Phase II study of combination human recombinant GM‐CSF with intermediate‐dose cytarabine and mitoxantrone chemotherapy in patients with high‐risk myelodysplastic syndromes (RAEB, RAEBT, and CMML): An Eastern Cooperative Oncology Group Study

A Phase II study of GM‐CSF with intermediate‐dose cytarabine and mitoxantrone was conducted in patients with high‐risk myelodysplastic syndrome. It was designed to evaluate if priming with growth factor could increase the efficiency of chemotherapy. In this older population only two of 10 patients achieved a bone marrow CR, including one patient whose leukemic blasts had an “S” phase increase of 2.55× at 48 hr. Unexpected hepatotoxicity was noted. This regimen cannot be recommended for this elderly population of patients. Am. J. Hematol. 66:23–27, 2001. © 2001 Wiley‐Liss, Inc.

[1]  E. Estey,et al.  Topotecan and cytarabine is an active combination regimen in myelodysplastic syndromes and chronic myelomonocytic leukemia. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  J. Liesveld,et al.  Effect of nitric oxide production and oxygen tension on progenitor preservation in ex vivo culture. , 1999, Experimental hematology.

[3]  P. Sonneveld,et al.  A randomized study of granulocyte colony-stimulating factor applied during and after chemotherapy in patients with poor risk myelodysplastic syndromes: a report from the HOVON Cooperative Group , 1998, Leukemia.

[4]  W. Hiddemann,et al.  Superiority of high-dose over intermediate-dose cytosine arabinoside in the treatment of patients with high-risk acute myeloid leukemia: results of an age-adjusted prospective randomized comparison , 1998, Leukemia.

[5]  T Hamblin,et al.  International scoring system for evaluating prognosis in myelodysplastic syndromes. , 1997, Blood.

[6]  J. Bennett,et al.  Morphology and classification of the myelodysplastic syndromes and their pathologic variants. , 1996, Seminars in hematology.

[7]  H. Zwierzina,et al.  Intensive chemotherapy for poor prognosis myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML) following MDS of more than 6 months duration. A pilot study by the Leukemia Cooperative Group of the European Organisation for Research and Treatment in Cancer (EORTC-LCG). , 1995, Leukemia.

[8]  J. Bennett,et al.  A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (> 55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). , 1995, Blood.

[9]  E. Hellström-Lindberg.  Efficacy of erythropoietin in the myelodysplastic syndromes: a meta‐analysis of 205 patients from 17 studies , 1995, British journal of haematology.

[10]  C. Schiffer,et al.  Effects of treatment with 5-azacytidine on the in vivo and in vitro hematopoiesis in patients with myelodysplastic syndromes. , 1993, Leukemia.

[11]  C. Bloomfield,et al.  Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  S. Yamaga,et al.  Effect of human recombinant granulocyte/macrophage colony-stimulating factor and native granulocyte colony-stimulating factor on clonogenic leukemic blast cells. , 1987, Cancer research.

[13]  R. Kamen,et al.  The human hematopoietic colony-stimulating factors. , 1987, Science.

[14]  E. Vellenga,et al.  The effects of GM-CSF and G-CSF in promoting growth of clonogenic cells in acute myeloblastic leukemia , 1987 .

[15]  J. Bennett.  Classification of the myelodysplastic syndromes. , 1986, Clinics in haematology.

[16]  K. Zsebo,et al.  Recombinant human granulocyte colony stimulating factor: molecular and biological characterization. , 1986, Immunobiology.

[17]  R. Donahue,et al.  Human recombinant granulocyte-macrophage colony-stimulating factor: a multilineage hematopoietin. , 1985, Science.

[18]  H. Gralnick,et al.  Proposals for the classification of the myelodysplastic syndromes , 1982, British journal of haematology.

[19]  N. Breslow,et al.  Statistical methods in cancer research. Vol. 1. The analysis of case-control studies. , 1981 .

[20]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[21]  N. Gattermann,et al.  Epidemiological and etiological aspects of myelodysplastic syndromes. , 1995, Leukemia & lymphoma.

[22]  W. Hiddemann,et al.  High-dose versus intermediate dose cytosine arabinoside combined with mitoxantrone for the treatment of relapsed and refractory acute myeloid leukemia: results of an age adjusted randomized comparison. , 1993, Leukemia & lymphoma.

[23]  G. Tricot.  Complications and treatment of the myelodysplastic syndromes. , 1992, Leukemia research.