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Bone Marrow Transplant 2022 Jun 25. Epub 2022 Jun 25.

Hematology, Saint Antoine University Hospital, Paris, France.

The optimal conditioning regimen prior haploidentical stem cell transplantation (Haplo-SCT) with post transplantation cyclophosphamide (PT-Cy) for acute myeloid leukemia (AML) remains unknown. A non-myeloablative conditioning (NMAC) regimen (cyclophosphamide + fludarabine + TBI 2 Gy [CyFluTBI]) is a safe approach, but relapse incidence remains high in this setting. Alternatively, a reduced intensity conditioning (RIC) regimen combining thiotepa and reduced-dose busulfan with fludarabine (TBF) may decrease AML relapse. Read More

Curr Hematol Malig Rep 2022 Jun 25. Epub 2022 Jun 25.

Diagnostic Laboratories, Versiti, 638 N 18th St, Milwaukee, WI, 53233, USA.

Purpose Of Review: This review describes ANKRD26-related thrombocytopenia (RT) from a molecular, clinical, and laboratory perspective, with a focus on the clinical decision-making that takes place in the diagnosis and management of families with ANKRD26-RT.

Recent Findings: ANKRD26-related thrombocytopenia (ANKRD26-RT) is a non-syndromic autosomal dominant thrombocytopenia with predisposition to hematologic neoplasm. The clinical presentation is variable with moderate thrombocytopenia with normal platelet size and absent to mild bleeding being the hallmark which makes it difficult to distinguish from other inherited thrombocytopenias. Read More

Cancer Chemother Pharmacol 2022 Jun 25. Epub 2022 Jun 25.

Novartis Pharma AG, CH-4002, Basel, Switzerland.

Purpose: Midostaurin, approved for the treatment of newly diagnosed, FLT3-mutated acute myeloid leukemia (AML), is metabolized by cytochrome P450 3A4 (CYP3A4). Midostaurin with concomitant strong CYP3A4 inhibitors use (e.g. Read More

Blood Cancer J 2022 Jun 24;12(6):95. Epub 2022 Jun 24.

Université Paris Cité, Génomes, biologie cellulaire et thérapeutique U944, INSERM, CNRS, F-75010, Paris, France.

Functional precision medicine in AML often relies on short-term in vitro drug sensitivity screening (DSS) of primary patient cells in standard culture conditions. We designed a niche-like DSS assay combining physiologic hypoxia (O 3%) and mesenchymal stromal cell (MSC) co-culture with multiparameter flow cytometry to enumerate lymphocytes and differentiating (CD11/CD14/CD15+) or leukemic stem cell (LSC)-enriched (GPR56+) cells within the leukemic bulk. After functional validation of GPR56 expression as a surrogate for LSC enrichment, the assay identified three patterns of response, including cytotoxicity on blasts sparing LSCs, induction of differentiation, and selective impairment of LSCs. Read More

Immunobiology 2022 Jun 11;227(4):152237. Epub 2022 Jun 11.

WG Immune Modulation, Medical Department III, University Hospital of Munich, Marchioninistraße 15, 81377 Munich, Germany. Electronic address:

The blastmodulatory Kit-M, composed of granulocyte-macrophage colony-stimulating-factor (GM-CSF) and Prostaglandin E1 (PGE), is known to convert myeloid leukaemic blasts (from AML patients) into leukaemia derived dendritic cells (DC), which activate immunoreactive cells to gain antileukemic/leukaemia-specific activity. In this study we had a special focus on the influence of Kit-M treated, DC/DCleu containing patients'whole blood (WB, n = 16) on the provision of immunosuppressive regulatory T-cells. We could confirm that Kit-M significantly increased frequencies of (mature) dendritic cells (DC) and DC from leukemic whole blood (WB) without induction of blast proliferation. Read More

Drug Dev Res 2022 Jun 24. Epub 2022 Jun 24.

Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy.

A series of [1,2]oxazolo[5,4-e]isoindole derivatives was evaluated against HL-60 cell line and its multidrug resistance (MDR) variant, HL-60R, resistant to doxorubicin and to other P-gp substrates by overexpressing the efflux pump. They displayed antiproliferative activities, with IC values ranging from 0.02 to 5. Read More

Expert Opin Emerg Drugs 2022 Jun 24. Epub 2022 Jun 24.

Department of Clinical Hematology, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre Bénite, France.

Introduction: Despite recent advances in the treatment of adult acute myeloid leukemia (AML), the clinical outcome of patients continues to be unsatisfactory especially among older patients, those with a high-risk profile, and in the relapsed/refractory setting. For this reason, recent clinical trials have explored novel therapeutic agents either used alone or in combination with intensive chemotherapy or low-intensity treatments.

