Mi-Mi Shu

A phase 2 study of methotrexate, etoposide, dexamethasone, and pegaspargase chemotherapy for newly diagnosed, relapsed, or refractory extranodal natural killer/T‐cell lymphoma, nasal type: a multicenter trial in Northwest China

The nasal type of extranodal natural killer/T‐cell lymphoma is a rare aggressive lymphoma with poor prognosis. To discover a successful treatment, we investigated the efficacy and safety of chemotherapy with methotrexate, etoposide, dexamethasone, and polyethylene glycol‐asparaginase (MESA). Three cycles of MESA were administered to 46 patients with new or relapsed/refractory natural killer/T‐cell lymphoma. Complete response after 3 treatment cycles was 43.5%, the overall response rate was 87%, and 2‐year overall survival was 83.4%. Complete response was significantly better for newly diagnosed patients than for patients with relapsed/refractory disease. Patients with newly diagnosed disease had a significantly better overall response rate after 1, but not after 2 or 3 treatment cycles. Overall survival and progression‐free survival did not differ over 2 years. Grade 1/2 toxicities were frequent, but MESA was associated with fewer grade 3/4 events or treatment‐related deaths. These results will require confirmation in larger prospective trials.

Natural Killer/T Cell Lymphoma, Nasal Type: A Retrospective Clinical Analysis in North-Western China

Background: Extranodal natural killer (NK)/T cell lymphoma (ENKTL) is an aggressive non-Hodgkins lymphoma with high mortality and poor prognosis despite radiotherapy and chemotherapy. The current analysis aimed to assess the pathological features, clinical features, and prognostic indicators of ENKTL. Material and Methods: 120 ENKTL patients were analyzed for pathologic diagnosis and clinical disease manifestations from April 2007 to October 2012. Complete remission, 2-year overall survival, and progression-free survival were analyzed. Results: Compared with the nasal group, a greater percentage of patients in the non-nasal group intended to receive autologous stem cell transplantation had Epstein-Barr virus (EBV) DNA, Ann Arbor stage IV, Ki-67 expression ≥ 60%, and abnormal ferroprotein and β-microglobulin levels. The rate of complete remission in the non-nasal group was higher than that in the nasal group. The overall survival rate was 74.9% at 24 months. Patients receiving chemotherapy and radiotherapy were more likely to have disease progression compared with patients who received chemotherapy or radiotherapy alone. Conclusions: Further understanding the pathological and clinical features of ENKTL will be critical for moving forward. Ki-67, β-microglobulin, EBV DNA, and primary site prognostic indicators may be useful to stratify patients into different risk groups, to gain insight into patient-specific treatments, and to potentially improve survival.

DNA damage response-initiated cytokine secretion in bone marrow stromal cells promotes chemoresistance of myeloma cells

Abstract Acquisition of chemoresistance accounts for a major cause of chemotherapy failure for multiple myeloma (MM). Bone marrow stromal cells (BMSCs) are considered to play a pivotal role in modulating drug resistance of MM cells. However, the underlying mechanism whereby BMSCs, particularly damaged stromal cells, affects chemoresistance has not been identified yet. Here, we show exposure to doxorubicin doxorubicin (Dox) induced dramatic ATM (ataxia-telangiectasia-mutated)-dependent DNA damage response (DDR) and increased secretion of interleukin (IL)-6 in HS-5 cell line and primary BMSCs derived from healthy donors. Specifically, IL-6-containing conditioned media (CM) derived from Dox-pretreated stromal cells displayed significant protective effect on Dox-induced apoptosis of MM cells. Also, treatment of BMSCs with ATM kinase inhibitor markedly reduced IL-6 secretion and concurrently, partially reversed CM-mediated chemoresistance in myeloma cells. These data indicate that DNA-damaging drug triggers an ATM-dependent DDR in BMSCs, leading to increased cytokine secretion and resistance of myeloma cells to chemotherapy-induced apoptosis.

Distribution of lymphoid neoplasms in Northwest China: Analysis of 3244 cases according to WHO classification in a single institution

To explore the distribution of lymphoid neoplasms in Northwest China, the clinical and pathological data of lymphoma patients from 2006 to 2014 were analyzed according to the WHO classification in Xijing Hospital. Of the 3244 cases, mature B-cell neoplasms occupied 60.7%, while mature T/NK-cell neoplasms and Hodgkins lymphomas (HL) occupied 26.2% and 8.1%, respectively. The most common subtype of lymphoma was diffuse large B-cell lymphoma (35.0%), followed by extranodal NK/T-cell lymphoma, nasal type (ENKTCL) (12.9%) and marginal zone B-cell lymphoma (7.8%). Mixed cellularity (34.0%) was the most common subtype of HL. The especially high proportion of ENKTCL was the most outstanding feature of our study in comparison to previous reports. The mean age of all lymphoid neoplasms cases was 51years and most subtypes showed male predominance, with an average male-female ratio of 1.6. Extranodal lymphomas took up about 60% of all cases and gastrointestinal tract was the most frequently involved site. In conclusion, the distribution of lymphoid neoplasms of Northwest China showed some features similar to previous reports of China and other countries, but some subtypes presented distinct features.

A Study to Compare the Efficacy and Safety of Obinutuzumab + Venetoclax versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia (CLL14)

This open-label, multicenter, randomized phase III study is designed to compare the efficacy and safety of a combined regimen of obinutuzumab and venetoclax versus obinutuzumab + chlorambucil in patients with chronic lymphocytic leukemia (CLL) and coexisting medical conditions. The anticipated time on study treatment will be approximately 1 year and the follow-up period will be up to 5 years.

Optimale Mobilisierungsstrategien für den individuellen Patienten

Die autologe Stammzelltransplantation ist eine etablierte Therapie bei Patienten mit multiplem Myelom oder Lymphomen. Für einen optimalen Therapieerfolg ist eine ausreichende Stammzellmobilisierung essentiell. Ist die Mobilisierung mit dem Granulozyten-Kolonien stimulierenden Faktor (G-CSF) nach Induktionschemotherapie nicht erfolgreich, kann die Stammzellernte mit zusätzlicher PlerixaforGabe gesteigert werden. Bei einem von der Firma Sanofi gesponserten Workshop gingen Prof. Dr. Kai Hübel, Uniklinik Köln, und Dr. Patrick Wuchter, Universitätsklinikum Heidelberg, im Rahmen des COSTEM (Controversies in Stem Cell Transplantation and Cellular Therapies)-Kongresses auf aktuelle Fragen der Stammzellmobilisierung ein.

Abirateronacetat: 43 Monate Überleben bei frühem Beginn

Die Entwicklung von Resistenzen ist auch unter der modernen antihormonellen Therapie des metastasierten kastrationsresistenten Prostatakarzinoms (mCRPC) möglich. Handelt es sich um Kreuzresistenzen, beeinträchtigen sie womöglich die Wirksamkeit von Folgetherapien. Daher stellt sich die Frage, welche Sequenz einen optimalen Lebenszeitgewinn für den Patienten erzielen könnte. Darüber hinaus gibt es aktuelle Diskussionen zum optimalen Therapiebeginn. Nach einer Subgruppenanalyse der Zulassungsstudie für den Einsatz nach Androgenentzugstherapie profitieren die Patienten bei einer Behandlung mit Abirateronacetat (Zytiga®) plus Prednison/Prednisolon womöglich davon, wenn sie diese noch bei relativ niedrigem PSA-Wert und somit früh nach Versagen der Kastration im Rahmen der Indikation erhalten [1].