MDS AML ALL Lymphoma Myeloma

CONTEXT: Germline variants in the TERT gene may lead to impaired telomere maintenance implicated in the pathogenesis of myelodysplastic syndromes (MDS) by unknown mechanisms. OBJECTIVE: To explore the clinical and genetic associations of germline TERT variants in patients with suspicion of myeloid neoplasm. DESIGN: We selected patients tested through our institutional amplicon-based sequencing panel (42 myeloid genes, including exons 2 to 16 of TERT, read depth >250X) that carried a TERT variant with allele frequency between 35% and 65%...

BACKGROUND: Allogeneic SCT is curative for large proportion of patients with high-risk hematologic malignancies. The introduction of posttransplant cyclophosphamide (PTCy)-based graft versus host disease (GVHD) prophylaxis led to significant improvements in haplo-SCT outcomes and a remarkable increase in its use in the past decade. We aimed from this study to assess long-term outcomes of patients who underwent haplo-SCT. METHODS: We included all consecutive adult patients who had their first haplo-SCT between 2/2009 and 3/2019...

CONTEXT: Efficacy of FLT3 inhibitors (FLT3-i) in patients with AML and t(6;9)(p22;q34)/DEK-NUP214 is not well-established. OBJECTIVE: We compared overall survival (OS) and event-free survival (EFS) of AML patients with t(6;9) who received frontline FLT3-i, regardless of their FLT3 mutation status. DESIGN: We evaluated patients with AML or high-risk myelodysplastic syndrome (HR-MDS) seen in our center between 1995-2021. Among 9936 patients, 55 patients (0...

CONTEXT: Although venetoclax+hypomethylating agent (HMA) therapy has improved outcomes for patients with ND AML who are unfit for intensive chemotherapy (IC), responses are often transient. Sabatolimab is a novel immuno-myeloid therapy targeting TIM-3. Sabatolimab+HMA has shown durable responses in a Phase Ib study in patients with ND-AML and myelodysplastic syndrome. Treatment with sabatolimab+venetoclax+azacitidine may also improve patient outcomes. OBJECTIVE: To report findings from the dose-escalation part of STIMULUS-AML1 (NCT04150029) Design: Phase II, single-arm study Patients: Adult patients with ND-AML ineligible for IC Interventions: In the dose-escalation part (safety run-in), patients received either 400 mg (Cohort 1) or 800 mg (Cohort 2) sabatolimab every 4 weeks, 400 mg venetoclax once daily, and 75 mg/m2 azacitidine on Days (D) 1-7, or D1-5+D8-9, or D1-6+D8 of a 28-day cycle...

CONTEXT: AML is an orphan hematological disease. Epidemiology, and data on genetic subgroups that impact prognosis, improves understanding of global disease burden. OBJECTIVE: Identify and consolidate incidence, prevalence, and mortality data in adult AML/MDS patients through targeted literature review (TLR). DESIGN: TLR of published data from the past 5 years. Sources included PubMed, ISPOR, ASH, ASCO, AACR, EHA, ESMO, and SOHO. PATIENTS: Newly diagnosed (ND), relapsed/refractory (R/R) AML or MDS...

CONTEXT: Patients with ulcerative colitis (UC) and Crohn's disease (CD) are at increased cancer risk. Very little data is available regarding the risk of secondary MN in patients with IBD. OBJECTIVE: To describe the clinical characteristics of secondary MNs in patients with IBD. METHODS: Retrospective study of patients with MNs previously treated for IBD. RESULTS: Between 2012 and 2020, 43 patients were identified as having developed secondary MN during or after IBD treatment; 63% were women, and 81% were of white ethnicity...

BACKGROUND: TP53-mutated (TP53mut) AML and high-risk MDS are often treated with hypomethylating agents (HMAs) combined with venetoclax (Ven); however, myelosuppression often leads to dose-reductions and/or cycle delays. Administration of noncytotoxic doses of decitabine (Dec) 1x/week decreases HMA-mediated myelosuppression while maintaining S-phase-dependent DNMT1-targeting. In pre-clinical studies, single-dose Ven given prior to HMA administration inhibited de novo pyrimidine synthesis, countering a major mechanism of resistance to HMAs without suppressing normal myelopoiesis...

CONTEXT: IDH1-mutated (IDH1+) myeloid malignancies depend on the anti-apoptotic protein BCL-2 for survival. Combining the IDH1 inhibitor ivosidenib (IVO) with the BCL-2 inhibitor venetoclax (VEN) may improve outcomes. We report the completed P1b portion of a P1b/II study investigating IVO (500 mg PO daily D15-continuous) with VEN (D1-14), with or without azacitidine (AZA; 75 mg/m2 D1-7) every 28 days. OBJECTIVES: Primary P1b objectives included safety, tolerability, and IWG-defined overall response (ORR: CR+CRi+CRh+PR+MLFS)...

CONTEXT: Leukemic infiltration of the eye and ocular adnexal site is rare with unknown risk factors and clinical outcomes. OBJECTIVE: To describe the clinical characteristics of extramedullary ocular adnexal (OA) leukemia in patients with myeloid malignancies. DESIGN: In a retrospective analysis, we screened all patients treated at our center between 1993 and 2022. We identified 50 patients with myeloid malignancies who presented with vision changes with available magnetic resonance imaging of the orbits...

