Outcomes of patients with acute myeloid leukemia and bone marrow fibrosis.

The outcomes of patients with acute myeloid leukemia (AML) and bone marrow fibrosis (MF) are not well defined. The study objectives were to evaluate the degrees of MF in AML, and corresponding response rates and outcomes. We performed a retrospective review of 2302 patients with AML.

Heterogenous lung inflammation CT patterns distinguish pneumonia and immune checkpoint inhibitor pneumonitis and complement blood biomarkers in acute myeloid leukemia: proof of concept.

Background: Immune checkpoint inhibitors (ICI) may cause pneumonitis, resulting in potentially fatal lung inflammation. However, distinguishing pneumonitis from pneumonia is time-consuming and challenging. To fill this gap, we build an image-based tool, and further evaluate it clinically alongside relevant blood biomarkers.

Early mortality in acute myeloid leukemia with KMT2A rearrangement is associated with high risk of bleeding and disseminated intravascular coagulation.

Background: Acute myeloid leukemia (AML) with rearrangement of lysine methyltransferase 2a gene (KMT2Ar) is characterized by chemotherapy resistance and high rates of relapse. However, additional causes of treatment failure or early mortality have not been well-defined in this entity.

Methods: In a retrospective analysis, causes and rates of early mortality following induction treatment were compared between a cohort of adults with KMT2Ar AML (N = 172) and an age-matched cohort of patients with normal karyotype AML (N = 522).

Non-intensive acute myeloid leukemia therapies for older patients.

Introduction: Acute myeloid leukemia (AML) is an aggressive disease predominantly affecting the elderly population. The elderly population represents a challenging group to treat and the prognosis is generally poor with significantly worse treatment outcomes compared to the younger population. While the goal of treatment for younger fit patients is cure and includes intensive chemotherapy and stem cell transplantation, these strategies are not always feasible for elderly unfit patients due to increased frailty, co-morbidities, and, subsequently, an increased risk of treatment-related toxicity and mortality.

SOHO State of the Art Updates and Next Questions |The Role of Maintenance Therapy in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is an aggressive disease predominantly affecting the elderly population. Although, up to 65% of patients with AML achieve a complete remission with standard induction chemotherapy, the majority of patients will relapse and succumb to the disease. Although maintenance therapy is a component of standard management for various hematological malignancies, such as acute lymphoblastic leukemia (ALL), acute promyelocytic leukemia (APL) or multiple myeloma, past studies investigating the role of maintenance therapy in AML were unable to demonstrate an advantage in overall survival, and therefore, it has not been an established practice in the treatment of AML.

A phase 1 study to evaluate the safety, pharmacology, and feasibility of continuous infusion nelarabine in patients with relapsed and/or refractory lymphoid malignancies.

Background: Nelarabine is a purine nucleoside analogue prodrug approved for the treatment of relapsed and refractory T-cell acute lymphoblastic leukemia (R/R T-ALL) and lymphoblastic lymphoma (T-LBL). Although effective in R/R T-ALL, significant neurotoxicity is dose-limiting and such neurotoxicity associated with nucleoside analogues can be related to dosing schedule.

Methods: The authors conducted a phase 1 study to evaluate the pharmacokinetics and toxicity of nelarabine administered as a continuous infusion (CI) for 5 days (120 hours), rather than the standard, short-infusion approach.

Pneumonitis after immune checkpoint inhibitor therapies in patients with acute myeloid leukemia: A retrospective cohort study.

Background: Immune checkpoint inhibitors (ICI), combined with hypomethylating agents, can be used to treat acute myeloid leukemia (AML), but this strategy results in a high rate of pneumonitis. The authors sought to determine risk factors for pneumonitis development and whether pneumonitis increased mortality.

Methods: The authors conducted a retrospective review of 258 AML patients who received ICI-containing regimens from 2016 to 2018.

IDH1/IDH2 Inhibition in Acute Myeloid Leukemia.

