bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies.
Authors: Khouri I F , Keating M , Körbling M , Przepiorka D , Anderlini P , O'Brien S , Giralt S , Ippoliti C , von Wolff B , Gajewski J , Donato M , Claxton D , Ueno N , Andersson B , Gee A , Champlin R 
Published: February 2017

PURPOSE To investigate the use of a nonmyeloablative fludarabine-based preparative regimen to produce sufficient immunosuppression to allow engraftment of allogeneic stem cells and induction of graft-versus-leukemia/lymphoma (GVL) as the primary treatment modality for patients with chronic lymphocytic leukemia (CLL) and lymphoma. PATIENTS AND METHODS Fifteen patients were studied. Six patients were in advanced refractory relapse, and induction therapy had failed in two patients. Patients with CLL or low-grade lymphoma received fludarabine 90 to 150 mg/m2 and cyclophosphamide 900 to 2,000 mg/m2. Patients with intermediate-grade lymphoma or in Richter's transformation received cisplatin 25 mg/m2 daily for 4 days; fludarabine 30 mg/m2; and cytarabine 500 mg/m2 daily for 2 days. Chemotherapy was followed by allogeneic stem-cell infusion from HLA-identical siblings. Patients with residual malignant cells or mixed chimerism could receive a donor lymphocyte infusion of 0.5 to 2 x 10(8) mononuclear cells/kg 2 to 3 months posttransplantation if graft-versus-host disease (GVHD) was not present. RESULTS Eleven patients had engraftment of donor cells, and the remaining four patients promptly recovered autologous hematopoiesis. Eight of 11 patients achieved a complete response (CR). Five of six patients (83.3%) with chemosensitive disease continue to be alive compared with two of nine patients (22.2%) who had refractory or untested disease at the time of study entry (P = .04). CONCLUSION These findings indicate the feasibility of allogeneic hematopoietic transplantation with a nonablative preparative regimen to produce engraftment and GVL against lymphoid malignancies. The ability to induce remissions with donor lymphocyte infusion in patients with CLL, Richter's, and low-grade and intermediate-grade lymphoma is direct evidence of GVL activity against these diseases. This approach appears to be most promising in patients with chemotherapy-responsive disease and low tumor burden.
Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program.
Authors: McLaughlin P , Grillo-López A J , Link B K , Levy R , Czuczman M S , Williams M E , Heyman M R , Bence-Bruckler I , White C A , Cabanillas F , Jain V , Ho A D , Lister J , Wey K , Shen D , Dallaire B K 
Published: February 2017

PURPOSE The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. PATIENTS AND METHODS This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. RESULTS From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. CONCLUSION The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.
Quality-adjusted time without symptoms or toxicity analysis of interferon maintenance in multiple myeloma.
Authors: Zee B , Cole B , Li T , Browman G , James K , Johnston D , Sugano D , Pater J 
Published: February 2017

PURPOSE In a randomized trial conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), interferon alpha-2b (IFN) maintenance therapy (2 mU/m2 subcutaneously three times per week) after successful induction with melphalan and prednisone was found to prolong time to progression in patients with multiple myeloma. A favorable effect on survival was also present, but this difference was of borderline significance. However, IFN toxicity was a concern. To evaluate the trade-off between the clinical benefits of IFN and the associated toxicity, we applied the method of quality-adjusted time without symptoms or toxicity (Q-TWiST). MATERIALS AND METHODS Three clinical health states were defined in this analysis: time with toxicity (TOX), time without disease relapse or toxicity (TWiST), and time following disease relapse (REL). Toxicity information for IFN had been collected using patient-completed diaries so the actual duration of each adverse event could be determined. The health states TOX and REL were weighted using utility scores to account for a possible decrement in quality of life, a weighted sum of the health state durations is used as a measure of quality-adjusted time. RESULTS The health state durations were calculated at 72 months median follow-up. Patients in the IFN group gained an average of 9.8 months without disease relapse (P = .001) and 5.8 months of overall survival (P = .074) versus the control group. However, the IFN group suffered an average of 4.1 months of moderate or worse toxicity (P < .001). CONCLUSION The clinical benefits of IFN outweigh the negative effects associated with treatment toxicity for a wide range of plausible utilities.
Decision-making about breast cancer susceptibility testing: how similar are the attitudes of physicians, nurse practitioners, and at-risk women?
Authors: Geller G , Bernhardt B A , Doksum T , Helzlsouer K J , Wilcox P , Holtzman N A 
Published: February 2017

