Leukemia immunotherapy in conjunction with non myeloablative allogeneic stem cell transplantation

S. Slavin, A. Nailer, E. Naparstek, R. Or, G. Varadi, R. Ben-Yosef, A. Hussien, M. Aker, G. Cividalii

Research output: Contribution to journalArticlepeer-review

Abstract

The sharp difference in the rate of relapse between recipients of autologous and syngeneic marrow grafts and recipients of equivalent doses of chemoradiotherapy receiving marrow allografts, as well as the beneficial effects of donor lymphocyte infusion (DLI) following allogeneic bone marrow transplantation (alloBMT) are clear indicators for the major therapeutic component mediated by alloreactivc donor lymphocytes in the course of alloBMT. Data obtained in animal models of human disease and preliminary clinical trials suggest (hat at the stage of minimal disease, which can be accomplished with conventional cytoreduclivc agents, complete eradication of all tumor cells of host origin may be accomplished by mechanisms of graft vs leukemia (GVL) effect with no need for further myeloablative conditioning. Based on solid data in experimental animals using murine leukemia (B cell leukemia (BCL1 ) of BALB/c mice and myelomonocylic leukemia (mAML) of SJL/J mice} and our clinical data involving >50 patients with malignancies, we would like to suggcsi re-evaluation of the dogma of treating patients with hematologie malignancies which normally requires myeloablative doses of chemoradiotherapy with the transplant procedure serving primarily as stem cell support. Available data suggests that the transplant procedure should be best utilized for safer induction of host vs graft tolerance as a necessary step for durable engraftment of donor lymphocytes to enable optimal GVL effects by alloreactivc donor lymphocytes prcsenl in the graft of donor lymphocyte infusion (DLI), given post-grafting, possibly on an outpatient basis when patient's condition is stable and hetnatopoietic reconstitution complete. Since (he rale of alloreactive donor T cells resulting in GVL effects may not compete favorably with rapidly developing acute leukemia cells eradication of residual tumor cells at the early phase of the disease, when tumor cells arc still susceptible to conventional doses of chemotherapy may be the treatment of choice for improving the overall disease Ircc survival in patients with poor prognosis hematologie malignancies with HLA matched siblings available. The feasibility to induce curative GVL effects with nonmyeloablative conditioning may enhance clinicians to consider alloBMT at an early stage of the disease for patients in all age groups while possibly avoiding primarily long term complications of currently available myeloablalive conditioning regimen following alloBMT.

Original languageEnglish
Pages (from-to)779
Number of pages1
JournalExperimental Hematology
Volume26
Issue number8
StatePublished - 1998
Externally publishedYes

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