Low intensity regimens with allogeneic hematopoietic stem cell transplantation as treatment of hematologic neoplasia

Abstract

Conventional myeloablative conditioning regimens for allografting rely on the use of toxic myeloablative and immunosuppressive therapies to achieve engraftment and control of hematologic neoplasias. Unfortunately, these regimens have resulted in substantial morbidity and mortality. Preclinical and pilot clinical studies have shown that conditioning regimens can be reduced in intensity (resulting in reduced morbidity and mortality) since stem cell allografts can create their own space in the host's bone marrow. Initial promising results with these attenuated conditioning regimens confirm that such an approach is feasible in patients with hematologic neoplasias and genetic diseases ineligible for conventional allografting because of age and/or organ toxicity. The combination of high-dose therapy/autografting followed by a low intensity conditioning regimen (Flu-Cy protocol) and donor mobilized hematopoietic stem cell infusion (mini-allografting) may ultimately be useful in advanced resistant hematologic neoplasia. Finally, these initial promising results with attenuated conditioning regimens have been achieved in transplants with HLA-identical siblings. In the future the main goal will be to explore non-toxic conditioning regimens in the context of transplants from related MHC-mismatched or unrelated MHC-matched donors by increasing the patient's immunosuppression.