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Background: Hepatitis C (HCV) infections have been shown to be associated a with higher risk of atherosclerotic cardiovascular disease (CVD). However, the use of antiviral therapy (AVT) and the risk of CVD has not been well established with limited literature. Objective: We sought to evaluate the association between AVT use post-HCV infection and cardiovascular outcomes. Methods: We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until 10th March 2023. Primary clinical outcomes were the incidence of any CVD. Secondary endpoints were all-cause of mortality, stroke, myocardial infarction, and peripheral artery disease. Results: A total of 394,452 patients were included in the analysis (111,076 in the AVT group and 283,376 patients in the NAVT group). The mean age of patients among AVT and NAVT groups was comparable (58.7 vs 58.18). The pooled analysis of primary outcomes showed that AVT was associated with a significantly reduced risk of any CVD (HR, 0.55(95%CI: 0.41–0.75), P

Ivosidenib is an oral inhibitor of mutant Isocitrate dehydrogenase 1 (IDH1). It is approved for treatment of patients with relapsed or refractory IDH1-mutated acute myeloid leukemia (AML) and patients with newly diagnosed IDH1-mutated AML who are 75 years or older or those who are ineligible to receive intensive chemotherapy. While generally well tolerated, differentiation syndrome has been reported in 15–20% of patients. Here, we report a case of acute febrile neutrophilic dermatosis or Sweet's syndrome in conjunction with the use of ivosidenib for the treatment of relapsed AML. We discuss the clinical presentation of this rare entity, review relevant literature, and comment on its association with differentiation syndrome.

A 78-year-old-male with chronic myeloid leukemia (CML) treated for seven years with dasatinib developed an acute promyelocytic leukemia complicated by disseminated intravascular coagulopathy. A promyelocytic blast crisis was diagnosed by demonstrating co-expression of chimeric BCL/ABL and PML/RARα translocations by karyotyping, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction. Promyelocytic blast crisis of CML is a rare event with historically poor outcomes. Treatment of our patient with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) resulted in complete morphologic remission. We review here the relevant literature of promyelocytic blast crisis and highlight the potential of ATRA/ATO as first line management. Keywords: ATRA, ATO, CML, Promyelocytic, Blast crisis

Anthracyclines constitute the backbone of intensive adult acute myeloid leukemia (AML) therapy. Cardiotoxicity is one of its most serious adverse effects, and its incidence increases with cumulative dose. Dexrazoxane is a cardioprotective agent used in conjunction with anthracycline therapy. There is limited data of its usage in adult AML patients. We report the outcomes of six older adults at high risk of anthracycline-induced cardiotoxicity who received dexrazoxane during induction/re-induction therapy. Five had preserved left-ventricular function while two proceeded onto stem-cell transplantation. Additional investigation of dexrazoxane in adult leukemia therapy is warranted, particularly in older patients at highest risk for cardiovascular mortality.

