Early allogeneic transplantation for refractory or relapsed acute leukaemia following remission induction with FLAG

Byrne, J L; Das‐Gupta, Emma; Pallis, Monica; Turzanski, J.; Forman, K.; Mitchell, Drake C.; Haynes, AP; Russell, NH

doi:10.1038/sj.leu.2401406

Cited by 33 publications

(15 citation statements)

References 13 publications

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“…75 Allogeneic HSCT may provide the highest likelihood of cure, presumably related to the generation of an immunologically mediated graft-versus leukemia reaction not present with salvage chemotherapy, preferably after induction of a second CR. [76][77][78][79] However, there is a lack of prospective data to definitively demonstrate a superior outcome with such a strategy. If a suitable histocompatible sibling donor is not available, transplantation from an alternative donor such as a matched unrelated donor 80 or a haploidentical stem-cell donor 81,82 can be considered.…”

Section: Treatment Of Patients With Relapsed or Refractory Amlmentioning

confidence: 99%

Drug therapy for acute myeloid leukemia

Tallman

Gilliland

Rowe

2005

Blood

596

459

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Although improvement in outcomes has IntroductionAcute myeloid leukemia (AML) is a heterogeneous group of diseases characterized by uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells and impaired production of normal hematopoiesis leading to neutropenia, anemia, and thrombocytopenia. 1 If untreated, patients die of infection or bleeding usually in a matter of weeks. Some older adults may have a slower progressive clinical course. An estimated 10 600 new cases occurred in the United States in 2002 and 7400 patients died of the disease. 2 The overall incidence is 3.4 cases per 100 000 population; 1.2 cases per 100 000 population at age 30 and more than 20 cases per 100 000 population at age 80 years. 2 The median age is 20 years and has been increasing over the past decade.Historically, the diagnosis and response to therapy were established from morphology and cytochemistry. Although morphology remains the initial diagnostic tool for any patient with acute leukemia, the past decade has witnessed increased reliance on cell-surface antigen expression by immunophenotyping, usually carried out by flow cytometry, as well as cytogenetic and molecular markers.During the past 4 decades, many studies have investigated a wide variety of cytotoxic antileukemic agents. Most recently, insights into the molecular pathogenesis of AML have led to the development of the more specific targeted therapy. This review focuses on current and evolving drug therapy in the treatment of adults with AML. Current treatment resultsApproximately 50% to 75% of adults with AML achieve complete remission (CR) with the deoxycytidine analog cytarabine and an anthracycline antibiotic, such as daunorubicin or idarubicin, or the anthracenedione mitoxantrone, which inhibit the enzyme topoisomerase IIa. However, only 20% to 30% of patients enjoy long-term disease-free survival (DFS). The majority of patients die of their disease, primarily because of persistent or relapsed AML. In an Eastern Cooperative Oncology Group (ECOG) analysis of the outcome of approximately 3000 patients with previously untreated AML entered on 5 successive clinical trials with cytarabine and daunorubicin for induction and with increasingly more intensive postremission therapy, 62% achieved CR, but 76% relapsed or died. 3,4 The 5-year overall survival (OS) rate among 2000 patients younger than 55 years has improved from 11% in the 1970s to 37% in the 1990s. (Figure 1A-C). In contrast, among 1000 patients age 55 years and older, progress over the past 3 decades has been very modest. 5 Prognostic factorsThe outcome for adults with AML depends on a variety of factors, including age of the patient, intensity of postremission therapy, and biologic characteristics of the disease, the most important of which are the cytogenetics at presentation. 4,[6][7][8] (Figure 2). Other factors include the presence of transmembrane transporter proteins, which extrude certain chemotherapy agents from the cell and confer multidrug resistance, 9 and mutations in or overex...

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Section: Treatment Of Patients With Relapsed or Refractory Amlmentioning

confidence: 99%

Drug therapy for acute myeloid leukemia

Tallman

Gilliland

Rowe

2005

Blood

596

459

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“…We have previously observed a high CR rate in response to FLAG in pgp-positive AML cases with primary resistance to DAT. 37 Furthermore, when using a flow cytometric assay of cell survival, we observed that in vitro responses to FLAG differed from DAT, depending upon pgp status. Pgp-positive AML blasts were more sensitive to the combination of fludarabine/AraC than to daunorubicin/AraC.…”

Section: P-glycoprotein (Pgp) In Amlmentioning

confidence: 89%

Strategies for overcoming p-glycoprotein-mediated drug resistance in acute myeloblastic leukaemia

Pallis

Russell

2004

Leukemia

Self Cite

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“…Thus, up to 50% of patients (10/12 with HR-AML and 7/12 with HR-ALL) were able to proceed to SCT. In contrast, only five out of 14 patients in CR proceeded to SCT in the GEMIA study 16 and 10/61 patients were able to receive consolidation with SCT after Months from Ara-amsa salvage with a combination of idarubicin and intermediatedose Ara-C. 22 The ability to treat a larger proportion of patients with SCT with the use of FLAG as a salvage regimen has been recently demonstrated, 23 although results from larger studies are awaited.…”

Section: Discussionmentioning

confidence: 99%

Stem cell transplantation after salvage therapy with high-dose cytarabine and amsacrine in adults with high-risk leukaemia

Tauro

Nitu-Whalley

et al. 2003

Bone Marrow Transplant

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Summary:Stem cell transplantation (SCT) may be the only curative option for patients with relapsed or refractory leukaemia, that is, high-risk (HR) leukaemia. Several salvage regimens have been used to cytoreduce disease before SCT, but disease progression or treatment toxicity limits numbers of patients receiving SCT. Here, we report our experience with high-dose cytarabine and amsacrine (Araamsa) to salvage patients with HR-leukaemia in the context of SCT. A total of 34 patients with HR-leukaemia (20 AML, 12 ALL, two advanced CML) received 3 g/m 2 / day cytarabine for 5 days and amsacrine 200 mg/m 2 /day for 3 days. Disease response was observed in 62% of patients. Toxicity was limited to neutropenic fever, one patient developed cerebellar toxicity and there was one treatment-related death. A total of 17 patients proceeded to SCT (12 allografts and five autografts). Median survival (OS) of all patients was 10.8 months (95% CI 7.8-21). Patients who were consolidated with SCT after salvage therapy had a superior median OS of 29.4 months (95% CI 12.5-upper limit not reached, n ¼ 17) than those who did not receive SCT (6.7 months, CI 1.5-8.6, Po0.0001). Median disease-free survival with SCT (23 months) was higher than after treatment with salvage chemotherapy alone (6.7 months, P ¼ 0.0002). Thus Araamsa can be used effectively to salvage HR-leukaemia, enabling further consolidation with SCT.

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Early allogeneic transplantation for refractory or relapsed acute leukaemia following remission induction with FLAG

Cited by 33 publications

References 13 publications

Drug therapy for acute myeloid leukemia

Drug therapy for acute myeloid leukemia

Strategies for overcoming p-glycoprotein-mediated drug resistance in acute myeloblastic leukaemia

Stem cell transplantation after salvage therapy with high-dose cytarabine and amsacrine in adults with high-risk leukaemia

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