Outcome in patients with acute myeloid leukemia (AML) ranges from death within a few days of beginning treatment (treatment related mortality, TRM) to likely cure. The major reason patients are not ...cured is resistance to treatment, often manifested as relapse from remission, rather than, even in older patients, TRM, whose incidence is decreasing. Knowledge of the pre‐treatment mutation status of various genes has improved our ability to assign initial treatment and, of particular importance, knowledge of whether patients ostensibly in remission have measurable residual disease should influence subsequent management. Several new drugs have been approved by the FDA and we discuss their role in treatment.
Management of AML involves choosing between purely palliative care, standard therapy and investigational therapy (“clinical trial”). Even most older patients likely benefit from treatment. Based on ...randomized trials CPX 351, midostaurin, gemtuzumab ozogamicin, and venetoclax, the latter three when combined with other drugs, should now be considered standard therapy. Knowledge of the likely results with these therapies is essential in deciding whether to recommend them or participate in a clinical trial, possibly including these drugs. Hence here, in the context of established prognostic algorithms, we review results with the recently‐ approved drugs compared with their predecessors and describe other potential options. We discuss benefit/risk ratios underlying the decision to offer allogeneic transplant and emphasize the importance of measurable residual disease. When first seeing a newly‐diagnosed patient physicians must decide whether to offer conventional treatment or investigational therapy, the latter preferably in the context of a clinical trial. As noted below, such trials have led to changes in what today is considered “conventional” therapy compared to even 1‐2 years ago. In older patients decision making has often included inquiring whether specific anti‐AML therapy should be offered at all, rather than focusing on a purely palliative approach emphasizing transfusion and antibiotic support, with involvement of a palliative care specialist.
The median age of patients with acute myeloid leukemia (AML) is 65 to 70 years. The majority of older patients with AML probably do not receive specific treatment, and those who receive standard ...regimens have a median survival time of less than 1 year. This suggests that, in general, older patients should receive investigational therapy; however, factors other than age influence survival after administration of standard treatment and need to be accounted for when making treatment recommendations. In some cases where investigational therapy is unavailable, palliative care may be the best option. Like AML, myelodysplastic syndrome (MDS) is a disease of the elderly. It is divided into higher and lower risk groups. The natural history of high-risk MDS (eg, > 10% marrow blasts) bears more resemblance to that of AML than to that of an indolent disorder; accordingly, similar therapeutic considerations apply. The more benign natural history of lower risk MDS leads to consideration of reduction in transfusion needs and improvement in quality of life as primary goals of therapy. Lenalidomide, azacitidine, and decitabine, each recently approved by the US Food and Drug Administration, are useful in achieving these objectives.
Patients with acute myeloid leukemia (AML) generally receive stereotypical treatment.
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For example, young patients receive cytarabine for 7 days and an anthracycline for 3 days (known as “7+3 ...induction”). Thus treated, some groups, predictably, have an approximately 50% chance of “cure” (“favorable risk”) whereas others, also predictably, have a survival of 6 to 18 months (“unfavorable risk”). This nonrandom heterogeneity after homogeneous treatment suggests that, like pneumonia, AML is several diseases.
Today, AML is primarily defined according to leukemia-cell karyotype and an increasing number of molecular aberrations.
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It follows that different types of AML should ideally be treated differently. This . . .
Since the comprehensive recommendations for the management of acute promyelocytic leukemia (APL) reported in 2009, several studies have provided important insights, particularly regarding the role of ...arsenic trioxide (ATO) in frontline therapy. Ten years later, a European LeukemiaNet expert panel has reviewed the recent advances in the management of APL in both frontline and relapse settings in order to develop updated evidence- and expert opinion–based recommendations on the management of this disease. Together with providing current indications on genetic diagnosis, modern risk-adapted frontline therapy, and salvage treatment, the review contains specific recommendations for the identification and management of the most important complications such as the bleeding disorder APL differentiation syndrome, QT prolongation, and other all-trans retinoic acid– and ATO-related toxicities, as well as recommendations for molecular assessment of the response to treatment. Finally, the approach to special situations is also discussed, including management of APL in children, elderly patients, and pregnant women. The most important challenges remaining in APL include early death, which still occurs before and during induction therapy, and optimizing treatment in patients with high-risk disease.
Patients with acute myeloid leukemia (AML) who are in morphologic complete remission are typically considered separately from patients with active disease (ie, ≥ 5% marrow blasts by morphology) in ...treatment algorithms for allogeneic hematopoietic cell transplantation (HCT), which implies distinct outcomes for these two groups. It is well recognized that the presence of minimal residual disease (MRD) at the time of transplantation is associated with adverse post-HCT outcome for those patients in morphologic remission. This effect of pre-HCT MRD prompted us to compare outcomes in consecutive patients in MRD-positive remission with patients with active AML who underwent myeloablative allogeneic HCT at our institution.
We retrospectively studied 359 consecutive adults with AML who underwent myeloablative allogeneic HCT from a peripheral blood or bone marrow donor between 2006 and 2014. Pre-HCT disease staging included 10-color multiparametric flow cytometry on bone marrow aspirates in all patients. Any level of residual disease was considered to be MRD positive.
Three-year relapse estimates were 67% in 76 patients in MRD-positive morphologic remission and 65% in 48 patients with active AML compared with 22% in 235 patients in MRD-negative remission. Three-year overall survival estimates were 26%, 23%, and 73% in these three groups, respectively. After multivariable adjustment, MRD-negative remission status remained statistically significantly associated with longer overall and progression-free survival as well as lower risk of relapse compared with MRD-positive morphologic remission status or having active disease, with similar outcomes between the latter two groups.
The similarities in outcomes between patients in MRD-positive morphologic remission and those with active disease at the time of HCT support the use of treatment algorithms that use MRD- rather than morphology-based disease assessments.
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