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Cytogenetic follow-up after allogeneic bone-marrow transplantation for Ph1-positive chronic myelogenous leukemia
G Alimena1, M R De Cuia, C Mecucci
1Department of Human Biopathology, University of Rome La Sapienza, Italy.
Insights
T cell depletion in allogeneic bone marrow transplants for chronic myelogenous leukemia significantly increases relapse risk. Non-T cell-depleted transplants show no relapses, highlighting the importance of T cells in preventing disease recurrence.
Area of Science:
- Hematology
- Oncology
- Transplantation Immunology
Background:
- Allogeneic bone marrow transplantation (BMT) is a curative option for Philadelphia chromosome-positive (Ph1+) chronic myelogenous leukemia (CML).
- The role of T cell depletion in modulating graft-versus-leukemia effects and relapse risk in CML BMT remains an area of active investigation.
Purpose of the Study:
- To investigate the impact of T cell depletion in allogeneic BMT on disease relapse in Ph1+ CML patients.
- To analyze the cytogenetic and chimerism status in patients experiencing relapse after T cell-depleted or non-T cell-depleted BMT.
Main Methods:
- Serial cytogenetic analysis was performed on 36 patients with Ph1+ CML undergoing allogeneic BMT.
- Donors were either of unlike sex (n=21) or like sex (n=15).
- T cell depletion was applied to 14 sex-mismatched and 12 sex-matched donor marrows.
Main Results:
- Disease relapse occurred in 19 of 26 patients receiving T cell-depleted marrow, versus none of 10 patients receiving non-T cell-depleted marrow.
- In relapsed patients with unlike sex donors, triple or double donor/recipient chimerism was observed.
- Chromosomal abnormalities were detected in Ph1-positive cells of 12 relapsed patients, with non-random breakpoints on chromosomes 1, 4, 7, and 12.
Conclusions:
- T cell depletion in allogeneic BMT for Ph1+ CML is associated with a significantly higher risk of disease relapse.
- Non-T cell-depleted BMT appears to confer protection against relapse, suggesting a crucial role for donor T cells.
- Relapse in CML after BMT can be associated with complex chromosomal changes in residual leukemic cells.
Abstract:
Serial cytogenetic studies were carried out on 36 patients with Ph1-positive chronic myelogenous leukemia treated with allogeneic bone-marrow transplantation from unlike sex (21 patients) or like sex (15 patients) donors. Fourteen of the 21 sex-mismatched and 12 of the 15 sex-matched donor marrows were T cell depleted. Disease relapse was documented in 19 of the 26 patients who received T cell-depleted marrow, and in none of the 10 patients who received non-T cell-depleted marrow. In the group of patients with unlike sex donor, a triple donor/normal recipient/Ph1-positive recipient or a double donor/Ph1-positive recipient chimerism was documented during the subsequent months, while on alpha-interferon treatment for relapse. Two of these patients subsequently showed a complete disappearance of the Ph1 chromosome. Unstable and/or stable, clonal or non-clonal chromosome changes were detected in Ph1-positive cells from 12 of the 19 patients who relapsed. Analysis of the identified stable changes showed a non-random distribution of breakpoints with clustering to chromosome nos. 1, 4, 7 and 12.