Affiliation:
1. From the Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah-Hebrew University Hospital, Jerusalem, Israel; the Tissue Typing Department, Hadassah-Hebrew University Hospital, Jerusalem, Israel; and the Department of Pediatrics, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
Abstract
Reduced-intensity or nonmyeloablative stem cell transplantation (NST) is designed to induce host-versus-graft tolerance by engraftment of donor stem cells. The rationale behind NST is to induce optimal graft-versus-leukemia (GVL) effects for elimination of all malignant cells by donor alloreactive immunocompetent cells as an alternative to standard high-dose myeloablative chemoradiotherapy. NST based on the use of fludarabine, low-dose busulfan, and anti–T-lymphocyte globulin (ATG) was employed in 24 patients aged 3 to 63 years with chronic myeloid leukemia (CML) in first chronic phase (CP). Graft-versus-host disease (GVHD) prophylaxis consisted of low-dose cyclosporine (CSP), in some cases with low-dose methotrexate. Early discontinuation of CSP was attempted in cases of mixed chimerism in an attempt to amplify GVL effects. All 24 patients showed rapid 3-lineage engraftment, mostly without complete aplasia; 6 patients did not require transfusion of any blood products. NST was associated with minimal procedure-related toxicity. The incidence of acute GVHD (grade I or higher) was 54%; however, this incidence increased following CSP withdrawal. After a follow-up of up to 70 months (median, 42 months), 21 of 24 patients remained alive and disease free. The GVL effects induced by donor immunocompetent lymphocytes eradicated all host hematopoietic cells, as evidenced by molecular testing. The Kaplan-Meier probability of survival and disease-free survival at 5 years is 85% ± 8% (95% confidence interval, 70%-100%). NST may successfully replace myeloablative stem cell transplantation, providing a safer, well-tolerated therapeutic option for all patients with CML in first CP with a matched donor. However, this conclusion must be tested in a prospective randomized clinical trial.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Reference50 articles.
1. Bone marrow transplantation for patients with chronic myeloid leukemia.;Goldman;N Engl J Med.,1986
2. Marrow transplantation for the treatment of chronic myelogenous leukemia.;Thomas;Ann Intern Med.,1986
3. Effect of hematopoietic chimerism on the course of Rauscher's viral mouse leukemia.;Sinkovics;Proc Am Assoc Cancer Res.,1963
4. Time pattern of the antileukemia effect of graft-vs-host reaction in mice. I. Cellular events.;Boranic;Cancer Res.,1971
5. Antileukemic effect of graft-versus-host disease contributes to improved survival after allogeneic marrow transplantation.;Weiden;Transplant Proc.,1981
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