Recently, the discovery of biological and clinical properties of mutated isoforms 1 and 2 mutations of isocitrate dehydrogenases (IDH) 1 and 2, affecting approximately 20% of patients with acute myeloid leukemia (AML), lead to the development of an individualized treatment strategy. Promoting differentiation and maturation of the malignant clone targeting IDH is an emerging strategy to promote clinical responses in AML. Phase I/II trials have shown evidence of safety, tolerability, and encouraging evidence of efficacy of two small molecule inhibitors targeting IDH2 and IDH1 gene mutations, respectively enasidenib and ivosidenib.

NCCN Guidelines Insights: Acute Myeloid Leukemia, Version 2.2021.

The NCCN Guidelines for Acute Myeloid Leukemia (AML) provide recommendations for the diagnosis and treatment of adults with AML based on clinical trials that have led to significant improvements in treatment, or have yielded new information regarding factors with prognostic importance, and are intended to aid physicians with clinical decision-making. These NCCN Guidelines Insights focus on recent select updates to the NCCN Guidelines, including familial genetic alterations in AML, postinduction or postremission treatment strategies in low-risk acute promyelocytic leukemia or favorable-risk AML, principles surrounding the use of venetoclax-based therapies, and considerations for patients who prefer not to receive blood transfusions during treatment.

The pharmacological management of hairy cell leukemia.

Introduction: Hairy cell leukemia (HCL) is a B-cell lymphoid malignancy that accounts for approximately 2% of all leukemias. Treatment with purine nucleoside analogs (PNA) results in a high response rate and remains the standard of care. Long term follow-up shows that most patients relapse and require retreatment.

Phase 2 study of hyper-CMAD with liposomal vincristine for patients with newly diagnosed acute lymphoblastic leukemia.

Liposomal vincristine is designed to reduce neurotoxicity and increase dose intensity delivery, and has been approved as salvage therapy in relapsed/refractory acute lymphoblastic leukemia (ALL). Our aim was to evaluate the response rate, toxicities, and outcome of adults with newly diagnosed ALL who received liposomal vincristine, rather than regular vincristine in combination with intensive chemotherapy (Hyper-CMAD). In a single-center, phase 2 study, patients ≥18 years with newly-diagnosed B-cell ALL were eligible to receive hyper-CMAD alternating with high-dose methotrexate and cytarabine.

Long-term results of a phase 2 trial of nilotinib 400 mg twice daily in newly diagnosed patients with chronic-phase chronic myeloid leukemia.

Background: Nilotinib is a potent, second-generation inhibitor of BCR-ABL1 tyrosine kinase and has been approved as frontline and salvage therapy for patients with chronic-phase chronic myeloid leukemia (CP-CML).

Methods: In this single-institution, phase 2 study, 122 patients with newly diagnosed CP-CML received nilotinib 400 mg twice daily. The median follow-up on study was 78.

Midostaurin In Acute Myeloid Leukemia: An Evidence-Based Review And Patient Selection.

() mutations occur in approximately a third of acute myeloid leukemia (AML) patients and confer an adverse prognosis. Numerous studies have evaluated targeting as single agent and in combination approaches in frontline and relapsed AML. At this time, midostaurin, a multikinase inhibitor, is the only FLT3-inhibitor that is US FDA approved to be used in combination with induction therapy in the frontline mutated AML setting based on improved overall survival noted in the RATIFY Phase III trial.

CPX-351 (vyxeos) in AML.

For decades, the standard induction for patients with acute myeloid leukemia (AML) has been the combination of cytarabine with anthracycline (7 + 3 regimen). In August 2017 the US FDA approved CPX-351 (vyxeos), a liposomal formulation of cytarabine and daunorubicin at a fixed 5:1 molar ratio, for the treatment of adults with newly diagnosed AML with myelodysplasia-related changes (AML-MRC) and therapy-related AML (t-AML). This is the first approved treatment specifically for patients with this subgroup of AML.

Hematologic malignancies and Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is an autosomal dominant condition associated with a high risk of a broad range of childhood- and adult-onset cancers. LFS is related to germline mutations of the tumor-suppressor gene The most common reported leukemia associated with LFS is hypodiploid acute lymphoblastic leukemia, but myeloid malignancies including acute myeloid leukemia (AML), chronic myeloid leukemia, and myelodysplastic syndrome (MDS) are also reported, often in the setting of therapy-related disease. We reviewed the clinicopathologic characteristics including cytogenetics and molecular analysis for seven adult patients with LFS and hematologic malignancies evaluated at the Hereditary Hematologic Malignancy Clinic (HHMC) at MD Anderson Cancer Center.

