bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapy-related acute promyelocytic leukemia: a report on 16 cases.
Authors: Detourmignies L , Castaigne S , Stoppa A M , Harousseau J L , Sadoun A , Janvier M , Demory J L , Sanz M , Berger R , Bauters F 
Published: February 2017

PURPOSE To analyze the type of prior tumor and treatment in therapy-related acute promyelocytic leukemia (tAPL) that occurs after chemotherapy and/or radiotherapy (RT), and the hematologic characteristics and outcome of tAPL. PATIENTS AND METHODS Sixteen patients with tAPL who were gathered during a 10-year period (1982 to 1991) in seven hematologic centers were analyzed retrospectively. RESULTS There were 13 women and three men. The median age was 46 years (range, 12 to 82). Prior tumor was breast carcinoma in 10 cases, another solid tumor in three cases, and lymphoma in three cases. Two patients had received RT alone, and 14 had received chemotherapy (with RT in 11 cases). Prior chemotherapeutic agents generally included a combination of cyclophosphamide (used for limited periods), fluorouracil (5-FU), vinca alkaloids, and doxorubicin, mitoxantrone, or etoposide (VP16). By contrast, alkylating agents other than cyclophosphamide had been used in only two patients. Median interval between onset of treatment for the prior tumor and diagnosis of APL was 25 months. No patient had a known preleukemic phase. Hematologic and cytogenetic characteristics of the cases of tAPL were identical to those of the usual de novo APL, which included the presence of t(15; 17) in nine of the 10 patients tested. Two patients had early death. Seven patients were treated with intensive chemotherapy, and six achieved complete remission (CR). Three of them subsequently relapsed. Seven patients were treated with all-trans-retinoic acid (ATRA), and four achieved CR through the differentiation of blasts into mature granulocytes. None has relapsed so far. CONCLUSIONS Our findings suggest that tAPL is not exceptional, and usually has several features in common with other types of therapy-related AML with specific karyotype (ie, t(8;21),t(9;11), inv(16)): solid tumor rather than hematologic malignancy as primary tumor, short interval of development, absence of known preleukemic phase, prior chemotherapy with a combination of several drugs that often included an agent that targets topoisomerase II (doxorubicin or mitoxantrone, but less often VP16). Hematologic characteristics and response to therapy (intensive chemotherapy or ATRA) in tAPL do not seem to differ from those of de novo APL.
Elevated soluble c-erbB-2 antigen levels in the serum and effusions of a proportion of breast cancer patients.
Authors: Leitzel K , Teramoto Y , Sampson E , Mauceri J , Langton B C , Demers L , Podczaski E , Harvey H , Shambaugh S , Volas G 
Published: February 2017

PURPOSE An enzyme-linked immunosorbent assay (ELISA) for the extracellular domain of the c-erbB-2 oncogene product was developed and evaluated to determine if soluble c-erbB-2 could be detected in the serum and effusions of cancer patients. PATIENTS AND METHODS Sera from 208 previously untreated or progressing cancer patients and 69 healthy controls were assayed in a double-antibody sandwich ELISA that used two monoclonal antibodies to the native extracellular domain of the c-erbB-2 receptor. Fisher's exact test was used to analyze the statistical significance of the frequency of elevated serum c-erbB-2 levels. Immunoprecipitation and Western blotting were used to characterize further the c-erbB-2 immunoreactivity in the serum of four breast cancer patients. RESULTS Sera from 12 of 53 patients (23%) with metastatic or locally advanced breast cancer, zero of 69 controls, one of 31 patients with ovarian cancer (3%), and two of 124 other cancer patients (2%) had soluble c-erbB-2 values greater than or equal to 5 U/mL. The number of breast cancer patients with elevated serum c-erbB-2 levels was significantly greater than that of the control group (P less than .0001), the ovarian cancer group (P less than .03), and the other cancers group (P less than .0001). Also, two of five effusions (40%) from breast cancer patients had an elevated soluble c-erbB-2 antigen level, compared with zero of 17 effusions from patients with benign diseases. Western blotting of four sera from breast cancer patients with elevated serum c-erbB-2 antigen levels produced bands of approximately 105 kD that seemed to correlate in intensity with increasing ELISA serum levels. CONCLUSION Serum c-erbB-2 levels are elevated in approximately one fourth of patients with locally advanced or metastatic breast cancer.
Fludarabine potentiates metabolism of cytarabine in patients with acute myelogenous leukemia during therapy.
Authors: Gandhi V , Estey E , Keating M J , Plunkett W 
Published: February 2017