PURPOSE To determine what consumers and providers would want to discuss about breast cancer susceptibility testing (BCST) and their preferred role in testing decisions. METHODS We surveyed 426 at-risk women, 143 nurse practitioners, and 296 physicians in five specialties in Maryland. RESULTS All groups believe it is important to discuss how the chance of breast cancer can be reduced and what the chances are of getting breast cancer if the test is positive. Both provider groups attributed more importance than consumers to discussing whether cancer can occur if the test is negative. Discussing the risk of depression and anxiety was more important to providers than consumers. Eighty-two percent of women would want their providers to make a recommendation about testing, but only 43% of nurse practitioners and 68% of physicians would do so. Eighteen percent of physicians underestimated the importance of informed consent for testing and 34% of discussing the risk of insurance discrimination. Fewer than 6% of women, if found to have a mutation, would be likely to undergo prophylactic mastectomy, whereas 12% of nurse practitioners and 34% of physicians would be likely to recommend such surgery. One third of respondents in all three groups supported testing a 13-year old daughter of a mutation-carrier. CONCLUSION Physicians should place greater value on informed consent and discussing practical aspects of testing, and physicians and nurse practitioners should pay more attention to the limitations of testing children, insurance discrimination, and consumers' desire for provider recommendations. In light of the limited discordance between nurse practitioners and consumers, nurse practitioners can play an increasing role in education and counseling about BCST.
Correlation of specific immune responses with survival in melanoma patients with distant metastases receiving polyvalent melanoma cell vaccine.
Authors: Hsueh E C , Gupta R K , Qi K , Morton D L 
Published: February 2017

PURPOSE The mechanisms that underlie the clinical efficacy of melanoma vaccines are not well understood. We hypothesized that the type and strength of the immune response generated by CancerVax (John Wayne Cancer Institute, Santa Monica, CA), a polyvalent melanoma cell vaccine (PMCV), might be correlated with its effect on overall survival (OS). PATIENTS AND METHODS Seventy-seven patients began PMCV therapy after complete surgical resection of distant metastatic melanoma. During the first two treatments, PMCV was administered with bacille Calmette-Guerin (BCG). Blood was drawn at 0, 2, 4, 8, and 12 weeks to measure serum titers of immunoglobulin G (IgG) and IgM antibodies against a tumor-associated 90-kd glycoprotein antigen (TA90) expressed on most melanoma cells, including those of PMCV. Cellular immune response to PMCV was assessed by delayed-type hypersensitivity (DTH). General immune competence was assessed by skin tests to purified protein derivative (PPD), mumps, and candida. RESULTS Median follow-up time was 31.5 months. Within the first 12 weeks of PMCV immunotherapy, there was a significant increase in the anti-TA90 IgM (P=.0001) and IgG titers (P=.0001), and in the DTH response to PMCV (P=.0001). Univariate analysis showed that high anti-TA90 IgM titer and strong PMCV-DTH were associated with improved survival (P=.051 and .0173, respectively), whereas elevated anti-TA90 IgG was correlated with decreased survival (P=.0119). Multivariate analysis considering clinical variables and PMCV immune responses identified anti-TA90 IgM, anti-TA90 IgG, and PMCV-DTH as significant independent variables influencing survival following PMCV immunotherapy (P=.0342, .0105, and .0082, respectively). These responses to PMCV were not correlated with immune responses to BCG and therefore were not a manifestation of general immune competence for responses to unrelated antigens. The median survival time and 5-year survival rate were more than 76 months and 75%, respectively, if both anti-TA90 IgM and PMCV-DTH responses were strong (> or = 800 and > or = 7 mm, respectively; n=29); 32 months and 36%, respectively, if only one response was strong (n=35); and 19 months and 8%, respectively, if neither was strong (n=13) (P < .0001). CONCLUSION PMCV induces both humoral and cell-mediated immune responses to melanoma-associated tumor antigens, the type and strength of which appear to be directly related to its therapeutic efficacy.
Open, randomized, multicenter trial of raltitrexed versus fluorouracil plus high-dose leucovorin in patients with advanced colorectal cancer. Tomudex Colorectal Cancer Study Group.
Authors: Cocconi G , Cunningham D , Van Cutsem E , Francois E , Gustavsson B , van Hazel G , Kerr D , Possinger K , Hietschold S M 
Published: February 2017

