Tolerability of CD19 CAR T cells in lymphoma, causes of platelet spherocytosis, and using prebiotics to reduce GVHD
In this week’s episode, we’ll discuss patient-reported outcomes in the phase 3 ZUMA-7 trial of CAR T-cell therapy in second-line relapsed/refractory large B-cell lymphoma, learn more about the association between the loss of α4A- and β1-tubulin and severe platelet spherocytosis, and discuss the interaction between prebiotic galactooligosaccharides and mouse gut microbiota in graft-versus-host disease.
Genomic profiling for clinical decision making in myeloid neoplasms and acute leukemia
Complementing the recently published Blood articles outlining the 2022 International Consensus Classifications for hematological malignancies (Vol. 140, Issue 11), this pair of Special Reports illustrates how molecular pathology can be applied to precision medicine. de Leval and colleagues summarize the potential of DNA sequencing of tumors and cell-free plasma, epigenetic profiling, and single-cell analyses to inform clinical decision-making about diagnosis, prognosis, and treatment for patients with lymphoid neoplasms. Similarly, Duncavage and colleagues cover genomic profiling for myeloid neoplasms and the acute leukemias, focusing principally on somatic changes but also with emphasis on the emerging importance of germline gene mutations in certain diseases. Both articles provide up-to-date references for how to apply genomic information to practice.
Genomic profiling for clinical decision making in lymphoid neoplasms
Complementing the recently published Blood articles outlining the 2022 International Consensus Classifications for hematological malignancies (Vol. 140, Issue 11), this pair of Special Reports illustrates how molecular pathology can be applied to precision medicine. de Leval and colleagues summarize the potential of DNA sequencing of tumors and cell-free plasma, epigenetic profiling, and single-cell analyses to inform clinical decision-making about diagnosis, prognosis, and treatment for patients with lymphoid neoplasms. Similarly, Duncavage and colleagues cover genomic profiling for myeloid neoplasms and the acute leukemias, focusing principally on somatic changes but also with emphasis on the emerging importance of germline gene mutations in certain diseases. Both articles provide up-to-date references for how to apply genomic information to practice.
Patient-reported outcomes in ZUMA-7, a phase 3 study of axicabtagene ciloleucel in second-line large B-cell lymphoma
Elsawy et al present the patient-reported outcomes after axicabtagene ciloleucel (axi-cel) administered as second-line therapy in large B-cell lymphoma compared to salvage chemotherapy followed by autologous stem cell transplantation (ASCT) in the ZUMA-7 trial. In clinical responders, treatment with axi-cel delivers better quality-of-life and an earlier return to baseline functioning compared to salvage chemotherapy followed by ASCT. The results imply that, in addition to improving progression-free survival, axi-cel is better tolerated than the previous standard.
Loss of α4A- and β1-tubulins leads to severe platelet spherocytosis and strongly impairs hemostasis in mice
The discoid shape of platelets has always intrigued hematologists. Kimmerlin et al explore the relationship between shape and function in α4A- and β1-tubulin double knockout mice, revealing that spherical platelets are dysfunctional. Despite normal activation and secretion of granules in vitro, under flow conditions in vivo mutant platelets show reduced adhesion, diminished thrombus formation, and increased bleeding.
Prebiotic galactooligosaccharides interact with mouse gut microbiota to attenuate acute graft-versus-host disease
Previous studies suggest that gut microbiome disruption induced by chemotherapy, dietary deficiencies, and/or antibiotics are associated with increased incidence of acute graft-versus-host disease (aGVHD) following hematopoietic stem cell transplantation (HSCT). In a murine model of antibiotic-induced gut microbiome disruption, Holmes and colleagues show that oral administration of galactooligosaccharides (GOS) as a prebiotic attenuates lethal aGVHD, highlighting the crosstalk between diet and gut microbiota. Their data encourage clinical trials of GOS prebiotic diets during HSCT.
