bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of T-cells reactive against CT-7 and BCMA peptides: Potential targets for T-cell immunotherapy of multiple myeloma
Authors: Anderson L. D. , Maloney D. G. , Riddell S. R. 
Published: March 2020

7615 Background: Multiple myeloma is a malignant plasma cell disorder that is incurable with chemotherapy or autologous stem cell transplantation (SCT), and novel therapies with lower toxicity are needed. There is evidence that T-cells can recognize myeloma and mediate anti-tumor effects, but the lack of defined target antigens other than idiotype has hindered the development of myeloma-specific T-cell therapy. We are investigating cancer-testis antigens and overexpressed “self”-proteins as candidate myeloma antigens, including MAGE-C1 (CT-7), which is expressed by >80% of myelomas, and B-Cell Maturation Antigen (BCMA), a plasma cell differentiation antigen commonly over-expressed in myeloma. Methods: To identify potential T-cell epitopes from CT-7 and BCMA, we scanned the protein sequences with computer algorithms and synthesized peptides predicted to bind to HLA-A2 and A3. CT-7 and BCMA are both “self” proteins to which the T-cell repertoire may be relatively tolerant, so we have utilized culture conditions that facilitate the expansion of rare myeloma-reactive T-cells. CD8+ T cells were stimulated in vitro with autologous dendritic cells pulsed with CT-7 or BCMA peptides in the presence of cytokines that avoid excessive nonspecific expansion of T-cells. Wells were screened for reactivity against peptide-pulsed target cells and myeloma cell lines. Results: A specific CD8+ T-cell response by both ELISPOT and cytotoxicity assays to at least one HLA-A2 peptide from each of the CT-7 and BCMA proteins has been identified in normal donors. CT-7 and BCMA-specific T-cells are being cloned in order to determine their ability to recognize primary myeloma cells. Experiments are also in progress to elicit responses to these peptides in myeloma patient samples and to screen HLA A3-binding epitopes. Conclusions: T-cells recognizing CT-7 and BCMA are detectable in the normal T-cell repertoire and can be isolated and expanded in vitro. We are currently pursuing the identification of additional antigenic epitopes in these proteins to define their potential utility as targets for vaccination or adoptive T-cell therapy. No significant financial relationships to disclose.
A pediatric phase I trial and pharmacokinetic (PK) study of erlotinib (ERL) followed by the combination of ERL with temozolomide (TMZ): A Children’s Oncology Group Study
Authors: Jakacki R. I. , Tersak J. , Blaney S. , Krailo M. , Hamilton M. , Dancy J. , Gilbertson R. , Ingle A. , Adamson P. C. 
Published: March 2020

9015 Background: EGFR is potently inhibited by ERL. Aberrant cell signaling via the EGFR family has been implicated in the development of several human cancers, including certain pediatric solid tumors. Methods: A phase I dose escalation study in children with refractory solid tumors was conducted to define the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of single agent ERL, determine the tolerability of the combination of ERL and TMZ, and to determine the PK of ERL. Pts received single agent ERL qd × 28 d followed by ERL qd continuously in combination with TMZ 180 mg/m2/day × 5d. Cycles were repeated q 28 d. ERL was initially administered using the IV formulation given orally. The tablet form was subsequently studied at the MTD to further evaluate PK. Results: 46 pts (36 fully evaluable for toxicity) median age 11.5 yrs (range 3–20 yrs), were enrolled in cohorts of 3–6 pts at ERL doses of 35, 50, 65, 85 and 110 mg/m2/d. At the 110 mg/m2/day dose level, 2/4 pts had DLT (1 rash, 1 hyperbilirubinemia). In the expanded cohort at the MTD of 85 mg/m2/d, (n=21), 3 pts had DLT (2 rash, 1 diarrhea). Non-DLTs observed during the single agent cycle included diarrhea (n=14), rash (n=9), hyperbilirubinemia (n=7), neutropenia and/or thrombocytopenia (n=5). 1 pt with a soft tissue sarcoma had a minor response after 28d of single agent ERL, continuing to a PR by cycle 4. 3 pts (2 neuroblastoma, 1 neurocytoma) had prolonged responses (13–20+ months) to the combination. Oral administration of the IV formulation resulted in a higher Cmax and a lower Cmin compared to the adult data using tablets. Median apparent clearance was 2.85 (range 1.61–6.37) L/hr/m2 with a terminal half of 8.45 (5.1–27.1) hr. No PK interaction was observed between ERL and TMZ and the combination was well tolerated. Conclusions: The pediatric recommended phase 2 dose of ERL of 85 mg/m2/day, either alone or in combination with TMZ, is well tolerated in children. A COG phase 2 trial is planned. [Table: see text]
Pediatric phase 1 study of pemetrexed: A report from the Children’s Oncology Group
Authors: Nicholson H. S. , Blaney S. M. , Ingle A. M. , Krailo M. , Stork L. C. , Ames M. M. , Adamson P. C. 
Published: March 2020

