bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bendamustine in combination with thalidomide and prednisolone (BPT) in patients with refractory or relapsed multiple myeloma: Results of a phase I clinical trial
Authors: Poenisch W. , Rozanski M. , Hoffmann F. , Boldt T. , Schwarzer A. , Ruffert U. , Rohrberg R. , Kreibich U. , Niederwieser D. 
Published: March 2020

7620 Background: Thalidomide is an active single agent in advanced relapsed or refractory multiple myeloma (MM). Combination of low dose thalidomide with bendamustine and prednisolone might be a way to maintain efficacy of the drug without dose limiting toxicity (DLT). Methods: The treatment consists of a fixed dose of bendamustine (60mg/qm) day 1, 8, and 15 and prednisolone (100 mg) day 1, 8, 15, and 22. At the same time, thalidomide was given in patients cohorts with escalating doses, starting with 50 mg to a maximum of 200 mg daily. 8 patients (4 after conventional chemotherapy and 4 after APBSCT) were enrolled at each dose level. Cycles were repeated every 28 days for a minimum of 2 and a maximum of 10 cycles until a maximal response was achieved, a DLT or a disease progression were observed. 23 patients ( 8 in the first dose level with 50 mg thalidomide, 8 in the second dose level with 100 mg and 7 patients in the third dose level with 200 mg) are enrolled until now. The number of prior treatment regimens was 2 or more in all patients. 6 patients were refractory for the last treatment. Median age was 67 years (range: 40 - 78). Results: All patients completed 2 cycles of BPT-treatment and were hence evaluable. Response was assessed using EBMT criteria modified to include near complete remission (nCR) and very good partial remission (VGPR). 20 of 23 patients responded after at least 2 cycles of chemotherapy with 3 CR, 5 VGPR, 11 PR and 2 MR. 2 patients had stable disease. With a median follow up of ten months, EFS and OS at twelfe months were 36 % and 85 %, respectively. Most common site effects were constipation (10 patients WHO grade 1, 8 patients WHO grade 2), polyneuropathy (14 patients WHO grade 1, 2 patients WHO grade 2) and somnolence (4 patients WHO grade 1). None of the 23 patients developed dose-limiting hematoxicity as defined by an ANC < 1,0 Gpt/l for > 7 days or an ANC < 0,5 Gpt/l for > 3 days or platelet count < 25 Gpt/l. Short neutropenia was reported in 8 patients (WHO grade 3 and 4) but no thrombocytopenia was observed. Conclusions: BPT with a dose between 50 and 200 mg thalidomide daily is well tolerated in patients with relapsed or refractory MM. No significant financial relationships to disclose.
Long-term outcome of high-dose chemotherapy and autologous stem cell transplantation in relapsed/refractory Hodgkin’s disease: A cohort of 199 pts from Royal Marsden Hospital
Authors: Sirohi B. , Cunningham D. , Norman A. R. , Oates J. , Wotherspoon A. , Chong G. , Arkenau T. , Horwich A. 
Published: March 2020

7622 Background: The purpose was to assess prognostic factors and outcome of pts with relapsed/refractory Hodgkin disease (HD) who have received high-dose chemotherapy and autologous stem cell transplant (ASCT). Methods: The retrospective study was approved by Research Ethics Committee. Primary end-point was overall (OS) and progression free survival (PFS). OS was defined as death from any cause measured from date of transplant and PFS defined as disease progression or death from any cause. Data on 199 pts who received ASCT between 1985–6/05 was reviewed. Results: Median time from 1st treatment(tx) to ASCT was 2.5 y (0.5–27.3). Demography at ASCT:61% Stage IV, median age 31y(18–69); median prior tx regimens 3 (1–7); median Hasenclever index 3 (0–6); 150 pts had responding disease (53 CR, 97 PR), 49 pts had stable/untested relapse/refractory disease. 62% pts received MBE as conditioning tx and bone marrow was source of stem cells in 57%. Post-ASCT, 61% (122/199) pts attained CR with an overall response (CR+PR) of 85%. 12 pts had non-relapse mortality;10 died before 1990 of interstitial pneumonitis (with higher dose BCNU). Of 122 pts attaining CR, 27 relapsed;3 after attaining CR for >5y and 1 after attaining CR for>10-y. 5-y risk of relapse in patients attaining CR was 21%. Median OS/PFS from ASCT was 9y/2.6y. 105 pts are alive at median follow-up of 10.3y. 5-y OS/PFS was 52/45% and 10-y OS/PFS was 49.5/41% for whole group. 10-y OS/PFS for pts in CR vs PR vs rest at ASCT was 72/66% vs 55/44% vs 11/5%. 20(10%) pts developed 2nd cancer (7 secondary AML/MDS). Probability of developing 2nd cancer at 10y is 6.9% (95%CI 3.6–13%) and 19.8% (95%CI 12–32%) at 20-y. Conclusions: These data provide the longest followup reported for patients receiving ASCT for relapsed/refractory HD. In addition to previously described prognostic factors, our data shows that Hasenclever index <3 influences outcome favorably and attaining CR at ASCT leads to a significantly better outcome. [Table: see text] No significant financial relationships to disclose.
ITCC phase II study of imatinib mesylate in children with solid tumors expressing imatinib-sensitive tyrosine kinase receptors
Authors: Vassal G. , Geoerger B. , Le Deley M. , Doz F. , Pichon F. , Frappaz D. , Gentet J. , Landman-Parker J. , Berthaud P. , Morland B. 
Published: March 2020

