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The European LeukemiaNet recently revised both the clinical (2022) and measurable residual disease testing (2021) guidelines for acute myeloid leukemia (AML). The updated World Health ...Organization and International Consensus Classification for myeloid neoplasms were also published in 2022. Together, these documents update the classification, risk stratification, prognostication, monitoring recommendations, and response assessment of patients with AML. Increased appreciation of the genetic drivers of AML over the past decade and our increasingly sophisticated understanding of AML biology have been translated into novel therapies and more complex clinical treatment guidelines. Somatic genetic abnormalities and germ line predispositions now define and guide treatment and counseling for the subtypes of this hematologic malignancy. In this How I Treat article, we discuss how we approach AML in daily clinical practice, considering the recent updates in the context of new treatments and discoveries over the past decade.
The European LeukemiaNet guidelines, the World Health Organization classification, and the International Consensus Classification have all been recently updated to provide new guidance on classification reflecting molecular abnormalities, risk stratification, prognosis, response assessment, and measurable residual disease monitoring for patients with acute myeloid leukemia (AML). In a timely How I Treat article, El Chaer et al use 4 illustrative cases to discuss how changes in these classification systems and guidelines influence clinical decision making.
Patients with hematologic malignancies and recipients of hematopoietic cell transplantation (HCT) are more likely to experience severe coronavirus disease 2019 (COVID-19) and have a higher risk of ...morbidity and mortality after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compared with the general population, these patients have suboptimal humoral responses to COVID-19 vaccines and subsequently increased risk for breakthrough infections, underscoring the need for additional therapies, including pre- and postexposure prophylaxis, to attenuate clinical progression to severe COVID-19. Therapies for COVID-19 are mostly available for adults and in the inpatient and outpatient settings. Selection and administration of the best treatment options are based on host factors; virus factors, including circulating SARS-CoV-2 variants; and therapeutic considerations, including the clinical efficacy, availability, and practicality of treatment and its associated side effects, including drug-drug interactions. In this paper, we discuss how we approach managing COVID-19 in patients with hematologic malignancies and recipients of HCT and cell therapy.
Patients infected with HIV remain at increased risk of mortality and morbidity from diseases that are preventable with vaccines partly due to the persisting immunopathology that results in impaired ...responses to vaccination despite virologic suppression. Because data on clinical effectiveness in patients who are immunocompromised remain limited, undervaccination of individuals with HIV poses a major concern. Multiple societies have published recommendations on vaccination in individuals infected with HIV. Many of these recommendations are based on extrapolation of data from clinical trials that usually exclude patients with HIV, although there is a growing body of data from patients infected with HIV as well. In this review, we describe the available literature on vaccine response in the adult patient with HIV as measured by immunogenicity or vaccine efficacy.
Currently, no standard of care exists for the treatment of relapsed or refractory acute myeloid leukemia (AML). We present our institutional experience with using either CLAG-M or HAM-pegA, a novel ...regimen that includes pegaspargase. This is a retrospective comparison of 34 patients receiving CLAG-M and 10 receiving HAM-pegA as first salvage cytotoxic chemotherapy in the relapsed or refractory setting. Composite complete response rates were 47.1% for CLAG-M and 90% for HAM-pegA (
= 0.027). Event-free survival was significantly different in favor of HAM-pegA (
= 0.045), though overall survival was similar between groups. There were no significant differences in toxicities experienced by patients treated with the two regimens, including adverse events of special interest related to pegaspargase (venous thromboembolism, hemorrhage, hepatotoxicity, pancreatitis, and hypersensitivity reactions). HAM-pegA is a novel regimen for relapsed or refractory AML that resulted in improved response rates and similar toxicities compared to CLAG-M.
MLL-Rearranged Acute Lymphoblastic Leukemia El Chaer, Firas; Keng, Michael; Ballen, Karen K.
Current hematologic malignancy reports,
04/2020, Volume:
15, Issue:
2
Journal Article
Peer reviewed
Purpose of Review
Rearrangements of the histone
lysine K-MethylTransferase 2A gene
(
KMT2A
) gene on chromosome 11q23, formerly known as the mixed-lineage leukemia (
MLL
) gene, are found in 10% and ...5% of adult and children ALL cases, respectively. The most common translocated genes are
AFF1
(formerly
AF4
),
MLLT3
(formerly
AF9
), and
MLLT1
(formerly
ENL
). The bimodal incidence of
MLL
-r-ALL usually peaks in infants in their first 2 years of life and then declines thereafter during the pediatric/young adult phase until it increases again with age.
MLL
-rearranged ALL (
MLL
-r-ALL) is characterized by hyperleukocytosis, aggressive behavior with early relapse, relatively high incidence of central nervous system (CNS) involvement, and poor prognosis.
Recent Findings
MLL
-r-ALL cells are characterized by relative resistance to corticosteroids (due to Src kinase-induced phosphorylation of annexin A2) and L-asparaginase therapy, but they are sensitive to cytarabine chemotherapy (due to increased levels of
hENT1
expression). Potential therapeutic targets include FLT3 inhibitors, MEK inhibitors, HDAC inhibitors, BCL-2 inhibitors, MCL-1 inhibitors, proteasome inhibitors, hypomethylating agents, Dot1L inhibitors, and CDK inhibitors.
Summary
In this review, we discuss
MLL
-r-ALL focusing on clinical presentation, risk stratification, drug resistance, and treatment strategies, including potential novel therapeutic targets.
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