Hematopoietic Growth Factors: Supportive and Priming Effects in AML

Büchner, Thomas; Hiddemann, Wolfgang; Zühlsdorf, M.; Wörmann, B.; Aswald, J.; Aswald, S.; Maschmeyer, Georg; Ludwig, Wolf‐Dieter; Sauerland, M. C.

doi:10.1007/978-3-642-71960-8_40

Cited by 5 publications

(7 citation statements)

References 14 publications

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“…Cytokine-mediated up-regulation of a survivin-dependent survival pathway might also explain the conflicting clinical results reported for cytokine "priming" strategies for the therapy of AML. 54 The binding of GM-CSF to its receptor activates multiple signaling pathways, which in turn lead to the proliferation, differentiation, and survival of various hematopoietic cells. 19,20,22 Here we provide the first evidence that, in addition to modulating the expression and function of Bcl-2 family members, GM-CSF-mediated activation of both the MEK/ERK and the PI3K signal transduction pathways regulates the expression of survivin at both the mRNA and the protein level.…”

Section: Discussionmentioning

confidence: 99%

Cytokine-regulated expression of survivinin myeloid leukemia

Carter

Milella

Altieri

et al. 2001

Blood

192

151

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Section: Discussionmentioning

confidence: 99%

Cytokine-regulated expression of survivinin myeloid leukemia

Carter

Milella

Altieri

et al. 2001

Blood

192

151

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“…29 Several important phase 2 studies suggested that in vivo blast cells could be recruited into the S-phase with little, if any, detrimental effect on the outcome of treatment. 30,31 The results of these studies have been confusing, [32][33][34][35][36][37][38][39][40][41] but broadly suggested that stimulation of leukemia was not generally a clinical problem. In contrast, only one study showed a beneficial effect of priming with cytokines in patients with AML.…”

Section: Unknown 19mentioning

confidence: 99%

A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group

Rowe

Neuberg

Friedenberg

et al. 2004

Blood

258

167

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The optimal induction for older adults with acute myeloid leukemia (AML) is unknown. Several anthracyclines have been proposed, but the data remain equivocal. Additionally, few prospective trials of priming with hematopoietic growth factors to cycle leukemia cells prior to induction chemotherapy have been conducted. Three hundred and sixtytwo older adults with previously untreated AML were randomized to either daunorubicin, idarubicin or mitoxantrone with a standard dose of cytarabine as induction therapy. In addition, 245 patients were also randomized to receive granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo beginning 2 days prior to induction chemotherapy and continuing until marrow aplasia. No difference was observed in the disease-free overall survival or in toxicity among patients receiving any of the 3 induction regimens or among those receiving growth factor or placebo for priming. However, the complete remission rate for the first 113 analyzable patients, who did not participate in the priming study and started induction therapy 3 to 5 days earlier than those who did, was significantly higher (50% versus 38%; P ‫؍‬ .03). None of the anthracyclines is associated with improved outcome in older adults. Priming with hematopoietic growth factor did not improve response when compared with placebo. Furthermore, delaying induction therapy in older adults may lead to a lower complete remission rate. IntroductionA combination of an anthracycline and a cytarabine is the most commonly used induction regimen in acute myeloid leukemia (AML). However, neither the best anthracycline nor the optimal dose has been established. Classic studies 2 decades ago established a standard induction regimen of 45 mg/m 2 daunorubicin intravenously for 3 days and 100 mg/m 2 cytarabine intravenously by continuous infusion for 7 days. 1-5 For patients younger than 55 to 60 years, multiple prospective randomized studies compared daunorubicin at a dose of 45 mg/m 2 with idarubicin, amsacrine, aclacinomycin A, and mitoxantrone, while keeping the dose of cytarabine constant. [6][7][8][9][10][11][12][13][14] Virtually all of these agents were at least as effective as, if not better than, daunorubicin at a dose of 45 mg/m 2 . However, the results for patients older than 55 to 60 years are equivocal and do not confirm the superiority of any anthracycline when compared with 45 mg/m 2 daunorubicin. 9,15 In this prospective randomized study, older adults received either daunorubicin, idarubicin, or mitoxantrone, each combined with the identical dose of cytarabine.Priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF) may modulate cell cycle kinetics of leukemic blasts and render them more susceptible to phase-specific agents such as cytarabine. 16 In this prospective trial, patients were also randomized to receive GM-CSF or placebo prior to induction therapy to determine the effect that induction therapy for AML had on efficacy and toxicity. Correlative labora...

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“…Third, hematopoietic growth factors may be of great value in the elderly, although they produce only limited benefits in younger patients (172,173). Several randomized studies demonstrated that both mortality associated with neutropenia and survival were significantly improved by using these cytokines in elderly patients with acute leukemia (174,175). Finally, a patient's tolerance to chemotherapy would correlate better with 'biological age' than with'chronological age' , because the rate of aging is not uniform among all individuals.…”

Section: Limitation Of This Review and Future Directionsmentioning

confidence: 99%

Cancer Chemotherapy in the Elderly

Sekine

Fukuda

Kunitoh

et al. 1998

Japanese Journal of Clinical Oncology

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As the geriatric population is growing, it is increasingly important to be familiar with chemotherapy for the elderly. Age-related changes in pharmacokinetics are documented for doxorubicin, etoposide, ifosfamide, daunorubicin, mitomycin, cisplatin and methotrexate. The hematological toxicity of most standard-dose chemotherapy is not affected by age in patients with normal organic functions and good performance status, although increased toxicity with aging is suggested in the use of actinomycin-D, etoposide, vinblastin, methotrexate, methyl-CCNU, doxorubicin and mitomycin, and in dose-intensive chemotherapy. Among non-hematological toxicities, only doxorubicin-induced cardiomyopathy and bleomycin-induced pulmonary toxicity are demonstrated to be accelerated in the elderly. There is no evidence that advanced age decreases the efficacy of chemotherapy for tumors, except for Hodgkin's disease and acute leukemia. These results suggest that advanced chronological age alone is not always associated with severe toxicity and poor prognosis, and that many elderly patients with cancer will benefit from chemotherapy. To answer questions regarding the optimal chemotherapy regimen, dose and intensity in this population, the influence of age should be analyzed in a multivariate approach in future studies.

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Hematopoietic Growth Factors: Supportive and Priming Effects in AML

Cited by 5 publications

References 14 publications

Cytokine-regulated expression of survivinin myeloid leukemia

Cytokine-regulated expression of survivinin myeloid leukemia

A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group

Cancer Chemotherapy in the Elderly

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