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Standard conditioning regimen and T-depleted donor bone marrow for transplantation in chronic myeloid leukemia
Insights
T-cell depletion of donor bone marrow using CAMPATH-1 effectively prevents graft-vs-host disease in chronic myeloid leukemia patients undergoing bone marrow transplantation. This approach shows promising survival rates, though relapses suggest a need for intensified conditioning regimens.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Allogeneic bone marrow transplantation (BMT) is a curative option for chronic myeloid leukemia (CML).
- Graft-versus-host disease (GvHD) and graft failure are significant complications following BMT.
- T-cell depletion strategies aim to mitigate GvHD while preserving graft-versus-leukemia effects.
Purpose of the Study:
- To evaluate the efficacy and safety of T-cell depleted donor bone marrow transplantation using CAMPATH-1 in Ph1-positive CML patients.
- To assess the impact of T-cell depletion on GvHD incidence, graft failure, and patient survival.
- To compare outcomes between patients receiving T-cell depleted marrow versus conventional BMT.
Main Methods:
- 18 Ph1-positive CML patients in chronic phase received HLA-identical sibling BMT.
- Conditioning regimen included cyclophosphamide (CTX) and fractionated total body irradiation (TBI).
- 10 patients received T-cell depleted donor marrow (CAMPATH-1) plus cyclosporin-A (CYA); 8 received untreated marrow with CYA.
Main Results:
- No GvHD or graft failure observed in the CAMPATH-1 treated group.
- Actuarial survival at 24 months was 90% for CAMPATH-1 patients versus 63.8% for the control group.
- Engraftment rates correlated with infused nucleated cell count; relapses occurred in the CAMPATH-1 group.
Conclusions:
- T-cell depletion with CAMPATH-1 is effective in preventing GvHD in CML BMT.
- Standard conditioning regimens with fractionated TBI and prolonged CYA are crucial for preventing graft failure.
- Higher relapse rates in the T-cell depleted group indicate a need for more aggressive anti-leukemic conditioning.
Abstract:
Between January 1984 to June 1985, 18 Ph1 positive chronic myeloid leukemia (CML) patients in chronic phase (CP) underwent allogeneic bone marrow transplantation (BMT) from HLA identical and MLC negative siblings. The median age was 32.5 yr and median disease duration of CML at time of BMT was 19.3 months. The pretransplant conditioning regimen consisted of cyclophosphamide (CTX) (120 mg/kg) and 10.20 Gy total body irradiation (TBI) at 6 doses of 1.7 Gy each, administered in 3 daily fractions over 2 days at a dose rate of 15-20 cGy/min. To prevent graft-vs-host disease (GvHD) we used methotrexate (MTX) in one patient and cyclosporin-A (CYA) in the other 17 patients. In addition to CYA, given until day +365, 10 patients received donor marrow depleted of T cells with CAMPATH-1. The residual marrow lymphocytes were always less than 1%. The rate of engraftment was significantly correlated with the number of nucleated cells infused. Neither GvHD nor graft failure were observed among CAMPATH-1 patients. In this group one cytogenetic and one hematologic relapse occurred. The overall actuarial survival at 24 months is 78%. Of the 10 patients treated with donor marrow depleted of T cells, 9 are alive after a median follow-up of 9 months (range 5-18), with an actuarial survival of 90%. Of the other 8 patients transplanted with untreated marrow, 5 are alive after a median follow-up of 19.3 months (range 3.7-24) and the actuarial survival is 63.8%. This pilot study seems to demonstrate that T-cell depletion of donor bone marrow with CAMPATH-1 is effective to prevent GvHD, while the risk of graft failure can be avoided using a "standard" conditioning regimen including a fractionated TBI with a fast dose rate and a prolonged administration of CYA at the maximum tolerable dosage. While the high frequency of relapses suggests the employ of more aggressive anti-leukemic conditioning regimens in CAMPATH-1 treated marrow recipients.