Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12

PURPOSE: For patients with relapsed or refractory aggressive lymphoma, we hypothesized that gemcitabine-based therapy before autologous stem-cell transplantation (ASCT) is as effective as and less toxic than standard treatment. PATIENTS AND METHODS: We randomly assigned 619 patients with relapsed/refractory aggressive lymphoma to treatment with gemcitabine, dexamethasone, and cisplatin (GDP) or to dexamethasone, cytarabine, and cisplatin (DHAP). Patients with B-cell lymphoma also received rituximab. Responding patients proceeded to stem-cell collection and ASCT. Coprimary end points were response rate after two treatment cycles and transplantation rate. The noninferiority margin for the response rate to GDP relative to DHAP was set at 10%. Secondary end points included event-free and overall survival, treatment toxicity, and quality of life. RESULTS: For the intention-to-treat population, the response rate with GDP was 45.2%; with DHAP the response rate was 44.0% (95% CI for difference, -9.0% to 6.7%), meeting protocol-defined criteria for noninferiority of GDP (P = .005). Similar results were obtained in a per-protocol analysis. The transplantation rates were 52.1% with GDP and 49.3% with DHAP (P = .44). At a median follow-up of 53 months, no differences were detected in event-free survival (HR, 0.99; stratified log-rank P = .95) or overall survival (HR, 1.03; P = .78) between GDP and DHAP. Treatment with GDP was associated with less toxicity (P < .001) and need for hospitalization (P < .001), and preserved quality of life (P = .04). CONCLUSION: For patients with relapsed or refractory aggressive lymphoma, in comparison with DHAP, treatment with GDP is associated with a noninferior response rate, similar transplantation rate, event-free survival, and overall survival, less toxicity and hospitalization, and superior quality of life

Salvage chemotherapy and autologous stem cell transplantation for transformed indolent lymphoma: A subset analysis of NCIC CTG LY12

The treatment of transformed indolent lymphoma (TRIL) often includes salvage chemotherapy (SC) and autologous stem cell transplant (ASCT). NCIC CTG LY12 is a randomized phase 3 trial comparing gemcitabine, dexamethasone, and cisplatin (GDP) with dexamethasone, cytarabine, and cisplatin (DHAP) before ASCT. This analysis compares the results of SC and ASCT for TRIL with de novo diffuse large B-cell lymphoma (DLBCL). Six-hundred nineteen patients with relapsed/refractory aggressive non-Hodgkin lymphoma were randomized to GDP or DHAP; 87 patients (14%) had TRIL and 429 (69%) had DLBCL. The response rate to SC was 47% in TRIL and 45% in DL (P = .81). Transplantation rates were similar: TRIL 53% and DL 52% (P = 1.0). With a median follow-up of 53 months, 4 year overall survival was 39% for TRIL and 41% for DL (P = .78); 4 year event-free survival (EFS) was 27% for TRIL and 27% for DL (P = .83). Post-ASCT, 4-year EFS was 45% for TRIL and 46% for DL. Histology (TRIL or DL) was not a predictor of any outcome in multivariate models. Patients with relapsed or refractory TRIL and DLBCL have similar outcomes with SC and ASCT; this therapy should be considered the standard of care for patients with TRIL who have received prior systemic chemotherapy. NCIC CTG LY12 is registered at ClinicalTrials.gov as #NCT00078949.

Fatal interstitial lung disease associated with oral erlotinib therapy for lung cancer

<p>Abstract</p> <p>Background</p> <p>Erlotinib is a Human Epidermal Growth Factor Receptor Type 1/tyrosine kinase (EGFR) inhibitor which is used for non-small-cell lung cancer treatment. Despite that erlotinib is considered to have a favorable safety profile, adverse events such as interstitial lung disease (ILD) were reported in pivotal studies. The authors report the first histologically confirmed case of fatal ILD associated with erlotinib therapy.</p> <p>Case Presentation</p> <p>The medical record of a patient who developed fatal ILD after receiving erlotinib treatment was reviewed to identify the cause of death and other factors potentially contributive to this adverse outcome. A 55-year-old smoker with no evidence of pre-existing interstitial disease developed bilateral ILD and respiratory failure which could be explained only as a toxicity of erlotinib. He had a history of stage IV left upper lobe squamous-cell carcinoma for which he had received three successive regimens of chemotherapy (ifosfamide plus gemcitabine, docetaxel, mitomycin plus navelbine), followed five months later by erlotinib. At initiation of erlotinib treatment there were no radiological signs suggestive of ILD disease or apparent clinical signs of respiratory distress. While the patient completed two months with erlotinib therapy he developed bilateral interstitial infiltrates; despite discontinuation of erlotinib he was admitted with respiratory failure two weeks later. Diagnostic work up for other causes of pneumonitis including infectious diseases, congestive cardiac failure and pulmonary infraction was negative. Empiric treatment with oxygene, corticosteroids and later with cyclophosphamide was ineffective and the patient progressively deteriorated and died. The clinical and post-mortem examination findings are presented and the possible association relationship between erlotinib induced ILD and previous chemotherapy is discussed.</p> <p>Conclusion</p> <p>Physicians should be alert to the fact that erlotinib related ILD, although infrequent, is potential fatal. The association between selective EGFR-inhibitors and ILD should be further investigated.</p

