scholarly journals How I treat the older patient with acute myeloid leukemia

Blood ◽  
2015 ◽  
Vol 125 (5) ◽  
pp. 767-774 ◽  
Author(s):  
Gert Ossenkoppele ◽  
Bob Löwenberg
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Comorbid Conditions ◽  
Older Patient ◽  
Molecular Features ◽  
Clinical Vignettes ◽  
Clinical Biology ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) in older patients presents a notable therapeutic challenge to the clinical hematologist. The clinical biology of AML among patients is highly heterogeneous. Interpatient variations are relevant for prognosis and treatment choice. Outcome of treatment for patients of advanced age is often compromised by comorbid conditions and an enhanced susceptibility to toxicities from therapy. Here we present selected clinical vignettes that highlight distinct representative situations derived from clinical practice. The vignettes are specifically discussed in light of the perspective of treating older patients with leukemia. We review the clinical significance of various cytogenetic and molecular features of the disease, and we examine the various currently available treatment options as well as the emerging prognostic algorithms that may offer guidance in regard to personalized therapy recommendations. The dilemmas in tailoring treatment selection in this category of patients with AML are the central theme in this discussion.

scholarly journals Advances in Acute Myeloid Leukemia Management: Focus on Secondary Disease and Older Patients

2020 ◽  
Vol 18 (12.5) ◽  
pp. 1785-1787
Author(s):  
Daniel A. Pollyea
Keyword(s):  
Acute Myeloid Leukemia ◽  
Supportive Care ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Management Strategies ◽  
Special Populations ◽  
Secondary Aml ◽  
Long Period ◽  
Acute Myeloid

The “Age of Induction” led to breakthroughs in the treatment landscape for acute myeloid leukemia (AML), and was immediately followed by a long period during which few drugs were approved. That all changed a few years ago, when 2017 began the “Age of Abundance.” With many treatment options now available, new management strategies have emerged for patients with secondary AML, as well as for older patients with AML. Treatment can now be tailored to these special populations, and providers should be aware of the unique supportive care considerations associated with these newer AML therapies.

scholarly journals A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia

Blood ◽  
2011 ◽  
Vol 117 (6) ◽  
pp. 1828-1833 ◽  
Author(s):  
Todd A. Fehniger ◽  
Geoffrey L. Uy ◽  
Kathryn Trinkaus ◽  
Alissa D. Nelson ◽  
Jeffery Demland ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Initial Therapy ◽  
Clinical Activity ◽  
High Dose ◽  
Phase 2 ◽  
Phase 2 Study ◽  
Acute Myeloid

Abstract Older patients with acute myeloid leukemia (AML) have limited treatment options and a poor prognosis, thereby warranting novel therapeutic strategies. We evaluated the efficacy of lenalidomide as front-line therapy for older AML patients. In this phase 2 study, patients 60 years of age or older with untreated AML received high-dose (HD) lenalidomide at 50 mg daily for up to 2 28-day cycles. If patients achieved a complete remission (CR)/CR with incomplete blood count recovery (CRi) or did not progress after 2 cycles of HD lenalidomide, they received low-dose lenalidomide (10 mg daily) until disease progression, an unacceptable adverse event, or completion of 12 cycles. Thirty-three AML patients (median age, 71 years) were enrolled with intermediate (55%), unfavorable (39%), or unknown (6%) cytogenetic risk. Overall CR/CRi rate was 30%, and 53% in patients completing HD lenalidomide. The CR/CRi rate was significantly higher in patients presenting with a low (< 1000/μL) circulating blast count (50%, P = .01). The median time to CR/CRi was 30 days, and duration of CR/CRi was 10 months (range, 1- ≥ 17 months). The most common grades ≥ 3 toxicities were thrombocytopenia, anemia, infection, and neutropenia. HD lenalidomide has evidence of clinical activity as initial therapy for older AML patients, and further study of lenalidomide in AML and MDS is warranted. This study is registered at www.clinicaltrials.gov as #NCT00546897.

