Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase

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.

Assessment of CD4 T-lymphocyte reactivity by the Cylex ImmuKnow assay in patients following allogeneic hematopoietic SCT

“…20 Low levels of ATP shown by the ImmuKnow assay are predictive of recurrent infections, relapse and poor prognosis due to the suboptimal immunological function of the graft even with a reasonable WBC, whereas normal levels shown by ImmuKnow assay predict few clinical complications even with a reduced WBC. WBC per se is not a reliable measure of immunocompetence because the majority of these cells are likely to be neutrophils.…”

Significance of one human leukocyte antigen mismatch on outcome of nonmyeloablative allogeneic stem cell transplantation from related donors using the Mexican schedule

“…[25][26][27][28][29][30][31] It has been the practice of this center to use one-antigen HLA-mismatched donors for patients with both standard-and high-risk disease using the same NST conditioning regimen and GVHD prophylaxis as their counterparts from HLAidentical sibling donors. Anasetti et al 32 found that overall SV was not compromised in the 119 recipients of oneantigen HLA-mismatched BMT when compared to a cohort of 967 recipients of HLA-matched sibling transplants.…”

The early referral for reduced-intensity stem cell transplantation in patients with Ph1 (+) chronic myelogenous leukemia in chronic phase in the imatinib era: results of the Latin American Cooperative Oncohematology Group (LACOHG) prospective, multicenter study

“…[1][2][3] The rationale behind reduced-intensity stem cell transplantation (RIST) is to induce optimal graft-versusleukemia (GVL) effects for elimination of all malignant cells by donor alloreactive-immunocompetent cells as an alternative to standard high-dose myeloablative chemoradiotherapy. [4][5][6][7] CML is one of the most sensitive malignancies to the GVL effect, 8 and studies describing the usefulness of RIST in both CP and accelerated phase of the disease have been published. [6][7] In 2002, we published a report on 21 patients with CML who were given an RIST, 6 using the 'Mexican approach', 4,9 which employs fludarabine, busulfan and cyclophosphamide; in that series, individuals with different phases of the disease (CP, blastic and accelerated phases) were included.…”

“…[4][5][6][7] CML is one of the most sensitive malignancies to the GVL effect, 8 and studies describing the usefulness of RIST in both CP and accelerated phase of the disease have been published. [6][7] In 2002, we published a report on 21 patients with CML who were given an RIST, 6 using the 'Mexican approach', 4,9 which employs fludarabine, busulfan and cyclophosphamide; in that series, individuals with different phases of the disease (CP, blastic and accelerated phases) were included. We report herein a multicenter, Latin American, prospective experience, using the same conditioning regimen, 4-6 in a group of 24 patients with CML in first CP.…”