PURPOSE A protocol was designed to test the hypothesis that fludarabine infusion before arabinosylcytosine (cytarabine [ara-C]) would increase the accumulation of the active metabolite ara-C triphosphate (ara-CTP) in acute myelogenous leukemia (AML) blasts during therapy. PATIENTS AND METHODS Patients (n = 5) received 1 g/m2 of ara-C infused intravenously (IV) for 2 hours, followed at 20 hours by 30 mg/m2 of fludarabine for 30 minutes. At 24 hours, another identical dose of ara-C was infused. To determine the optimal duration of ara-C infusion following fludarabine, five additional patients were treated on an amended protocol in which the ara-C infusion was extended to 3 g/m2 infused over 6 hours. RESULTS Comparison of ara-CTP pharmacokinetics in circulating AML cells demonstrated that the area under the curve (AUC) of ara-CTP increased significantly (median, 1.8-fold; range, 1.6 to 2.4; P = .004) after fludarabine infusion. Neither the median plasma ara-C concentrations, the levels of its deamination product arabinosyluracil, nor the rate of ara-CTP elimination from circulating blasts was affected by fludarabine infusion. However, the rate of ara-CTP accumulation by AML cells was increased by a median of 2.0-fold (range, 1.8 to 2.2; P = .001) after fludarabine; the peak occurred within 1 hour of the end of the infusion. In vitro incubation of these cells with arabinosyl-2-fluoroadenine (F-ara-A) before ara-C also produced a median 1.7-fold increase in the ara-CTP accumulation rate. Pharmacology studies in patients receiving 6-hour infusions of ara-C demonstrated that the rate of ara-CTP accumulation was potentiated beyond 2 hours, but not for 6 hours. CONCLUSION Infusion of fludarabine before ara-C augments the rate of ara-CTP synthesis in circulating AML blasts during therapy. Evaluation of 6-hour ara-C infusions demonstrated that potentiation of ara-CTP synthesis is maximal up to 4 hours in most patients; this pharmacologically optimized regimen should be considered for combination with other antileukemia drugs.
Infectious complications associated with interleukin-2 administration: a retrospective review of 935 treatment courses.
Authors: Pockaj B A , Topalian S L , Steinberg S M , White D E , Rosenberg S A 
Published: February 2017

PURPOSE To determine if interleukin-2 (IL-2)-treated patients are prone to develop clinically significant infections, a retrospective review of 519 patients who received 935 treatment courses over a 38-month period was conducted. MATERIALS AND METHODS Treatment records of patients receiving intravenous (IV) bolus IL-2 were reviewed. Clinically significant infectious episodes were identified by retrieving data on antibiotic usage and cross-referencing this with microbiology records and chart review. RESULTS One hundred thirty-nine documented infectious episodes occurred in 122 treatment courses (13.0%); 11 courses were associated with more than one episode of infection. Predominantly urinary tract infections (6.8%) and infections related to IV catheters (5.3%) were encountered. Fifty-eight percent of the catheter-related infections were associated with bacteremia. Other infections included respiratory tract infections (1.0%), skin/muscle infections (0.9%), and miscellaneous infections (0.9%). Bacteria were isolated from the majority of infections. Almost all patients were successfully treated for their infection, with only two septic deaths (0.2%). No difference was noted in infected versus non-infected patients with regard to diagnosis or previous therapy. There was a significant tendency for those patients who developed infection to be older (P2 = .002, Mantel test for trend). Risk factors for the development of infection included vascular access catheters, open wounds, biliary obstruction, or incomplete treatment of previous infections. Over the 3-year study period, the incidence of infection declined from 23% to 7% (P2 < .0001, Mantel test for trend) due to rigorous patient screening, vigilant monitoring for infection, liberal use of antibiotics for suspected infection, and use of prophylactic antibiotics for central venous catheter placement. CONCLUSION Although treatment with IL-2 may be associated with a slightly increased incidence of bacterial infections, these infections can be successfully managed in the great majority of cases.
Octreotide versus loperamide in the treatment of fluorouracil-induced diarrhea: a randomized trial.
Authors: Cascinu S , Fedeli A , Fedeli S L , Catalano G 
Published: February 2017

