Treatment strategies in acute myeloid leukemia (AML)

Hiddemann, Wolfgang; Büchner, Thomas

doi:10.1007/bf01720270

Cited by 40 publications

(18 citation statements)

References 64 publications

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“…24,25 The optimal form of postremission treatment, however, remains in dispute. Prolonged schedules of maintenance therapy have been replaced by more effective regimes including multiple cycles of HIDAC-based consolidation.…”

Section: Discussionmentioning

confidence: 99%

Long-term outcome of autologous transplantation of peripheral blood progenitor cells as postremission management of adult acute myelogenous leukemia in first complete remission

et al. 2003

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In order to improve leukemia-free survival (LFS) without the treatment-related morbidity of allogeneic bone marrow transplantation or multiple prolonged cycles of consolidation chemotherapy, we evaluated the long-term outcome of autologous transplantation of peripheral blood progenitor cells (PBPCs) as postremission therapy in 129 patients aged 18-71 years (median 49 years) with newly diagnosed acute myelogenous leukemia (AML) in first complete remission (CR1). The median follow-up from remission for surviving patients was 62.2 months (range 3.7-127.9 months). A total of 57 patients were alive and leukemia free at the end of the study. The LFS and overall survival 5 years from remission were 40.2% (79.2%) and 41.4% (79.4%), respectively. The median LFS and overall survival are 17.3 and 23.3 months, respectively. Multivariate analysis identified age as the most significant predictor for both LFS and overall survival. Karyotype was also found to be predictive of outcome. Our results show that autologous transplantation of PBPC procured after a single cycle of highdose cytarabine-based consolidation chemotherapy for a population of adult patients with AML in CR1 produces a high likelihood of long-term LFS, offering a state of clinical minimal residual disease for the investigation of future therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Long-term outcome of autologous transplantation of peripheral blood progenitor cells as postremission management of adult acute myelogenous leukemia in first complete remission

et al. 2003

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“…1 When CR is achieved in advanced AML (eg second or later remissions, refractory disease), remission duration and survival are usually brief. 2 …”

Section: Discussionmentioning

confidence: 99%

“…The likelihood of such patients achieving another CR is approximately 40%. 2 Even when these patients do achieve a CR, the median duration of remission is only approximately half as long as the preceding remission, and long-term survival and cure is only obtainable after autologous or allogeneic bone marrow transplantation. 2 Whether any chemotherapy less intensive than that employed in bone marrow transplantation can prolong later remissions in advanced AML is unclear.…”

Section: Introductionmentioning

confidence: 99%

“…2 Even when these patients do achieve a CR, the median duration of remission is only approximately half as long as the preceding remission, and long-term survival and cure is only obtainable after autologous or allogeneic bone marrow transplantation. 2 Whether any chemotherapy less intensive than that employed in bone marrow transplantation can prolong later remissions in advanced AML is unclear. The fact that many patients with advanced disease are elderly and/or variably compromised by complications from previous treatment raised the question of whether low-dose maintenance chemotherapy would be tolerable and of benefit.…”

Section: Introductionmentioning

confidence: 99%

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Low-dose cytarabine maintenance therapy vs observation after remission induction in advanced acute myeloid leukemia: an Eastern Cooperative Oncology Group Trial (E5483)

Robles

Oken³

et al. 2000

Leukemia

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The Eastern Cooperative Oncology Group (ECOG) conducted a prospective phase III study in patients with relapsed/refractory acute myeloid leukemia (AML) to evaluate whether administration of repeated courses of low-dose cytarabine (LDAC) maintenance therapy after induction of complete remission in advanced AML would improve disease-free and overall survival. Patients with AML in second/later relapse or refractory disease were first treated with a combination of high-dose cytarabine and amsacrine. Those who achieved complete remission were then randomized to observation or to receive LDAC, 10 mg/m 2 subcutaneously twice a day ؋2 21 days every 2 months until relapse occurred. Of 86 patients eligible for randomization, 41 patients were assigned to receive LDAC and 45 patients to observation. The median disease-free survival was 7.4 months for patients assigned to LDAC compared to 3.3 months for patients receiving no additional therapy, P = 0.084. The median survival from randomization was 10.9 months and 7.0 months for patients receiving LDAC maintenance chemotherapy and observation, respectively (P = 0.615). The data from this study suggest that LDAC maintenance therapy given to patients with advanced AML who achieve complete remission can increase disease-free survival compared to observation, but does not improve overall survival. Nevertheless, because of the ineffectiveness and toxicity of intensive post-remission chemotherapy in this circumstance, LDAC maintenance therapy, a tolerable outpatient regimen, offers the potential for improved quality of life. Leukemia (2000) 14, 1349-1353.