Areas Covered: The current paper reviews the clinical development of monoclonal antibody-based therapies in AML, their current status and phases 2 and 3 prospective trials. Read More

ACS Chem Biol 2022 Jun 24. Epub 2022 Jun 24.

Department of Chemistry, Yale University, New Haven, Connecticut 06511, United States.

The RNA decapping scavenger protein, DcpS, has recently been identified as a dependency in acute myeloid leukemia (AML). The potent DcpS inhibitor RG3039 attenuates AML cell viability, and shRNA knockdown of DcpS is also antiproliferative. Importantly, DcpS was found to be non-essential in normal human hematopoietic cells, which opens a therapeutic window for AML treatment by DcpS modulation. Read More

Rev Esp Enferm Dig 2022 Jun 24. Epub 2022 Jun 24.

Gastroenterology , Centro Hospitalar Universitário de São João, Portugal.

A 60-year-old female was diagnosed with acute myeloid leukemia. After initial remission with chemotherapy, she relapsed and underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two months later, she presented to emergency department with watery diarrhea, abdominal pain and fever. Read More

J Oncol Pharm Pract 2022 Jun 23:10781552221110826. Epub 2022 Jun 23.

103564Facultad de Medicina y Hospital Universitario "Dr José Eleuterio González" Haematology service, Universidad Autónoma de Nuevo León, Monterrey, Mexico.

Case Report: We report the first case of orbital myeloid sarcoma that was successfully treated with a standard venetoclax dose of 25%. A 38-year-old man with acute myeloid leukemia (AML) post-haplo-hematopoietic stem cell transplantation (HSCT) presented with a nine-month history of progressive right proptosis and a visual acuity deficit. The patient was treated with venetoclax (100 mg orally on days 1-28), cytarabine (40 mg subcutaneously, days 1-10), and itraconazole (100 mg twice daily orally on days 1-28). Read More

Hemasphere 2022 Jul 17;6(7):e742. Epub 2022 Jun 17.

Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Germany.

Indian J Hematol Blood Transfus 2022 Jul 28;38(3):499-507. Epub 2021 Sep 28.

Department of Medical Oncology/Hematology, All India Institute of Medical Sciences, Bhubaneswar, India.

Leukocyte cell population data (CPD) generated by hematology auto analyzers are reported to be useful in screening of sepsis patients. However, there is a paucity of literature highlighting the utility of CPD in screening of acute leukemias (AL). Leucocyte CPD obtained by Sysmex XN1000 hematology analyzer from 210 cases of ALs [22 acute promyelocytic leukemia (APL), 79 non-APL acute myeloid leukemia (non-APL-AML) and 109 acute lymphoblastic leukemia (ALL)] were compared with 100 healthy and 52 reactive controls. Read More

Indian J Hematol Blood Transfus 2022 Jul 5;38(3):481-491. Epub 2021 Aug 5.

Stem Cell Laboratory and Department of Hematology, Affiliated Hospital of Southwest Medical University, Sichuan Province, Luzhou City, China.

To investigate the expression and clinical significance of Bridging INtegrator 1 () and cyclin D2 () in newly diagnosed cytogenetically heterogenous adult acute myeloid leukemia patients. Real-time quantitative PCR (RQ-PCR) was used to detect the expression of and genes in 49 newly diagnosed adult patients with AML, and their clinical significance was analyzed. and genes are highly expressed in patients with AML, which suggest their potential as molecular markers. Read More

Indian J Hematol Blood Transfus 2022 Jul 27;38(3):464-472. Epub 2021 Jul 27.

Department of Biostatistics and Medical Informatics, Medical Faculty, Kocaeli University, İzmit, Kocaeli Turkey.

Purpose: We aimed to evaluate the expression level of programmed death ligand-1 (PD-L1) and its effects on prognosis in acute myeloid leukemia. Methods: The flow cytometry was used to detect PD-L1 expression on leukemic cells of 86 de novo acute myeloid leukemia patients with longitudinal follow-up. Results: Median follow-up was 13 (0-73) months. Read More

Ther Adv Hematol 2022 17;13:20406207221090882. Epub 2022 Jun 17.

Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Introduction: Azacitidine (AZA) either single-agent or with donor lymphocytes infusions (DLI) has been used as a salvage treatment for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) relapsing after allogeneic hematopoietic stem cell transplantation (HSCT). To date, the majority of data come from patients relapsed after HSCT from full-matched donors.

