bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral blast counts at diagnosis of late isolated bone marrow relapse of childhood acute lymphoblastic leukemia predict response to salvage chemotherapy and outcome. Berlin-Frankfurt-Münster Relapse Study Group.
Authors: Bührer C , Hartmann R , Fengler R , Rath B , Schrappe M , Janka-Schaub G , Henze G 
Published: February 2017

PURPOSE In newly diagnosed childhood acute lymphoblastic leukemia (ALL), a high tumor burden indicates a poor prognosis, while no such link has been established yet after relapse. The impact of the absolute peripheral blast count (PBC) at the time of relapse on the response to salvage chemotherapy after a late isolated bone marrow (BM) relapse is the subject of this prospective analysis. PATIENTS AND METHODS Since 1983, 260 children with a first isolated BM relapse of ALL that occurred 6 months or later after elective cessation of front-line therapy were enrolled onto four consecutive multicenter trials of the Berlin-Frankfurt-Münster (BFM) Relapse Study Group. All patients received intensive multiagent induction and consolidation chemotherapy for 6 months, followed by maintenance therapy with methotrexate (MTX) and thioguanine for 2 years. Treatment of subclinical meningeal leukemia consisted of high-dose intravenous MTX and intrathecally administered cytostatic drugs, which was augmented by cranial irradiation since 1988. RESULTS At the time relapse was diagnosed, PBC varied considerably among patients (median, 1,060/microL; range, 0 to 106,800/microL). Achievement of a second complete remission (CR) was not significantly different in children without detectable circulating blasts at relapse (37 of 38) and those with moderate (1 to 9,999/microL) PBC (165 of 171). In contrast, only 42 of 51 children with high PBC (> or = 10,000/microL) achieved a second CR (P = .0015). At a median follow-up time of 40 months, the 10-year event-free survival (EFS) probability was significantly (P = .0001) higher in children without circulating blasts (.64) than in children with moderate PBC (.32) or high PBC (.10). There was a preponderance of boys in the group without detectable circulating blasts, while the three PBC-defined groups did not differ with respect to frontline treatment, age at initial diagnosis, age at relapse, time off therapy, or salvage treatment protocol. On sequential univariate and multivariate analysis, only duration of first remission > or = 48 months was an additional independent indicator of adverse prognosis, while preventive cranial irradiation improved outcome independently of PBC. CONCLUSION The absence of blasts on peripheral-blood smears at the time of a first late isolated BM relapse of childhood ALL is associated with a favorable response and prognosis in chemotherapy-treated children, who should be regarded as ineligible for bone marrow transplantation (BMT) unless a second round of chemotherapy has failed to produce a response.
Adjuvant radiation versus observation: a cost analysis of alternate management schemes in early-stage testicular seminoma.
Authors: Sharda N N , Kinsella T J , Ritter M A 
Published: February 2017

PURPOSE This study was designed to compare costs of adjuvant radiation versus observation in the management of early-stage testicular seminoma after inguinal orchiectomy. MATERIALS AND METHODS A line-by-line inspection of the charges generated during a course of adjuvant pelvic and paraaortic radiotherapy and of three cycles of bleomycin, etoposide, and platinum salvage chemotherapy was performed for five patients who received irradiation and five patients who received salvage chemotherapy. The average charge for either treatment was then calculated. Only those charges directly associated with the diagnosis of seminoma were included in the analysis. Follow-up charges were also generated from the patients' billing records. The optimum follow-up regimen for either management option was derived from a synthesis of the international literature. A 5% rate of failure was assumed if adjuvant irradiation was administered, and a 15% rate of failure was assumed if observation was the option chosen. Charges were truncated at 5 years. RESULTS The total charge generated over 5 years based on following a policy of observation is $27,223 per patient versus $19,557 if the option of adjuvant irradiation in chosen. Using University of Wisconsin institutional reimbursement rates, the estimated costs were $20,487 and $14,722 for the option of observation and adjuvant radiation, respectively. The cost equivalence point between the two options occurs at 2.5 years, when the initial cost of adjuvant radiotherapy is matched by the cost generated during the period of observation. The maximum cost difference is achieved by 5 years. CONCLUSION Following a policy of observation postorchiectomy for early-stage testicular seminoma generates 39% more medical costs per patient over a 5-year follow-up period than does following the standard policy of adjuvant irradiation to the pelvic and paraaortic regions, with no reported difference in outcome.
Impact of preexisting CNS involvement on the outcome of bone marrow transplantation in adult hematologic malignancies.
Authors: van Besien K , Przepiorka D , Mehra R , Giralt S , Khouri I , Gajewski J , Andersson B , Champlin R 
Published: February 2017

