bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative trial of BBR 2778 (pixantrone) + rituximab vs single agent rituximab in the treatment of relapsed/refractory indolent non-Hodgkin’s lymphoma (NHL)
Authors: Santoro A. , Voglova J. , Gabrail N. , Ciuleanu T. , Liberati M. , Hancock B. W. , Stromatt S. , Caballero D. 
Published: March 2020

7578 Background: BBR 2778 is a novel aza-anthracenedione that shows structural similarities to the anthracyclines, demonstrates single agent activity in patients with NHL, and does not exhibit cardiotoxic effects in animal models. This phase III open-label study was designed to compare the efficacy and tolerability of combination rituximab and BBR 2778, with that of single agent rituximab, in patients (pts) with relapsed or refractory indolent NHL. Methods: Pts were randomly assigned to receive both rituximab and BBR 2778 (experimental arm), or rituximab alone (control arm). In the experimental arm, pts received 375 mg/m2 rituximab IV on days 1 and 8 of cycles 1 and 2 only, and 90 mg/m2 BBR 2778 IV on days 2 and 8 of cycle 1, and on days 1 and 8 of all subsequent cycles. Pts could receive six 21-day cycles of BBR 2778. In the control arm, pts received 375 mg/m2 rituximab IV on days 1, 8 and 15 of cycle 1 and day 1 of cycle 2 only. Disease response was assessed every other cycle according to International Workshop to Standardize Response Criteria for NHL. Toxicities were assessed throughout the study using NCI-CTC criteria. Study was closed early due to poor enrollment. Results: 38 pts (20 experimental, 18 control) were enrolled. Mean age was 66 and 59 years in the experimental and control arm, respectively. Most patients were males and most had ECOG performance status 0 or 1. Efficacy is summarized in the table. Response rate (75 vs 33%) and time to progression (13.2 vs 8.1 months) were better in the BBR 2778 arm. Only pts in the experimental arm had study drug related serious adverse events (2 febrile neutropenia, 1 pneumonia, 1 neutropenia) and adverse events resulting in withdrawal (6 vs 0). Conclusions: Combination of BBR 2778 and rituximab is superior to rituximab alone with regard to time to progression and overall response rate. BBR 2778 combined with rituximab appeared to be a generally well tolerated regimen in patients with relapsed/refractory indolent NHL. [Table: see text] [Table: see text]
Clinical characteristics and prognostic factors in diffuse large B-cell lymphoma with bone marrow involvement
Authors: Lee K. , Yi J. , Choi I. , Kim J. , Kim D. , Lee J. , Heo D. , Bang Y. , Cho H. , Kim N. 
Published: March 2020

7588 Background: Although several studies have been reported about non-Hodgkin’s lymphomas (NHL) with bone marrow (BM) involvement, most of them have not performed immunophenotypic studies and contained heterogeneous NHL histologies. Until now, only a few studies with small sample sizes have been reported about clinical characteristics and prognostic factors in diffuse large B-cell lymphoma (DLBCL) with BM involvement. Methods: Between January 1993 and March 2004, 486 patients were diagnosed with DLBCL. Among 84 DLBCL patients who had BM involvement at initial diagnosis, 9 were not ineligible because of the lack of clinical data or unavailability of BM specimen. So, clinical factors and patterns of BM involvement of 75 patients were analyzed in this study. Results: At initial diagnosis, the median age was 57 years (range: 25∼79). In addition to BM, lymph nodes (76%), spleen (23%), Waldeyer’s ring (19%), gastrointestinal tract (16%), lung/pleura (15%), bone (15%), central nervous system (9%), nasal cavity (8%) and liver (7%) were also involved. Among 75 patients, 67 patients received anthracycline-containing chemotherapy; 4 patients received non-anthracycline-containing chemotherapy and 4 could not receive systemic chemotherapy because of combined medical conditions. The median survival was 32.3 months (5-year overall survival [OS]: 38%). In univariate analysis for prognostic factors, high-intermediate or high international prognostic index (IPI), B-symptoms, leucopenia, anemia, thrombocytopenia, pattern of BM involvement (interstitial or diffuse pattern), > 10% replacement of BM area by lymphoma cells, > 10% of large cell infiltration in BM-involved area by lymphoma at initial diagnosis were associated with poor OS (p < 0.05). Multivariate analysis indicated that > 10% replacement of BM area by lymphoma cells (p < 0.001), peripheral thrombocytopenia (p = 0.001) and high-intermediate or high IPI (p = 0.042) were independent predictors of poor OS. Conclusions: To our knowledge, this is the largest study about DLBCL patients with BM involvement. The BM areas involved by lymphoma cells, peripheral thrombocytopenia and IPI at initial diagnosis are independent prognostic factors in these patients. No significant financial relationships to disclose.