9003 Background: Imatinib mesylate inhibits selectively specific activations of the platelet-derived growth factor receptor (PDGFR), c-KIT and BCR/ABL tyrosine kinases and is approved for the treatment of chronic myeloid leukemia and gastro-intestinal stromal tumors (GIST). This study evaluated efficacy of imatinib in solid childhood tumors. Methods: Phase II study of imatinib as single agent in children and adolescents with refractory or relapsing solid tumor expressing at least one of the receptors. Patients were to be treated at 340 mg/m2, a dose escalation allowed to 440 mg/m2 after 2 months in case of insignificant improvement. C-KIT, PDGFRα and β expression was determined on archive tissue sections by immunohistochemistry prior to study entry. Gene mutations, pharmacokinetics, pharmacogenetics, and positron emission tomography imaging were assessed. Results: 36 patients, 21 boys, median age 13.7 years (2.2–22.5 y), 12 with brain tumors, 6 fibromatosis, 8 mesenchymal/bone tumors, and 10 other solid tumors, including 1 GIST and 3 chordoma, were treated at 340 mg/m2 daily during a total of 168 months (median 1.9 month/patient, range 0.5–19). 18/36 expressed c-KIT, 10 PDGFRα, 21 PDGRβ; 12 expressed more than one receptor. Ten patients were escalated to 440 mg/m2 due to lack of efficacy. During the 1st month, 17 patients experienced mild toxicity (grade 1 and 2) related to study treatment: gastro-intestinal (n=22), face edema (n=7), asthenia (n=5), tumor induration (n=2), skin toxicity (n=2), thrombocytopenia (n=1). No partial or complete response was observed; 5 patients (2 fibromatosis, 1 GIST, 1 medulloblastoma, 1 pseudo-inflammatory tumor) experiencing durable stable disease have been under treatment for more than 12 months. Interesting tumor stabilization during 10 and 7 months, respectively, was achieved in a brain stem glioma and a renal carcinoma. Glucose uptake on 18FDG PET scan was reduced in a chordoma, although the child progressed and died due to disease. Pharmacokinetic and genetic data are currently evaluated. Conclusions: Imatinib as single agent was well tolerated, but—as used in our study —failed to show measurable anti-tumor effects according the standard criteria in the pediatric malignancies studied. No significant financial relationships to disclose.
Immunotherapy for HER2-positive medulloblastoma: Regression of experimental tumors by transfer of HER2-redirected T cells in vivo
Authors: Ahmed N. M. , Ratnayake M. K. , Savoldo B. , Perlaky L. , Dotti G. P. , Wels W. , Bhattacharjee M. , Shine D. H. , Rooney C. M. , Heslop H. E. , Gottschalk S. 
Published: March 2020