9019 Background: Pemetrexed is a new multi-targeted antifol that inhibits enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Methods: A phase 1 dose escalation and pharmacokinetic study (PK) was performed in children with refractory solid tumors to define the dose limiting toxicities (DLTs) and a recommended phase 2 dose. Pemetrexed was administered as a 10 min iv infusion every 21 days. All patients received folic acid (400 mcg/day po), vitamin B12 (500–1000 mcg every 3rd course IM) and dexamethasone (0.1 mg/kg/dose bid × 3 days each course) . Cohorts of 3 to 6 children were enrolled at dose levels of 400, 520, 670, 870, 1,130, 1,470, 1,910 and 2,480 mg/m2. DLT was defined as any Gr. 3 or 4 non-hematological toxicity (except nausea/vomiting, alopecia, or AST/ALT elevation that returns to Gr. 1), Gr. 4 neutropenia or Gr. 4 thrombocytopenia ≥ 7 days. Results: 33 subjects (31 fully evaluable for toxicity), median age of 12 yrs (range, 1–21), with diagnoses including osteosarcoma (12), Ewing’s sarcoma (3), hepatoblastoma (2), renal cell carcinoma (2), brainstem glioma (3), glioma (3), and other (n=8) were enrolled. DLT occurred in 1/6 patients at 1,470 mg/m2 (Gr. 3 AST and ALT), and in 2/4 at 2,480 mg/m2 (Gr. 3 ANC and Gr. 3 rash in both). Other DLTs at 2,480 mg/m2 that occurred in 1 patient included Gr. 3 diarrhea and rectal hemorrhage, and Gr. 4 thrombocytopenia, lipase, GGT, hypophosphatemia, hypokalemia and hyponatremia. At 1,910 mg/m2, 0/6 patients had DLT. The median number of courses administered was 1 (range 1 to 17). No CRs or PRs have been observed. Results of PK and other correlative studies will be presented. Conclusions: The recommended phase 2 dose of pemetrexed for children and adolescents with recurrent solid tumors is 1,910 mg/m2 administered q21 days with dexamethasone, folic acid and B12 supplementation. A phase II COG study is planned. No significant financial relationships to disclose.
Outcome of adolescents with acute lymphoblastic leukemia (ALL) treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocols, 1991–2000
Authors: Barry E. , Levy D. E. , Goldwasser M. A. , Loh M. L. , Deangelo D. J. , Sallan S. E. , Silverman L. B. 
Published: March 2020

9023 Background: Historically, adolescents with ALL have had inferior outcomes compared with younger pediatric patients (pts). Recent studies suggest that older adolescents treated on pediatric protocols have better outcomes than similarly aged pts treated on adult protocols. We report the outcome of adolescents enrolled on two consecutive DFCI ALL Consortium protocols conducted between 1991–2000. Methods: Pts aged 1–18 years (yrs) with newly diagnosed ALL were enrolled on two consecutive protocols, 91–01 (1991–1995) and 95–01(1995–2000). All adolescent pts received 20–30 weeks asparaginase (post-remission consolidation), 18 Gy cranial radiation and doxorubicin (cumulative dose 300 mg/m2). Results: 847 pts were enrolled. Median follow-up was 6.5 yrs. Presenting characteristics and outcome of pts according to age are displayed in the table below. Older pts (age ≥ 10 yrs) were more likely to experience pancreatitis (p=0.007) and thromboembolic complications (p<0.001) from asparaginase, but had similar rates of asparaginase-related allergic events (p=0.21) compared to younger pts. Conclusions: Older adolescents (aged 15–18 yrs) with ALL are more likely to present with T-cell phenotype and TEL/AML1-negative disease than younger children. Despite these biologic differences, older adolescents (aged 15–18 yrs) fared relatively well on DFCI ALL Consortium protocols, with a 5-year EFS of 75 ± 6%. This EFS rate compares favorably to published outcomes for older adolescents treated on other childhood ALL protocols. Although adolescents had an increased risk of asparaginase-related toxicity, this therapy was well-tolerated overall. Based on this experience, we are currently piloting our treatment regimen in adults aged 18–50 yrs. [Table: see text] No significant financial relationships to disclose.
Effect of prophylactic cranial irradiation dose on CNS relapse, late cognitive decline and learning disabilities in children treated for acute lymphoblastic leukemia
Authors: Meshref M. M. , Elshazly N. , Nasr M. , Abdelhai R. 
Published: March 2020