Phase I trial of subcutaneous (SQ) alemtuzumab (A) and CHOP in T-cell lymphoma: Preliminary results
Authors: Porcu P. , Baiocchi R. A. , Lee J. , Lin T. S. , Blum K. , Grady T. , Grever M. R. , Byrd J. C. 
Published: March 2020

7594 Background: T-cell lymphomas are highly chemoresistant. Cure rates with combination chemotherapy do not exceed 25–30%. We showed that A, a humanized IgG1 targeting the CD52 antigen expressed on most human leukocytes, is cytotoxic for malignant T-cells in vitro and in vivo, regardless of p53 mutational status (Blood 106, 3380, 2005). Thus, we initiated a Phase I study with A and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in T-cell lymphoma. Methods: Accrual goal: 15–18 patients (pts) with untreated (u) or relapsed (r) peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL), excluding ALK-1-positive anaplastic large cell lymphoma. Primary objective: maximal tolerated dose (MTD). All pts receive single agent SQ A loading (3, 10, 30 mg) over 5 days, followed by one SQ A dose with each CHOP every 21 days for a total of 8 cycles. A dose levels: 3, 10, 20 and 30 mg. All pts receive valacyclovir and trimethoprim-sulfamethoxasole, plus G-CSF and erythropoietin according to guidelines. Results: Eight of the nine enrolled pts on cohort 1 (A=3 mg) and cohort 2 (A=10 mg) are evaluable for toxicity (uPTCL= 4, rPTCL=1, rCTCL=3). All pts completed single agent A loading on time and tolerated well further SQ A. No cycle was delayed due to myelosuppression. There were no opportunistic infections or neutropenic fevers. Four pts completed all planned therapy. Three pts did not complete therapy due to progression (2) or toxicity (1). One pt remains on study after 4 cycles. There were no Grade 4 adverse events (AEs). Grade 3 AEs included fatigue (1), anemia (1), dyspnea (1) and emesis (1). Cohort 1 was expanded due asymptomatic cytomegalovirus [CMV] reactivation requiring hospitalization for thrice daily foscarnet, thus resulting in Grade 3 AE. Protocol was amended and subsequent asymptomatic CMV reactivations (2) were treated with oral valganciclovir. No symptomatic CMV reactivation occurred. Conclusions: At current dose levels, SQ A can be easily and safely administered with CHOP chemotherapy and growth factor support, without excessive myelosuppression or infectious AEs. Asymptomatic CMV reactivation can be managed with oral valganciclovir. Further A dose escalation is in progress. [Table: see text]
Dactinomycin (A) and vincristine (V) with or without cyclophosphamide (C) and radiation therapy (RT) for newly diagnosed patients with low-risk embryonal/botryoid rhabdomyosarcoma (RMS). An IRS-V report from the Soft Tissue Sarcoma Committee of the Children’s Oncology Group (STS COG)
Authors: Walterhouse D. O. , Meza J. L. , Raney R. B. , Anderson J. , Wiener E. S. , Donaldson S. S. , Qualman S. J. , Meyer W. 
