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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-02-0535.
Submitted February 20, 2002
Accepted August 19, 2002
Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase
Reuven Or, Michael Y Shapira, Igor Resnick, Avraham Amar, Aliza Ackerstein, Simcha Samuel, Memet Aker, Elizabeth Naparstek, Arnon Nagler, and Shimon Slavin*
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel
Department of Tissue Typing, Hadassah University Hospital, Jerusalem, Israel
Department of Pediatrics, Hadassah University Hospital, Jerusalem, Israel
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel; Department of Hematology, Souraski Medical Center, Tel Aviv, Israel
* Corresponding author; email: slavin{at}cc.huji.ac.il.
Reduced intensity, or non-myeloblative 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 with chronic myeloid leukemia (CML) in first chronic phase (CP) aged 3-63 years. Graft-versus-host disease (GVHD) prophylaxis consisted of low-dose cyclosporine (CSP), some 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 was 54%, however, this increased following CSP withdrawal. After a follow-up of up to 70 (median 42) months 21/24 patients remain alive and free of disease. 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% (confidence interval 70-100%). NST may successfully replace myeloablative stem cell transplantation, thus 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.
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