PURPOSE To compare raltitrexed (Tomudex; Zeneca Pharmaceuticals Ltd, Macclesfield, United Kingdom) a direct, specific thymidylate synthase (TS) inhibitor with fluorouracil (5-FU) plus high-dose leucovorin (LV) as first-line treatment for advanced colorectal cancer (ACC). PATIENTS AND METHODS A total of 495 patients were randomized to raltitrexed (3 mg/m2) once every 3 weeks or 5-FU (400 mg/m2) plus LV (200 mg/m2) daily for 5 days every 4 weeks. RESULTS The randomized groups were well balanced demographically. With a minimum 17-month follow-up, median survival was comparable between groups (10.9 months raltitrexed v 12.3 months 5-FU/LV; hazards ratio, 1.15; 95% confidence interval [CI], 0.93 to 1.42; P=.197), although time to progression was statistically significantly shorter in the raltitrexed group. Overall objective responses were comparable (19% raltitrexed v 18% 5-FU/LV), with more than 50% of patients in each group having stable disease. Significantly less World Health Organization (WHO) grade 3 and 4 stomatitis (2% v 16%, P < .001) and a reduced incidence of leukopenia (6% v 13%) and diarrhea (10% v 19%) occurred in the raltitrexed group (particularly at cycle 1 ). This resulted in fewer dose reductions at cycle 2 (4% raltitrexed v 28% 5-FU/LV) and early quality-of-life (QoL) benefits for raltitrexed patients. Reversible, clinically insignificant increases in transaminases were reported in 13% of raltitrexed patients. Palliative benefits of weight gain, improved performance status, and reduced disease-related symptoms were evident in both groups. CONCLUSION Raltitrexed is confirmed as an effective option in the first-line palliative management of ACC, with comparable efficacy to and tolerability advantages (in terms of reduced incidence of stomatitis, diarrhea, and leukopenia) over 5-FU/LV. Raltitrexed has the added convenience of an every 3 weeks dosing schedule.
Phase I trial of continuous infusion flavopiridol, a novel cyclin-dependent kinase inhibitor, in patients with refractory neoplasms.
Authors: Senderowicz A M , Headlee D , Stinson S F , Lush R M , Kalil N , Villalba L , Hill K , Steinberg S M , Figg W D , Tompkins A , Arbuck S G , Sausville E A 
Published: February 2017

PURPOSE We conducted a phase I trial of the cyclin-dependent kinase inhibitor, flavopiridol (National Service Center [NSC] 649890), to determine the maximum-tolerated dose (MTD), toxicity profile, and pharmacology of flavopiridol given as a 72-hour infusion every 2 weeks. PATIENTS AND METHODS Seventy-six patients with refractory malignancies with prior disease progression were treated with flavopiridol, with first-cycle pharmacokinetic sampling. RESULTS Forty-nine patients defined our first MTD, 50 mg/m2/d x 3 with dose-limiting toxicity (DLT) of secretory diarrhea at 62.5 mg/kg/d x 3. Subsequent patients received antidiarrheal prophylaxis (ADP) to define a second MTD, 78 mg/m2/d x 3 with DLT of hypotension at 98 mg/m2/d x 3. Other toxicities included a proinflammatory syndrome with alterations in acute-phase reactants, particularly at doses >50 mg/ m2/d x 3, which in some patients prevented chronic therapy every 2 weeks. In some patients, ADP was not successful, requiring dose-deescalation. Although approximately 70% of patients displayed predictable flavopiridol pharmacology, we observed unexpected interpatient variability and postinfusion peaks in approximately 30% of cases. At the two MTDs, we achieved a mean plasma flavopiridol concentration of 271 nM (50 mg/m2/d x 3) and 344 nM (78 mg/m2/d x 3), respectively. One partial response in a patient with renal cancer and minor responses (n=3) in patients with non-Hodgkin's lymphoma, colon, and renal cancer occurred. CONCLUSION The MTD of infusional flavopiridol is 50 mg/m2/d x 3 with dose-limiting secretory diarrhea at 62.5 mg/m2/d x 3. With ADP, 78 mg/m2/d x 3 was the MTD, with dose-limiting hypotension at 98 mg/m2/d x 3. Based on chronic tolerability, 50 mg/m2/d x 3 is the recommended phase II dose without ADP. Antitumor effect was observed in certain patients with renal, prostate, and colon cancer, and non-Hodgkin's lymphoma. Concentrations of flavopiridol (200 to 400 nM) needed for cyclin-dependent kinase inhibition in preclinical models were achieved safely.
Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants.
Authors: Gerald W L , Ladanyi M , de Alava E , Cuatrecasas M , Kushner B H , LaQuaglia M P , Rosai J 
Published: February 2017