Efficacy, Safety, and Biomarkers of Response to Azacitidine and Nivolumab in Relapsed/Refractory Acute Myeloid Leukemia: A Nonrandomized, Open-Label, Phase II Study.

Preclinical models have shown that blocking PD-1/PD-L1 pathways enhances antileukemic responses. Azacitidine upregulates PD-1 and IFNγ signaling. We therefore conducted this single-arm trial, in which patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) were treated with azacitidine 75 mg/m days 1 to 7 intravenously or subcutaneously with nivolumab 3 mg/kg intravenously on days 1 and 14, every 4 to 6 weeks.

A phase 2 study of ruxolitinib in combination with azacitidine in patients with myelofibrosis.

Ruxolitinib (RUX)-based combinations may provide benefit for patients with myelofibrosis (MF). In this open-label, nonrandomized, prospective phase 2 study, patients with MF initially received RUX twice per day continuously in 28-day cycles for the first 3 cycles. Azacitidine (AZA) 25 mg/m (days 1-5) was added starting with cycle 4 and could be subsequently increased to 75 mg/m (days 1-5).

Philadelphia chromosome-positive acute lymphoblastic leukemia in adults: current treatments and future perspectives.

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) accounts for approximately one-fourth of cases of adult ALL. It typically presents with an aggressive clinical course, responds poorly to standard chemotherapy, and carries a high risk for relapse. The landscape of Ph+ ALL therapy has changed favorably since the development of tyrosine kinase inhibitors (TKIs).

Secondary Philadelphia chromosome acquired during therapy of acute leukemia and myelodysplastic syndrome.

The Philadelphia chromosome resulting from t(9;22)(q34;q11.2) or its variants is a defining event in chronic myeloid leukemia. It is also observed in several types of de novo acute leukemia, commonly in B lymphoblastic leukemia, and rarely in acute myeloid leukemia, acute leukemia of ambiguous lineage, and T lymphoblastic leukemia.

Health-Related Quality of Life of Patients with Acute Myeloid Leukemia: A Systematic Literature Review.

Introduction: Patients with acute myeloid leukemia (AML), especially those with relapsed or refractory AML, have poor clinical prognosis and outcomes. Health-related quality of life (HRQoL) assessments have become increasingly important in oncology, aiding in identifying and informing supportive therapy needs during treatment and beyond; however, HRQoL in hematology, and AML in particular, has received relatively minor attention. The aim was to identify and summarize estimates of HRQoL in patients with AML, including patients with relapsed or refractory AML.

The evolution of arsenic in the treatment of acute promyelocytic leukemia and other myeloid neoplasms: Moving toward an effective oral, outpatient therapy.

The therapeutic potential of arsenic derivatives has long been recognized and was recently rediscovered in modern literature. Early studies demonstrated impressive activity of this compound in patients with relapsed acute promyelocytic leukemia (APL). Over the last 2 decades, intravenous arsenic trioxide has been used successfully, both alone and in combination with other agents, for the treatment of APL and, with some success, of other myeloid neoplasms.

Augmented Berlin-Frankfurt-Münster therapy in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL).

Background: Various trials have reported improved outcomes for adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) who received treatment with pediatric-based regimens. Those reports prompted the current investigation of the pediatric augmented Berlin-Frankfurt-Münster (ABFM) regimen in AYA patients. The results were compared with those from a similar population that received the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) regimen.

A phase I study of fludarabine, cytarabine, and oxaliplatin therapy in patients with relapsed or refractory acute myeloid leukemia.

Purpose: The combination of cytarabine and fludarabine was associated with superior clinical outcomes compared with those of high-dose cytarabine in relapse acute myeloid leukemia (AML). We conducted a phase I study combining oxaliplatin with cytarabine and fludarabine therapy for patients with relapsed or refractory AML.

Patients And Methods: Between January 2008 and November 2009, 27 patients were registered in the study.