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Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Preoperative chemotherapy improves the outcome in patients with colorectal cancer with liver metastases. In the current study, the authors evaluated the activity of a conversion treatment with the combination of capecitabine plus oxaliplatin (XELOX) used in association with panitumumab in patients with unresectable, liver-only, metastatic colon cancer., Methods: Chemotherapy-naive patients with unresectable liver metastases from colon cancer with no other metastatic disease sites were enrolled. All patients received upfront therapy with XELOX plus panitumumab (P-XELOX) and were reevaluated for resectability every 4 cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints were overall survival (OS), progression-free survival, the percentage of patients whose disease became radically resectable, and the safety of the P-XELOX combination., Results: A total of 49 patients were recruited, 35 of whom had wild-type KRAS (wtKRAS) and 14 of whom (who were enrolled before study amendment) had unknown (9 patients) or mutated (5 patients) KRAS mutational status. Forty-six patients were evaluable for response. After conversion P-XELOX therapy, the ORR in the general population was 54%, with 2 complete responses, 23 partial responses, and 14 cases of stable disease. In patients with wtKRAS, the ORR of the patients reached 65% (2 CRs and 19 PRs), which allowed 15 patients with initial unresectable liver metastasis to be reclassified as having resectable disease. Survival analysis demonstrated a median progression-free survival of 8.5 months and a median OS of 21.9 months. Patients who underwent surgery were found to have a significantly better OS when compared with those who did not undergo surgery (P < .001). Overall, toxicities were found to be predictable and manageable, with the most common being cutaneous, gastrointestinal, and neurologic toxicities., Conclusions: Conversion P-XELOX therapy yields high response and resectability rates for patients with metastatic colon cancer with extensive liver involvement., (Copyright © 2013 American Cancer Society.)

Breast cancer is a major health issue in developed countries. Overexpression of HER2, a member of epidermal growth factor receptor family, occurs in 20%-30% of breast cancers. HER2 drives the cancer cells to develop a more aggressive phenotype, to metastasize to viscera and central nervous system, and to be less sensitive to chemotherapeutic agents. Trastuzumab (Herceptin®) is a monoclonal antibody directed against the extracellular domain of HER2. As single agent or with chemotherapy, trastuzumab improves survival of HER2-positive breast cancers. In the past years, trastuzumab has completely revolutionized the scenario of the treatment of HER2-positive breast cancer, representing one of the most remarkable examples of targeted therapy in oncology. However, issues such as the best chemotherapeutic companion to associate with trastuzumab, cardiac toxicities, and clinical resistance still require tremendous efforts by researchers. Here, we review pharmacology, efficacy studies, and toxicities of trastuzumab in metastatic breast cancer. Moreover, we provide some insights on resistance to therapy. Finally, we briefly discuss trastuzumab's place in the clinical setting.

We describe an automated system for high-resolution profiling of human mitochondrial DNA (mtDNA) based upon multiplexed polymerase chain reaction (PCR) followed by desolvation and direct analysis using electrospray ionization mass spectrometry (PCR/ESI-MS). The assay utilizes 24 primer pairs that amplify targets in the mtDNA control region, including the hypervariable regions typically sequenced in a forensic analysis. Profiles consisting of product base compositions can be stored in a database, compared to each other, and compared to sequencing results. Approximately 94% of discriminating information obtained by sequencing is retained with this technique. The assay is more discriminating than sequencing minimum HV1 and HV2 regions because it interrogates more of the mitochondrial genome. A profile compared to a population database can be subjected to the same statistics used for assessing the significance of concordant mtDNA sequences. The assay is not hindered by length heteroplasmy, can directly analyze template mixtures, and has a sensitivity of <25 pg of total DNA per reaction. Analysis of 3331 independent trials of the same sample over 28 months produced an average mass measurement uncertainty of 10.1 +/- 8.0 ppm, with >99% of trials producing a full profile with automated analysis. The technique has direct application to analysis of forensic biological evidence.