CONTEXT: Targetable mutations such as FLT3, a receptor tyrosine kinase, are present in 30% of cases with acute myeloid leukemia (AML). Direct inhibitors of FLT3 are promising therapeutic agents such as midostaurin and gilteritinib. The use of FLT3 inhibitors as single agents remains to be limited with short-lived responses. For treatment-naïve AML patients with FLT3 mutation, the standard treatment entails induction with intensive chemotherapy in physically fit or younger patients and in combination with an FLT3 inhibitor...

CONTEXT: Breast cancer survivors are at increased risk of developing second hematological malignancies (SHM). As the survival rates increase in breast cancer patients, SHM have become a cause of concern. OBJECTIVE: To determine the incidence of various SHM in breast cancer survivors at a large tertiary care center in India. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study was conducted at the All India Institute of Medical Sciences, New Delhi, India...

BACKGROUND: Patients with multiple myeloma (MM) have an increased risk of developing second malignancies, especially myeloid neoplasms (t-MDS/AML). However, little is known about the occurrence of lymphoid malignancies, in particular acute lymphoblastic leukemias (ALLs). METHODS: We retrospectively analyzed the disease characteristics and outcomes of patients diagnosed with ALL following MM who presented to the MD Anderson Cancer Center between 2005 and 2018. RESULTS: A total of 9 patients were identified...

CONTEXT: Relapsed and/or refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with few available salvage options and usually carries a dismal outcome with only 10% of patients surviving at 5 years. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) efficacy in R/R T-ALL remains problematic, as up to half of patients will relapse post allo-HSCT. Post-transplant maintenance in acute myeloid leukemia (AML) has long been debated, with recent implementation by transplant centers, especially the use of hypomethylating agents (HMAs) and targeted agents such as FLT3 inhibitors...

Background: FxCycleTM Violet (FCV) based flow cytometric (FCM) DNA ploidy analysis is a rapid and simple tool that can substantiate in characterizing the biological behaviour across the spectrum of haematological malignancies and correlates with cytogenetic studies. Materials and Methods: In this prospective study, we performed simultaneous immunophenotyping with FCV based on ploidy analysis in n=132 consecutive new samples, comprising n=110 samples of haemato-lymphoid neoplasms, including acute leukemias (n=67, 60...

The "heterozygote advantage" hypothesis has been postulated regarding the role of human leukocyte antigen (HLA) in non-Hodgkin lymphoma (NHL), where homozygous loci are associated with an increased risk of disease. In this retrospective study, we analyzed the HLA homozygosity of 3789 patients with aplastic anemia (AA), acute lymphocytic leukemia (ALL), acute myeloblastic leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), myelodysplastic syndrome (MDS), multiple myeloma (MM), and non-Hodgkin lymphoma (NHL) at HLA-A, B, C, DRB1 and DQB1 loci compared to 169,964 normal controls...

BACKGROUND: After several cases of peculiar hematological malignancies following introduction of new oral anti-hepatitis C virus (HCV) treatments in our recent practice, we aimed to systematically identify all cases of hematological malignancies (HM) in patients with chronic HCV infection and to compare them according to the prescription of oral anti-HCV Direct Acting Antivirals (DAA) treatment or not. MATERIAL/METHODS: In this single-center retrospective observational study, we included all patients with confirmed HM and chronic HCV infection managed between 2010 and 2019 in the Pitié-Salpêtrière hospital, Paris...

Background: Data on the association between coronavirus disease 2019 (COVID-19) and the epidemiology and outcomes of hematological malignancies are limited. Hence, the present study aimed to assess the imaging findings using chest multidetector computed tomography (MDCT) in patients with hematologic malignancies who developed COVID-19 pneumonia. Methods: This retrospective study included two groups, the first group consisted of COVID-19 infected patients with hematologic malignancies (100 patients), while the second group consisted of COVID-19 infected patients without hematologic malignancies or other comorbidities (100 patients)...

BACKGROUND: Haematological cancers are clonal diseases of the blood and blood-forming organs, with the distribution pattern not known in our locality. This study aimed to describe the distribution pattern and prevalence of haematological cancers among adults in Abakaliki, Nigeria. MATERIALS AND METHODS: This was an 8-year retrospective study in which the hospital records/case notes of adult patients diagnosed and managed for haematological cancers from May 2012 to April 2020 were reviewed...

Epigenetic dysregulation leads to aberrant DNA hypermethylation and is common in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). A large number of clinical trials in AML, MDS, and other hematologic malignancies have assessed hypomethylating agents (HMAs), used alone or in combination with other drugs, in the frontline, maintenance, relapsed/refractory, and peritransplant settings. Effective maintenance therapy has long been a goal for patients with AML in remission. Previous large, randomized clinical trials of maintenance with HMAs or other agents had not shown meaningful improvement in overall survival...

There are limited data on outcomes of patients with prior Coronavirus disease 2019 (COVID-19) who proceeded to autologous or allogeneic hematopoietic cell transplantation (HCT). Whether these patients are more susceptible to poor outcomes and recurrence of COVID-19 is unknown. We report a retrospective analysis of outcomes of 15 consecutive patients with hematologic malignancies who experienced COVID-19 and subsequently underwent autologous (n = 8) or allogeneic (n = 7) HCT between June 17, 2020, and February 17, 2021...