Published: March 2020

9001 Background: The STS COG defines patients with low-risk RMS as those with localized tumors of embryonal histology that occur in favorable sites or occur in unfavorable sites and are grossly resected. Intergroup Rhabdomyosarcoma Studies (IRS)-III (1984–1991) and -IV (1991–1997) found that these patients had a 5-year failure-free survival (FFS) of 83% and an overall survival of 95%. Methods: Two subsets were identified for the IRS-V low-risk RMS study (D9602) (1997–2004) based on the hypothesis that they required different treatment intensities to achieve similar excellent outcomes. Patients assigned to Subset A (Stage [Sg] 1 Group [Gp] I/IIA, Sg 1 Gp III orbit, Sg 2 Gp I) received VA (cumulative doses over 1 year of treatment: V: 54 mg/m2, A: 24 mg/kg) ± local RT. Patients assigned to Subset B (Sg 2 Gp IIB/C, Sg 1 Gp III non-orbit, Sg 2 Gp II, Sg 3 Gp I/II) received VA + C (C: 28.6 g/m2) ± RT. The RT dose was reduced to 36 Gy (instead of 41.4 Gy on IRS-IV) for Gp IIA patients and to 45 Gy (instead of 50.4 or 59.4 Gy on IRS-IV) for Gp III orbit patients. The primary endpoint was FFS. Results: Estimated 3-yr FFS was 89% (95% CI 84%, 93%) for Subset A (n=263) and 89% (95% CI 77%, 95%) for Subset B (n=79). Median follow-up was 2.9 years. Estimated 3-yr FFS was 80% (95% CI 64%, 89%; n=59) for patients with Sg 1 Gp IIA disease and 88% (95% CI 77%, 94%; n=76) for Gp III orbit disease. Conclusions: There is not evidence to suggest that outcome for these patients differs from outcomes observed in similar patients treated on IRS-III and IRS-IV. No significant financial relationships to disclose.
131I-Metaiodobenzylguanidine (131I-MIBG) double infusion with autologous stem cell transplant for neuroblastoma: A New Approaches to Neuroblastoma Therapy (NANT) study
Authors: Matthay K. K. , Quach A. , Huberty J. , Franc B. , Groshen S. , Shusterman S. , Veatch J. , Brophy P. , Yanik G. , Maris J. 
Published: March 2020

9011 Background: 131I-MIBG provides targeted radiotherapy with >30% response in refractory neuroblastoma, but the activity infused is limited by radiation safety and hematologic toxicity. The goal was to determine the maximum tolerated dose of 131I-MIBG in two consecutive infusions at a 2-week interval, supported by autologous stem cell transplant (ASCT) 2 weeks after the second dose. Methods: The 131I-MIBG was escalated in a 3+3 Phase I trial design, with levels calculated by total red marrow radiation index (RMI) from the double infusion. The first infusion of 131I-MIBG was 12, 15, 18 and 21 mCi/kg for levels 1, 2, 3 and 4 respectively. Using detailed dosimetry, the second infusion was adjusted to achieve the target RMI, except at Level 4, where the second infusion was capped at 21 mCi/kg. Results: Twenty-one patients were enrolled at Level 1–4, with 18 evaluable for toxicity. Median age at enrollment was 7 years, all were heavily pretreated, including 12 with prior high dose therapy and ASCT, and 12 patients had bone marrow tumor. Cumulative 131I-MIBG given to achieve the target RMI ranged from 18 mci/kg to 49 mCi/kg. RMI delivered per mCi of MIBG decreased in 15/19 patients by mean of 0.21 cGy/mCi with the second infusion. Hematologic toxicity was acceptable, with median time to ANC>500 after ASCT of 13 (4–27) days. Platelet transfusion was required in 15/18 patients, with median time to platelet independence of 18 (6–47) days after ASCT. There were no non-hematologic toxicities above grade 2 attributed to therapy, though 9 patients had grade 1–2 elevations of transaminase, and 1 had grade 2 hypothyroidism. Responses in 17 evaluable patients included 1 PR, 4 MR, 6 SD, and 6 PD. Eleven patients are alive at median of 361 days (46–483); 5 died of PD and 1 of unrelated toxicity. Conclusion: The lack of toxicity with this approach allowed dramatic dose intensification of 131I-MIBG, with minimal toxicity and the possibility of improved response. [Table: see text] No significant financial relationships to disclose.
