Intensive versus less-intensive antileukemic therapy in older adults with acute myeloid leukemia: A systematic review

To compare the effectiveness and safety of intensive antileukemic therapy to less-intensive therapy in older adults with acute myeloid leukemia (AML) and intermediate or adverse cytogenetics, we searched the literature in Medline, Embase, and CENTRAL to identify relevant studies through July 2020. We reported the pooled hazard ratios (HRs), risk ratios (RRs), mean difference (MD) and their 95% confidence intervals (CIs) using random-effects meta-analyses and the certainty of evidence using the GRADE approach. Two randomized trials enrolling 529 patients and 23 observational studies enrolling 7296 patients proved eligible. The most common intensive interventions included cytarabine-based intensive chemotherapy, combination of cytarabine and anthracycline, or daunorubicin/idarubicin, and cytarabine plus idarubicin. The most common less-intensive therapies included low-dose cytarabine alone, or combined with clofarabine, azacitidine, and hypomethylating agent-based chemotherapy. Low certainty evidence suggests that patients who receive intensive versus less-intensive therapy may experience longer survival (HR 0.87; 95% CI, 0.76–0.99), a higher probability of receiving allogeneic hematopoietic stem cell transplantation (RR 6.14; 95% CI, 4.03–9.35), fewer episodes of pneumonia (RR, 0.25; 95% CI, 0.06–0.98), but a greater number of severe, treatment-emergent adverse events (RR, 1.34; 95% CI, 1.03–1.75), and a longer duration of intensive care unit hospitalization (MD, 6.84 days longer; 95% CI, 3.44 days longer to 10.24 days longer, very low certainty evidence). Low certainty evidence due to confounding in observational studies suggest superior overall survival without substantial treatment-emergent adverse effect of intensive antileukemic therapy over less-intensive therapy in older adults with AML who are candidates for intensive antileukemic therapy.

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Geriatric assessment among older adults receiving intensive therapy for acute myeloid leukemia: Report of CALGB 361006 (Alliance)

Journal of Geriatric Oncology ◽

10.1016/j.jgo.2019.10.002 ◽

2020 ◽

Vol 11 (1) ◽

pp. 107-113 ◽

Cited By ~ 5

Author(s):

Heidi D. Klepin ◽

Ellen Ritchie ◽

Brittny Major-Elechi ◽

Jennifer Le-Rademacher ◽

Drew Seisler ◽

...

Keyword(s):

Older Adults ◽

Acute Myeloid Leukemia ◽

Geriatric Assessment ◽

Myeloid Leukemia ◽

Intensive Therapy ◽

Acute Myeloid

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Acute Myeloid Leukemia and Myelodysplastic Syndromes in Older Adults

Journal of Clinical Oncology ◽

10.1200/jco.2014.55.1564 ◽

2014 ◽

Vol 32 (24) ◽

pp. 2541-2552 ◽

Cited By ~ 69

Author(s):

Heidi D. Klepin ◽

Arati V. Rao ◽

Timothy S. Pardee

Keyword(s):

Older Adults ◽

Decision Making ◽

Acute Myeloid Leukemia ◽

Myelodysplastic Syndromes ◽

Myeloid Leukemia ◽

Tumor Biology ◽

Treatment Strategies ◽

Hematopoietic Stem ◽

Age Related ◽

Acute Myeloid

Treatment of older adults with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is challenging because of disease morbidity and associated treatments. Both diseases represent a genetically heterogeneous group of disorders primarily affecting older adults, with treatment strategies ranging from supportive care to hematopoietic stem-cell transplantation. Although selected older adults can benefit from intensive therapies, as a group they experience increased treatment-related morbidity, are more likely to relapse, and have decreased survival. Age-related outcome disparities are attributed to both tumor and patient characteristics, requiring an individualized approach to treatment decision making beyond consideration of chronologic age alone. Selection of therapy for any individual requires consideration of both disease-specific risk factors and estimates of treatment tolerance and life expectancy derived from evaluation of functional status and comorbidity. Although treatment options for older adults are expanding, clinical trials accounting for the heterogeneity of tumor biology and aging are needed to define standard-of-care treatments for both disease groups. In addition, trials should include outcomes addressing quality of life, maintenance of independence, and use of health care services to assist in patient-centered decision making. This review will highlight available evidence in treatment of older adults with AML or MDS and unanswered clinical questions for older adults with these diseases.

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American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults

Blood Advances ◽

10.1182/bloodadvances.2020001920 ◽

2020 ◽

Vol 4 (15) ◽

pp. 3528-3549 ◽

Cited By ~ 3

Author(s):

Mikkael A. Sekeres ◽

Gordon Guyatt ◽

Gregory Abel ◽

Shabbir Alibhai ◽

Jessica K. Altman ◽

...

