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EDITORIAL

Commissioned and introduced by Associate Editors Irene Roberts and Thomas Ortel, this Review Series focuses on common areas in pediatric hematology practice, emphasizing new therapeutic and diagnostic developments. The specific challenges of managing hemostatic and thrombotic disorders in children are described by O’Brien and Zia. Distinguishing acquired immune diseases from inherited disorders of blood counts is a common problem for pediatric hematologists, and this is tackled in reviews by Grace and Lambert for thrombocytopenias and by Dokal et al for bone marrow failure. Finally, Gallagher provides a stepwise approach to the diagnosis and treatment of anemia in infancy and childhood, at both the individual patient level and the population level.

BLOOD COMMENTARIES

REVIEW SERIES

Commissioned and introduced by Associate Editors Irene Roberts and Thomas Ortel, this Review Series focuses on common areas in pediatric hematology practice, emphasizing new therapeutic and diagnostic developments. The specific challenges of managing hemostatic and thrombotic disorders in children are described by O’Brien and Zia. Distinguishing acquired immune diseases from inherited disorders of blood counts is a common problem for pediatric hematologists, and this is tackled in reviews by Grace and Lambert for thrombocytopenias and by Dokal et al for bone marrow failure. Finally, Gallagher provides a stepwise approach to the diagnosis and treatment of anemia in infancy and childhood, at both the individual patient level and the population level.

Commissioned and introduced by Associate Editors Irene Roberts and Thomas Ortel, this Review Series focuses on common areas in pediatric hematology practice, emphasizing new therapeutic and diagnostic developments. The specific challenges of managing hemostatic and thrombotic disorders in children are described by O’Brien and Zia. Distinguishing acquired immune diseases from inherited disorders of blood counts is a common problem for pediatric hematologists, and this is tackled in reviews by Grace and Lambert for thrombocytopenias and by Dokal et al for bone marrow failure. Finally, Gallagher provides a stepwise approach to the diagnosis and treatment of anemia in infancy and childhood, at both the individual patient level and the population level.

Commissioned and introduced by Associate Editors Irene Roberts and Thomas Ortel, this Review Series focuses on common areas in pediatric hematology practice, emphasizing new therapeutic and diagnostic developments. The specific challenges of managing hemostatic and thrombotic disorders in children are described by O’Brien and Zia. Distinguishing acquired immune diseases from inherited disorders of blood counts is a common problem for pediatric hematologists, and this is tackled in reviews by Grace and Lambert for thrombocytopenias and by Dokal et al for bone marrow failure. Finally, Gallagher provides a stepwise approach to the diagnosis and treatment of anemia in infancy and childhood, at both the individual patient level and the population level.

Commissioned and introduced by Associate Editors Irene Roberts and Thomas Ortel, this Review Series focuses on common areas in pediatric hematology practice, emphasizing new therapeutic and diagnostic developments. The specific challenges of managing hemostatic and thrombotic disorders in children are described by O’Brien and Zia. Distinguishing acquired immune diseases from inherited disorders of blood counts is a common problem for pediatric hematologists, and this is tackled in reviews by Grace and Lambert for thrombocytopenias and by Dokal et al for bone marrow failure. Finally, Gallagher provides a stepwise approach to the diagnosis and treatment of anemia in infancy and childhood, at both the individual patient level and the population level.

CLINICAL TRIALS AND OBSERVATIONS

Yamamoto and colleagues modeled the cost-effectiveness of daratumumab as part of first-line combination therapy for newly diagnosed transplant-eligible patients with multiple myeloma. Using randomized trial data and cost estimates from Japan and the United States, they compared first- versus second-line use of daratumumab and report that first-line use delivers additional quality-adjusted life years over second-line use and is more cost-effective. These data suggest that if daratumumab is to be used in 1 line of therapy, then it should be in the first line.

HEMATOPOIESIS AND STEM CELLS

IMMUNOBIOLOGY AND IMMUNOTHERAPY

Diorio et al harnessed new “base editing” technology to develop a quadruple gene-edited CD7-specific chimeric antigen receptor (CAR) T-cell product for “off-the-shelf” use in patients with T-cell acute lymphoblastic leukemia (T-ALL) and other CD7+ malignancies. The authors’ data show potent activity in vitro and in vivo in patient-derived xenografts. Their methodology proposes an allogeneic approach that is promising for clinical translation and showcases the potential of base editing for improved and more accessible CAR T-cell therapies.

LYMPHOID NEOPLASIA

The metabolic state of any cell varies with cell cycle and interactions with the microenvironment. Chen and colleagues studied changes in chronic lymphocytic leukemia cell metabolism in samples from patients recently started on ibrutinib and modeled these changes in vitro. Their data indicate major changes in glycolysis, the tricarboxylic acid cycle and amino acid metabolism, implicating these in the modulation of responses to therapies and suggesting that limiting glutamine may enhance responses to venetoclax.

MYELOID NEOPLASIA

Mutations in the CSF3R and SETBP1 genes commonly co-occur in chronic neurophilic leukemia (CNL) and atypical chronic myeloid leukemia, 2 rare BCR-ABL1-negative myeloid neoplasms displaying prominent granulocytosis. Carratt and colleagues modeled this occurrence in mice, revealing that SETBP1 induces a Myc-driven transcriptional program that promotes leukemogenesis on a CSF3R mutant background. Execution of this program is dependent on LSD1, and in vivo data suggest that combining inhibitors of JAK2 and LSD1 may be effective in treating CNL.

LETTER TO BLOOD

BLOOD WORK

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