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Stem cell self-renewal considerations in bone marrow transplantation
P Mauch1, J Ferrara, S Hellman
1Joint Center for Radiation Therapy, Harvard Medical School, Boston, MA.
Bone Marrow Transplantation
|November 1, 1989
Summary
Autologous bone marrow transplantation can impair long-term hematopoietic stem cell self-renewal. Optimizing donor marrow quantity and quality, and avoiding prior cytotoxic agents, can mitigate this risk in cancer patients.
Area of Science:
- Hematology
- Oncology
- Stem Cell Biology
Background:
- Autologous bone marrow transplantation (ABMT) is increasingly used for malignant diseases.
- Concerns exist regarding long-term hematopoietic function post-ABMT.
- Bone marrow stem cells have limited self-renewal capacity.
Purpose of the Study:
- To investigate the long-term consequences of ABMT on hematopoietic stem cell self-renewal.
- To identify factors contributing to the loss of stem cell self-renewal capacity.
- To propose strategies for optimizing ABMT outcomes.
Main Methods:
- Review of evidence on stem cell self-renewal post-transplantation.
- Analysis of factors causing stem cell damage (cytotoxic agents, proliferative stress).
- Assessment of methods to measure stem cell self-renewal capacity.
Main Results:
- ABMT can lead to a permanent loss of bone marrow stem cell self-renewal.
- This loss is not immediately apparent in peripheral blood counts or marrow cellularity.
- Animal studies suggest decreased survival associated with impaired stem cell self-renewal.
Conclusions:
- Optimizing donor marrow quantity and quality is crucial to limit adverse effects.
- Transplanting the maximum feasible number of marrow cells is recommended.
- Avoiding prior exposure to cytotoxic agents that damage early stem cells is advised.
- Careful monitoring of lymphokines and peripheral stem cell harvests is necessary.