9032 Background: Prophylactic cranial irradiation is still standard in treatment of high risk childhood acute lymphoblastic leukemia. In this study we assessed the effect of cranial irradiation dose of 1,800 cGy and 1200 cGy on CNS relapse as well as the late cognitive decline and learning disabilities in both groups versus a control group using neurophysiologic and psychometric studies. Methods: 42 patients treated from acute lymphoblastic leukemia and categorized to be at high risk of relapse were assessed in this study. 28 patients received prophylactic cranial irradiation at a dose of 1,800 cGy and 14 received a dose of 1,200 cGy. A control group of 42 age and sex matched normal children was also assessed. Visual and auditory P300 studies were carried out to assess high visual and auditory processing functions. Several selected subscales of Wechsler Intelligence scale for children were applied to both subgroups as well as the control group. Results: Mean age at receiving irradiation was 5.7 years. Mean testing age was 10 years. Mean follow up period was 4.6 years.There was one CNS relapse in the group who received 1,800 cGy (3.5%) and one in the group who received 1,200 cGy (7%). As compared to the control group the group of patient who received 1,800 cGy showed a high statistically significant delay in the latency and significant reduction in the amplitude of the Visual P300 (p <0.001, =0.01 respectively). The Auditory P300 showed a significant delay in latency (p=0.01). In the group receiving 1,200 cGy only the latency of the visual P300 was significantly affected(p=0.01). The other parameters in the 1,200 cGy subgroup were not significantly affected. As for the psychometric studies there were significant differences in several subscales between controls and 1,800 cGy subgroup namely in similarities, total performance and picture compilation which were not found between controls and 1,200 cGy subgroup. Conclusions: These findings reflects that there is impairment in the intellectual abilities as well as visual and auditory processing functions in the subgroup receiving 1,800 cGy compared to the controls which was much less in the subgroup receiving 1,200 cGy at no significant increased protection from CNS relapse. No significant financial relationships to disclose.
The use of IV pentamidine as second line prophylaxis for pneumocystis pneumonia
Authors: Chuk M. K. , Dabb A. A. , Kim S. Y. , Glenn D. J. , Loeb D. M. 
Published: March 2020

9043 Background: Pneumocystis jirovecii, formerly carinii, pneumonia (PCP) poses a serious risk to pediatric oncology patients. The use of trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis greatly reduces the risk of infection, however many children cannot take TMP-SMZ because of bone marrow suppression, drug allergy or patient noncompliance in taking oral medication. Inhaled pentamidine has been used successfully as second line prophylaxis, with a breakthrough PCP rate of 2.7%. However, many centers are unable to administer this specialized respiratory treatment to pediatric patients and in very young children, there are concerns about the effectiveness of the drug delivered in this manner. We performed a retrospective analysis of the use of intravenous pentamidine to assess its efficacy as second line prophylaxis. Methods: We conducted a retrospective review of all pediatric oncology patients at our institution who received at least one dose of pentamidine in the year 2005. The total number of doses dispensed allowed us to calculate the patient-months of pentamidine used. The charts of these patients were reviewed for the justification for the change from TMP-SMZ to pentamidine. Children who developed symptoms of pneumonia underwent diagnostic bronchoscopy, allowing us to calculate the breakthrough rate. Results: A total of 100 patients received 506 doses of pentamidine (4 mg/kg) administered monthly over a twelve month period. The main reasons for discontinuing TMP-SMZ were bone marrow suppression and drug allergy. Two children developed PCP, resulting in a breakthrough rate of 2% (or 0.4% per patient-months of treatment). Conclusions: The use of IV pentamidine once a month as second line prophylaxis against PCP results in a breakthrough rate of 2%. These results are similar to the breakthrough rate observed with inhaled pentamidine. When possible, we encourage the use of TMP-SMZ prophylaxis, however, when needed, the use of IV pentamidine is effective as second line prophylaxis. No significant financial relationships to disclose.
Central venous access in the pediatric cancer patient—Problems unique to developing countries: 5-year experience at a regional cancer center in Western India
Authors: Pandey R. , Patel A. A. , Shah S. A. , Patel K. M. , Shah P. M. , Shukla S. N. , Parikh B. J. , Anand A. S. , Talati S. S. , Panchal H. P. 
Published: March 2020