Background: Pacritinib is a JAK2/IRAK1/ACVR1 inhibitor that is approved in the United States for the treatment of patients with myelofibrosis who have a platelet count < 50 × 109/L. Phase 3 clinical studies of pacritinib included patients across a wide range of baseline platelet and hemoglobin levels., Patients and Methods: In order to assess the impact of baseline blood counts on pacritinib efficacy, an analysis of efficacy outcomes by baseline platelet and hemoglobin levels was performed using data pooled from 2 Phase 3 studies of pacritinib in patients with MF (PERSIST-1 and PERSIST-2)., Results: Of 276 patients evaluable for spleen response, spleen volume reduction occurred consistently across platelet subgroups (< 100 × 109/L or ≥ 100 × 109/L) and hemoglobin subgroups (< 8 g/dL, ≥ 8 to < 10 g/dL, or > 10 g/dL), with no diminution in treatment effect in patients with severe thrombocytopenia or anemia. Among 159 patients evaluable for symptoms response, improvement in total symptom score (TTS) was similar across platelet subgroups. A ≥ 50% improvement of TSS occurred more frequently in patients with baseline hemoglobin < 8 g/dL compared with those with baseline hemoglobin ≥ 8 to < 10 g/dL or > 10 g/dL. Patients with baseline hemoglobin < 8 g/dL also experienced improved hemoglobin sustained over 24 weeks, whereas subgroups with less severe anemia had stable hemoglobin levels over time. Symptom improvement as assessed using the Patient Global Impression of Change instrument was generally consistent across platelet and hemoglobin subgroups., Conclusion: Pacritinib demonstrates consistent efficacy in patients with MF regardless of baseline platelet and hemoglobin counts., Competing Interests: Disclosure Nico Gagelmann: has consulted for Morphosys and Kite/Gilead; and has received travel support from Kite/Gilead, Janssen, and Neovii. Prithviraj Bose: has consulted for or received honoraria from AbbVie, Blueprint, BMS, Cogent, CTI BioPharma Corp., a Sobi company, Disc Medicine, GSK, Incyte, Ionis, Jubilant, Karyopharm, Morphic, MorphoSys, Novartis, PharmaEssentia, and Sumitomo; and has received research funding from Blueprint, BMS, Cogent, CTI BioPharma Corp., a Sobi company, DISC Medicine, Geron, Incyte, Ionis, Janssen, Kartos, Karyopharm, MorphoSys, Sumitomo, and Telios. Vikas Gupta: has consulted for AbbVie, BMS-Celgene, CTI BioPharma Corp., a Sobi company, GSK, Imago, Incyte, Karyopharm, MorphoSys, Novartis, Pfizer, Roche; has received research funding from Novartis, Incyte; has participated in advisory boards for AbbVie, BMS- Celgene, Constellation, CTI BioPharma Corp., a Sobi company, GSK, Incyte, Novartis, Pfizer. Donal P. McLornan: has received speakers fees from AbbVie, BMS/Celgene, Jazz Pharmaceuticals and Novartis; has received research funding from BMS/Celgene and Jazz Pharmaceuticals; and has participated on advisory boards and received travel assistance from Jazz Pharmaceuticals. Pankit Vachhani: has received honoraria from AbbVie, Amgen, Blueprint Medicines, Cogent Biosciences, Incyte, CTI BioPharma., a Sobi company, Daiichi Sankyo, GSK, Karyopharm, Novartis, Pfizer, Genetech, Inc., Servier, Stemline, MorphoSys, and LAVA Therapeutics; and has participated in speaker's bureaus for Incyte, CTI BioPharma Corp., a Sobi company, and Blueprint Medicines. Hafia Kathrin Al-Ali: has received research funding from BMS and Incyte; has participated on advisory boards and/or received honoraria: AbbVie, AOP Pharma, Blueprint, BMS, GSK, Otsuka, and Novartis; and has received travel assistance from AbbVie, BMS and Alexion. Haris Ali: has received research/ grant support from Incyte, has consulted for Karyopharm, GSK, and PharmaEssentia, and has participated in speakers bureaus for BluePrint and BMS. Philipp Treskes: consults for Sobi Inc. Sarah Buckley: is employed by Sobi Inc. and has received payment of unvested equity awards from CTI BioPharma Corp., a Sobi company, following its acquisition in June 2023 by the Swedish Orphan Biovitrum AB (publ). Karisse Roman-Torres: is employed by Sobi Inc. and has received payment of unvested equity awards from CTI BioPharma Corp., a Sobi company, following its acquisition in June 2023 by the Swedish Orphan Biovitrum AB (publ). Bart Scott: has participated on the data and safety monitoring board for Nektar and Johnson and Johnson; has participated in advisory panels for BMS, Celgene, Jazz Pharmaceuticals, and Novartis; has consulted for Alexion, Celgene, BMS, and Incyte; has received honoraria from Celgene, and BMS; and has received research funding from BMS and Novartis., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Prefibrotic primary myelofibrosis (prefibrotic PMF) is a myeloproliferative neoplasm with distinct characteristics comprising histopathological and clinico-biological parameters. It is classified as a subtype of primary myelofibrosis. In clinical practice, it is essential to correctly distinguish prefibrotic PMF from essential thrombocythemia especially but also overt PMF besides other myeloid neoplasms. Risk stratification and survival outcomes for prefibrotic PMF are worse than that of ET but better than that of overt PMF. Rates of progression to overt PMF and blast phase disease are also higher for prefibrotic PMF than ET. In this review we first discuss the historical context to the evolution of prefibrotic PMF as an entity, its presenting features and diagnostic criteria. We emphasize the differences between prefibrotic PMF, ET, and overt PMF with regards to presenting features and disease outcomes including thrombohemorrhagic events and progression to fibrotic and blast phase disease. Next, we discuss the risk stratification models and contextualize these in the setting of clinical management. We share our view of personalizing treatment to address unique patient needs in the context of currently available management options. Lastly, we discuss areas of critical need in clinical research and speculate on the possibility of future disease course modifying therapies in prefibrotic PMF., Competing Interests: Disclosure P.V. has Consulting or Advisory Role: Abbvie, Amgen, Blueprint Medicines, Cogent Biosciences, Incyte, CTI BioPharma Corp (now Sobi), Daiichi Sankyo, GlaxoSmith Kline, Karyopharm, Novartis, Pfizer, Genentech, Servier, Stemline, MorphoSys, LAVA therapeutics. Speakers' Bureau: Incyte, CTI BioPharma Corp, Blueprint Medicines. S.L.: consultant/advisory: Guidepoint, QualWorld, Gerson Lehrman Group, Abbvie, Daiichi Sankyo, BluePrint Medicine, Caris Diagnostics, Recordat, VJ HemeOnc; AlphaSight, Arima; honorarium/speaking: OncLive, PeerView, MD Education, VJ HemeOnc, NCCN, MashUp Media, Binay Foundation, American Society of Hematology (ASH). P.B. discloses research support from Incyte, BMS, CTI (now Sobi), Morphosys, Kartos, Telios, Disc Medicine, Sumitomo, Janssen, Geron, Ionis, Cogent, Blueprint and Karypharm; and honoraria from Incyte, BMS, CTI (now Sobi), GSK, Blueprint, Cogent, Novartis, Pharma Essentia, Morphosys, Abbvie, Karyopharm, Ionis, Sumitomo, Morphic and Jubilant., (Copyright © 2024. Published by Elsevier Inc.)

