Issue Archive

Hairy cell leukemia (HCL) is characterized by a high prevalence of BRAF V600E mutation, which renders it sensitive to the BRAF inhibitor vemurafenib. Purine nucleoside analogs induce complete response in 80-95% of patients, so vemurafenib is usually reserved for relapsed/ refractory (R/R) patients. Handa and colleagues report on the long-term follow-up of 36 patients in a previously reported study of limited-duration vemurafenib for R/R HCL, finding that response rates are high, but relapses off therapy are frequent; however, most patients respond to retreatment with vemurafenib.

Batty et al report on the long-term efficacy of adeno-associated vector (AAV)-mediated gene therapy as a treatment for severe canine hemophilia A. After a median follow-up of almost 11 years, persistent low-level factor VIII (FVIII) levels were seen in 6/6 responding dogs (2/8 dogs had no response), with improved bleeding rates and FVIII levels in the mild hemophilia range. Overall, this supports the long-term efficacy and safety of AAV-mediated gene therapy.

CD7 is expressed on many T-cell malignancies and is an attractive target for CAR T-cell therapy for T-cell leukemia/lymphoma, but concurrent CD7 expression on CAR T cells predisposes to cell loss through fratricide. Freiwan and colleagues report on selection to enrich CD7-negative T cells as targets for CAR T-cell engineering and demonstrate that they have enhanced antitumor activity, suggesting a potentially attractive strategy for optimizing CAR T-cell therapy for T-cell malignancies.

Kambhampati and colleagues examine the cost-effectiveness of the inclusion of polatuzumab vedotin (pola-R-CHP) in therapy for treatment-naïve diffuse large B-cell lymphoma. The POLARIX study showed a 6.5% improvement in 2-year progression-free survival (PFS) with no difference in overall survival using pola-R-CHP compared to R-CHOP. In their model, pola-R-CHP is cost-effective in 56.6% of iterations, suggesting marginal cost-effectiveness that is highly dependent on long-term PFS projections and the cost of CAR T-cell therapy.

Patients with chronic lymphocytic leukemia (CLL) and monoclonal B-lymphocytosis (MBL) respond poorly to the COVID-19 vaccination. Shen et al report on the incremental increase in successful immunization with repeated vaccination in 258 patients with CLL and MBL. With repeated redosing of the vaccine up to 6 doses, overall seroconversion is achieved in 94% of patients with CLL and 100% of patients with MBL, with concurrent increases in antibody levels and T-cell responses.

Initial testing for heparin-induced thrombocytopenia (HIT) depends on an enzyme-linked immunosorbent assay (ELISA) for antiplatelet factor-4 (PF4) antibodies, which is highly sensitive but can be nonspecific. Kanack and colleagues describe a novel functional assay for HIT using cryopreserved platelets to detect release of thrombospondin-1, a platelet α-granule protein in response to treatment with heparin or PF4. While several pitfalls need to be addressed, this assay could quicken the diagnosis of HIT and provide a more robust test feasible outside of reference laboratories.

Hod and colleagues report on the results of a double-blind randomized trial of intravenous iron vs placebo in nonanemic blood donors with iron depletion. The authors demonstrate that iron repletion does not improve cognition or well-being measures in donors, nor does it have an impact on red cell storage quality or posttransfusion red cell recovery.

Kong and colleagues demonstrate a close relationship between pathologic features of chronic autoimmune disease and chronic graft-versus-host disease (cGVHD). The authors report that peripheral T helper cells (Tph), an important contributor to autoimmune diseases, are expanded in patients with cGVHD. Tph expansion correlates with increased pathogenic tissue-resident T helper (Trh) cells, which form lymphoid aggregates in target tissues. They further show that Tph and Trh cells traffic between the peripheral blood and target tissues in GVHD in an expansion dependent on IL-21R-BCL6 signaling.