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“…However, patients with chemosensitive relapse and subsequent consolidation by allogeneic or autologous stem cell transplantation (SCT) have a disease-free survival (DFS) rate of 20-50% [5,6]. Most salvage regimens still have incorporated cytarabine (Ara-C) because this drug represents the most effective single agent in the treatment of AML [7]. Starting from the observation reported by Gandhi et al [8] that a further increase of the intracellular concentration of the active metabolite Ara-C triphosphate (Ara-CTP) can be achieved upon pretreatment with fludarabine, the fludarabine and Ara-C (FA) protocol containing this combination was developed [9].…”

Section: Introductionmentioning

confidence: 99%

Mito-FLAG as Salvage Therapy for Relapsed and Refractory Acute Myeloid Leukemia

et al. 2001

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Background: This study was performed to examine the feasibility and toxicity of the combination of mitoxantrone, fludarabine, cytarabine as bolus (B) or continuous infusion (CI) and granulocyte- colony stimulating factor (G-CSF) in patients with recurrent and refractory acute myeloid leukemia (AML). Patients and Methods: 29 patients with relapsed (n =17) or refractory (n =12) AML were treated with the Mito-FLAG protocol consisting of mitoxantrone (7 mg/m², days 1/3/5), fludarabine (15mg/m², every 12 h, days 1–5), cytarabine (Ara-C) as bolus infusion (1000 mg/m² over 1 h, every 12 h, days 1–5) (n =15) or as continuous infusion (100–150 mg/m² over 24 h, days 1–5) (n =14), and G-CSF (5 µg/ kg/day, day 0 until a neutrophile count of 0.5 ×10⁹/l). Results: 17 patients (59%) and 1 patient (3%) achieved complete remission (CR) and partial remission (PR), respectively; thus the overall response rate was 62%. Following Mito-FLAG, 5 patients with CR underwent high-dose therapy (HDT) with allogeneic (n = 2) or autologous (n = 3) stem cell transplantation (SCT).With a median follow-up of 28 (range 6–54) months, 4 transplanted patients are alive in CR (n = 2) or in relapse (n = 2). The median duration of event-free survival (EFS) and overall survival (OS) was 3.2 and 6.8 months, and probabilities of EFS and OS after 1 year were 14 and 34%, respectively. The 1-year rates for EFS and OS in this group were 18 and 53%, respectively. Median duration of WHO grade 4 granulocytopenia and thrombocytopenia was 20 and 23 days, respectively. Nonhematological side effects were moderate, predominantly reaching WHO grades 1–2. Neutropenic fever was seen in 85% of courses, with a median duration of 4 (1–38) days. Four patients (14%) suffered an early death because of aplasia (n = 2), pneumonia (n =1) or progressive AML (1 nonresponding patient). Conclusions: Our data suggest that the Mito-FLAG protocol is feasible and can be safely performed with both schedules of Ara-C. In this study the regimens have shown high efficacy and acceptable toxicity in patients with relapsed or refractory AML. We currently examine the importance of bolus versus continuous infusion of Ara-C as part of the Mito-FLAG regimen in a prospective randomized multicenter trial.

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Treatment strategies in acute myeloid leukemia (AML)

Cited by 40 publications

References 64 publications

Long-term outcome of autologous transplantation of peripheral blood progenitor cells as postremission management of adult acute myelogenous leukemia in first complete remission

Long-term outcome of autologous transplantation of peripheral blood progenitor cells as postremission management of adult acute myelogenous leukemia in first complete remission

Low-dose cytarabine maintenance therapy vs observation after remission induction in advanced acute myeloid leukemia: an Eastern Cooperative Oncology Group Trial (E5483)

Mito-FLAG as Salvage Therapy for Relapsed and Refractory Acute Myeloid Leukemia

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