PURPOSE To determine the impact of prior or current CNS disease on the outcome of high-dose chemotherapy for patients with hematologic malignancies. PATIENTS AND METHODS In a 54-month period, 373 patients with hematologic malignancies underwent allogeneic or autologous bone marrow transplantation (BMT) or blood stem-cell transplantation using high-dose thiotepa, busulfan, and cyclophosphamide (TBC) as the preparative regimen. Four patients with active CNS disease at BMT and 20 patients with a history of prior CNS disease were identified. The outcomes of those with a history of CNS disease were compared with those of a matched control group. RESULTS Of four patients with active CNS disease at the time of BMT, two had CNS recurrences and one recurred in the bone marrow. One patient died of treatment-related toxicity. Four of 20 patients with prior CNS involvement currently remain free of disease. At 2 years, the disease-free survival (DFS) rate was 23% +/- 19%, and the DFS rate for the control group 39% +/- 24% (P = .053). An increased rate of treatment-related toxicity and especially grades II to IV CNS toxicity accounted for the poorer outcome of patients who had a history of CNS disease. Recurrence rates were not significantly different between the two groups. Prior radiation to the CNS correlated with CNS complications posttransplant (p = .01). CONCLUSION Consolidation with TBC and BMT can induce prolonged DFS in a proportion of patients with a history of CNS disease. Such patients are at increased risk for CNS complications that lead to an inferior overall outcome when compared with a control group.
Topotecan, an active drug in the second-line treatment of epithelial ovarian cancer: results of a large European phase II study.
Authors: Creemers G J , Bolis G , Gore M , Scarfone G , Lacave A J , Guastalla J P , Despax R , Favalli G , Kreinberg R , Van Belle S , Hudson I , Verweij J , Ten Bokkel Huinink W W 
Published: February 2017

PURPOSE Topotecan is a topoisomerase I inhibitor with preclinical activity against various tumor types. We conducted a large multicenter phase II study with topotecan in ovarian cancer in patients who had failed to respond to one prior cisplatin-based chemotherapeutic regimen. PATIENTS AND METHODS Topotecan 1.5 mg/m2/d was administered intravenously by 30-minute infusion for 5 days repeated every 3 weeks. As the cisplatin-free interval relates to response in subsequent treatment, patients were stratified in subgroups, ie, cisplatin-refractory, cisplatin-resistant, and cisplatin-sensitive. RESULTS One-hundred eleven patients entered the study. Nineteen patients were considered to be ineligible; 92 patients were assessable for response. A total of 552 courses were given (median, four per patient; range, one to 17). The major toxicities were leukocytopenia and neutropenia, which were grade 3 to 4 in 54.2% and 69.1% of courses, respectively, but with only 4.3% of these being grade 4 neutropenia plus fever or infectious complications. Prophylactic granulocyte colony-stimulating factor (G-CSF) was given in 20.5% of courses to maintain dose-intensity. Other relatively frequent side effects were alopecia (82%), nausea (36.4%), and vomiting (17.5%). The overall response rate was 16.3%, with one complete response (CR) and 14 partial responses (PRs). In the cisplatin-refractory, cisplatin-resistant, and cisplatin-sensitive strata, the response rates were 5.9%, 17.8%, and 26.7%, respectively. The median duration of time of documented response was 21.7 weeks (range, 4.6 to 41.9). CONCLUSION Topotecan in a daily-times-five schedule is an effective regimen as second-line treatment in ovarian cancer. Further investigations of topotecan in ovarian cancer, including first-line use and combination with other active agents, are indicated.
Prevalence of contralateral testicular intraepithelial neoplasia in patients with testicular germ cell neoplasms.
Authors: Dieckmann K P , Loy V 
Published: February 2017