Left sided inferior vena cava duplication and venous thromboembolism: case report and review of literature

The etiology of venous thromboembolism in young patients is frequently associated with hereditary coagulation abnormalities, immunologic diseases, and neoplasia. The advent of radiological advances, namely Computed Tomography (CT) scans and venography has identified vena cava malformations as a new etiologic factor worthy of consideration. In this case report, we describe the unusual occurrence of venous thromboembolism in association with a duplicated inferior vena cava. Duplications of the inferior vena cava (IVC) are seen with an incidence of 0.2% to 3.0% in the general population. Embryogenesis of the IVC is a complex process involving the intricate formation and regression of numerous anastomoses, potentially leading to various anomalies. We present a 23-year-old Caucasian woman with IVC duplication who developed a deep venous thrombosis and multiple pulmonary emboli. Anomaly of the IVC is a rare example of a congenital condition that predisposes to thromboembolism, presumably by favoring venous stasis. This diagnosis should be considered in patients under the age of 30 with spontaneous occurrence of blood clots

Clinical anticancer drug development: targeting the cyclin-dependent kinases

Cell division involves a cyclical biochemical process composed of several step-wise reactions that have to occur once per cell cycle. Dysregulation of cell division is a hallmark of all cancers. Genetic and epigenetic mechanisms frequently result in deranged expression and/or activity of cell-cycle proteins including the cyclins, cyclin-dependent kinases (Cdks), Cdk inhibitors and checkpoint control proteins. The critical nature of these proteins in cell cycling raises hope that targeting them may result in selective cytotoxicity and valuable anticancer activity

Multilevel Modeling to Predict Factors Influencing the Length of Stay for An Inpatient Malignant Hematology Service

Abstract Abstract 4733 Purpose: Inpatient care represents a significant cost and resource allocation issue for hospitals. The purpose of this study was to examine factors in an administrative dataset that might predict the length of stay (LOS) for inpatients with a variety of hematological malignancies and to create a simple predictive model. There is a lack of published models for this in malignant hematology patients. Methods: Data was obtained from the Discharge Abstract Database (DAD) maintained by Canadian Institute for Health Information (CIHI) for the years 2002–2005. The data abstracted included patient demographics, type and route of admission, length of stay, resource intensity weights (RIW) and a complexity code. The disease category/diagnosis is based on the case mix group (CMG) which is a simplified grouping of diseases based on the International Classification of Diseases (ICD) system. The Juravinski Hospital and Cancer Centre is a tertiary referral center dealing with all varieties of adult hematological malignancies including stem cell transplantation. The data for this study did not include patients who were treated with an allogeneic stem cell transplant. Potential factors collected on admission were modeled to be nested among individual patients using longitudinal multi-level modeling. Factors entered in the model included: age and age2, route of entry to the hospital (direct vs. emergency room vs. other), area of residence, gender, day of the admission (weekday vs. weekend) and diagnosis (CMG). We also added the number of previous admissions as a baseline variable. Institutional research ethics board approval was granted for this study. Results: Data was collected on 713 patients representing 1,739 admissions and 17,661 days of in-patient services. The number of admissions ranged from 1 to 15 with a mean of 2.5 and median 2.0 admissions per patient. The range for LOS was 1 to 155 days with mean of 10.6 days (SD 13.8) and median of 64 days. The median age of patients was 62.6 years with a range of 17–95 years, and 45% of patients were female. Thirty-nine percent of patients had a diagnosis related to a lymphoproliferative disorder or a chronic leukemia and 19 percent related to the administration of chemotherapy. Factors with non-significant B (slope) value were omitted from the model. Age is centered around the mean. Errors and residuals (μ , r) have a mean of zero and a normal distribution. Age and previous number of admissions were the most important factors in predicting LOS. The final model for estimated LOS is as follows: LOS = 3.9658+μ 0+(0.2068+μ 1)(age-65)+(4.508+μ 2)(number of previous admissions) +r The variances for the different residuals have been estimated from the model as: μ 0=73.82, μ 1=0.2436, μ 2=0.2436 and r=69.47. For each increment by 5 years above the average age, the LOS increases by 1 day and for each previous admission the LOS increases by 4.5 days. The Pseudo-R squared is approximately 0.50. Conclusion: Of the factors considered in this administrative database, age and the number of previous admissions were the only relevant factors at the time of admission which could predict LOS. This model represents a relatively simple method to estimate the LOS for patients with hematological malignancies admitted to a dedicated hematological unit. Such a model highlights patients at risk of prolonged LOS and may allow health care practitioners to focus on interventions geared towards shortening length of stay. Disclosures: No relevant conflicts of interest to declare. </jats:sec