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with historically poor outcomes and no worldwide consensus treatment approach. Unique among most hematologic malignancies for its frequent cutaneous involvement, BPDCN can also invade other extramedullary compartments, including the central nervous system. Generally affecting older adults, many patients are unfit to receive intensive chemotherapy, and although hematopoietic stem cell transplantation is preferred for younger, fit individuals, not all are eligible. One recent therapeutic breakthrough is that all BPDCNs express CD123 (IL3Rα) and that this accessible surface marker can be pharmacologically targeted. The first-in-class agent for BPDCN, tagraxofusp, which targets CD123, was approved in December 2018 in the United States for patients with BPDCN aged ≥2 years. Despite favorable response rates in the frontline setting, many patients still relapse in the setting of monotherapy, and outcomes in patients with relapsed/refractory BPDCN remain dismal. Therefore, novel approaches targeting both CD123 and other targets are actively being investigated. To begin to formally address the state of the field, we formed a new collaborative initiative, the North American BPDCN Consortium (NABC). This group of experts, which includes a multidisciplinary panel of hematologists/oncologists, hematopoietic stem cell transplant physicians, pathologists, dermatologists, and pediatric oncologists, was tasked with defining the current standard of care in the field and identifying the most important research questions and future directions in BPDCN. The position findings of the NABC's inaugural meetings are presented herein., (© 2023 by The American Society of Hematology.)

Older patients with acute myeloid leukemia (AML) have high relapse risk and poor survival after allogeneic hematopoietic cell transplantation (HCT). Younger patients may receive myeloablative conditioning to mitigate relapse risk associated with high-risk genetics or measurable residual disease (MRD), but older adults typically receive reduced-intensity conditioning (RIC) to limit toxicity. To identify factors that drive HCT outcomes in older patients, we performed targeted mutational analysis (variant allele fraction ≥2%) on diagnostic samples from 295 patients with AML aged ≥60 years who underwent HCT in first complete remission, 91% of whom received RIC, and targeted duplex sequencing at remission in a subset comprising 192 patients. In a multivariable model for leukemia-free survival (LFS) including baseline genetic and clinical variables, we defined patients with low (3-year LFS, 85%), intermediate (55%), high (35%), and very high (7%) risk. Before HCT, 79.7% of patients had persistent baseline mutations, including 18.3% with only DNMT3A or TET2 (DT) mutations and 61.4% with other mutations (MRD positive). In univariable analysis, MRD positivity was associated with increased relapse and inferior LFS, compared with DT and MRD-negative mutations. However, in a multivariable model accounting for baseline risk, MRD positivity had no independent impact on LFS, most likely because of its significant association with diagnostic genetic characteristics, including MDS-associated gene mutations, TP53 mutations, and high-risk karyotype. In summary, molecular associations with MRD positivity and transplant outcomes in older patients with AML are driven primarily by baseline genetics, not by mutations present in remission. In this group of patients, where high-intensity conditioning carries substantial risk of toxicity, alternative approaches to mitigating MRD-associated relapse risk are needed., (© 2022 by The American Society of Hematology.)