PURPOSE Testicular intraepithelial neoplasia ([TIN], so-called carcinoma in situ of the testis) is hypothesized to be the precursor of testicular germ cell neoplasms. According to previous studies, it can be detected by testicular biopsy. Since patients with a unilateral testicular tumor are at high risk of a second testicular tumor, it seemed feasible to examine the prevalence of contralateral TIN in patients with testicular germ cell cancer and correlate it with the known prevalence of bilateral testicular tumors. The aim was to provide more evidence for the role of TIN as the preinvasive stage of testicular cancer. PATIENTS AND METHODS Nineteen hundred fifty-four consecutive patients with a unilateral testicular germ cell tumor underwent contralateral biopsy. All specimens were examined immunohistologically. RESULTS TIN was observed in 4.9% (95% confidence interval [CI], 3.95% to 5.91%). Testicular atrophy and a history of undescended testis were more frequently observed in patients with contralateral TIN, but only atrophy was shown to be independently associated by multivariate analysis. Patients with testicular atrophy have a 4.3-fold increased risk of having contralateral TIN. Sixty-four percent of TIN cases were found in normal testes. Patients with TIN were significantly younger than those without (P < .0017). Three patients developed a second testicular tumor despite a negative biopsy for TIN. CONCLUSION The prevalence of contralateral TIN corresponds well to the known prevalence of bilateral testicular tumors. Testicular atrophy is a strong indicator for the presence of TIN, but approximately 60% of TIN cases occur without atrophy. The present data are in accordance with the theory that TIN is an early step in the histogenesis of testicular germ cell neoplasms.
Vinblastine, bleomycin, and methotrexate chemotherapy plus extended-field radiotherapy in early, favorably presenting, clinically staged Hodgkin's patients: the Gruppo Italiano per lo Studio dei Linfomi Experience.
Authors: Gobbi P G , Pieresca C , Frassoldati A , Carotenuto M , Di Renzo N , La Sala A , Berté R , Avanzini P , Federico M , Silingardi V , Ascari E 
Published: February 2017

PURPOSE To ascertain whether vinblastine, bleomycin, and methotrexate (VBM) (CT) combined with extended-field radiotherapy (EF RT) is effective enough to spare laparotomy in early, favorably presenting Hodgkin's disease (HD) patients. PATIENTS AND METHODS Fifty patients with clinical stage IA or IIA HD with favorable histology and no bulky masses entered a prospective multicenter study started in January 1988. The median follow-up time was 38 months. RESULTS All patients achieved a complete remission (CR). Five relapsed after 3 to 40 months and underwent successful salvage therapy. The actuarial remission rate was 0.89% at 3 years and 0.82% at 5 years. Two patients died in CR: one of severe pulmonary toxicity, the other of a second neoplasia (adenocarcinoma of the lung), 2 and 43 months after the end of therapy, respectively. The hematologic toxicity recorded during VBM CT was mild on the whole. Major toxicity was represented by pulmonary side effects and neurologic symptoms. Multiple regression analysis demonstrated that pulmonary toxicity was significantly related only to the amount of RT delivered to the mediastinum and not to the relative dose of bleomycin, to the dose-intensities of the three drugs in the regimen, or to patient age or sex. The same statistical technique showed that the only clinical factor related to grade of neurotoxicity was vinblastine dosage. CONCLUSION VBM CT combined with EF RT is an effective treatment for early, clinically staged, favorable HD patients. However, the toxicity of this combination suggests that certain modifications should be evaluated.
Leukemia following low-dose total body irradiation and chemotherapy for non-Hodgkin's lymphoma.
Authors: Travis L B , Weeks J , Curtis R E , Chaffey J T , Stovall M , Banks P M , Boice J D 
Published: February 2017

PURPOSE Low-dose total body irradiation (TBI) is used to treat non-Hodgkin's lymphoma (NHL) and several other malignancies. Large volumes of bone marrow and other tissue receive considerable exposure, but few studies have quantified late carcinogenic sequelae. PATIENTS AND METHODS A cohort of 61 2-year survivors of NHL treated initially with low-dose TBI was monitored for second cancer occurrence. Data on primary and subsequent therapy were collected, and cumulative dose of radiation to active bone marrow (ABM) (median, 5.2 Gy) was reconstructed. RESULTS Thirteen second primary cancers occurred. Four patients developed acute nonlymphocytic leukemia (ANLL), which represents a relative risk (RR) of 117 (95% confidence interval [CI], 31.5 to 300) compared with population rates. A fifth patient was diagnosed with myelodysplastic syndrome (MDS). All five patients with secondary hematologic malignancies subsequently received salvage treatment, with either alkylating agents alone (n = 1) or combined modality therapy (CMT) (n = 4). Overall, eight solid tumors were observed (RR = 2.0; 95% CI, 0.9 to 4.0). The 15-year cumulative risks of all second cancers and secondary ANLL were 37% and 17%, respectively. CONCLUSIONS Despite the small number of subjects, a considerable risk of leukemia was observed among patients treated with low-dose TBI in combination with CMT including alkylating agents. Based on these results, approximately eight to nine excess ANLLs might be expected to occur among 100 NHL patients treated with low-dose TBI and salvage treatment and followed-up for 15 years.
Comparative effects of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor after high-dose cyclophosphamide cancer therapy.
Authors: Bregni M , Siena S , Di Nicola M , Dodero A , Peccatori F , Ravagnani F , Danesini G , Laffranchi A , Bonadonna G , Gianni A M 
Published: February 2017

