Journal Article

A novel clofarabine bridge strategy facilitates allogeneic transplantation in patients with relapsed/refractory leukemia and high-risk myelodysplastic syndromes

van Besien, K, Le Beau, M M, White, C, Artz, A, Gurbuxani, S, Stock, W, Kunnavakkam, R, Liu, H, Agarwal, R, Larson, R A, Locke, F, Sipkins, D, Odenike, O, Godley, L A, Thirman, M J

2013

Overview

Patients with relapsed/refractory leukemias or advanced myelodysplastic syndrome (MDS) fare poorly following allogeneic hematopoietic cell transplant (HCT). We report prospective phase II study results of 29 patients given clofarabine 30 mg/m 2 /day i.v. × 5 days followed immediately by HCT conditioning while at the cytopenic nadir. A total of 15/29 patients (52%) were cytoreduced according to pre-defined criteria (cellularity <20% and blasts <10%). Marrow cellularity ( P <0.0001) and blast% ( P =0.03) were reduced. Toxicities were acceptable, with transient hyperbilirubinemia (48%) and gr3–4 infections (10%). In all, 28/29 proceeded to transplant; 27 received ATG or alemtuzumab. Post HCT, 180 day non-relapse mortality (NRM) was 7% (95% confidence interval (CI): 1–21), relapse was 29% (95% CI: 13–46) and OS was 71% (95% CI: 51–85), comparing favorably to published data for high-risk patients. Two-year graft vs host disease incidence was 40% (95% CI: 21–58) and 2 year OS was 31% (95% CI: 14–48). Disease at the nadir correlated with inferior OS after HCT (HR=1.22 for each 10% marrow blasts, 95% CI: 1.02–1.46). For AML/MDS patients, there was a suggestion that successful cytoreduction increased PFS (330 vs 171 days, P =0.3) and OS (375 vs 195 days, P =0.31). Clofarabine used as a bridge to HCT reduces disease burden, is well tolerated, and permits high-risk patients to undergo HCT with acceptable NRM. Late relapses are common; thus, additional strategies should be pursued. NCT-00724009.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/250/1904 / 692/699/67/1990/1673 / 692/699/67/1990/283 / 692/700/565/1436 / Acute myeloid leukemia / Adenine Nucleotides - administration & dosage / Adult / Aged / Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy / Antimetabolites, Antineoplastic - administration & dosage / Arabinonucleosides - administration & dosage / Biological and medical sciences / Bone marrow / Bone marrow, stem cells transplantation. Graft versus host reaction / Cancer / Care and treatment / Cell Biology / Confidence intervals / Graft-versus-host reaction / Hematologic and hematopoietic diseases / Hematology / Hematopoietic Stem Cell Transplantation - methods / Hematopoietic stem cells / Humans / Hyperbilirubinemia / Internal Medicine / Leukemia / Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis / Medical sciences / Medicine / Medicine & Public Health / Middle Aged / Monoclonal antibodies / Myelodysplastic syndrome / Myelodysplastic syndromes / Myelodysplastic Syndromes - drug therapy / Myelodysplastic Syndromes - surgery / Myelodysplastic Syndromes - therapy / Neoplasm Recurrence, Local - drug therapy / Neoplasm Recurrence, Local - surgery / Neoplasm Recurrence, Local - therapy / original-article / Prospective Studies / Public Health / Relapse / Retrospective Studies / Risk / Risk groups / Stem cell transplantation / Stem Cells / Toxicity / Transfusions. Complications. Transfusion reactions. Cell and gene therapy / Transplantation / Transplantation Conditioning - methods / Transplantation, Homologous / Transplants & implants / Young Adult