Ivosidenib is an oral inhibitor of mutant Isocitrate dehydrogenase 1 (IDH1). It is approved for treatment of patients with relapsed or refractory IDH1-mutated acute myeloid leukemia (AML) and patients with newly diagnosed IDH1-mutated AML who are 75 years or older or those who are ineligible to receive intensive chemotherapy. While generally well tolerated, differentiation syndrome has been reported in 15-20% of patients. Here, we report a case of acute febrile neutrophilic dermatosis or Sweet's syndrome in conjunction with the use of ivosidenib for the treatment of relapsed AML. We discuss the clinical presentation of this rare entity, review relevant literature, and comment on its association with differentiation syndrome., (Copyright © 2022. Published by Elsevier Ltd.)

Less-intensive induction therapies are increasingly used in older patients with acute myeloid leukemia (AML). Using an AML composite model (AML-CM) assigning higher scores to older age, increased comorbidity burdens, and adverse cytogenetic risks, we defined 3 distinct prognostic groups and compared outcomes after less-intensive vs intensive induction therapies in a multicenter retrospective cohort (n = 1292) treated at 6 institutions from 2008 to 2012 and a prospective cohort (n = 695) treated at 13 institutions from 2013 to 2017. Prospective study included impacts of Karnofsky performance status (KPS), quality of life (QOL), and physician perception of cure. In the retrospective cohort, recipients of less-intensive therapies were older and had more comorbidities, more adverse cytogenetics, and worse KPS. Less-intensive therapies were associated with higher risks of mortality in AML-CM scores of 4 to 6, 7 to 9, and ≥10. Results were independent of allogeneic transplantation and similar in those age 70 to 79 years. In the prospective cohort, the 2 groups were similar in baseline QOL, geriatric assessment, and patient outcome preferences. Higher mortality risks were seen after less-intensive therapies. However, in models adjusted for age, physician-assigned KPS, and chance of cure, mortality risks and QOL were similar. Less-intensive therapy recipients had shorter length of hospitalization (LOH). Our study questions the survival and QOL benefits (except LOH) of less-intensive therapies in patients with AML, including those age 70 to 79 years or with high comorbidity burdens. A randomized trial in older/medically infirm patients is required to better assess the value of less-intensive and intensive therapies or their combination. This trial was registered at www.clinicaltrials.gov as #NCT01929408., (© 2021 by The American Society of Hematology.)

Introduction: The benefit of immediate reinduction chemotherapy for patients with indeterminate day 14 bone marrow results (≤ 20% cellularity and 5%-20% blasts) remains unclear. We report our experience with patients with acute myeloid leukemia (AML) with indeterminate day 14 bone marrow biopsy results treated with reinduction chemotherapy versus observation alone., Materials and Methods: We performed a retrospective study to assess the outcomes of adult patients with newly diagnosed AML treated with or without reinduction chemotherapy for indeterminate day 14 bone marrow results., Results: We identified 50 patients with indeterminate day 14 bone marrow results. Of the 50 patients, 25 (50%) had received reinduction therapy and 25 (50%) had not. Of the 50 patients, 24 (48%) had poor risk disease, 12 in the reinduction arm (10 with an abnormal karyotype and 2 with a normal karyotype with molecular abnormalities) and 12 in the observation arm (6 with an abnormal karyotype and 6 with a normal karyotype with molecular abnormalities). The overall response rate (complete remission plus complete remission with incomplete count recovery) was similar in both treatment arms (80% vs. 80%). No statistically significant difference was found in the median overall survival (13 months vs. 21 months; P = .88) or relapse-free survival (13 months vs. 33 months; P = .53) between the 2 treatment arms., Conclusion: Our study did not find a statistically significant difference in the overall response rates or survival outcome measures for patients with AML and indeterminate day 14 bone marrow in the 2 treatment groups. Our findings question the utility of immediate reinduction chemotherapy and raise concern regarding overtreatment in this patient population. Larger studies investigating similar outcomes are warranted to validate our clinical findings., (Copyright © 2019 Elsevier Inc. All rights reserved.)