Treating octogenarian and nonagenarian acute myeloid leukemia patients—Predictive prognostic models

Harb, Antoine; Tan, Wenfeng; Wilding, Gregory E.; Ford, LaurieAnn; Sait, Sheila N.J.; Block, AnneMarie W.; Barcos, Maurice; Wallace, Paul K.; Wang, Eunice S.; Wetzler, Meir

doi:10.1002/cncr.24285

Cited by 24 publications

(26 citation statements)

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“…The comorbidities of elderly patients are well known to predict TRM and represent independent prognostic factors when they receive intensive induction chemotherapy [40,41]. In other words, high-CCI score and poor ECOG performance scale are related to poor tolerability to intensive induction regimens in elderly patients.…”

Section: Discussionmentioning

confidence: 99%

Fludarabine, cytarabine, and attenuated‐dose idarubicin (m‐FLAI) combination therapy for elderly acute myeloid leukemia patients

et al. 2012

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We performed a phase II trial to evaluate the efficacy and safety of the modified fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) regimen in elderly acute myeloid leukemia (AML) patients. Elderly (60 years) AML patients who had not previously received chemotherapy were enrolled in the study. Patients received two consecutive cycles of m-FLAI chemotherapy as an induction. The m-FLAI regimen comprised fludarabine (25 mg/m 2 , days 1-4), cytarabine (1,000 mg/m 2 , days 1-4), and attenuated-dose idarubicin (5 mg/ m 2 , days 1-3). The primary end point was complete remission (CR) rate. Secondary end points were overall survival (OS), event-free survival (EFS), and treatment-related mortality (TRM). There were 108 patients (median age 68.4 years, M:F 5 64:44) enrolled in the study. CR was achieved in 56.5% of patients, and the TRM rate was 21.3%. Median OS and median EFS were 10.2 and 6.6 months, respectively. The mortality at 30 and 60 days was 15 and 21%, respectively. Performance status and comorbidity did not have prognostic value in this patient cohort. Bone marrow expression of CD117 was associated with increased EFS and OS. m-FLAI is an effective induction regimen for previously untreated AML in elderly patients. In addition, bone-marrow CD117 expression is an independent favorable prognostic factor in elderly AML patients. (ClinicalTrials.gov number, NCT01247493). Am. J. Hematol. 88:10-15, 2013. V

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Section: Discussionmentioning

confidence: 99%

Fludarabine, cytarabine, and attenuated‐dose idarubicin (m‐FLAI) combination therapy for elderly acute myeloid leukemia patients

et al. 2012

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“…Intensive chemotherapy led to a CR rate of 26% and an improved median survival of 4.0 months. 22 Wetzler et al recently evaluated the outcomes of 90 "very old" patients (median age 82 years, range 80-89) with AML considered fit enough to be treated with intensive chemotherapy on cooperative group clinical trials. 23 They found an overall CR rate of 46%, median overall survival of 6 months, and a 1-year survival rate of 36%.…”

Section: Selection Of the Appropriate Upfront Therapy For Older Aml Pmentioning

confidence: 99%

Treating acute myeloid leukemia in older adults

Wang

2014

Hematology

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Acute myeloid leukemia (AML) is a disease of older adults, with a median age of 67 years at presentation. In the past, only a third of older patients (defined as individuals older than 60-65 years of age) with AML received definitive therapy for their disease due to concerns about their overall fitness and potential treatment-related mortality. However, compelling epidemiological data have shown unequivocally that older AML patients up to 80 years old both tolerate and survive longer after therapy than their untreated counterparts. Current therapeutic options for elderly individuals with AML include intensive chemotherapy with a cytarabine and anthracycline backbone, hypomethylating agents (decitabine and azacitidine), low-dose cytarabine, investigational agents, and supportive care with hydroxyurea and transfusions. Over the last few years, there has been increasing debate regarding the appropriate therapeutic approach to take in older adults given the diversity of the geriatric patient population and heterogeneous AML disease biology. This article discusses how performance status, comorbidities, disease characteristics, quality of life concerns, and long-term treatment goals affect the selection of appropriate therapy for older adults with AML. Risks and benefits of each treatment approach based on the most recent medical literature are discussed. Finally, a treatment algorithm summarizing these data and incorporating geriatric assessment and molecular and cytogenetic markers predictive of therapeutic response is proposed to aid in the clinical decision-making process. Learning Objective• To identify appropriate therapeutic strategies for the older patient with AML, taking into consideration the patient's performance status, comorbidities, disease characteristics, and goals

