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Haploidentical related transplants and unrelated donor transplants with T cell addback
Insights
Alternative donor bone marrow transplants (BMT) for children now offer outcomes similar to matched family donors. This study shows comparable survival and disease-free survival rates for unrelated donor and haploidentical parental donors compared to matched family donors.
Area of Science:
- Hematology
- Pediatric Oncology
- Transplantation Immunology
Background:
- Limited availability of matched family donors (MFD) for pediatric bone marrow transplantation (BMT).
- Alternative donor sources include unrelated donors (UD) and haploidentical parental donors (Haplo).
- Historically, alternative donor BMT had inferior outcomes due to graft rejection and graft-versus-host disease (GVHD).
Purpose of the Study:
- To analyze and compare the outcomes of pediatric BMT using MFD, UD, and Haplo donors.
- To evaluate the efficacy of different preparative regimens and T-cell depletion strategies in alternative donor BMT.
- To determine if alternative donor BMT outcomes have improved to parallel MFD outcomes.
Main Methods:
- Analysis of 121 consecutive pediatric BMT cases between 1994-1997 (MFD, UD, Haplo).
- Varied preparative regimens including total body irradiation (TBI) and chemotherapy.
- T-cell depletion strategies: Campath 1M for MFD, add-back of T cells for UD, and CD34+ cell selection for Haplo.
Main Results:
- Stable engraftment rates were 95.8% (MFD), 85.4% (UD), and 77.8% (Haplo).
- Median follow-up was 12 months for all groups.
- Survival rates were 74% (MFD), 77% (UD), 78% (Haplo); disease-free survival was 69% (MFD), 67% (UD), 67% (Haplo).
- Death rates were 27% (MFD), 23% (UD), 23% (Haplo).
Conclusions:
- Outcomes of alternative donor BMT (UD and Haplo) now parallel those of MFD BMT in children.
- Modern BMT strategies have improved the success rates of alternative donor transplants.
- Alternative donor sources provide viable options for pediatric patients lacking a matched family donor.
Abstract:
Only 30% of children have a matched family donor (MFD). Alternative donors can be found from volunteer unrelated donor (UD) panels, and almost every child has a haploidentical parental donor (Haplo). The outcome of alternative donor BMT has previously been inferior due to increased graft rejection and GVHD. The recent outcome of 121 consecutive children undergoing MFD, UD, and Haplo BMT between 1994 and 1997 was analysed. [table in text] Preparative regimens for MFD/UD/Haplo BMT respectively included TBI in 30%/36%/11%, chemotherapy only in 59%/64%/89%, Campath 1G or none n 14%/ 0%/0%. The balance of GVHD and rejection was addressed by T-cell depletion (Campath 1M) in 2/71 MFD BMTs, T-cell depletion with addback of 5 x 10(4) T cells/kg on day zero in 33/41 UD BMTs, and T cell depletion of purified mobilised peripheral blood CD34+ cells and bone marrow in 9/9 Haplo BMTs. Stable engraftment was achieved in 68/71, and 35/41 (one patient after 2nd BMT) and 7/9 MFD, UD, and Haplo BMTs respectively. Median follow up, survival, disease free survival and, death rates for MFD/UD/Haplo BMT were 12/12/12 months, 74%/77%/78%, 69%/67%/67%, and 27%/23%/23% respectively. Within a wide range of paediatric diseases the outcome of alternative donor BMT now parallels that of MFD BMT.