Intensive chemotherapy of poor prognosis myelodysplastic syndromes (MDS) and acute myeloid leukemia following MDS with idarubicin and cytarabine

doi:10.1016/S0145-2126(96)00116-6

Leukemia Research

Volume 21, Issue 2, February 1997, Pages 133-138

https://doi.org/10.1016/S0145-2126(96)00116-6 Get rights and content

Abstract

Forty patients with high risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) preceded by MDS were treated with intensive induction and consolidation chemotherapy in a prospective multicenter pilot study. They were given two cycles of cytarabine 100mg/m² with 12-h intervals on days 1–7 and idarubicin 12 mg/m² on days 5–7, both intravenously. Patients who were in remission after these two cycles were given two further cycles of cytarabine on days 1–5 and idarubicin on day 5. No maintenance treatment was given. Eleven out of 19 MDS patients (58%) and 10 out of 21 AML patients (48%), in total 21 out of 40 patients (53%), entered remission. Eight patients underwent allogeneic bone marrow transplantation. The follow-up time was 13–48 (median 33) months. At the time of the analysis, seven patients survived, four patients with MDS all of whom had been treated with bone marrow transplantation (three in continuous remission), and three patients with AML treated with chemotherapy only (two in continuous remission). The median survival of the patients treated with chemotherapy only was 12 months, with the median progression-free survival being 8 months. In view of the poor prognostic factors of the patients, the remission rate was satisfactory, but the responses as well as the survival were short. The post-remission treatment needs to be improved.

References (25)

T.J. Hamblin
Intensive chemotherapy in myelodysplastic syndromes
Blood Rev.
(1992)
G.F. Sanz et al.
Prognostic factors in myelodysplastic syndromes
Leukemia Res.
(1992)
H. Löffler et al.
Intensive chemotherapy and bone marrow transplantation for myelodysplastic syndromes
Hematol Oncol. Clin. N. Am.
(1992)
T. Fukushima et al.
Influence of idarubicinol on the antileukemic effect of idarubicin
Leukemia Res.
(1994)
E. Berman et al.
Comparative cellular pharmacology of daunorubicin and idarubicin in human multidrug-resistant leukemia cells
Blood
(1992)
E. Berman et al.
Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia
Blood
(1991)
F. Mandelli et al.
A randomized clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute nonlymphoid leukemia
Euro. J. Cancer
(1991)
P.H. Wiernik et al.
Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia
Blood
(1992)
T. De Witte et al.
Bone marrow transplantation for myelodysplastic syndrome and secondary leukaemias
Br. J. Haematol.
(1993)
A. Ganser et al.
Clinical course of myelodysplastic syndromes
Hematol. Oncol. Clin. N. Am.
(1992)

P. Fenaux et al.

The role of intensive chemotherapy in myelodysplastic syndromes

Leukemia and Lymphoma

(1992)

T. De Witte 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)

Leukemia

(1995)

Cited by (32)