9008 Background: The long-term objective of this project is to develop an innovative HER2-targeted immunotherapeutic approach for medulloblastoma, the most common malignant brain tumor of childhood. HER2 is expressed in 40% of medulloblastomas and at present less than one third of patients with HER2-positive tumors are cured by conventional therapies. The aim of this study was to determine if T cells grafted with a HER2-specific chimeric antigen receptor (CAR) recognize and kill HER2-positive medulloblastomas. Methods: Mitogen-activated T cells from healthy donors and medulloblastoma patients were transduced with a retroviral vector encoding a HER2-specific CAR with a ζ-signaling domain (HER2T-cells). We analyzed the ability of HER2T-cells to 1) proliferate, 2) produce immunostimulatory cytokines (IFN-γ and IL-2), and 3) kill HER2-positive targets in cytoxicity assays upon exposure to HER2-positive primary medulloblastoma cells and cell lines. The in vivo function was tested in an orthotopic murine xenograft model of human medulloblastoma, which allows for serial imaging by bioluminescence. Results: HER2T-cells killed both HER2-positive primary medulloblastoma cells and cell lines in cytotoxicity assays, whereas HER2-negative tumor cells were not killed. Stimulation of HER2T-cells resulted in T-cell proliferation and secretion of IFN-γ and IL-2 in a HER2-dependent manner. No functional difference was observed between cells generated from medulloblastoma patients receiving dexamethasone and healthy donors. In vivo, the adoptive transfer of HER2T-cells resulted in sustained regression of established medulloblastomas in an orthotopic murine xenograft model as judged by bioluminescence imaging. In contrast, delivery of non-transduced T cells did not change tumor growth in comparison to untreated tumors. Conclusions: This study shows for the first time that HER2 is a target antigen for the immunotherapy of medulloblastoma. HER2-redirected T-cells not only recognized and killed HER2-positive medulloblastomas ex vivo, but also induced regression of experimental medulloblastoma in vivo. Hence, adoptive transfer of HER2-redirected T-cells may represent a promising immunotherapeutic approach for medulloblastoma. No significant financial relationships to disclose.
Vascular endothelial growth factor (VEGF-A) serum levels in standard risk ALL pediatric patients (CCG-1962 study)
Authors: Avramis I. A. , Panosyan E. H. , Dorey F. , Holcenberg J. S. , Avramis V. I. 
Published: March 2020

9026 Background: Many molecular pathways including cell-cycle control, angiogenesis & drug resistance mediate tumor growth and survival. Activation of Akt, PI3K and Ras can be induced by the activation of receptor tyrosine kinases, such as the VEGF-R and related growth factor receptors. VEGF-A serum levels <40 and >100 pg/ml have been associated with good and poor prognoses, respectively. The higher the VEGF-A levels the greater the chance of MRD blasts surviving chemotherapy. ALL blasts secrete VEGF-A and express VEGF-R. The hypothesis was that serum VEGF-A levels in SR ALL pediatric patients at entry of Induction (IND) are predictive of Event-Free Survival (EFS). Methods: 117 patients were entered in CCG-1962 study and were randomized into the Native & PEG-ASNase arms. VEGF-A serum levels in Induction were quantified by an ELISA assay. Results: . All patients had a decrease in VEGF-A levels by Day 14 of IND, but they later dichotomized; with EFS group levels remained low and Event group increasing. The VEGF-A levels at the end of IND remained unchanged in all patients in the DI1 and DI2 treatment phases. A linear relationship exists between high VEGF-A levels at entry to IND and time to Event. Moreover, 7 yr EFS patients have lower VEGF-A average levels of 28±2 pg/ml than Event patients, >100 pg/ml (P<0.01). VEGF-A levels were analyzed by STATA-9 to yield Kaplan-Meier curves. Various cut-off values of VEGF-A were used, with the 30 and 60 pg/ml being the most significant. Low VEGF-A levels at entry or at the end of IND had superior EFS (P<0.0001). In addition, these patients were examined for Δ-VEGF-A positive or not positive. These analyses produced a significant difference, in that patients who had an increase in serum levels of VEGF-A from IND to a later treatment phase had an Event and the patients who had a decrease or no change were EFS (P<1E-6). Bifurcation by Native or PEG-ASNase arm did not alter these results. Conclusions: These results taken together with the results from other studies, strongly support that high VEGF-A serum concentrations in IND and no increase in Δ-VEGF-A are treatment-independent surrogate markers for EFS. Since many studies have demonstrated the same fact, an anti-VEGF-A modality may be useful to enhance the outcome of the ALL patients. No significant financial relationships to disclose.
The outcome of infant ALL: Experience at King Abdulaziz Medical City, Jeddah, western Region of Kingdom of Saudi Arabia
Authors: Khattab T. M. , Felimban S. K. , Atra A. 
Published: March 2020