A phase I study of bevacizumab in children with refractory solid tumors: A Children’s Oncology Group study
Authors: Glade Bender J. L. , Adamson P. C. , Baruchel S. , Shaked Y. , Chen H. X. , Reid J. M. , Ingle A. M. , Blaney S. M. , Kandel J. J. , Yamashiro D. J. 
Published: March 2020

9017 Background: Bevacizumab is a humanized monoclonal antibody targeting the vascular endothelial growth factor (VEGF-A) that has demonstrated significant growth inhibition in several pre-clinical models of pediatric solid tumors. However, the agent has never been tested in pediatric patients. Methods: A phase I dose escalation study in children with refractory solid tumors was conducted to define the dose limiting toxicities (DLTs), and to determine the pharmacokinetics (PK) and recommended phase II dose of bevacizumab administered by IV infusion every 2 weeks in 28-day cycles. Cohorts were enrolled at dose levels of 5, 10, and 15 mg/kg; the final dose level was expanded to include at least 3 children <6 years of age. Serial blood samples were collected for PK, plasma VEGF concentration, and circulating mature and progenitor endothelial cells (CECs/CEPs). Results: 20 patients (10 male), median age 13 yrs (range 1–21), were enrolled at dose levels 5 (n=3), 10 (n=3), and 15 (n=14) mg/kg. 18 patients were fully evaluable for toxicity (one withdrew consent prior to treatment and the second was removed for rapid disease progression). A total of 67 cycles were administered with a median of 3 per patient (range 1–16). Treatment was well tolerated and no DLTs were observed. Only one grade 3 toxicity, lymphopenia, was attributed to drug. Non-dose limiting, grade 1–2 toxicities included infusional reaction (n=3), rash (n=3), mucositis (n=2), and proteinuria (n=3). There was no hypertension, hemorrhage or thrombosis reported. There were no partial or complete responses; 3 pts with Ewings and 2 pts with soft tissue sarcoma had disease stabilization for > 3 months. The serum exposure to bevacizumab as measured by AUC appeared to increase in proportion to dose. The median clearance of bevacizumab was 4.1 ml/day/kg (range 3.2–15.9), and the median T1/2 was 11.8 days (range 3.9–14.6). In some patients, a rapid rate of rise in plasma VEGF, increase in mature CECs or decrease in CEPs was observed. Conclusion: Bevacizumab at doses up to 15mg/kg every two weeks is well tolerated in children with solid tumors. No significant financial relationships to disclose.
Randomized trial and pharmacokinetic study of pegfilgrastim vs. filgrastim in children and young adults with newly diagnosed sarcoma treated with dose intensive chemotherapy
Authors: Fox E. , Jayaprakash N. , Widemann B. C. , Hawkins D. , Dagher R. , Mansky P. , Mackall C. , Helman L. J. , Steinberg S. , Balis F. M. 