Methods: We report a multicenter, collaborative, retrospective analysis of 71 patients with hematologic ( = 40, 56%) and molecular relapse ( = 31, 44%) of myeloid neoplasms after HSCT from alternative donors (mismatched unrelated,  = 39, 55%; haploidentical,  = 29, 41%) consecutively treated at three European centers with AZA ± DLI. Read More

Cureus 2022 May 20;14(5):e25162. Epub 2022 May 20.

Neurological Surgery, University of Miami Miller School of Medicine, Miami, USA.

Treatment for vertebral osteomyelitis varies depending on the extent of pathology and includes both medical and surgical approaches. Pathogen-directed antibiotic therapy is often the first-line treatment, however, refractory cases or those with sepsis, segmental instability, or epidural abscess may be candidates for surgical treatment. Patients with extensive bony destruction often require a corpectomy with the placement of a cage for anterior column reconstruction. Read More

Cureus 2022 May 21;14(5):e25196. Epub 2022 May 21.

Hematology, Hamad General Hospital, Doha, QAT.

Coronavirus disease 2019 (COVID-19) is a respiratory viral illness caused by coronavirus 2 (SARS-CoV-2). The disease often presents with non-specific symptoms, including fever, and fatigue, usually associated with respiratory symptoms (eg., cough) and other systemic involvement. Read More

Molecules 2022 Jun 18;27(12). Epub 2022 Jun 18.

Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, Gębali 6, 20-093 Lublin, Poland.

Acute myeloid leukemia (AML) accounts for approximately 15-20% of all childhood leukemia cases. The overall survival of children with acute myeloid leukemia does not exceed 82%, and the 5-year event-free survival rates range from 46% to 69%. Such suboptimal outcomes are the result of numerous mutations and epigenetic changes occurring in this disease that adversely affect the susceptibility to treatment and relapse rate. Read More

Molecules 2022 Jun 7;27(12). Epub 2022 Jun 7.

Department of Pharmacy, University of Pisa, 56126 Pisa, Italy.

Human dihydroorotate dehydrogenase (hDHODH) is an enzyme belonging to a flavin mononucleotide (FMN)-dependent family involved in de novo pyrimidine biosynthesis, a key biological pathway for highly proliferating cancer cells and pathogens. In fact, hDHODH proved to be a promising therapeutic target for the treatment of acute myelogenous leukemia, multiple myeloma, and viral and bacterial infections; therefore, the identification of novel hDHODH ligands represents a hot topic in medicinal chemistry. In this work, we reported a virtual screening study for the identification of new promising hDHODH inhibitors. Read More

J Clin Med 2022 Jun 9;11(12). Epub 2022 Jun 9.

Division of Hematology and Stem Cell Transplantation, ASUFC, University of Udine, 33100 Udine, Italy.

The Minimal Residual Disease(MRD) monitoring in acute myeloid leukemia (AML) is crucial to guide treatment after morphologic complete remission, to define the need for consolidation with allogeneic stem cell transplantation (Allo-SCT), and to detect impending relapse allowing early intervention. However, more than 50% of patients with AML lack a specific or measurable molecular marker to monitor MRD. We reviewed the key studies on WT1 overexpression as a marker of MRD in AML patients undergoing an intensive chemotherapy program, including Allo-SCT. Read More

Int J Mol Sci 2022 Jun 16;23(12). Epub 2022 Jun 16.

BIOCEV, 1st Medical Faculty, Charles University, 25250 Vestec, Czech Republic.

The transcription factor PU.1 (Purine-rich DNA binding, SPI1) is a key regulator of hematopoiesis, whose level is influenced by transcription through its enhancers and its post-transcriptional degradation via microRNA-155 (miR-155). The degree of transcriptional regulation of the gene is influenced by repression via DNA methylation, as well as other epigenetic factors, such as those related to progenitor maturation status, which is modulated by the transcription factor Myeloblastosis oncogene (MYB). Read More

Int J Mol Sci 2022 Jun 12;23(12). Epub 2022 Jun 12.

Gehr Family Center for Leukemia Research, Hematology Malignancies and Stem Cell Transplantation Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.

Venetoclax (VEN) in combination with hypomethylating agents induces disease remission in patients with de novo AML, however, most patients eventually relapse. AML relapse is attributed to the persistence of drug-resistant leukemia stem cells (LSCs). LSCs need to maintain low intracellular levels of reactive oxygen species (ROS). Read More

Biology (Basel) 2022 Jun 15;11(6). Epub 2022 Jun 15.

University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA.

