Clinical prognostic factors and outcomes of essential thrombocythemia when transformed to myelodysplastic syndromes and acute myeloid leukemia.

Transformation of essential thrombocythemia (ET) to myelodysplastic syndromes or acute myeloid leukemia is infrequent, comprising 1-5% of cases with dismal clinical outcome. Studies on prognosis in ET patients with leukemic transformation are limited. The large cohort included 40 patients (1990-2014) with ET transformation (median age of 59 years, M:F of 1:1). Median time from ET diagnosis to transformation was 76 months (26-481) with median follow-up time of 15 years. Advanced age, myelofibrosis (grade 2-3), and leukocytosis at the time of transformation were associated with inferior OS from transformation (p<0.05). Given rarity of the clinical scenario, multicenter efforts are encouraged.

Association of Lymphomagenesis and the Reactivation of Hepatitis B Virus in Non-Hodgkin Lymphoma.

BACKGROUND: Hepatitis B virus (HBV) has been associated with the development of non-Hodgkin lymphoma (NHL) and can be reactivated in patients being treated for NHL. METHODS: Articles published between 2000 and 2015 that discussed an association between NHL and HBV, mechanisms of HBV induction of NHL, and HBV reactivation in patients with NHL were reviewed and the results compiled to help health care professionals better understand the risk of developing NHL in HBV-seropositive individuals, describe potential etiologies by which HBV infection may lead to lymphomagenesis, and highlight the recent medical literature with respect to the reactivation of HBV in the setting of NHL. RESULTS: An association exists between HBV infection and NHL development. Immunosuppression due to HBV, chronic viral stimulation, and dysregulation of the immune system are possible ways in which lymphoma can develop in patients with HBV infection. All patients being treated with anti-CD20 antibodies or those from or living in HBV-endemic regions should be tested for hepatitis B surface antigen, core antibody, and surface antibody prior to initiating therapy. HBV DNA polymerase chain reaction (PCR) may also be useful in certain cases. Among HBV-seropositive patients or those with detectable HBV DNA, prophylaxis with an antiviral agent should be initiated for 1 year after NHL therapy. HBV DNA PCR monitoring should be undertaken each month during the course of treatment and every 3 months after treatment for a 1-year duration. CONCLUSIONS: Health care professionals should become more comfortable treating these high-risk patients with NHL as they become more informed about potential lymphomagenesis and the reactivation of HBV.

Phase I study of combination of pasireotide LAR + gemcitabine in locally advanced or metastatic pancreatic cancer.

PURPOSE: Pasireotide LAR (SOM230 LAR) is a cyclohexapeptide engineered to bind to multiple somatostatin receptor subtypes to mimic the action of naturally occurring somatostatin with higher affinity to these receptors than octreotide and is a potent inhibitor of insulin-like growth factor-1 (IGF-1). Somatostatin receptors and IGF receptors are highly expressed in pancreatic cancer, thereby potentially making it a valuable target. This phase I study evaluated safety, tolerability and preliminary tumor response of pasireotide LAR in combination with gemcitabine in locally advanced or metastatic pancreatic cancer. METHODS: Patients with previously untreated metastatic pancreatic cancer were included. A 3 + 3 dose-escalation design was used. Patients received gemcitabine on days 1, 8 and 15 and pasireotide LAR IM monthly in a 28-day cycle. Two dose levels of pasireotide LAR were planned: 40 mg IM and 60 mg. Cohort was expanded by ten more patients at the highest tested dose to further assess the safety and efficacy. RESULTS: Twenty patients were consented on this trial, and 16 patients were evaluable for safety and efficacy. No dose-limiting toxicities were observed. Two out sixteen patients (12%) had partial response, and nine of sixteen (56%) had stable disease as best response. Median progression-free survival was 4.1 months (range 1-16 months), and median overall survival was 6.9 months (range 1-25 months). Most common grade 3 or 4 toxicities were hyperglycemia (n = 5), hyperbilirubinemia (n = 1) and thrombocytopenia (n = 2). Median baseline IGF-1 level was lower in patients with stable disease than in those with progressive disease (63 vs 71 ng/ml). CONCLUSION: Pasireotide in combination with gemcitabine was well tolerated with disease control rate of 68%. Larger trials are needed in the future to establish its efficacy in the treatment of pancreatic cancer. CLINICAL TRIAL: NCT01385956.

Salvage therapy with high-dose chemotherapy and peripheral blood stem cell transplant in patients with primary mediastinal nonseminomatous germ cell tumors.

Salvage therapy with high-dose chemotherapy (HDCT) and bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) has curative potential in patients with recurrent germ cell tumor. However, patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCTs) have had poor results with any form of salvage chemotherapy including HDCT. We switched from BMT to PBSCT in 1996. One hundred sixteen of 184 patients (63%) with recurrent or refractory germ cell tumors treated from 1996 to 2004 were alive and continuously disease-free. PMNSGCTs were excluded from that study because of poor results in the patient population with HDCT and BMTs. In 2006, we resumed treating patients with recurrent PMNSGCT with 2 consecutive courses of HDCT consisting of carboplatin 700 mg/m(2) × 3 plus etoposide 750 mg/m(2) × 3 and each followed by an infusion of autologous peripheral-blood hematopoietic stem cells with a second course 3 to 4 weeks later. Twelve patients were treated: 11 as initial salvage chemotherapy and 1 as fourth-line therapy. Eight of the 12 patients had major thoracic resections at the time of the relapse after initial chemotherapy. Three of the 12 patients achieved complete remission (CR; 10, 15, and 50 months' duration). One patient remains continuously with no evidence of disease (NED) at 50 months. An additional patient is currently NED at 52 months with HDCT and subsequent surgery. Median survival for the 12 patients was 11 months (range, 4-52 months). Results with tandem transplant for recurrent PMNSGCT remain poor compared to primary testis cancer, but durable CR and probable cure can be achieved in a small subset of patients with PMNSGCT. In our opinion, salvage surgical resection if anatomically feasible is the preferred option for patients with PMNSGT progressing after initial chemotherapy.