PURPOSE Diarrhea is a prominent feature of fluorouracil (5FU) gastrointestinal toxicity, especially when 5FU is combined with leucovorin (LV) or interferon (IFN). No treatment for this condition has been well defined, although drugs, such as diphenoxylate or loperamide, generally are used. The efficacy of octreotide in the treatment of 5FU-induced diarrhea recently has been reported. We performed a randomized trial that compared octreotide with loperamide, the drug most commonly used for therapy for this disorder. PATIENTS AND METHODS Forty-one patients with grade 2 (four to six stools per day) or grade 3 (seven to nine stools per day; National Cancer Institute toxicity criteria) diarrhea after chemotherapy with a 5FU-containing regimen for colorectal cancer in 28 cases, gastric cancer in six cases, pancreatic cancer in five cases, and breast cancer in two cases, were entered onto the study. Twenty-one patients received octreotide at a dosage of 0.1 mg subcutaneously twice per day for 3 days, and 20 patients received loperamide 4 mg orally initially and then 2 mg every 6 hours for 3 days. The two arms were comparable for age, sex, and primary tumor. Patients were evaluated for response each treatment day; all patients were assessable. RESULTS Diarrhea resolved in 19 patients in the octreotide arm (one within the first day; four within the second day; and 14 within the third day) versus only three (all after the third day of therapy) in the loperamide arm (P < .005). Median frequency of stools in the 3 days of therapy was four, three, and zero in the octreotide arm and five, five, and five in the loperamide arm. No side effects were observed in both arms. Ten patients on the loperamide arm and only one on the octreotide arm required hospitalization for parenteral replenishment of fluids and electrolytes. CONCLUSION Octreotide seems to be more effective than loperamide in control of diarrhea and elimination of the need for replenishment of fluids and electrolytes.
Cathepsin D expression detected by immunohistochemistry has independent prognostic value in axillary node-negative breast cancer.
Authors: Isola J , Weitz S , Visakorpi T , Holli K , Shea R , Khabbaz N , Kallioniemi O P 
Published: February 2017

PURPOSE Increased expression of the lysosomal protease cathepsin D (CD) has been implicated in the metastatic progression of breast cancer. This study was designed to determine the prognostic significance of CD expression in axillary node-negative (ANN) breast cancer. The relationship of CD expression and onset of soft tissue recurrences and visceral metastatases was also studied. PATIENTS AND METHODS We analyzed a population-based group of 262 ANN breast cancer patients, none of whom had received any adjuvant chemotherapy or endocrine therapy. An immunohistochemical method based on a new monoclonal antibody (1C11) with a distinct epitope specificity made it possible to study CD expression from archival paraffin-embedded specimens and to distinguish staining in tumor cells from the high-level expression found in tumor-infiltrating macrophages. RESULTS High-level CD expression, as defined by cytoplasmic immunoreactivity in greater than 10% of the cancer cells, was found in 95 cases (36%). High-level CD expression was associated with large primary tumor size (P = .014), but not with histologic grade, estrogen and progesterone receptors, DNA index, or S-phase fraction, or with c-erbB-2 and p53 overexpression. Patients with CD-positive tumors developed significantly more often both soft tissue recurrences and visceral metastases (P = .0007) and had a significantly shorter disease-free survival (P < .0001). Eight-year overall survival of patients with high-level CD expression was 64% as compared with 90% in those with low-level expression (relative risk, 2.97; 95% confidence interval [Cl], 1.6 to 4.4; P < .0001). According to a Cox multivariate model and a regression-tree analysis, high-level CD expression was an independent predictor of poor overall survival in conjunction with tumor size and S-phase fraction. CONCLUSION These results indicate that CD expression determined by immunohistochemistry is a powerful prognostic factor in ANN breast cancer. The most significant prognostic information was obtained when CD expression (predicting metastatic activity) was combined with estimate of cell-proliferation rate (S-phase fraction).
High-dose chemotherapy and autologous hematopoietic stem-cell transplantation for aggressive non-Hodgkin's lymphoma.
Authors: Vose J M , Anderson J R , Kessinger A , Bierman P J , Coccia P , Reed E C , Gordon B , Armitage J O 
Published: February 2017