PURPOSE We compared hematologic and clinical effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) after treatment with high-dose cyclophosphamide (HD-CTX, 7 g/m2), given as the first phase of a high-dose sequential chemotherapy program that includes a myeloablative therapy with mobilized progenitor cell autografting. PATIENTS AND METHODS Forty-nine consecutive patients with non-Hodgkin's lymphoma, Hodgkin's disease, or poor-prognosis breast cancer received GM-CSF (n = 27) or G-CSF (n = 22) after HD-CTX in two consecutive, nonrandomized studies. Cytokines were administered in continuous intravenous (i.v.) infusion for 14 to 15 days at a median dose of 5.5 and 10 micrograms/kg/d, respectively, starting 24 hours after HD-CTX. RESULTS Neutrophil recovery was faster with G-CSF administration (11.5 v 13.2 days; P = .01), whereas platelet counts recovered more rapidly with GM-CSF (13.7 v 16.6 days; P = .01). Prophylactic platelet transfusions were administered more frequently to patients treated with G-CSF than with GM-CSF (66% v 22% of the patients; P = .02). No clinically significant difference was observed between the two groups concerning days of absolute neutropenia or neutropenic fever. Both cytokines reduced the time to eligibility for subsequent chemotherapy administration compared with historical controls not given cytokine (14 to 16 v 20 days). Both cytokines increased circulation of hematopoietic progenitors. Most side effects were World Health Organization (WHO) median grade 1 to 2, were more frequent during GM-CSF than during G-CSF treatment, and were reversible by simple supportive measures and/or by dose reduction or suspension of the cytokine. Permanent suspension of cytokine administration was never required in either group. CONCLUSION GM-CSF or G-CSF administration after HD-CTX reduces hematologic toxicity of high-dose chemotherapy and induces circulation of large amounts of hematopoietic progenitors suitable for autografting in cancer patients.
Early lymphopenia after cytotoxic chemotherapy as a risk factor for febrile neutropenia.
Authors: Blay J Y , Chauvin F , Le Cesne A , Anglaret B , Bouhour D , Lasset C , Freyer G , Philip T , Biron P 
Published: February 2017