Multicenter, Phase II Study of Decitabine for the First-Line Treatment of Older Patients With Acute Myeloid Leukemia

2010 ◽  
Vol 28 (4) ◽  
pp. 556-561 ◽  
Author(s):  
Amanda F. Cashen ◽  
Gary J. Schiller ◽  
Margaret R. O'Donnell ◽  
John F. DiPersio
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Phase Ii ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Response Rate ◽  
Phase Ii Study ◽  
Treatment Options ◽  
Multicenter Phase ◽  
Acute Myeloid

Purpose Older patients with acute myeloid leukemia (AML) have limited treatment options because of the lack of effectiveness and the toxicity of available therapies. We investigated the efficacy and toxicity of the hypomethylating agent decitabine as initial therapy in older patients with AML. Patients and Methods In this multicenter, phase II study, patients older than 60 years who had AML (ie, > 20% bone marrow blasts) and no prior therapy for AML were treated with decitabine 20 mg/m2 intravenously for 5 consecutive days of a 4-week cycle. Response was assessed by weekly CBC and bone marrow biopsy after cycle 2 and after each subsequent cycle. Patients continued to receive decitabine until disease progression or an unacceptable adverse event occurred. Results Fifty-five patients (mean age, 74 years) were enrolled and were treated with a median of three cycles (range, one to 25 cycles) of decitabine. The expert-reviewed overall response rate was 25% (complete response rate, 24%). The response rate was consistent across subgroups, including in patients with poor-risk cytogenetics and in those with a history of myelodysplastic syndrome. The overall median survival was 7.7 months, and the 30-day mortality rate was 7%. The most common toxicities were myelosuppression, febrile neutropenia, and fatigue. Conclusion Decitabine given in a low-dose, 5-day regimen has activity as upfront therapy in older patients with AML, and it has acceptable toxicity and 30-day mortality.

scholarly journals RUNX1 Mutations Are Associated With Poor Outcome in Younger and Older Patients With Cytogenetically Normal Acute Myeloid Leukemia and With Distinct Gene and MicroRNA Expression Signatures

2012 ◽  
Vol 30 (25) ◽  
pp. 3109-3118 ◽  
Author(s):  
Jason H. Mendler ◽  
Kati Maharry ◽  
Michael D. Radmacher ◽  
Krzysztof Mrózek ◽  
Heiko Becker ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Expression Profiles ◽  
Disease Free Survival ◽  
Microrna Expression ◽  
Wild Type ◽  
Free Survival ◽  
Molecular Features ◽  
Acute Myeloid

Purpose To determine the association of RUNX1 mutations with therapeutic outcome in younger and older patients with primary cytogenetically normal acute myeloid leukemia (CN-AML) and with gene/microRNA expression signatures. Patients and Methods Younger (< 60 years; n = 175) and older (≥ 60 years; n = 225) patients with CN-AML treated with intensive cytarabine/anthracycline-based first-line therapy on Cancer and Leukemia Group B protocols were centrally analyzed for RUNX1 mutations by polymerase chain reaction and direct sequencing and for established prognostic gene mutations. Gene/microRNA expression profiles were derived using microarrays. Results RUNX1 mutations were found in 8% and 16% of younger and older patients, respectively (P = .02). They were associated with ASXL1 mutations (P < .001) and inversely associated with NPM1 (P < .001) and CEBPA (P = .06) mutations. RUNX1-mutated patients had lower complete remission rates (P = .005 in younger; P = .006 in older) and shorter disease-free survival (P = .058 in younger; P < .001 in older), overall survival (P = .003 in younger; P < .001 in older), and event-free survival (P < .001 for younger and older) than RUNX1 wild-type patients. Because RUNX1 mutations were more common in older patients and almost never coexisted with NPM1 mutations, RUNX1 mutation–associated expression signatures were derived in older, NPM1 wild-type patients and featured upregulation of genes normally expressed in primitive hematopoietic cells and B-cell progenitors, including DNTT, BAALC, BLNK, CD109, RBPMS, and FLT3, and downregulation of promoters of myelopoiesis, including CEBPA and miR-223. Conclusion RUNX1 mutations are twice as common in older than younger patients with CN-AML and negatively impact outcome in both age groups. RUNX1-mutated blasts have molecular features of primitive hematopoietic and lymphoid progenitors, potentially leading to novel therapeutic approaches.

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