9049 Background: Central venous catheter (CVC) is required in the pediatric cancer patient for chemotherapy administration and supportive care. This study was carried out to review our experience with CVC, with special reference to issues unique to developing countries. Methods: 178 children who underwent 181 CVC insertions at our institute between January 2001 and October 2005 were retrospectively analysed for demographics, diagnosis, type of CVC, infective and non infective complications. Continuous data were assessed using the t test or the Wilcoxon rank sum test and categorical data by the chi square test or the Fisher’s exact test. Results: Median age was 6.5 years (0.6–13 yr). Commonest diagnosis was acute lymphoid leukemia (ALL) (n=60). CVC used were Hickman (n=162), subcutaneous ports (n=9) and peripherally inserted central catheters (n=10). Patients with hickman catheters had 164 insertions for 162 patients with a total of 14,090 catheter days, an average of 86.9 days/catheter. There were 5.36 culture positive infections /1000 catheter days. The commonest isolate was Coagulase negative S. Aureus (CNS) (44/80 cases). CVC infection with CNS was associated with higher risk of recurrent infections (OR=3.5 {95%CI=2.12–8.23} p=0.01). Patients having recurrent CVC infections received antibiotics for a median of 9.4 days as against a median of 10 days for those with non-recurrent infections (p=0.01, Wilcoxon rank sum). In 58 ALL patients, early (within 15 days of induction) insertion of CVC was associated with increased risk of culture positive infection as against late (after 15 days of induction) insertion (OR=2.3, 95%CI=1.0–5.2, p=0.05). Other complications were thrombosis (n=3), exit-site infection (n=5), tunnel infection (n=3), catheter fracture (n=1) and dislodgement (n=3). Conclusions: As most patients do not afford port, Hickman is the most preferred CVC in pediatric oncology in a developing country. Most patients are of low literacy and poor socioeconomic status. This is reflected in significantly high rates of CVC infection. Communication between the inserting doctor, nursing staff and proper counseling of the patient is the key to reduce complications No significant financial relationships to disclose.
Preliminary data of a phase I-II clinical and pharmacokinetic study of plitidepsin in children with malignant tumors. On behalf of the European ITCC (Innovative Therapies for Children with Cancer) Consortium
Authors: Geoerger B. , Doz F. , Estlin E. , Kearns P. , Lopez-Martin J. , Vassal G. , Bezares S. , Ruiz M. 
Published: March 2020

9060 Background: Plitidepsin (Aplidin) is a cyclic depsipeptide isolated from the tunicate Aplidium albicans, nowadays manufactured by synthesis. It is a rapid and potent inductor of apoptosis. Phase I trials in adults explored 5 different schedules. Muscle and liver toxicities were dose-limiting; hematological toxicity was not observed at the recommended dose (RD). Methods: This is a multicentre, open-label, non-randomized phase I-II study with a dose finding stage in children with solid tumors, and two expanded cohorts in leukemia and solid tumors at the RD. Plitidepsin was administered as a 3 h iv infusion every 2 weeks (=1 cycle). The initial dose level was 4 mg/m2 (80% of the RD in adults), with a classical escalation to 5 and 6 mg/m2. Results: 16 patients have been entered to date with median age 7.5 years (range 2–17). 54 cycles in 15 patients were evaluable for toxicity. 8 patients were treated at 4 mg/m2, five at 5 mg/m2 and three at 6 mg/m2. One patient presented dose-limiting G2 myalgia lasting more than 2 weeks at 4mg/m2. The Maximum Tolerated Dose (MTD) has not been reached at 6 mg/m2. Non-hematological toxicities included G1-G2 muscle side effects: (myalgia, CPK elevation, muscle weakness), G1–2 fatigue, G3 vomiting. One G3 hypersensitivity reaction was observed without prophylactic treatment. Pharmacokinetic data are similar to those reported in adult (extensive tissue distribution, a long half-life); if any, clearance was slightly higher and half-life shorter. Partial response was observed in a pancreatoblastoma and disease stabilization in a progressive medulloblastoma. Conclusions: Plitidepsin was well tolerated in children, with muscular side effects being the most relevant toxicity observed. The MTD for the pediatric population has not yet been achieved at a dose 1.2 fold above the RD in adults. [Table: see text]
Solid-pseudopapillary tumor of the pancreas and pancreatoblastoma in children: Experience over 18 years at a Pediatric Oncology Center
Authors: Rizzatti M. , Gatti E. , Brandalise S. R. , Oliveira Filho A. G. , Cardinalli I. A. , Aguiar S. D. 
Published: March 2020