9038 Background: Infants with ALL have a worse prognosis than older children. Several regimens has been used with a 4 years event free survival ranging from 25%-40%. An international collaborative treatment protocol (Interfant 99) based on the understanding of the biology of infant ALL was introduced aiming to improve the outcome and study the role of allogeneic bone marrow transplantation (BMT). To review the clinical features, treatment outcome and causes of treatment failure of all infant ALL treated at our center. Methods: We retrospectively reviewed all case notes of children with ALL diagnosed between 1986–2005 to identify infants <12 months with ALL. The age, WBC and CNS disease at diagnosis were reviewed. Treatment details and survival were studied. Results: Among 351 patients with ALL, 12 were infants (4.2%). Patients charachteristics are shown in table below. Six were boys and 6 were < 6 month at diagnosis. Nine patients (75%) had WBC count >100,000 and 4/12 CNS disease at presentation. Immunophenotyping showing lacking CD10 7/12, biphentyping 3/12, unknown 2/12 and t (4:11) found in 2/12. Treatment consisted of UKALL-based in 7 patients and Interfant 99 protocol in 5. Two patients received BMT, one from unrelated donor and the other with one antigen mismatch from his mother. Six patients (50%) died of toxicity and 3(25%) of recurrent leukemia including one who had unrelated donor BMT. Three patients survive in full remission including one who had BMT from his mother. Conclusions: This small single center study confirms the inferior outcome of infant ALL. Toxic death remains a major cause of treatment failure. Because of the rarity of infant ALL, international collaboration is required to study the role of different chemotherapy regimens and assess the role of allogeneic BMT. [Table: see text] No significant financial relationships to disclose.
Chemotherapy followed by low dose radiotherapy in childhood Hodgkin’s disease. Retrospective analysis of results and prognostic factors
Authors: Viani G. , Novaes P. , Salvajoli J. , Ferrigno R. , Pellizzon C. , Fogaroli R. , Maia M. 
Published: March 2020

9039 Background: To report on treatment results and prognostic factors of young patients with Hodgkin’s disease treated with chemotherapy (CT) followed by low dose radiotherapy (RT). Methods: This retrospective series analysed 166 patients under 18 years old, treated from January 1985 to December 2003. Median age was 10 years (range 2–18). The male to female ratio was 2,3:1. Adenomegalia was the most frequent complaint (68%), and the time of symptom duration was smaller than 6 months in 55% of the patients. In histological analysis Nodular Sclerosis was the most prevalent type (43%) followed by Mixed Celularity (41%). The disease was restricted to two nodal group ( stage II) in 60% and to adjacent groups in 55% (stage III). The most frequent site of metastasis ware the bone marrow (38%) and lungs (42%). Standard treatment consisted of chemotherapy (drug combination varied according to treatment protocols vigent). Radiotherapy consisted of 21 Gy dose in 17 fractions in most part of patients (90.2%), delivered to involved field or mantle field. 13,86% patients did not receive RT. Results: The OS and EFS in 10 years were 88.6% and 82.4%.Survival according to clinical stage as 94.4%, 94.25%, 90.6% and 71.5% for stages I to IV (p=0.0215). The OS in 90.5% of patients who received RT and in 75.6% of patients who did not (p=0.001). Multivariate analysis showed presence of B symptoms and low platelet count to be associated with a worse prognosis. Conclusions: This study shows that combining chemotherapy and low dose RT is an effective treatment for HL in childhood, providing high rates of cure and disease control (88.6% in 10 years), and that so far it is not possible to abdicar RT. And yet, attention to platelet count should be payed in order to improve survival. Also, B symptom presenting children may be involved in more aggressive protocols so survival can be improved. As the disease is highly curable, any data of long term follow-up should be presented in order to better direct therapy, improving outcome and lowering side effects. No significant financial relationships to disclose.
Influence of tumor site on cognitive deficits in children with cerebellar tumors at diagnosis
Authors: Riccardi R. , Peruzzi L. , Iuvone L. , Colosimo C. , Tamburrini G. , Massimi L. , Caldarelli M. , Lazzareschi I. , Ridola V. , Di Giannatale A. , Di Rocco C. 
Published: March 2020