PURPOSE To evaluate clinical and tumor characteristics in patients receiving high-dose chemotherapy and autologous peripheral stem-cell transplantation (PSCT) or bone marrow transplantation (ABMT) for relapsed or primary refractory non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS One hundred fifty-eight patients with NHL received high-dose chemotherapy and ABMT or PSCT. A multivariate analysis of characteristics was performed for comparison of the long-term failure-free survival (FFS) rate. RESULTS Using a multivariate analysis, a prognostic model was constructed with patients in the good-prognosis group being those without a mass > or = 10 cm at the time of transplant, and no more than one of the following characteristics: three or more prior chemotherapy regimens, lactate dehydrogenase (LDH) level above normal, and chemotherapy resistance. Patients in the poor-prognosis group had a mass > or = 10 cm, or two of the other characteristics noted. The poor-prognosis group had a 3-year FFS rate of 10%, compared with a 45% 3-year FFS in the good-prognosis group (P < .001). Within the prognostic groups, there was no difference in the 3-year FFS rate of the poor-prognosis patients who received ABMT versus PSCT (10% v 12%; not significant). However, in the good-prognosis group, patients who received ABMT had a 3-year FFS rate of 32%, compared with 70% for those who received PSCT (P < .008). CONCLUSION This prognostic model can identify patients with good and poor prognoses following high-dose chemotherapy and ABMT or PSCT for aggressive NHL. In good-prognosis patients, those who received PSCT had a superior FFS rate.
Involved-field radiotherapy and intra-Ommaya methotrexate/cytarabine in patients with AIDS-related lymphomatous meningitis.
Authors: Chamberlain M C , Dirr L 
Published: February 2017

PURPOSE To evaluate combined limited-field radiotherapy and concentration times time (C X T) intra-CSF chemotherapy in patients with AIDS-related lymphomatous meningitis (LM). PATIENTS AND METHODS Fourteen men and one woman with AIDS had cytologically documented LM. Eleven patients had systemic non-Hodgkin's lymphoma (NHL) (all B-cell histology, including six immunoblastic, four large cell, one small cell) with leptomeningeal metastases and four patients had primary CNS lymphoma (PCNSL) (all B-cell histology, including two immunoblastic, two large cell) with CSF dissemination. Presenting neurologic examinations included cranial neuropathies (n = 7), normal (n = 4), abulia (n = 2), paraparesis (n = 2), ataxia (n = 1), hemiparesis (n = 1), and aphasia (n = 1). Standardized pretreatment evaluations included contrast cranial magnetic resonance/computed tomography (MR/CT), placement of an intraventricular reservoir, CT myelogram/contrast spine MR, ophthalmologic examination, and indium 111-pentetic acid (DTPA) CSF flow studies. Regions of bulky or symptomatic disease were treated with limited-field radiation therapy, which included whole brain in 10 patients combined with spinal cord irradiation in five patients. Concurrent systemic chemotherapy was administered in 12 patients. All patients were scheduled to receive intraventricular methotrexate (MTX) 2 mg/d for 5 consecutive days biweekly for 8 weeks (induction), followed in cytologically responding patients by MTX administered in a similar manner every 4 weeks (maintenance). In MTX-responsive and consenting patients with cytologic relapse, intraventricular cytarabine (ara-C) was administered, 25 mg/d for 3 consecutive days weekly for 4 weeks (induction), followed by ara-C administered in a similar manner every 4 weeks (maintenance). CSF cytology and neurologic examinations were performed biweekly. RESULTS In 13 assessable patients (two patients refused CNS directed therapy following standardized pretreatment evaluations), median time to tumor progression was 60 days (range, 3 to 260) and median survival duration was 125 days (range, 44 to 260). Response rate, determined clinically (four of 13 patients) and cytologically (nine of 13), was 69%. Complications included reservoir infection (n = 2) and myelosuppression (n = 11); the latter was felt to be a consequence of coadministered systemic chemotherapy. CONCLUSION There were no treatment-related deaths. We conclude that involved-field irradiation and intraventricular MTX/ara-C is effective palliative treatment of AIDS-related LM.
Effect of dietary counseling on food intake, body weight, response rate, survival, and quality of life in cancer patients undergoing chemotherapy: a prospective, randomized study.
Authors: Ovesen L , Allingstrup L , Hannibal J , Mortensen E L , Hansen O P 
Published: February 2017

