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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-02-0535.
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Blood, 15 January 2003, Vol. 101, No. 2, pp. 441-445
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
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
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.
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.
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