplant immunosuppression, in our case cyclosporin A, on the interaction between normal and Ph1-positive hemopoietic cells, may deserve further attention.