Erythroid-predominant myelodysplastic neoplasms exhibit a distinct genomic landscape with poor outcomes after venetoclax-based therapy.

Erythroid differentiation confers BCL-XL dependence and venetoclax resistance in acute myeloid leukemia (AML). However, whether myelodysplastic neoplasms (MDS) with erythroid predominance (EP), defined by ≥50% erythroid bone marrow elements, have distinct biology and drug sensitivities remains unknown. To study this, we evaluated an MDS patient cohort (n = 371) and showed that EP MDS (n = 67, 18%) are characterized by higher TP53 (multihit TP53: 36% vs 17%, p = 0.

Landscape and clinicopathologic features of RAS pathway mutations in chronic myelomonocytic leukemia.

RAS pathway mutations (RASMT) induce proliferative features and promote transformation in chronic myelomonocytic leukemia (CMML). However, the unique clonal landscape and hierarchy of distinct RASMT remain unexplored. To characterize the landscape, architecture and implications of unique RASMT in CMML we evaluated a cohort of 814 patients with CMML.

PTPN11 mutations define a rare but highly adverse subset of myelodysplastic syndromes.

Not available.

Blastemia portrays a poor prognosis in acute leukemia patients with invasive pulmonary aspergillosis.

Objectives: Severe and prolonged neutropenia is associated with poor outcomes of invasive pulmonary aspergillosis (IPA) in leukemia patients. Given the high frequency of IPA in patients with relapsed/refractory leukemia, we studied the association of peripheral blood blast burden (blastemia), IPA outcomes, and antifungal immune failure, even without neutropenia.

Methods: We retrospectively reviewed adult patients with acute leukemia (AL) or myelodysplastic syndrome and culture-positive proven/probable IPA (2011-2022).

A Phase 2 Trial of CPX-351 Combined With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia.

Outcomes in patients with relapsed/refractory (RR) AML are poor. We sought to investigate if CPX-531 in combination with venetoclax (CPX + VEN) was tolerable and effective in RR AML. This was a single institution phase 1b/2 trial of CPX + VEN.

Characteristics and outcomes of newly diagnosed acute myeloid Leukemia with KMT2A rearrangements.

Acute myeloid leukemia (AML) with KMT2A rearrangement (KMT2Ar) has poor outcomes. We analyzed 1,611 patients with AML and 4.3% demonstrated rearrangements in KMT2A.

BLAST: a globally applicable and molecularly versatile survival model for chronic myelomonocytic leukemia.

We sought to develop a survival model in chronic myelomonocytic leukemia (CMML) that is primarily based on clinical variables and examine additional impact from mutations and karyotype. A total of 457 molecularly annotated patients were considered. Multivariable analysis identified circulating blasts ≥2% (1 point), leukocytes ≥13 × 109/L (1 point), and severe (2 points) or moderate (1 point) anemia as preferred risk variables in developing a clinical risk stratification tool for overall survival (OS), acronymized to "BLAST": low risk (0 points; median, 63 months); intermediate risk (1 point; median, 28 months; hazard ratio [HR], 2.

Reduced venetoclax exposure to 7 days vs standard exposure with hypomethylating agents in newly diagnosed AML patients.

Hypomethylating agent (HMA) plus venetoclax (VEN) regimens are standard of care in patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. While the VEN label recommends continuous 28-day cycles, shortened VEN durations may induce similar response rates and improve tolerability. It is unknown how a VEN exposure reduced to 7 days during cycles compares to standard HMA + VEN.

Oral decitabine cedazuridine with and without venetoclax in higher-risk myelodysplastic syndromes or chronic myelomonocytic leukemia: a propensity score-matched study.

Hypomethylating agents (HMA) are indicated in the treatment of higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The combination of hypomethylating agents with venetoclax (Ven) has demonstrated promising results in these diseases, although randomized clinical trials are needed for validation. In this retrospective study, we compared two matched cohorts of patients with MDS or CMML: one receiving oral decitabine-cedazuridine (DEC-C, n = 73) and one receiving DEC-C and Ven (DEC-C-Ven, n = 51), in three contemporary clinical trials.