Published: March 2020

9020 Background: Daily subcutaneous (SC) filgrastim reduces the duration of severe neutropenia in children receiving dose intensive chemotherapy. A single SC dose of pegfilgrastim may be as efficacious. Methods: We conducted a randomized, non-inferiority trial comparing neutrophil recovery, tolerability, and pharmacokinetics of pegfilgrastim (100 mcg/kg SC once/cycle) to filgrastim (5 mcg/kg SC daily until post nadir ANC >10,000) in children and young adults with newly diagnosed sarcoma treated with vincristine, doxorubicin, and cyclophosphamide (VDC) for cycles 1, 2, 5, 9, 11, 13 alternating with etoposide and ifosfamide (IE) for cycles 3, 4, 6–8, 10, 12, 14. Local control with radiation or surgery was initiated after cycle 5. Serum GCSF concentrations were monitored during cycle 1 and measured by ELISA. Complete blood counts were monitored thrice weekly during cycles 1–4. Cycle duration was collected for all cycles. Results: Accrual has been completed. 34 patients (median age 19 y, range 3–25 y) were enrolled, 28 have completed 4 cycles, and 26 have completed therapy. Growth factor associated toxicity included reversible transaminase elevation and arthralgias and was similar on the 2 treatment arms. For filgrastim (n=13) the median (range) GCSF Cmax was 12 ng/mL (4–16 ng/mL), Css was 7 ng/mL (2–9 ng/mL) and Tmax was 6 h (4–8 h). For pegfilgrastim (n=13), the median (range) GCSF Cmax was 69 ng/mL (11–235 ng/mL), Css was 43 ng/mL (7–151 ng/mL) and Tmax was 28 h (4–168 h). Median (range) neutrophil recovery and cycle duration are presented in the table. Conclusion: Pegfilgrastim was well tolerated. Peak and steady state serum GCSF concentrations were higher in patients receiving pegfilgrastim but more variable. The number of days of severe neutropenia and the cycle duration with single dose pegfilgrastim appear to be at least equivalent to daily filgrastim. [Table: see text] No significant financial relationships to disclose.
Results of randomized study on dexrazoxane administration in children with de novo acute leukemia
Authors: De Berranger E. , Vaksmann G. , Thebaud-Leculee E. , Wyckaert I. , Mazingue F. , Francart C. , Dalle J. , Nelken B. 
Published: March 2020

9037 Background: Anthracyclins and anthracenediones represent major drugs for both AML and ALL. Among other mechanisms, these drugs induce free radical production responsible of cardiac toxicity. It appeared very important to protect cardiomyocytes. Dexrazoxane (DZ) was developed in this goal. In adult patients, its efficiency was demonstrated both to protect heart and to respect anticancer therapy. We conducted a prospective single bind randomized study using DZ in pediatric acute leukemia. Methods: From Dec 00 to Sept 03, 16 patients (pts) were enrolled for receiving or not DZ (1g for 50mg of doxorubicin equivalent dose) with chemotherapy. Cardiac function was evaluated by echocardiogram before induction and after each chemotherapy course of either EORTC 58951 (arm VHR) or LAME01 trials and each year after treatment completion. The cardiologist operator did not know if child received DZ or not. The cumulative equivalent doxorubicin doses were 310 and 450mg/m2 for EORTC 58951 and LAME01, respectively. The primary end-point was cardiac function evolution. The secondary end points were OS, EFS and the respect of therapy schedule. Results: 16 pts (9M/7F, 11AML/5ALL), median age 8.5y (2.4 - 16.1) were enrolled. 5 AML and 3 ALL pts received DZ. Median f-up was 28.5 months (10–47). Mean left ventricular shortening fractions were 39 and 35% in pts without DZ and 40 and 39% in pts with DZ before chemotherapy and 1 year after diagnosis, respectively. Mean wall stress values were 50 and 50g/cm2 for patients without DZ and 39 and 38g/cm2 for pts with DZ. All these values were comparable. 12 pts were alive, 6 in each arm. 1 pt relapsed in DZ arm and 3 in the other arm. 2 pts died of disease and 2 from infection equally dispatched in the 2 arms. Mean time between successive chemotherapy courses was identical in different groups. 2 patients given DZ presented severe hepatic toxicity (≥grade 3 of WHO classification) followed by quick and spontaneous regression. None other toxicity > grade 1 were observed. Conclusions: DZ may be used safely in children receiving anthracycline. No difference in OS and DFS appear in our study. Median follow-up was probably too short for distinguishing any cardiac alteration, and patient number was low. No significant financial relationships to disclose.
Fertility preservation in children newly diagnosed with cancer: Existing standards of practice in Australia and New Zealand
Authors: Heath J. A. , Stern C. J. 