PURPOSE Febrile grade four (ie, < or = 500/microL) neutropenia (FN) is a frequent life-threatening complication of cancer chemotherapy. Although its incidence correlates to the dose of chemotherapy, FN may occur after almost any cytotoxic regimen. At present, there is no predictive method to identify patients who will experience FN. PATIENTS AND METHODS Univariate and multivariate analyses of risk factors for FN were performed on a retrospective cohort of 112 consecutive patients treated with various chemotherapy regimens. Two independent risk factors were identified by the logistic regression and used to create a risk model for FN. The validity of the model was tested in three distinct groups of patients: two prospective groups of patients treated in two institutions (Centre Léon Berard [CLB] and Institut G. Roussy [IGR]) and the group of patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) treated with the doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) regimen between 1988 and 1992 at CLB. RESULTS Within the retrospective group, 23 of 47 (49%) patients with lymphocyte counts < or = 700/microL at day 5 after chemotherapy experienced FN compared with seven of 65 (11%) of other patients (P = .00002). The type of chemotherapy (high dose v others) was also significantly correlated to FN (48% v 11%, P = .0003). Age, performance status, the number of previous chemotherapy cycles, or polymorphonuclear leukocyte (PMN) counts, were not significantly correlated to the incidence of FN in univariate analyses. Two independent risk factors were identified in the logistic regression: day 5 lymphocyte counts (beta = 1.97 +/- 0.53) and the type of chemotherapy regimen (beta = 1.91 +/- 0.53). The calculated probability to experience FN in patients with none, one, and both of these risk factors was 4.3%, 24.0%, and 68.8%, respectively. The validity of this model was tested in the three groups of patients used as validation samples. The observed incidences of FN in the above defined risk subgroups were 3%, 19%, and 67%, respectively, within the CLB prospective series and 6%, 19%, and 75% within the IGR prospective series. In the ACVBP group, the incidence of FN was 33% and 72%, respectively, in patients from the intermediate- and high-risk groups. In the two prospective groups and in the ACVBP series, the observed numbers of FN in the different risk groups did not differ significantly from those calculated by the model (P = .89, P = .86, and P = .72 for these three groups, respectively). CONCLUSION Day 5 lymphocyte counts < or = 700/microL and the type of chemotherapy regimen enable oncologists to define subgroups of patients treated with chemotherapy as those with a high intermediate, and low risk of FN. These criteria could be used to select subjects in whom prophylactic measures for FN, in particular hematopoietic growth factors, should be proposed.
Phase I study of pharmacologically based dosing of carboplatin with filgrastim support in women with epithelial ovarian cancer.
Authors: Lind M J , Ghazal-Aswad S , Gumbrell L , Fishwick K , Craigs D , Millward M J , Bailey N P , Dore-Green F , Chapman F , Simmons D , Proctor M , Oakey A , Robson L , Middleton I , McCann E , Sinha D , Calvert A H 
Published: February 2017

PURPOSE The aim of this study was to increase the dose intensity of carboplatin in women with International Federation of Gynecology and Obstetrics (FIGO) Stage Ic-IV epithelial ovarian cancer with the use of granulocyte colony-stimulating factor (G-CSF; filgrastim; Amgen, Thousand Oaks, CA). PATIENTS AND METHODS A phase I study of escalating target area under the curves (AUCs) of carboplatin with G-CSF (filgrastim) ws undertaken. The target AUCs were 5 mg/mL.min every 21 days for four cycles, 5 mg/mL.min every 14 days for four cycles, 7 mg/mL.min every 14 days for four cycles, 9 mg/mL.min every 14 days for four cycles, and 11 mg/mL.min every 14 days for four cycles. G-CSF was given at a dose of 5 microg/kg/d starting 24 hours after carboplatin administration and lasting until 24 hours before the next cycle and until day 14 after the last cycle. RESULTS We were able to escalate to an AUC level of 9 mg/mL.min every 14 days for four cycles. At this dose, severe thrombocytopenia, that necessitated dosage delays, and failure to give subsequent cycles of carboplatin were observed. We then reduced the AUC level to 8 mg/mL.min every 14 days for four cycles. However, severe thrombocytopenia was also observed at this level. CONCLUSION An AUC of 7 mg/mL.min every 14 days for four cycles is the maximum tolerated AUC level that can be achieved with G-CSF. Further escalations may be possible using either combinations of cytokines or peripheral stem-cell collections.
Evaluation of race as a prognostic factor in multiple myeloma. An ancillary of Southwest Oncology Group Study 8229.
Authors: Modiano M R , Villar-Werstler P , Crowley J , Salmon S E 
Published: February 2017

PURPOSE The objective of this investigation was to assess the impact of race (black v white) on the survival of patients with multiple myeloma treated within the context of a large clinical trial. PATIENTS AND METHODS A cohort of patients randomized to receive one of two treatment regimens and monitored for at least 10 years was studied to assess the impact of race as a prognostic factor, after adjusting for other known factors such as stage of disease. Patients were recruited from the referral network of the Southwest Oncology Group (SWOG), a national multiinstitutional consortium that includes both academic and community treatment centers. Patients had a diagnosis of multiple myeloma and had not previously been treated for this disease. They were carefully characterized as to demographic and clinical features, and were randomized to receive one of two treatment regimens, which proved to have virtually identical outcomes. The outcome measure was survival, measured from the date of randomization to the date of last contact. Patients still alive at last contact date were treated as censored observation. RESULTS Survival for black myeloma patients was similar to that for white patients, both overall and adjusted for prognostic factors such as stage. CONCLUSION Observed differences in mortality between blacks and whites cannot be attributed to differences in survival after diagnosis, given comparable treatment.