Publications

Histone deacetylase inhibitors (HDACi) are active agents for peripheral T-cell lymphoma (PTCL). Anecdotally angioimmunoblastic T-cell lymphoma (AITL) appears to respond better than PTCL-not otherwise specified (NOS) to HDACi. The new World Health Organization classification shows that a subgroup of PTCL carries similarities in phenotype and gene expression profiling to AITL, comparable to T follicular helper (TFH) cells. The disease might behave similarly to AITL when treated with HDACi. We analyzed 127 patients with AITL or PTCL-NOS treated with HDACi at relapse as a single agent or in combination. We re-reviewed the pathology of all PTCL-NOS to identify the TFH phenotype. Patients received HDACi at relapse as a single agent in 97 cases (76%, 59 TFH, 38 non-TFH) or in combination in 30 cases (24%, 18 TFH, 12 non-TFH) including duvelisib, lenalidomide, lenalidomide plus carfilzomib, and pralatrexate. Seven PTCL-NOS had TFH phenotype; 2 PTCL-NOS were reclassified as AITL. Overall response rate (ORR) was 56.5% (28.9% complete response [CR]) in TFH and 29.4% (19.6% CR) in non-TFH phenotype patients (P = .0035), with TFH phenotype being an independent predictor of ORR (P = .009). Sixteen patients sufficiently responded to HDACi or HDACi in combination with another agent to proceed directly to allogeneic transplantation; 1 of 16 responded to donor lymphocyte infusion (12 TFH, 4 non-TFH). Our results, although retrospective, support that HDACi, as a single agent or in combination, may have superior activity in TFH-PTCL compared with non-TFH PTCL. This differential efficacy could help inform subtype-specific therapy and guide interpretation of HDACi trials.

Shingrix is poorly immunogenic following allogeneic hematopoietic cell transplantation independent of age, CD4, and B-cell recovery. In hematopoietic cell transplantation recipients with antibody response to the vaccine, varicella zoster virus reactivation risk is not null.

We used the International Society for Heart and Lung Transplantation (ISHLT) Registry for Mechanically Assisted Circulatory Support (IMACS) database to examine 1) gender differences in post-left ventricular assist device (LVAD) mortality in the contemporary era and 2) preimplant clinical factors that might mediate any observed differences. Adults who received continuous-flow (CF)-LVAD from January 2013 to September 2017 (n = 9,565, age: 56.2 ± 13.2 years, 21.6% female, 31.1% centrifugal pumps) were analyzed. An inverse probability weighted Cox proportional hazards model was used to estimate association of female gender with all-cause mortality, adjusting for known covariates. Causal mediation analysis was performed to test plausible preimplant mediators mechanistically underlying any association between female gender and mortality. Females had higher mortality after LVAD (adjusted hazard ratio [HR]: 1.36; p < 0.0001), with significant gender × time interaction (p = 0.02). An early period of increased risk was identified, with females experiencing a higher risk of mortality during the first 4 months after implant (adjusted HR: 1.74; p < 0.0001), but not after (adjusted HR: 1.18; p = 0.16). More severe tricuspid regurgitation and smaller left ventricular end-diastolic diameter at baseline mediated ≈21.9% of the increased early hazard of death in females; however, most of the underlying mechanisms remain unexplained. Therefore, females have increased mortality only in the first 4 months after LVAD implantation, partially driven by worsening right ventricular dysfunction and LV-LVAD size mismatch.