Patterns of failure with increasing intensification of induction chemotherapy for acute myeloid leukaemia

  title={Patterns of failure with increasing intensification of induction chemotherapy for acute myeloid leukaemia},
  author={Jane P. Matthews and James F. Bishop and Graham A. R. Young and Surender K Juneja and Ray M. Lowenthal and O. Margaret Garson and Ralph Cobcroft and Anthony J. Dodds and Arno Enno and E. A. Gillett and Reichenspurner Hermann and Douglas Edgar Joshua and David D. F. Ma and Jeffrey Szer and Kerry McDonald Taylor and Max M Wolf and Km Bradstock},
  journal={British Journal of Haematology},
Patterns of failure were studied in two consecutive randomized trials of intensified induction therapy carried out by the Australian Leukaemia Study Group (ALSG) between 1984 and 1991 to determine the impact of dose intensification. Patients received standard dose cytarabine and daunorubicin (7‐3), 7‐3 plus etoposide (7‐3‐7) or 7‐3 plus high‐dose cytarabine (HIDAC‐3‐7) chemotherapy. Patients with FAB M3 morphology were excluded. Time to failure (TTF) was defined as the time from randomization… 

A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine.

Intensive induction chemotherapy incorporating high-dose cytarabine results in high complete remission rates, but further intensive consolidation treatment does not appear to confer additional benefit.

High-Dose Cytarabine in Acute Myeloid Leukemia Treatment: A Systematic Review and Meta-Analysis

HDAC treatment led to lower relapse rate in induction and consolidation therapy than SDAC treatment, especially for the favorable-risk group, and Auto-BMT/allo- BMT was more beneficial in prolonging RFS than HDAC.

Comparative efficacy and safety of eleven induction chemotherapy regimens for young adult patients with newly diagnosed acute myeloid leukemia: a network meta-analysis

DAC was potentially the top choice for young adult patients with newly diagnosed AML, with highest CR rate, low early mortality, and incidence of early infection.

Control of relapsed or refractory acute myeloid leukemia by clofarabine in preparation for allogeneic stem cell transplant

The clofarabine-AraC salvage strategy combines pronounced anti-leukemic activity with an acceptable toxicity profile and allows the majority of patients with relapsed or refractory AML to proceed to allo-SCT, even in cytogenetically defined high risk situations.

The role of interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with solid tumors, lymphoma, acute myeloid leukemia and bone marrow failure syndromes

With the availability of a platelet growth factor, recombinant human interleukin (IL)-11, an effective way to prevent chemotherapy-induced thrombocytopenia and accelerate platelet recovery, can now be provided to patients.

Impairment in functional status and survival in patients with acute myeloid leukaemia

In patients with AML, FS and not age is a major predictor of survival and the influence of FS is independent from cytogenetic risk group, and impaired KPS and IADL significantly influenced median survival in univariate analysis.

Enhanced sensitivity to glucocorticoids in cytarabine-resistant AML

This study shows that development of cytarabine resistance is associated with increased sensitivity to glucocorticoids in a subset of AML, suggesting a new therapeutic strategy that should be explored in a clinical trial of chemorefractory AML patients carrying wild-type FLT3.

Reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia

The indications for allogeneic transplants in AML are reviewed and reduced-intensity conditioning regimens are discussed, providing the benefit of the graft-versus-leukemia effect to a larger number of patients in need.

The prevalent predicament of relapsed acute myeloid leukemia.

  • J. Szer
  • Medicine, Biology
    Hematology. American Society of Hematology. Education Program
  • 2012
All patients with relapsed AML should be considered for an appropriate clinical trial and a decision made about the appropriateness of intensive therapy and whether a potentially curative allogeneic stem cell transplantation (allo-SCT) is possible.



A randomized study of high-dose cytarabine in induction in acute myeloid leukemia.

It is concluded that a dose-effect exists for cytarabine in AML and that HIDAC-3-7 prolongs remission duration and disease-free survival and is tolerable when used as initial induction therapy in patients with de novo AML.

Double induction strategy for acute myeloid leukemia: the effect of high-dose cytarabine with mitoxantrone instead of standard-dose cytarabine with daunorubicin and 6-thioguanine: a randomized trial by the German AML Cooperative Group.

High-dose versus standard-dose cytarabine proved a safe and effective strategy and a new way of delivering early intensification treatment for AML and may contribute a specific benefit to poor-risk patients that requires further substantiation.

Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia.

It is concluded that, at the doses and schedule used in this study, A + I is superior to A + D for induction therapy of AML in adults.

A phase III trial of high-dose cytosine arabinoside with or without etoposide in relapsed and refractory acute myelogenous leukemia. A Southeastern Cancer Study Group trial.

The addition of etoposide to a high-dose cytosine arabinoside regimen had at best a marginal effect at the expense of some increase in toxicity.

Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group.

Induction and consolidation therapy intensified with etoposide resulted in significantly improved remission duration but not survival, and in older patients, 7-3-7 was more toxic, with significantly more severe [World Health Organization (WHO) grade 3 or 4] stomatitis and no additional clinical benefit.

Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B.

The concept of a dose-response effect for cytarabine in patients with AML who are 60 years of age or younger is supported and the results with the high-dose schedule in this age group are comparable to those reported in similar patients who have undergone allogeneic bone marrow transplantation during a first remission.

Prognostic impact of cytogenetic abnormalities in patients with de novo acute nonlymphocytic leukemia.

Detailed cytogenetic analyses were performed on specimens from 198 patients with de novo acute nonlymphocytic leukemia, including high-resolution banding studies in 79 patients, suggesting patients with abnormalities associated with poor responses may be considered for investigational approaches and may provide insights into mechanisms of drug resistance.

A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study.

Patients who received both HDAC induction and consolidation had the best postremission outcomes; however, the proportion of CR patients who did not go on to protocol consolidation therapy was more than twice as high afterHDAC induction compared with SDAC.

Comparison of 1 + 5 DAT and 3 + 10 DAT followed by COAP or MAZE consolidation therapy in the treatment of acute myeloid leukemia: MRC ninth AML trial.

Analysis of the reasons for failure to enter remission continues to show that inadequate supportive care remains an important reason why the remission rates are not higher and the more intensive regimen of DAT 3 + 10 achieves remission more quickly and requires less supportive care.

A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group Study.

This trial demonstrated that IDR was more effective than DNR in remission induction in AML.