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“…known, 12-16 but few groups 6,7,17,18 have studied its effect in octogenarian AML patients and conclusions have been mixed. This may stem from the differences in classification systems among studies, treatments, inadequate numbers of patients or all of the above.…”

confidence: 99%

“…2 However, the patients' median age was 72 years in that study, which included only a few octogenarian patients. Two trials 3,4 studying patients aged ≥75 years, comprising 22 and 62 patients, and three trials [5][6][7] evaluating 29, 24 and 45 patients aged ≥80 years demonstrated a marginal, if any, advantage in overall survival for intensively-treated patients.…”

Section: Introductionmentioning

confidence: 99%

Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification

et al. 2013

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© F e r r a t a S t o r t i F o u n d a t i o nknown, 12-16 but few groups 6,7,17,18 have studied its effect in octogenarian AML patients and conclusions have been mixed. This may stem from the differences in classification systems among studies, treatments, inadequate numbers of patients or all of the above. We, therefore, evaluated whether the European LeukemiaNet (ELN) classification, 19 a modified ELN classification (i.e., a classification based only on karyotype, without molecular markers), and the ELN-associated molecular alterations FLT3-ITD and NPM1 mutations have prognostic significance in octogenarian AML patients receiving intensive induction treatment. Methods Patients, treatment, cytogenetic and molecular analysesWe analyzed octogenarian AML patients treated with intensive induction [cytarabine and anthracycline (7+3) or similar regimens] for whom pretreatment karyotyping information was available. The patients were drawn from the German-Austrian AML Study Group [AMLSG; 5 (0.5%) Pretreatment karyotype analyses were performed by the Cooperative Groups' institutional cytogenetic laboratories with the results confirmed by central karyotype review, or were performed centrally. The diagnosis of cytogenetically normal AML (CN-AML) was based on the analysis of ≥20 metaphase cells in bone marrow specimens subjected to short-term culture. 31 We used both a modified, karyotype only, ELN-based classification [including t(8;21) Statistical analysesEstimated probabilities of relapse-free survival and overall survival were calculated using the Kaplan-Meier method, and the logrank test evaluated differences between survival distributions. Associations for baseline demographic, clinical, and molecular features were compared using the Fisher exact and Wilcoxon rank sum tests for categorical and continuous variables, respectively. All analyses were two-sided, with a P-value <0.05 considered statistically significant.Response criteria are described in the Online Supplementary Material. ResultsThe 138 patients had a median age of 82 years (range, 80-89 years); 81 (59%) were male. One-hundred fifteen patients had de novo AML, 13 had secondary AML following an antecedent hematologic disorder (s-AML), nine had therapy-related AML (t-AML) and one had both s-AML and t-AML. Because there was no difference in complete response, relapse-free survival and overall survival rates between patients with de novo AML and s-AML/t-AML, all patients were considered together for outcome analyses. Thirteen (11%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 71 (58%) had a PS of 1, 31 (25%) had a PS of 2, six (5%) had a PS of 3 and one (1%) patient had a PS of 4; information on PS was not available for 16 of the patients. Normal karyotype was the most common cytogenetic finding (47.1%), followed by complex karyotype (14.5%) and sole +8 (9.4%). We first categorized patients according to the modified ELN classification into favorable (n=2), intermediate-I (n=65), intermediate-II (n=42) ...

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Treating octogenarian and nonagenarian acute myeloid leukemia patients—Predictive prognostic models

Abstract: BACKGROUND: Treating the octogenarian and nonagenarian patients who have acute myeloid leukemia (AML) with intensive chemotherapy is controversial. Several models to predict outcome were proposed,

Cited by 24 publications

References 32 publications

Fludarabine, cytarabine, and attenuated‐dose idarubicin (m‐FLAI) combination therapy for elderly acute myeloid leukemia patients

Fludarabine, cytarabine, and attenuated‐dose idarubicin (m‐FLAI) combination therapy for elderly acute myeloid leukemia patients

Treating acute myeloid leukemia in older adults

Intensive induction is effective in selected octogenarian acute myeloid leukemia patients: prognostic significance of karyotype and selected molecular markers used in the European LeukemiaNet classification

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