Diagnostic challenges of high-grade myeloid malignancies with partial plasmacytoid dendritic cell differentiation: report of two cases with literature review.

The diagnosis of myeloid neoplasms with plasmacytoid dendritic cell (pDC) differentiation can be challenging due to immunophenotypic overlap requiring detailed characterization by flow cytometry and immunohistochemistry. We describe two patients with a history of myeloproliferative neoplasm (MPN) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN) who presented years later with leukocytosis, lymphadenopathy, splenomegaly, and cachexia, with rapid clinical deterioration and death. Lymph node biopsy specimens revealed involvement by myeloid sarcoma with prominent pDC differentiation.

Management of hemolytic transfusion reactions in a patient with chronic myelomonocytic leukemia and rare antibodies: A case report.

Delayed hemolytic transfusion reaction (DHTR) poses a significant challenge in patients receiving blood transfusions. This case report highlights the complexities of managing DHTR in a newly diagnosed chronic myelomonocytic leukemia (CMML) patient with clinically significant JKa and little c antibodies during induction chemotherapy. A 46-year-old woman with CMML-2 who presented for induction chemotherapy was found to have hemolytic anemia.

Challenges and practical considerations in the management of blastic plasmacytoid dendritic cell neoplasm: A single-center experience.

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a rare and often life-threatening complex hematologic malignancy that can commonly infiltrate the skin, lymph nodes, central nervous system, and bone marrow. In the setting of the infrequency of confirmed diagnoses of BPDCN, and given limited prospective studies, it has been associated with lackluster outcomes with a median overall survival between 9 and 23 months. We herein discuss our experience treating five consecutive patients with BPDCN at our center since the approval of TAG.

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.

Janus kinase inhibitor monotherapy and combination therapies for myelofibrosis: what's the current standard of care?

Introduction: JAK inhibitors (JAKi) have changed the treatment paradigm of myelofibrosis (MF). Currently, 4 JAKis are approved in the US as monotherapy (mono) to treat patients with MF. JAKis are also being studied in combination (combo) with novel agents.

Glutaminase inhibition in combination with azacytidine in myelodysplastic syndromes: a phase 1b/2 clinical trial and correlative analyses.

Malignancies are reliant on glutamine as an energy source and a facilitator of aberrant DNA methylation. We demonstrate preclinical synergy of telaglenastat (CB-839), a selective glutaminase inhibitor, combined with azacytidine (AZA), followed by a single-arm, open-label, phase 1b/2 study in persons with advanced myelodysplastic syndrome (MDS). The dual primary endpoints evaluated clinical activity, safety and tolerability; secondary endpoints evaluated pharmacokinetics, pharmacodynamics, overall survival, event-free survival and duration of response.

Overcoming Tagraxofusp-Erzs Monotherapy Resistance in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) in a Real-World Clinical Setting.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and clinically aggressive hematologic malignancy with limited treatment options. Currently, standard treatment strategies include clinical trials; chemotherapy regimens such as hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD); and tagraxofusp-erzs (TAG, previously SL-401) which is the first-in-class targeted therapy against CD123. TAG received Food and Drug Administration approval for frontline BPDCN treatment in December 2018 and has increasingly become an alternative to chemotherapy, offering potentially more effective and less toxic options.

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.

Polycythemia vera: past, present and future.

There has been remarkable progress in the development of novel therapeutic approaches for patients with polycythemia vera (PV). Historically, therapy goals in PV were to mitigate thrombotic risks and control blood counts and symptoms. There is now increased focus on disease modification through progressive attrition of -mutant stem/progenitor cells.

Clonal evolution of hematopoietic stem cells after cancer chemotherapy.

Normal hematopoietic stem and progenitor cells (HSPCs) inherently accumulate somatic mutations and lose clonal diversity with age, processes implicated in the development of myeloid malignancies . The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal HSPCs is not well defined. We conducted whole-genome sequencing on 1,032 single-cell-derived HSPC colonies from 10 patients with multiple myeloma (MM), who had undergone various chemotherapy regimens.