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Bone marrow transplantation for chronic myeloid leukemia (CML) from unrelated and sibling donors: single center
T Lamparelli1, M T Van Lint, F Gualandi
1Divisione Ematologia II, Ospedale San Martino, Genova, Italy.
Insights
Allogeneic bone marrow transplants for chronic myeloid leukemia (CML) using matched unrelated donors (MUD) show similar survival to sibling donors (SIB). MUD recipients experienced more graft-versus-host disease (GVHD) but had lower relapse rates, suggesting comparable long-term outcomes.
Area of Science:
- Hematology
- Oncology
- Transplantation Immunology
Background:
- Allogeneic bone marrow transplantation (BMT) is a curative option for chronic myeloid leukemia (CML).
- Graft-versus-host disease (GVHD) and relapse are major complications following BMT.
- The choice of donor, either HLA-identical sibling (SIB) or matched unrelated donor (MUD), impacts outcomes.
Purpose of the Study:
- To compare the outcomes of allogeneic BMT in chronic myeloid leukemia (CML) patients receiving grafts from HLA-identical sibling (SIB) donors versus matched unrelated donors (MUD).
- To evaluate differences in engraftment, GVHD, cytomegalovirus (CMV) infection, transplant-related mortality, relapse, and survival between SIB and MUD BMT.
Main Methods:
- A cohort of 60 consecutive CML patients undergoing allogeneic BMT was analyzed.
- Patients received unmanipulated bone marrow grafts after conditioning with cyclophosphamide and total body irradiation.
- GVHD prophylaxis included cyclosporin A and methotrexate; CMV prophylaxis varied by donor type.
Main Results:
- MUD recipients were younger, had younger donors, longer pre-transplant intervals, and received fewer nucleated cells compared to SIB recipients.
- Engraftment kinetics were similar, but SIB recipients had better early platelet recovery.
- MUD recipients experienced significantly higher rates of acute GVHD (33% vs 6% severe), while chronic GVHD and CMV antigenemia were comparable.
- Three-year survival was similar (78% SIB vs 82% MUD), with comparable transplant-related mortality (12% SIB vs 17% MUD) and relapse rates (18% SIB vs 6% MUD).
Conclusions:
- Allogeneic BMT from well-matched MUDs offers survival outcomes comparable to SIB donors for CML patients.
- The increased incidence of acute GVHD in MUD recipients may be offset by a reduced risk of leukemia relapse.
- Careful donor selection and management of GVHD are crucial for successful MUD BMT in CML.
Abstract:
This is a report on 60 consecutive patients with chronic myeloid leukemia (CML) who received an allogeneic bone marrow transplant (BMT) in this Unit. Donors were HLA-identical siblings (SIB) (n = 36) or unrelated donors (MUD) (n = 24) matched by serology for HLA A and B and by molecular biology for HLA DR. All patients were prepared with cyclophosphamide 120 mg/kg and fractionated total body irradiation 10-12 Gy. GVHD prophylaxis consisted of cyclosporin A (CsA) starting on day -7 and short-course methotrexate. Bone marrow was unmanipulated in all cases. Cytomegalovirus prophylaxis consisted of acyclovir for SIBs and foscarnet for MUDs. When compared to SIB transplants, MUD patients were younger (29 vs 36 years; P = 0.002), had younger donors (31 vs 39; P = 0.001), had a longer interval between diagnosis and BMT (1459 vs 263 days; P < 0.001) and received a smaller number of nucleated cells at transplant (3.3 vs 4.4 x 10(8)/kg; P = 0.003). More MUDs had advanced disease (50 vs 17%, P = 0.005). The median day to 0.5 x 10(9)/l neutrophils was similar in both groups (18 days for SIBs vs 17 days for MUDs; P = 0.06); the median platelet count on days +30, +50, +100 was significantly (P < 0.01) higher in SIB than in MUD patients (122 vs 38, 113 vs 50 and 97 vs 45 x 10(9)/l, respectively). Acute GVHD was scored as absent-mild, moderate, or severe, in 36, 58 and 6% of SIBs vs 25, 42 and 33% in MUD patients (P = 0.01). Chronic GVHD was comparable (P = 0.1). The actuarial risk of CMV antigenemia at 1 year was 60% in both groups. There were six deaths in SIB patients (two leukemia, two infections, one GVHD, one pneumonitis) and four deaths in MUD patients (three acute GVHD and one infection). Fifty patients survive with a median follow-up of 656 days for SIBs and 485 for MUDs. The actuarial 3-year transplant-related mortality is 12% in SIBs and 17% in MUDs (P = 0.5); the actuarial relapse is 18% in SIBs vs 6% in MUDs (P = 0.4) and 3-year survival 78% in SIBs vs 82% in MUDs (P = 0.7). This study suggests that survival of CML patients after marrow transplantation from unrelated or sibling donors is currently similar, provided the former are well matched. The increased incidence of GVHD in MUD patients is possibly compensated by a lower risk of relapse.