PURPOSE Intense investigation has reshaped concepts about undifferentiated tumors occurring in young people (small round-cell tumors). Tumors associated with t(11;22)(p13;q12) and descriptively designated desmoplastic small round-cell tumor (DSRCT) are a distinctive, rare, poorly understood member of this family. We reviewed 109 cases of DSRCT to further characterize this entity better. METHODS Clinical information and histology were reviewed. Immunohistochemistry and immunoblotting were performed using standard techniques. Chimeric EWS-WT1 RNA and DNA were detected by polymerase chain reaction (PCR) and genomic translocation breakpoints mapped in a subset of cases. RESULTS There were 90 males and 19 females from 6 to 49 years of age (mean, 22 years). A total of 103 had tumor in the abdominal cavity, four in the thoracic region, one in the posterior cranial fossa, and one in the hand. Typical histologic and immunohistochemical features were usually evident in well-sampled tumors, but variations in cellularity, stromal components, cytology, architecture, and immunoreactivity occurred. Tumor cells were usually reactive with antibodies to keratin (67 of 78 cases, 86%), epithelial membrane antigen (50 of 54, 93%), vimentin (64 of 66, 97%), desmin (70 of 78, 90%), neuron-specific enolase (60 of 74, 81%), and the EWS-WT1 chimeric protein (25 of 27, 93%); typically nonreactive for muscle common actin (one of 58, 2%), myogenin (zero of eight, 0%), and chromogranin (one of 46, 2%); and variably reactive for MIC2 (nine of 47, 20%) and p53 (five of 17 with > 20% tumor cells reactive). Functional EWS-WT1 gene fusion was evident in 25 of 26 cases with genomic breakpoints in WT1 intron 7, and EWS introns 7, 8, and 9. Prognosis in general is poor, but tumors are responsive to aggressive therapy. CONCLUSION This large review identifies a greater degree of clinical, pathologic, and molecular variation than originally appreciated for tumors associated with t(11;22)(p13;q12). Translocation and functional fusion of the EWS and WT1 genes appears to be a consistent feature of this unique tumor.
Phase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children's Cancer Group.
Authors: Nicholson H S , Krailo M , Ames M M , Seibel N L , Reid J M , Liu-Mares W , Vezina L G , Ettinger A G , Reaman G H 
Published: February 2017

PURPOSE The Children's Cancer Group conducted a phase I trial of temozolomide stratified by prior craniospinal irradiation (CSI). PATIENTS AND METHODS Children and adolescents with recurrent or progressive cancer were enrolled. Temozolomide was administered orally daily for 5 days, with subsequent courses administered every 21 to 28 days after full hematologic recovery. Dose levels tested included 100, 150, 180, 215, 245, and 260 mg/m2 daily. RESULTS Twenty-seven patients on the non-CSI stratum were assessable for hematologic toxicity. During the first three dose levels (100, 150, and 180 mg/m2 daily), only grades 1 and 2 hematologic toxicity occurred. One patient at 215 mg/m2 daily had grade 3 hematologic toxicity. Three of eight patients (38%) treated at 245 to 260 mg/m2 daily had dose-limiting toxicity (DLT), which included both neutropenia and thrombocytopenia. Twenty-two patients on the CSI stratum were assessable for hematologic toxicity. Hematologic DLT occurred in one of six patients (17%) at 100 mg/m2 daily and in two of four patients (50%) at 215 mg/m2 daily. No nonhematologic DLT occurred; nausea and vomiting occurred in more than half of the patients. After two courses of temozolomide, 10 patients had stable disease (SD), and three patients had a partial response (PR), one of whom subsequently had a complete response (CR) that persists through 24 months of follow-up. CONCLUSION The maximum-tolerated dose (MTD) of temozolomide for children and adolescents without prior CSI is 215 mg/m2 daily and for those with prior CSI is 180 mg/m2 daily for 5 days, with subsequent courses that begin on day 28. Temozolomide is well tolerated and should undergo phase II testing in children and adolescents.
Southwest Oncology Group phase II trial of concurrent carboplatin, etoposide, and radiation for poor-risk stage III non-small-cell lung cancer.
Authors: Lau D H , Crowley J J , Gandara D R , Hazuka M B , Albain K S , Leigh B , Fletcher W S , Lanier K S , Keiser W L , Livingston R B 
Published: February 2017