PURPOSE This study examined the effect of frequent nutritional counseling on oral intake, body weight, response rate, survival, and quality of life in patients with cancer of the lung (small-cell), ovary, or breast undergoing cyclic chemotherapy. PATIENTS AND METHODS Of 105 assessable patients, 57 were randomized to receive nutritional counseling, and 48 to receive no nutritional counseling and consumption of an ad lib oral intake. The intervention group was counseled to achieve a daily energy and protein intake according to recommended dietary allowances. Counseling was standardized and performed by a trained dietitian, and took place twice monthly during a 5-month period from start of chemotherapy. RESULTS Dietary counseling increased daily energy intake by approximately 1 MJ and protein intake by 10 g over the entire study period. There was no change in the control group. Counseling led to an insignificant increase in body weight, but triceps skinfold measurement increased significantly after 5 months. Response rate and overall survival did not differ between the groups. Quality of life measured by the Quality-of-Life index (QL-index) increased significantly in both groups, but did not differ between groups. CONCLUSION No clinical benefit could be demonstrated despite long-term and continuous improved food intake in cancer patients with solid tumors undergoing aggressive chemotherapy.
Dose-dependent interleukin-3 stimulation of thrombopoiesis and neutropoiesis in patients with small-cell lung carcinoma before and following chemotherapy: a placebo-controlled randomized phase Ib study.
Authors: D'Hondt V , Weynants P , Humblet Y , Guillaume T , Canon J L , Beauduin M , Duprez P , Longueville J , Müll R , Chatelain C 
Published: February 2017

PURPOSE To evaluate the safety, tolerance, and hematologic effects of recombinant human interleukin-3 (IL-3) in patients with small-cell lung cancer (SCLC) before and following multiagent antineoplastic therapy in a placebo-controlled, randomized, double-blind study. PATIENTS AND METHODS Twenty-eight patients (22 men and six women; median age, 60 years) with previously untreated SCLC entered the study. Patients were assigned to six groups of escalating-dose IL-3 ranging from 0.25 to 10 micrograms/kg/d administered by continuous infusion for 7 days, with one patient in each group receiving placebo. After a 1-week interval, the first of three cycles of carboplatin, etoposide (VP16), and epirubicin (CVE) given every 3 weeks was administered. The second cycle of CVE was followed by 7 days of IL-3 administered at the same daily dose as administered during the first infusion. RESULTS The maximum-tolerated dose was not encountered in this study. Fever was the most frequently observed side effect. Before any chemotherapy, World Health Organization (WHO) grade II fever only appeared at doses > or = 2.5 micrograms/kg/d. Other side effects included rash, headache, and myalgia. During the first infusion of IL-3, before administration of chemotherapy, dose-dependent increases in peripheral-platelet counts (r = .613; P < .001) and neutrophil counts (r = .505; P = .007) were observed. Following the second cycle of CVE, recovery of peripheral platelet counts was faster as compared with the first cycle of CVE for patients treated with 7.5 and 10 micrograms/kg of IL-3 (P = .021). Chemotherapy postponements due to myelotoxicity were also less frequent following the second cycle of CVE as compared with the first for patients treated with > or = 2.5 micrograms/kg of IL-3 (P = .036). Compared with an age-matched historical group receiving identical chemotherapy (n = 191), administration of IL-3 did not modify either disease-free survival or overall patient survival rates. CONCLUSION IL-3 is well tolerated at doses up to 10 micrograms/kg/d. In the absence of chemotherapy, biologic effects on both neutrophils and platelets were seen at doses > or = 2.5 micrograms/kg/d. IL-3 infusion following the second cycle of CVE appears to reduce chemotherapy-induced myelosuppression, but does not alter tumor response or patient survival rates.