Keyword(s):

Older Adults ◽

Acute Myeloid Leukemia ◽

Health Care Professionals ◽

Myeloid Leukemia ◽

Intensive Therapy ◽

Geriatric Oncology ◽

Patient Reported ◽

American Society ◽

Supportive Management ◽

Acute Myeloid

Abstract Background: Older adults with acute myeloid leukemia (AML) represent a vulnerable population in whom disease-based and clinical risk factors, patient goals, prognosis, and practitioner- and patient-perceived treatment risks and benefits influence treatment recommendations. Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about management of AML in older adults. Methods: ASH formed a multidisciplinary guideline panel that included specialists in myeloid leukemia, geriatric oncology, patient-reported outcomes and decision-making, frailty, epidemiology, and methodology, as well as patients. The McMaster Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline-development process, including performing systematic evidence reviews (up to 24 May 2019). The panel prioritized clinical questions and outcomes according to their importance to patients, as judged by the panel. The panel used the GRADE approach, including GRADE’s Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 6 critical questions in managing older adults with AML, mirroring real-time practitioner-patient conversations: the decision to pursue antileukemic treatment vs best supportive management, the intensity of therapy, the role and duration of postremission therapy, combination vs monotherapy for induction and beyond, duration of less-intensive therapy, and the role of transfusion support for patients no longer receiving antileukemic therapy. Conclusions: Treatment is recommended over best supportive management. More-intensive therapy is recommended over less-intensive therapy when deemed tolerable. However, these recommendations are guided by the principle that throughout a patient’s disease course, optimal care involves ongoing discussions between clinicians and patients, continuously addressing goals of care and the relative risk-benefit balance of treatment.

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Second Relapse of Pediatric Patients with Acute Myeloid Leukemia: A Report on Current Treatment Strategies and Outcome of the AML-BFM Study Group

Cancers ◽

10.3390/cancers13040789 ◽

2021 ◽

Vol 13 (4) ◽

pp. 789

Author(s):

Mareike Rasche ◽

Emma Steidel ◽

Martin Zimmermann ◽

Jean-Pierre Bourquin ◽

Heidrun Boztug ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Pediatric Patients ◽

Intensive Therapy ◽

Treatment Strategies ◽

Population Based ◽

Study Group ◽

Curative Intent ◽

Hematopoietic Stem ◽

Acute Myeloid

Successful management of relapse is critical to improve outcomes of children with acute myeloid leukemia (AML). We evaluated response, survival and prognostic factors after a second relapse of AML. Among 1222 pediatric patients of the population-based AML-Berlin–Frankfurt–Munster (BFM) study group (2004 until 2017), 73 patients met the quality parameters for inclusion in this study. Central review of source documentation warranted the accuracy of reported data. Treatment approaches included palliation in 17 patients (23%), intensive therapy with curative intent (n = 46, 63%) and other regimens (n = 10). Twenty-five patients (35%) received hematopoietic stem cell transplantation (HSCT), 21 of whom (88%) had a prior HSCT. Survival was poor, with a five-year probability of overall survival (pOS) of 15 ± 4% and 31 ± 9% following HSCT (n = 25). Early second relapse (within one year after first relapse) was associated with dismal outcome (pOS 2 ± 2%, n = 44 vs. 33 ± 9%, n = 29; p < 0.0001). A third complete remission (CR) is required for survival: 31% (n = 14) of patients with intensive treatment achieved a third CR with a pOS of 36 ± 13%, while 28 patients (62%) were non-responders (pOS 7 ± 5%). In conclusion, survival is poor but possible, particularly after a late second relapse and an intensive chemotherapy followed by HSCT. This analysis provides a baseline for future treatment planning.

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Acute myeloid leukemia: negative prognostic impact of early blast persistence can be in part overcome by a later remission prior to post-induction therapy

Haematologica ◽

10.3324/haematol.2021.279134 ◽

2021 ◽

Author(s):

Jana Ihlow ◽

Sophia Gross ◽

Leonie Busack ◽

Anne Flörcken ◽

Julia Jesse ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Residual Disease ◽

Intensive Therapy ◽

Dynamic Parameter ◽

Prognostic Impact ◽

Consolidation Chemotherapy ◽

Related Factors ◽

Hematopoietic Stem ◽

Acute Myeloid

In acute myeloid leukemia (AML), there is an ongoing debate on the prognostic value of the early bone marrow (BM) assessment in patients receiving intensive therapy. In this retrospective study, we have analyzed the prognostic impact of the early response in 1008 newly diagnosed AML patients, who were treated at our institution with intensive chemotherapy followed by consolidation chemotherapy and/or allogeneic hematopoietic stem cell transplantation (allo-HSCT). We found that early blast persistence has an independent negative prognostic impact on overall survival (OS), event-free survival (EFS) and relapsefree survival (RFS). This negative prognostic impact may only be overcome in patients showing at least a partial remission at the early BM assessment and who subsequently achieve blast clearance by additional induction chemotherapy prior to consolidation therapy with allo-HSCT. In accordance, we propose that the time slope of remission is an additional leukemia-related dynamic parameter that reflects chemosensitivity and thus may inform postinduction therapy decision-making. In addition to patient-related factors, European LeukemiaNet (ELN) risk group, measurable residual disease (MRD) monitoring and donor availability, this may particularly apply to ELN intermediate risk patients, in whom a decision between consolidation chemotherapy and allo-HSCT remains challenging in many cases.

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