9062 Background: Malignant pancreatic tumor is a rare disease in the pediatric population. Guidelines for treatment, including management in advanced disease are controversial until this moment (REBHANDL, 2001). Regarding to the pathology findings, pancreatoblastoma and solid-pseudopapillary tumor of the pancreas (Frantz’s tumor) are the more frequent pancreatic tumors in childhood. The aim of this study was a retrospective analysis of all malignant pancreatic tumors diagnosed at Boldrini’s Children Cancer Center during a period of 18 years. Methods: A retrospective analysis of eight cases of malignant pancreatic tumors, admitted at the Boldrini’s Children Cancer Center, from January 1987 to April 2005. All the data concerning age, sex, clinical presentation, stage, treatment and follow-up were collected. Results: The patient’s population refers to 8 children. There were 4 boys and 4 girls. Age ranged from 1 month to 15 years old (median age of 14 years). Main symptom was the increase of abdominal volume. None of them had metastatic disease at diagnosis. Regarding to pathology, 4 patients had pancreatoblastoma and 4 Frantz’s tumor. One patient (who had pancreatoblastoma) received chemotherapy before surgery, with a partial response, and then had a complete tumor ressection. All others (7 patients) had complete surgery as first treatment. Only one patient with Frantz’s tumor had pancreatic injury during tumor ressection and is now receiving enzimatic reposition. All the patients are alive, free of disease, from 6 months to 11 years (median follow-up of 2 years). Table I . Conclusions: Total pancreatectomy is the most important treatment in pancreatoblastoma and Frantz’s tumor. Neoadjuvant chemotherapy may be an important tool in unresectable tumors, increasing the disease-free survival. [Table: see text] No significant financial relationships to disclose.
Spontaneous pneumothorax in children with osteosarcoma
Authors: Kebudi R. , Fayda M. , Ayan I. , Görgün Ö. , Dizdar Y. , Aksu G. , Gün F. 
Published: March 2020

9070 Background: Spontaneous pneumothorax (SPx) is an emergency situation and early diagnosis and management is very important. SPx may sometimes be seen as a complication of malignancy or its treatment. SPx have been reported in some osteosarcoma patients, mostly in adults. The incidence of SPx in children with osteosarcoma is not well documented. The aim of this paper is to investigate the incidence, treatment and outcome of children with osteosarcoma in a single institution and to review the literature. Methods: Files of all children with osteosarcoma diagnosed and treated in a single institute during September 1989 and December 2002 and followed up until September 2005 were investigated retrospectively for the development of SPx and its outcome. Results: Three of the 81 children (3.7%) developed pneumothorax during their follow-up. Two cases had lung metastases and one case had a broncho-pleural fistula but no metastatic foci at the time pneumotorax was detected. He subsequently developed lung metastasis. Retrospectively, it was suspected that the bronchopleural fistula might have been a manifestation of an undetected micrometastasis. The incidence of developing spontaneous pneumotorax in children with osteosarcoma was 3.7% (3/81) in this single institution survey. We have also reviewed the 45 osteosarcoma cases with pneumothorax in the literature. Including the three cases reported in this paper, 39 of the 48 (81%) were metastatic. Conclusions: Although spontaneous pneumothorax is a rare event in the cancer patient, it should be kept in mind if there is worsening of pulmonary symptoms or shoulder pain. SPx is encountered mostly in metastatic patients, although it may occur in non-metastatic cases. No significant financial relationships to disclose.