PURPOSE A phase II study was conducted by the Southwest Oncology Group (SWOG) to assess the efficacy and toxicity of concurrent carboplatin, etoposide, and thoracic radiation (XRT) in a defined population of poor-risk patients with stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients with stage III NSCLC were eligible if they were excluded from cisplatin-based protocols because of poor pulmonary or renal function, history of congestive heart failure, hearing loss, peripheral neuropathy, or weight loss. Carboplatin 200 mg/m2 daily intravenously days 1, 3, 29, and 31 and etoposide 50 mg/m2 daily intravenously days 1 through 4 and 29 through 32 were administered. Beginning day 1, XRT was delivered at 1.8 to 2.0 Gy daily to a total dose of 61 Gy. RESULTS Within a period of 1 year, 63 patients were registered and 60 were eligible. Patient characteristics were age 47 to 79 years, performance status 0 to 1 (82%) and 2 (18%), and stages IIIA (60%) and IIIB (40%) NSCLC. The most common grades 3 and 4 toxicities included leukopenia (50%), thrombocytopenia (23%), and esophagitis (15%). There were no treatment-related deaths. The overall confirmed response rate was 29%, and median overall survival was 13 months (95% confidence interval, 11 to 14 months). The 2-year survival rate was 21%. CONCLUSION This chemoradiotherapy regimen is well tolerated in poor-risk patients and yields a median survival similar to that of good-risk patients who received cisplatin-based chemoradiotherapy. This chemoradiotherapy regimen will be compared with XRT alone in poor-risk patients with stage III NSCLC in a randomized phase III trial.
Prevalence and predictors of sexual dysfunction in long-term survivors of marrow transplantation.
Authors: Syrjala K L , Roth-Roemer S L , Abrams J R , Scanlan J M , Chapko M K , Visser S , Sanders J E 
Published: February 2017

PURPOSE To describe the prevalence of sexual difficulties in men and women after marrow transplantation (MT), and to define medical, demographic, sexual, and psychologic predictors of sexual dysfunction 3 years after MT. PATIENTS AND METHODS Four hundred seven adult MT patients were assessed pretransplantation. Survivors repeated measures of psychologic and sexual functioning at 1 and 3 years posttransplantation. RESULTS Data were analyzed from 102 event-free 3-year survivors who defined themselves as sexually active. Men and women did not differ in sexual satisfaction pretransplantation. At 1 and 3 years posttransplantation, women reported significantly more sexual dysfunction than men. Eighty percent of women and 29% of men reported at least one sexual problem by 3 years after MT. No pretransplantation variables were significant predictors of 3-year sexual satisfaction for women. For men, pretransplantation variables of older age, poorer psychologic function, not being married, and lower sexual satisfaction predicted sexual dissatisfaction at 3 years (R2=.28; P < .001). Women who were more dissatisfied 3 years after MT did not receive hormone replacement therapy (HRT) at 1 -year posttransplantation and were less satisfied at 1 year, but not pretransplantation (R2=.35; P < .001). CONCLUSION Sexual problems are significant in the lives of MT survivors, particularly for women. Although HRT before 1 year posttransplantation improves sexual function, it does not ensure sexual quality of life. Intervention for women is needed to apply hormonal, mechanical, and behavioral methods to prevent sexual difficulties as early after transplantation as possible.