Granulocyte‐macrophage colony‐stimulating factor to increase efficacy of mitoxantrone, etoposide and cytarabine in previously untreated elderly patients with acute myeloid leukaemia: a Swedish multicentre randomized trial

Abstract

Summary A total of 110 patients, aged 64 years or over, with de novo acute myeloid leukaemia (AML) and white blood cell counts <50 × 109/l were treated with 3 d of cytarabine 1 g/m2 twice daily, mitoxantrone 12 mg/m2 and etoposide 200 mg/m2, randomized with or without the addition of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) 200 μg/m2. The primary aim was to evaluate the effect of GM‐CSF on the remission rate. Secondary aims included comparison of duration of remission, survival and infectious complications and the impact of maintenance therapy with thioguanine. Complete remission (CR) was achieved by 64% of patients without GM‐CSF, and by 65% of patients who received GM‐CSF, the median remission duration was 13 vs. 6 months, the median overall survival (OS) was 14 vs. 9 months, the mean time to neutrophil recovery was 25 vs. 17 d (P = 0·03) and the number of positive blood cultures was 46 vs. 39 (P = 0·05) respectively. The impact of thioguanine remains unanswered since only 30 patients remained in CR after consolidation therapy. We conclude that induction therapy is feasible with acceptable toxicity in elderly patients with AML, albeit with a high relapse rate and short OS. GM‐CSF prior to, and in combination with, induction treatment reduced the time to neutrophil recovery and the number of neutropenic septicaemia cases but did not improve the OS of AML in the elderly.

Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: final results of AML-13, a randomized phase-3 study

“…Only a recent Swedish study used an induction chemotherapy with the same 3 agents used in our trial, although delivered with a different schedule. 22 In that study, the administration of GM-CSF prior to and in combination with induction treatment did not improve either the response rate or OS. However, it should be underlined that the response rates in both arms were very high (64% in patients without GM-CSF, and 65% in patients who received GM-CSF), despite the fact that the median age was considerably higher (77 years) than the average of the other studies.…”

“…The NN score was applied only when a minimum number of 20 mitoses had been evaluated; in case of an examination of fewer metaphases, the analysis was considered inadequate. Abnormalities 16q (22) and t(8;21) were considered favorable risk abnormalities, whether other abnormalities were present or not. NN karyotypes or those with only ϪY were classified as intermediate risk.…”

“…13,14,[16][17][18][20][21][22]36,37 However, a careful analysis reveals a great variability in study conditions, with very few identical study designs (Table 7). When analyzing different clinical trials addressing similar questions, it is particularly important to compare patients' age, disease state (whether de novo AML or sAML), and the induction regimen used.…”

“…These results are largely in line with other trials conducted to date. [6][7][8][9][10]13,14,17,18,22 The shortened period of neutropenia was probably the reason for less antibiotic and antifungal use as well as shorter hospitalization in this group of patients. These positive clinical findings definitely encourage the use of G-CSF as an adjunct to standard supportive care in AML.…”

“…12 On the other hand, attempts to improve the response rate by sensitizing leukemic cells with hematopoietic growth factors, administered before or concurrently with remission-induction therapy, have yielded conflicting results. [13][14][15][16][17][18][19][20][21][22] In this report, we present the final results of a multicenter randomized phase-3 study in which glycosylated recombinant human G-CSF (lenograstim) was given during and/or after an intensive remission induction regimen in patients 61 years of age and older with AML. Our aims were to assess the impact of lenograstim on the efficacy and toxicity of chemotherapy.…”