Mutation dynamics from diagnosis to relapse in acute myeloid leukemia with chromosomal 7 deletions.

Monosomy 7 and 7q deletions (-7/del(7q)) are the most common adverse cytogenetic event in acute myeloid leukemia (AML), linked to high relapse rates. We analyzed 115 AML patients with -7/del(7q) who achieved remission after induction therapy to characterize the mutational landscape from diagnosis to relapse. Median overall survival (OS) was 10.

A retrospective study of outcomes across time and treatment regimens in newly diagnosed, FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia.

Background: FMS-like tyrosine kinase 3 (FLT3) mutations, either internal tandem duplications (FLT3-ITD) or tyrosine kinase domain (FLT3-TKD), are common in acute myeloid leukemia (AML). FLT3-ITD confers an adverse prognosis.

Methods: The authors performed a retrospective study including 619 patients to evaluate outcomes in newly diagnosed FLT3-mutated AML across treatment regimens.

Characteristics and survival outcomes of patients with myelodysplastic syndromes with isolated 11q deletion.

Myelodysplastic syndrome (MDS) with isolated deletion 11q is a rare favorable cytogenetic abnormality with a low risk of progression to acute myeloid leukemia (AML). The aim of this study is to describe the clinical characteristics and long-term outcomes of patients with isolated del(11q) MDS. Between August 1997 and January 2024, 52 patients with MDS and isolated del(11q) were diagnosed, representing 0.

Clinico-Genomic Interrogation of Secondary-Type Acute Myeloid Leukemia: Response and Outcomes to Contemporary Therapies.

Ontogeny of acute myeloid leukemia (AML) provides prognostic information, however closer interrogation with respect to AML characteristics, genomics, and various treatments are warranted. We defined untreated clinical secondary (CS) AML as AML with a diagnosis of antecedent myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MDS-MPN) without exposure to hypomethylating agents or chemotherapy; genomic secondary (GS) AML included patients with myelodysplasia related cytogenetics (MRC) or myelodysplasia related mutations (MRM) without a known antecedent myeloid neoplasm or prior chemo-radiotherapy for non-myeloid neoplasms. Among newly diagnosed AML patients classified as untreated CS-AML (n = 133) or GS-AML (n = 389), median relapse-free survival (RFS) (11.

Mayo Genetic Risk Models for Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax + Hypomethylating Agent.

Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery.

Outcomes of Patients With Newly Diagnosed AML and Hyperleukocytosis.

Purpose: AML presenting with hyperleukocytosis is associated with poor outcomes. We aim to understand the factors associated with early mortality and overall survival (OS) to help guide management and improve early mortality.

Methods: We retrospectively reviewed data from 129 consecutive patients with newly diagnosed AML and a WBC count ≥100 × 10/L between January 2010 and April 2020.

Lower intensity therapy with cladribine/low dose cytarabine/venetoclax in older patients with acute myeloid leukemia compares favorably with intensive chemotherapy among patients undergoing allogeneic stem cell transplantation.

Background: Allogeneic stem cell transplantation (SCT) remains the best consolidative modality in most patients with acute myeloid leukemia (AML). Along with factors directly pertaining to SCT, pretransplantation disease control, performance status, and prior treatment-related complications are important factors that affect posttransplantation survival outcomes.

Methods: The authors compared the survival outcomes of patients ≥60 years of age treated on the phase 2 clinical trial of venetoclax (Ven) added to cladribine (CLAD) and low dose cytarabine (LDAC) alternating with azacitidine (CLAD/LDAC/Ven arm) (NCT03586609) who underwent allogeneic SCT in first remission to a retrospective cohort of patients ≥60 years of age who underwent SCT after intensive chemotherapy.

Outcomes and genetic dynamics of acute myeloid leukemia at first relapse.

Patients with relapsed acute myeloid leukemia (AML) experience dismal outcomes. We performed a comprehensive analysis of patients with relapsed AML to determine the genetic dynamics and factors predicting survival. We analyzed 875 patients with newly diagnosed AML who received intensive treatment or low-intensity treatment.