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Table of Contents

BLOOD COMMENTARIES

PLENARY PAPER

In a study reported in this Plenary Paper, Ko et al used a multi-“omic” analysis of paired chronic phase and blast crisis (BC) chronic myeloid leukemia samples to demonstrate strikingly convergent patterns of gene expression underlying BC. Diverse genetic changes occurring with progression converged on modifications of the polycomb repressor complex that induce epigenetic changes, favoring stem cell proliferation and survival at the expense of differentiation.

HOW I TREAT

Using 3 illustrative cases, Geyer and colleagues explore issues surrounding the use of opioids to manage pain in patients with hematologic malignancies.

CLINICAL TRIALS AND OBSERVATIONS

A multicenter retrospective study of patients with stage I-II nodular lymphocyte-predominant Hodgkin lymphoma confirmed excellent overall survival regardless of treatment by observation, chemotherapy, radiotherapy, or combined modality therapy.

HEMATOPOIESIS AND STEM CELLS

Catarina Maia,on behalf of the PETHEMA/GEM Cooperative Group,Noemi Puig,on behalf of the PETHEMA/GEM Cooperative Group,Maria-Teresa Cedena,on behalf of the PETHEMA/GEM Cooperative Group,Ibai Goicoechea,on behalf of the PETHEMA/GEM Cooperative Group,Rafael Valdes-Mas,on behalf of the PETHEMA/GEM Cooperative Group,Iria Vazquez,on behalf of the PETHEMA/GEM Cooperative Group,Maria-Carmen Chillon,on behalf of the PETHEMA/GEM Cooperative Group,Paula Aguirre,on behalf of the PETHEMA/GEM Cooperative Group,Sarai Sarvide,on behalf of the PETHEMA/GEM Cooperative Group,Francisco Javier Gracia-Aznárez,on behalf of the PETHEMA/GEM Cooperative Group,Gorka Alkorta,on behalf of the PETHEMA/GEM Cooperative Group,Maria-Jose Calasanz,on behalf of the PETHEMA/GEM Cooperative Group,Ramon Garcia-Sanz,on behalf of the PETHEMA/GEM Cooperative Group,Marcos Gonzalez,on behalf of the PETHEMA/GEM Cooperative Group,Norma C. Gutierrez,on behalf of the PETHEMA/GEM Cooperative Group,Joaquin Martinez-Lopez,on behalf of the PETHEMA/GEM Cooperative Group,José J. Perez,on behalf of the PETHEMA/GEM Cooperative Group,Juana Merino,on behalf of the PETHEMA/GEM Cooperative Group,Cristina Moreno,on behalf of the PETHEMA/GEM Cooperative Group,Leire Burgos,on behalf of the PETHEMA/GEM Cooperative Group,Diego Alignani,on behalf of the PETHEMA/GEM Cooperative Group,Cirino Botta,on behalf of the PETHEMA/GEM Cooperative Group,Felipe Prosper,on behalf of the PETHEMA/GEM Cooperative Group,Sergio Matarraz,on behalf of the PETHEMA/GEM Cooperative Group,Alberto Orfao,on behalf of the PETHEMA/GEM Cooperative Group,Albert Oriol,on behalf of the PETHEMA/GEM Cooperative Group,Ana-Isabel Teruel,on behalf of the PETHEMA/GEM Cooperative Group,Raquel de Paz,on behalf of the PETHEMA/GEM Cooperative Group,Felipe de Arriba,on behalf of the PETHEMA/GEM Cooperative Group,Miguel T. Hernandez,on behalf of the PETHEMA/GEM Cooperative Group,Luis Palomera,on behalf of the PETHEMA/GEM Cooperative Group,Rafael Martinez,on behalf of the PETHEMA/GEM Cooperative Group,Laura Rosiñol,on behalf of the PETHEMA/GEM Cooperative Group,Maria-Victoria Mateos,on behalf of the PETHEMA/GEM Cooperative Group,Juan-Jose Lahuerta,on behalf of the PETHEMA/GEM Cooperative Group,Joan Blade,on behalf of the PETHEMA/GEM Cooperative Group,Jesus F. San Miguel,on behalf of the PETHEMA/GEM Cooperative Group,Bruno Paiva,on behalf of the PETHEMA/GEM Cooperative Group

Maia et al prospectively analyzed marrow biopsies of 285 newly diagnosed multiple myeloma patients for flow and DNA evidence of dysplastic hematopoiesis, revealing 33 patients with evidence of dysplasia, half with clonal hematopoiesis (CH). CH was independently associated with inferior survival in this group and in a retrospective analysis including over 1000 patients on previous protocols.

IMMUNOBIOLOGY AND IMMUNOTHERAPY

The authors used a preclinical animal model to examine the determinants of graft-versus-host disease that can predict potential therapies for treating this major complication of allogeneic stem cell transplantation. They elucidated the role of ATG16L1, a polymorphic gene in humans, in T-cell attack on intestinal organoids and demonstrated that it can be inhibited by blocking necroptosis.

LYMPHOID NEOPLASIA

Tausch et al assessed the prognostic impact of IGHV mutational status and genomic mutations in chronic lymphocytic leukemia (CLL) for treatment-naïve patients in a trial comparing obinutuzumab and chlorambucil (GClb) vs obinutuzumab and venetoclax (VenG). With the exception of del(17p), mutations associated with decreased progression free survival (PFS) with GClb treatment do not confer worse PFS upon treatment with VenG.

THROMBOSIS AND HEMOSTASIS

HLA loci predisposing to immune thrombotic thrombocytopenic purpura (TTP) in the white population have been described. In this study, analysis of the HLA haplotypes in 52 Japanese immune TTP patients identifies a different predisposing haplotype from that in whites. Interestingly, modeling different predisposing DRB1 alleles in the Japanese and white populations predicts binding to the same ADAMTS13 peptide.

TRANSFUSION MEDICINE

Polyclonal anti-D is thought to successfully treat immune thrombocytopenia (ITP) by blocking the reticuloendothelial system through opsonization and phagocytosis of red blood cells (RBCs). Khan et al demonstrated by a combination of in vitro and in vivo studies that successful targeting of RBCs is necessary but insufficient to predict successful interruption of platelet phagocytosis.

LETTERS TO BLOOD

BLOOD WORK

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