Hematopoietic stem cell transplantation for MDS
2010, Hematology/Oncology Clinics of North America
The myelodysplastic syndromes: Diagnosis and treatment
2006, Mayo Clinic Proceedings
Citation Excerpt :
The 40% to 50% of patients with MDS who are short-term responders in clinical trials of chemotherapy regimens are usually a selected group, younger and healthier than the typical older patient with aggressive MDS. Almost all patients with MDS who achieve remission via chemotherapy promptly experience relapse.268–270 Only about 5% of patients who receive high-dose therapy are alive at 3 years, but there are occasional long-term responders.271
The myelodysplastic syndromes (MDSs) are common, acquired, clinically challenging hematologic conditions that are characterized by bone marrow failure and a risk of progression to acute leukemia. These disorders can arise de novo, especially in elderly patients or, less often, as a consequence of prior chemotherapy or radiotherapy for an unrelated disease. The MDS classification systems were revised recently and updated. These refined classification and prognostic schemes help stratify patients by their risk of leukemia progression and death; this knowledge can help clinicians select appropriate therapy. Although many treatments for MDS have been proposed and evaluated, at present, only hematopoietic stem cell transplantation offers any real hope for cure, and no available therapy beyond general supportive care offers benefit to more than a minority of patients. However, recent clinical trials enrolling patients with MDS have reported encouraging results with use of newer drugs, including lenalidomide, decitabine, and darbepoetin alfa. Other exciting treatment regimens are being tested. Here, we present a contemporary, practical clinical approach to the diagnosis and risk-stratified treatment of MDS. We review when to suspect MDS, detail how to evaluate patients who may have a form of the condition, explain key features of treatments that are currently available in the United States, and summarize a general, common-sense therapeutic approach to patients with MDS.
Nucleoside analogs and antimetabolite therapies for myelodysplastic syndrome
2004, Best Practice and Research: Clinical Haematology
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic disorders. Therapeutic interventions for MDS other than allogeneic bone marrow transplantation have been palliative. Because most of the patients are elderly and may not be candidates for ablative transplant conditioning regimens, treatment has focused on supportive care. Recently, several novel biological and chemotherapeutic agents have demonstrated activity in MDS and are being incorporated into the treatment paradigm. These agents are based on specific mechanisms aimed at angiogenesis in the bone marrow, secretion of growth factors and/or their receptors, and modulators in their intracellular pathways. Several agents are in the initial stages of clinical trial, including anti-vascular endothelial growth factor, bevacizumab, receptor tyrosine kinase inhibitors, farnesyl transferase inhibitors, protein kinase C inhibitors, matrix metalloproteinase inhibitors and other agents such as thalidomide and arsenic trioxide. Novel chemotherapeutic agents include topoisomerase inhibitors such as topotecan and rubitecan, and deoxyadenosine analogues such as troxacitabine, tezacitabine, and clofarabine. Prognostic factors predicting response in MDS patients treated with intensive chemotherapy have been identified and include younger age and favorable cytogenetics
The myelodysplastic syndrome(s): A perspective and review highlighting current controversies
2003, Leukemia Research
The myelodysplastic syndrome (MDS) includes a diverse group of clonal and potentially malignant bone marrow disorders characterized by ineffective and inadequate hematopoiesis. The presumed source of MDS is a genetically injured early marrow progenitor cell or pluripotential hematopoietic stem cell. The blood dyscrasias that fall under the broad diagnostic rubric of MDS appear to be quite heterogeneous, which has made it very difficult to construct a coherent, universally applicable MDS classification scheme. A recent re-classification proposal sponsored by the World Health Organization (WHO) has engendered considerable controversy.
Although the precise incidence of MDS is uncertain, it has become clear that MDS is at least as common as acute myelogenous leukemia (AML). There is considerable overlap between these two conditions, and the former often segues into the latter; indeed, the distinction between AML and MDS can be murky, and some have argued that the current definitions are arbitrary. Despite the discovery of several tantalizing pathophysiological clues, the basic biology of MDS is incompletely understood. Treatment at present is generally frustrating and ineffective, and except for the small subset of patients who exhibit mild marrow dysfunction and low-risk cytogenetic lesions, the overall prognosis remains rather grim. In this narrative review, we highlight recent developments and controversies within the context of current knowledge about this mysterious and fascinating cluster of bone marrow failure states.
Energy metabolism and drug response in myeloid leukaemic stem cells
2019, British Journal of Haematology
Characterization and targeting of malignant stem cells in patients with advanced myelodysplastic syndromes
2018, Nature Communications

View all citing articles on Scopus

View full text

Original articleIntensive chemotherapy of poor prognosis myelodysplastic syndromes (MDS) and acute myeloid leukemia following MDS with idarubicin and cytarabine

Abstract

Blood Rev.

Leukemia Res.

Hematol Oncol. Clin. N. Am.

Leukemia Res.

Blood

Blood

Euro. J. Cancer

Blood

Br. J. Haematol.

Hematol. Oncol. Clin. N. Am.

The role of intensive chemotherapy in myelodysplastic syndromes

Leukemia and Lymphoma

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)

Leukemia

Original article
Intensive chemotherapy of poor prognosis myelodysplastic syndromes (MDS) and acute myeloid leukemia following MDS with idarubicin and cytarabine