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Problems and strategies for bone marrow transplantation in acute leukemia and chronic myelogenous leukemia
1Johns Hopkins Oncology Center, Baltimore, MD 21205.
Insights
Hematopoietic stem cell transplantation offers 50-70% survival for acute leukemia. New strategies, including thalidomide for graft-versus-host disease (GVHD), are being explored to improve outcomes.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Hematopoietic stem cell transplantation (HSCT) shows promise for acute leukemia (AL) with 50-70% disease-free survival.
- Graft-versus-host disease (GVHD) and viral infections are major causes of mortality post-HSCT.
- Cytoreductive treatment toxicities also contribute to post-transplant deaths.
Purpose of the Study:
- To review current HSCT protocols for acute leukemia.
- To discuss strategies for preventing and treating GVHD.
- To explore alternative donor sources and autologous transplantation.
Main Methods:
- Review of existing HSCT protocols and outcomes in acute leukemia.
- Evaluation of GVHD prophylaxis and treatment methods, including lymphocyte depletion and immunosuppressants like Cyclosporine (CsA).
- Discussion of novel therapeutic agents like thalidomide and alternative donor strategies.
Main Results:
- Current HSCT protocols achieve 50-70% long disease-free survival in acute leukemia.
- Acute and chronic GVHD, viral infections, and treatment toxicities remain significant challenges.
- Limited success with mismatched/unrelated donors; autologous transplantation shows promise.
Conclusions:
- While HSCT has improved outcomes for acute leukemia, GVHD and toxicities persist.
- Thalidomide demonstrates efficacy in preventing/treating GVHD in preclinical models and warrants clinical investigation.
- Further research into donor selection, T-cell manipulation, and alternative transplant approaches is crucial for advancing AL treatment.
Abstract:
Certain marrow transplant protocols can now result in a 50-70% long disease-free survival and low relapse rates in acute leukemia (AL) in CR1, CR2, or CML following cytoreduction and HLA-identical marrow infusion. Two-thirds of deaths are due to acute and chronic graft-versus-host disease (GVHD) or viral infection. The other deaths are due to toxicities of the cytoreductive treatment. Prevention of GVHD has been tried by treatment after the transplant or treating the marrow (lymphocyte depletion). Cyclosporine (CsA) or CsA plus methotrexate has reduced acute GVHD but not chronic GVHD. Marrow has been treated with monoclonal antibodies and lectins or elutriated to decrease numbers of T lymphocytes. Some studies have been effective, but the majority have shown an increased number of rejections or leukemic relapses. Apart from teratogenic effects, thalidomide has minimal toxicity. It effectively prevents and treats acute and chronic GVHD in rodent models. Clinical trials will soon begin. Mismatched related or matched unrelated donors have been employed in the clinic with limited success. Alternatively, autologous transplantation in acute leukemia has shown promising results. Possible solutions to remaining problems and strategies will be discussed.