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BLOOD COMMENTARIES

PLENARY PAPER

Fit older patients with acute myeloid leukemia (AML) are often offered treatment with standard chemotherapy, but it is not clear how many benefit from intensive therapy. In a Plenary Paper that is also this month's CME article, Itzykson and colleagues sequenced AML-associated somatic mutations in 471 older patients treated with standard intensive chemotherapy. They developed a simple prognostic model, based on cytogenetics and somatic mutations in 7 genes, that identifies 3 prognostic groups; the decision tool can guide decisions governing intensive therapy.

HOW I TREAT

Brentuximab vedotin and anti-PD-1 antibodies have changed the treatment landscape for classical Hodgkin lymphoma (cHL). Using 3 illustrative cases, Epperla and Herrera discuss how they integrate these therapies in the treatment of cHL.

CLINICAL TRIALS AND OBSERVATIONS

Wudhikarn and colleagues report on the outcomes of 38 patients progressing after CD19 chimeric antiget receptor (CAR) T-cell therapy for relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). CAR T-cell therapy induced remission in over 80% of adults with relapsed or refractory B-ALL, but relapse was common. Relapsed patients had a median survival of 7.5 months despite further therapy, with most dying of progressive leukemia or toxicity, highlighting the need for novel therapies for this patient population.

LYMPHOID NEOPLASIA

Beckmann et al report on phosphoproteomic analysis of immunoglobulin heavy-chain variable gene (IGHV)—mutated and unmutated chronic lymphocytic leukemia (CLL) cells to provide insight into response to Bruton tyrosine kinase (BTK) inhibitors. The 2 groups showed striking differences, with unmutated CLL (UM-CLL) having higher basal phosphorylation levels than mutated CLL. The study focused on MARCKS, which is much more highly expressed and phosphorylated in UM-CLL and modulates cell migration, perhaps explaining the higher treatment-induced leukocytosis and decreased nodal disease in UMCLL when exposed to BTK inhibitors.

MYELOID NEOPLASIA

Borella et al investigated the cross talk between pediatric AML cells and the bone marrow niche. They demonstrate that AML cells reprogram mesenchymal stromal cells (MSCs) within the niche and modulate their transcriptional pathways to facilitate leukemia cell expansion. In an in vitro 3-dimensional niche implanted in mice, suppressing MSCs in combination with chemotherapy acted synergistically to suppress AML cell proliferation.

PLATELETS AND THROMBOPOIESIS

Palandri and colleagues reviewed the outcomes of 384 patients over age 60 treated with thrombopoietin receptor agonists (TRAs) for primary immune thrombocytopenia (ITP). Responses to eltrombopag and romiplostim were achieved in 74% to 80% of patients, with sustained responses in 67% and sustained responses off therapy in a small fraction (13.8%). Thromboses (9%) were associated with prior thrombosis history. TRAs are safe and effective in older patients, but patients with a history of thrombosis need appropriate antithrombotic therapy.

BLOOD WORK

CONTINUING MEDICAL EDUCATION (CME) QUESTIONS

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