Juan Pablo Alderuccio

Frontline brentuximab vedotin in breast implant-associated anaplastic large-cell lymphoma

We report a woman who developed BIA‐ALCL 9 years after saline implant placement. The lymphoma manifested as a mass lesion associated with axillary lymphadenopathy. She was successfully treated with brentuximab vedotin with minimal toxicity. Brentuximab vedotin may be a promising frontline therapeutic modality for patients with BIA‐ALCL.

Rapid complete response to blinatumomab as a successful bridge to allogeneic stem cell transplantation in a case of refractory Richter syndrome

Richter’s syndrome (RS), also known as Richter’s transformation, is defined as a transformation of chronic lymphocytic leukemia (CLL) to a more aggressive subtype, typically diffuse large B-cell ly...

Decreased survival in hepatitis C patients with monomorphic post-transplant lymphoproliferative disorder after liver transplantation treated with frontline immunochemotherapy

Abstract Post-transplant lymphoproliferative disorder (PTLD) develops in 1–3% of liver transplant recipients and no consensus exists about therapeutic management. From 2006 to 2016, 1489 liver transplants were performed at our institution with 20 patients (incidence 1.3%) developing PTLD. Hepatitis C virus (HCV) was the leading cause (n = 10) of liver transplant in PTLD patients. Diffuse large B-cell lymphoma was the most frequent histologic subtype (n = 17), and we report our experience in the management of these patients. Patients were treated with frontline immunochemotherapy without immunosuppression reduction. All evaluable patients achieved a complete remission. Statistically significant decreased survival was identified in HCV-positive patients. Six patients (60%) exhibited increases in HCV RNA levels during therapy. Four patients (40%) developed graft failure and three of them (30%) died from liver dysfunction. This is the first study providing evidence of decreased survival in HCV-positive PTLD patients after liver transplant receiving immunochemotherapy.

Risk Factors for Transformation to Higher-Grade Lymphoma and Its Impact on Survival in a Large Cohort of Patients With Marginal Zone Lymphoma From a Single Institution

PURPOSE Given the paucity of data on higher-grade transformation (HGT) to aggressive lymphoma in patients with marginal zone lymphoma (MZL), we report on a large cohort of patients, identify risk factors, and determine HGT impact on overall survival (OS). METHODS We analyzed 453 patients with biopsy-proven MZL seen at our institution between 1995 and 2016. Kaplan-Meier, Cox proportional hazards regression, and competing risk methods were used in analyses of time-to-event outcomes. RESULTS Thirty-four patients (7.5%) had biopsy-proven HGT to diffuse large B-cell lymphoma, including seven (21%) diagnosed at the time of initial MZL diagnosis. Among 27 incident patients, median time to HGT was 29 months (range, 1.3 to 135 months). Higher risk of HGT was observed in those with nodal/splenic MZL (subdistribution hazard ratio [SHR], 2.60; P = .023). On multivariable competing risk analysis, elevated lactate dehydrogenase (SHR, 2.71), more than four nodal sites (SHR, 2.97), and failure to achieve complete remission (CR) after initial treatment (SHR, 3.76) conveyed significantly higher risk for HGT ( P < .02). International Prognostic Index (IPI), Follicular Lymphoma IPI, and Mucosa-Associated Lymphoid Tissue Lymphoma IPI were only significant predictors of HGT univariably. Patients with HGT had shorter OS (5-year rate, 65% v 86%; P < .001). Patients who presented with HGT within 12 months since MZL diagnosis had shorter OS than those with HGT at MZL diagnosis combined with those with HGT more than 12 months later (4-year rate, 43% v 81%, P < .001). Non-CR and higher scores of IPI, Follicular Lymphoma IPI, and Mucosa-Associated Lymphoid Tissue Lymphoma IPI were the main significant predictors for shorter progression-free survival and OS. CONCLUSION Failure to achieve CR after initial treatment, elevated lactate dehydrogenase, and more than four nodal sites at the time of MZL diagnosis are the main predictors of increased risk of HGT. Patients with HGT have shorter OS.

Smoothened stabilizes and protects TRAF6 from degradation: A novel non-canonical role of smoothened with implications in lymphoma biology

Tumor necrosis factor receptor-associated factor 6 (TRAF6), an (K63) E3-ligase, plays a role in many biological processes and its activity is relevant in diffuse large B cell lymphoma (DLBCL) biology. Although molecules that trigger TRAF6 activation have been defined, those that stabilize TRAF6 and/or enhance TRAF6 function remain largely unclear. We found that TRAF6 amplifies pAKT signaling in DLBCL. Moreover, TRAF6 activation and stabilization of its ubiquitination profile are facilitated by smoothened (SMO), signal transducer of canonical Hedgehog signaling. Here, we report that SMO is needed to facilitate and maintain TRAF6-dependent elevated pAKT levels, and that the SMO/TRAF6 axis contributes to doxorubicin resistance in DLBCL. Mechanistically, we found that SMO, through its C-terminal tail, stabilizes and protects TRAF6 from degradation, an effect mediated by ubiquitin-specific protease-8. Moreover, this functional link between SMO and TRAF6 is reflected in DLBCL patients where high expression of both molecules correlates with poor prognosis. In summary, our study reveals a novel cell survival mechanism in which SMO stabilizes and protects TRAF6 from degradation. The axis SMO/TRAF6/AKT is highly relevant in the biology of DLBCL and is involved in doxorubicin resistance.

Characteristics and outcomes of lymphoblastic lymphoma – the University of Miami experience

Juan Pablo Alderuccio, Pooja Amarapurkar, Jennifer R. Chapman, Francisco Vega and Izidore S. Lossos Department of Medicine, Division of Hematology–Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Medicine, Division of Internal Medicine, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Pathology and Laboratory Medicine, Division of Hematopathology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA

Hepatosplenic T-cell lymphoma associated with membranoproliferative glomerulonephritis

Glomerulonephritis (GN) is an uncommon complication of lymphoma which has been most commonly described in Hodgkin lymphoma (HL); however, association between GN and non-Hodgkin lymphoma (NHL) is al...