Published: March 2020

9047 Background: Over the past two decades, rapid advances have occurred in both the successful treatment of childhood cancers and reproductive medicine. We sought to establish the current level of clinical practice for sperm, oocyte and gonadal tissue collection and storage in children newly diagnosed with cancer in Australia and New Zealand (ANZ). Methods: A cross-sectional survey of all pediatric oncology services in ANZ was performed. Comparisons to recently published North American practices and to current recommendations for best practice were also made. Results: Of the 13 centers invited to participate, 12 (92%) completed the survey. All centers had offered sperm conservation, but only ten (83%) had offered oocyte/ovarian tissue conservation. Available methods of gamete collection and storage were not consistent. Two centers were using GnRH agonists as fertility protection in post-pubertal females. Forty-two per cent had offered fertility conservation to males and females prior to completion of sexual development. All centers were more likely to offer sperm conservation than oocyte conservation for any given disease. The most common diseases for which conservation was offered were lymphomas and sarcomas. The anticipated cumulative dose at which centers elected to offer fertility preservation varied widely, both for the alkylator cyclophosphamide (1g/m2 to 10g/m2) and for abdominal/pelvic irradiation (any to 12 Gy) and spinal irradiation (any to 18Gy). Fertility counseling was offered in a variety of settings by 82% of centers. Despite 92% of centers agreeing that fertility preservation guidelines would be helpful, only two (17%) had any in place. Overall, there was greater uptake and consistency of utilization of fertility services in ANZ when compared with published North American data. Conclusions: There are inconsistencies regarding the indications for and methods of gamete conservation in pediatric oncology centers throughout ANZ. Unresolved medical, legal and ethical issues suggest the development of guidelines and a voluntary code of practice would be helpful. No significant financial relationships to disclose.
Intensity modulated radiotherapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) for children with head-and-neck rhabdomyosarcoma
Authors: Combs S. E. , Behnisch W. , Kulozik A. , Muenter M. W. , Debus J. , Schulz-Ertner D. 
Published: March 2020

9065 Background: To evaluate intensity-modulated radiotherapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) for children with head-and-neck rhabdomyosarcoma (RMS) with special regard to radiation induced toxicity. Methods: From 1995 to 2005, we treated 19 children with head-and-neck RMS with FSRT (n=14) or IMRT (n=5). The median age at the time of RT was 62.5 months. All children received systemic chemotherapy according to the German Soft Tissue Sarcoma Study protocols (CWS). Patients were grouped classified according to the grouping system used in Intergroup Rhabdomyosarcoma Study Group (IRSG) trials. Patients were immobilized using an individual mask fixation system. For treatment planning contrast-enhanced MRI- and CT-scans were performed. Median size of PTV for RT was 93,4 ml. We applied a median total dose of 45 Gy (range 32 - 54 Gy) using a median fractionation of 5 × 1,8 Gy/week (range 1,6 - 1,8 Gy / week). Deep sedation or general anaesthesia was required for children < 5 years. Results: RT was well tolerated in all children and could be completed without interruptions > 4 days. Minor RT-induced side effects included skin erythema, alopecia, conjunctivitis, mucositis and nausea / vomiting, however no toxicities >CTC grade II developed. The median follow-up time after precision RT was 17 months. Until now, no secondary malignancies developed. After RT, the 3- and 5-year survival rate was 94%. The 3- and 5-year actuarial local control rate after RT was 89%. With respect to tumor localization, the 3- and 5-year local control rates were 100% for patients with RMS of the orbit and 91% for patients with parameningeal tumors. The actuarial freedom of distant metastases rate was 89% at 5 years. For patients with RMS of the orbit only, the actuarial distant progression-free survival rate was 100% at 5 years. The actuarial 3- and 5-year distant metastases-free survival rate was 91%, in children with parameningeal RMS. Conclusions: High precision RT techniques such as IMRT and FSRT offer good coverage of complex shaped target volumes in critical locations with the necessary RT dose while adhering to the tolerance doses of nearby critical normal tissue structures. Local and distant control rates are not reduced. No significant financial relationships to disclose.