The prognostic significance of the length of internal tandem duplication (ITD) insertions in mutant genes in acute myeloid leukemia (AML) is controversial. We conducted a retrospective study to evaluate the correlation between the ITD base-pair (bp) insertion length and clinical outcomes. The mutational status of the gene was evaluated in 402 of 467 consecutive AML patients treated at the University of Maryland Greenebaum Comprehensive Cancer Center between 2013 and 2020; 77 had -ITD mutations. Read More

Cells 2022 Jun 13;11(12). Epub 2022 Jun 13.

Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8N 3Z5, Canada.

The generation of human hematopoietic stem cells (HSCs) from human pluripotent stem cells (hPSCs) represents a major goal in regenerative medicine and is believed would follow principles of early development. HSCs arise from a type of endothelial cell called a "hemogenic endothelium" (HE), and human HSCs are experimentally detected by transplantation into SCID or other immune-deficient mouse recipients, termed SCID-Repopulating Cells (SRC). Recently, SRCs were detected by forced expression of seven transcription factors (TF) (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1, and SPI1) in hPSC-derived HE, suggesting these factors are deficient in hPSC differentiation to HEs required to generate HSCs. Read More

Cancers (Basel) 2022 Jun 18;14(12). Epub 2022 Jun 18.

GIMEMA Foundation, 00182 Roma, Italy.

/ mutations are common in acute myeloid leukemia (AML) and represent a therapeutic target. The GIMEMA AML1516 observational protocol was designed to study the prevalence of / mutations and associations with clinico-biological parameters in a cohort of Italian AML patients. We analyzed a cohort of 284 AML consecutive patients at diagnosis, 139 females and 145 males, of a median age of 65 years (range: 19-86). Read More

Cancers (Basel) 2022 Jun 17;14(12). Epub 2022 Jun 17.

Hematology & BMT Unit, Fondazione IRCCS Ca' Granda Policlinico Ospedale Maggiore di Milano, 20122 Milan, Italy.

Immunotherapy is changing the therapeutic landscape of many hematologic diseases, with immune checkpoint inhibitors, bispecific antibodies, and CAR-T therapies being its greatest expression. Unfortunately, immunotherapy in acute myeloid leukemia (AML) has given less brilliant results up to now, and the only approved drug is the antiCD33 antibody-drug conjugate gemtuzumab ozogamicin. A promising field of research in AML therapy relies on anti-leukemic vaccination to induce remission or prevent disease relapse. Read More

Cancers (Basel) 2022 Jun 14;14(12). Epub 2022 Jun 14.

Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.

Gemtuzumab ozogamicin (GO) improves outcomes when added to intensive AML chemotherapy. A meta-analysis suggested the greatest benefit when combining fractionated doses of GO (GO3) with 7 + 3. To test whether GO3 can be safely used with high intensity chemotherapy, we conducted a phase 1/2 study of cladribine, high-dose cytarabine, G-CSF, and dose-escalated mitoxantrone (CLAG-M) in adults with newly diagnosed AML or other high-grade myeloid neoplasm (NCT03531918). Read More

Cancers (Basel) 2022 Jun 13;14(12). Epub 2022 Jun 13.

Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.

Allogeneic stem cell transplantation is used in the treatment of high-risk hematological malignancies. However, this treatment is associated with severe treatment-related morbidity and mortality. The metabolic status of the recipient may be associated with the risk of development of transplant-associated complications such as graft-versus-host disease (GVHD). Read More

Cancers (Basel) 2022 Jun 8;14(12). Epub 2022 Jun 8.

Hematology Unit, S. Eugenio Hospital, ASL Roma 2, 00144 Rome, Italy.

Therapy-related acute myeloid leukemia (t-AML) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) represent aggressive diseases characterized by a dismal prognosis if compared with de novo acute myeloid leukemia, especially in older patients. In these AML subsets, standard chemotherapy regimens produce poor response rates and unsatisfactory outcomes. Historically, conventional approaches consisted of an anthracycline combined with continuous infusion of cytarabine for 7 days, the "3+7" regimen. Read More

Biomedicines 2022 Jun 14;10(6). Epub 2022 Jun 14.

Department of Oncology/Hematology, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.

The tumor microenvironment (TME) plays an essential role in the development, proliferation, and survival of leukemic blasts in acute myeloid leukemia (AML). Within the bone marrow and peripheral blood, various phenotypically and functionally altered cells in the TME provide critical signals to suppress the anti-tumor immune response, allowing tumor cells to evade elimination. Thus, unraveling the complex interplay between AML and its microenvironment may have important clinical implications and are essential to directing the development of novel targeted therapies. Read More