A Double-blind Controlled Study of G-CSF Started Two Days Before Induction Chemotherapy in Refractory Acute Myeloid Leukemia

Ohno, Ryuzo; Naoe, Tomoki; Kanamaru, Akihisa; Yoshida, Masayuki; Hiraoka, A; Kobayashi, Toshimitsu; Ueda, Takanori; Minami, Saburo; Morishima, Yasuo; Saito, Yoshiko; Furusawa, Shinpei; Imai, Kenichiro; Takemoto, Yoshinobu; Miura, Yasusada; Teshima, Hideo; Hamajima, Nobuyuki

doi:10.1007/978-3-642-78907-6_25

Cited by 31 publications

(57 citation statements)

References 13 publications

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“…[43][44][45][46][47] The unique reported randomized study involving the administration of G-CSF during chemotherapy did not show any effect on relapse rate. 48 Two studies using GM-CSF in newly diagnosed AML 43,46 and our present study using GM-CSF in relapsed or refractory AML showed a favorable effect on relapse rate. Noteworthy, in two of these three studies, GM-CSF administration was initiated either after day 1 of cytotoxic chemotherapy or at time of chemotherapy initiation.…”

Section: Discussionsupporting

confidence: 52%

“…Numerous randomised studies in AML were designed to take advantage of the potential sensitization of leukemic cells to cytotoxic agents by GM-CSF 32,43-47 or G-CSF. 48 However, these studies involved the administration of the growth factor not only during chemotherapy, but also for one 43 or two 44,45,47,48 days preceding chemotherapy, or after chemotherapy, until recovery from aplasia. [43][44][45][46][47] The unique reported randomized study involving the administration of G-CSF during chemotherapy did not show any effect on relapse rate.…”

Section: Discussionmentioning

confidence: 99%

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True

1999

Leukemia

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The EMA86 study showed efficacy of intensive sequential chemotherapy with mitoxantrone, 12 mg/m 2 day on days 1-3, etoposide, 200 mg/m 2 /day as a continuous infusion on days 8-10 and cytarabine (araC), 500 mg/m 2 /day as continuous infusion on days 1-3 and 8-10 (EMA regimen) in previously treated patients with AML. The goal of the EMA91 study was to determine whether administration of GM-CSF between the two sequences of EMA chemotherapy and during the second sequence could increase therapeutic efficacy by potentially increasing leukemic cell recruitment into the S phase of cell cycle before the second sequence. One hundred and ninetytwo patients aged less than 65 years with previously treated AML received GM-CSF, 5 g/kg/day or placebo from day 4 to day 8 of EMA chemotherapy. One hundred and twenty were refractory and 72 were in first relapse after a complete remission (CR) of more than 6 months duration. CR rates after one course of chemotherapy were 65% in the GM-CSF group (refractory: 51%; first relapse: 89%), not significantly different from the 59% CR rate (refractory: 46%; first relapse: 81%) in the placebo group. Median time to recovery of neutrophils was 38 and 37 days and median time to last platelet transfusion 32 and 32 days respectively in the GM-CSF and placebo groups. WHO grade у3 non-hematologic toxicities were mainly sepsis (45% and 51%, respectively) and mucositis (34% and 31%) and did not differ between the two groups. Toxic death rate was 5% and 8%, respectively, in the GM-CSF and placebo groups. Patients achieving CR were scheduled to receive six courses of maintenance with reduced-dose EMA. Time to progression tended to be longer in the GM-CSF group (median 154 vs 115 days, progression-free rate at 18 months 33% vs 19%, P ‫؍‬ 0.08), particularly in refractory patients (P ‫؍‬ 0.06). However, at the current follow-up, this did not translate into a significantly longer disease-free survival and survival. Cell cycle studies showed increased recruitment of cells in the S phase between day 4 and day 8 in the GM-CSF group compared to placebo (P ‫؍‬ 0.006). However, this did not significantly relate to prognosis in this cohort of patients. GM-CSF might marginally increase efficacy of sequential chemotherapy without increasing its toxicity in the absence of any detected relationship between this effect and observed leukemic cell recruitment into the cell cycle.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

True

1999

Leukemia

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“…Non-haematological adverse effects in the first induction course with AVG therapy AVG regimen regarding the degree of mylosuppression (data was not shown). Several studies about the role of G-CSF during and/or after induction therapy were initiated, but no conclusion could be made in this regard [12,21,22]. It is possible that the priming effect with G-CSF is different between intensive regimens and low dose regimens.…”

Section: Discussionmentioning

confidence: 99%

Continuous drip infusion of low dose cytarabine and etoposide with granulocyte colony‐stimulating factor for elderly patients with acute myeloid leukaemia ineligible for intensive chemotherapy

Kanemura¹,

Tsurumi²,

Kasahara³

et al. 2007

Hematological Oncology

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Backgrounds and objectives: The optimal strategy for the management of elderly patients with acute myeloid leukaemia (AML) is still controversial. We previously reported the effectiveness of low dose cytarabine (Ara-C) and etoposide (VP-16) (AV therapy) for those elderly AML patients ineligible for intensive chemotherapy. We initiated the present feasibility study to improve the efficacy by using glanulocyte-colony stimulating factor (G-CSF) with AV therapy (AVG therapy). Patients and methods: The eligibility for enrolment was AML patients according to the World Health Organization (WHO) criteria who were over 60 years of age and who had difficulty in tolerating intensive chemotherapy due to their poor performance status (PS) or some comorbidities. They were given continuous drip infusion of Ara-C (20 mg/body) and VP-16 (50 mg/body) for 7-14 days, and were also simultaneously administered G-CSF (150 mg/m 2 ) once daily. Results: The median age of consecutively enrolled 25 patients was 73 years. Eighteen (72%) patients achieved complete remission (CR). The 1-year overall survival (OS) and the 3-year OS rates were 69% and 22%, respectively. The 1-year disease free survival (DFS) rate in CR patients was 44%. The major regimen related toxicities of grade 3 or 4 were only febrile neutropenia in 15 patients (60%). No regimen-related mortality was observed. Conclusion: AVG therapy was therefore found to be an effective and well-tolerated regimen for remission induction in elderly AML patients with poor PS or comorbidity.

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“…However, further clinical analysis will be required regarding the merits and demerits of G-CSF administration to Ph1-positive leukemia patients, since it may improve prognosis by preventing severe infections and/or shortening the interval between programs of chemotherapy as reported in AML. 51 On the other hand, it might be possible that G-CSF enhance the cytotoxic effect of anti-leukemic agents in Ph1-positive leukemia by promoting leukemic cells into chemotherapy-sensitive G 1 -and S-phases as attempted in AML cells. 52 Thus, it might be effective to use G-CSF together with preconditioning regimen in autologous or allogeneic bone marrow transplantation for Ph1-positive leukemia.…”

Section: Figurementioning

confidence: 99%