9045 Background: Children with cerebellar tumor are at risk for cognitive deficits (CD) depending on surgery and radiotherapy. Only few studies analyze the role of tumor itself in mental functioning (Ellenberg et al., ‘87). Data about neuropsychological organization before any treatment are essential to understand the effect of tumor and have a baseline for analyzing the negative impact of the different treatments in the CD. Aim of this study is to prospectively analyze cognitive functions before treatment in patients (pts) with cerebellar tumors. Methods: Twenty-five pts with cerebellar tumor were assessed at diagnosis.Children with previous and severe neurological disturbances neurological were excluded. Intelligence quotient (IQ) and sectorial cognitive abilities (memory, attention, language, visuospatial and executive functions) were evaluated. Neurological examination (BUSPAR) and magnetic resonance imaging (MRI) were performed in the same period of cognitive assessment. Neurological deficits were classified as major, mild or absent in relation with the results of BUSPAR. Results: Twenty pts were selected; males/females: 12/8; age: 7.6 years (range: 18 m-14.8 y); histhology: pilocytic astrocytoma (9 pts), medulloblastoma (9), ependymoma (1) and atypical teratoid-rabdoid (1); tumor location: right cerebellar hemisphere (4), left (4), vermal (12); neurological examination: major neurological signs (2 pts), mild (10), absent (6); hydrocephalus: 50% of pts. Three pts had IQ values below the average level, although mean IQ values were normal (mean: 99.6; range: 78–118). Sixteen/20 pts had selective CD mainly involving working memory, executive functions, attention, and visual motor integration. Language processing was defective in 6 pts (2/4 right-sides lesions, 4/12 vermal lesion). Conclusions: Sectorial CD are present before treatment in about 80% of pts, mainly related to the location of tumor. Preliminar data suggest a correlation between specific sites inside cerebellum and selective CD, with language problems mainly in right hemispheric tumor. Complex cognitive impairment was present in 15% of pts before treatment. These data will represent the baseline for further analysis about the impact of treatment on cognitive outcome. No significant financial relationships to disclose.
Risk factors for low bone mineral density (BMD) in pediatric sarcoma survivors
Authors: Ahn H. , Kaste S. C. , Liu T. , Billups C. A. , Hudson M. M. , Spunt S. L. 
Published: March 2020

9059 Background: The incidence of and risk factors for low BMD in patients treated for sarcoma in childhood is unknown. Methods: Retrospective medical record review of 99 patients with pediatric sarcoma diagnosed between 12/82 and 2/03 who had undergone QCT evaluation more than 1 year after completion of treatment. Low BMD was defined as >1.5 standard deviations below the mean. A Z-test was used to assess whether BMD was lower in our patient population than in the normal reference population. Logistic regression was used to examine factors predictive of low BMD. Risk factors analyzed included demographic variables, tumor features, treatment exposures, endocrine/renal dysfunction, and health habits. Results: Twenty-six of the 99 sarcoma survivors (26%) had low BMD. The mean (−0.8) and median (−0.75) QCT Z-scores were significantly lower than those of the normal reference population (mean and median = 0, p<0.0001). Factors associated with lower BMD included young age at sarcoma diagnosis (p=0.044) or at QCT measurement (p=0.001), greater weight at diagnosis (p=0.045), non-lower extremity tumor site (p=0.023), higher cumulative cyclophosphamide dose (p=0.007), smaller size at QCT measurement [height (p=0.018), weight (p=0.012)], and low serum creatinine [at diagnosis (p=0.033), at QCT measurement (p=0.014)]. Gender, race, ifosfamide/methotrexate/etoposide exposure, radiotherapy, endocrinopathy, and health habits were not predictive of low BMD. Conclusions: Survivors of childhood sarcoma are at high risk for low BMD. Risk factors include young age, non-lower extremity tumor site, and high cumulative cyclophosphamide exposure. Prospective studies are needed to confirm these risk factors, and to guide implementation of effective screening guidelines and therapeutic measures. No significant financial relationships to disclose.
Large volume peripheral blood progenitor cell (PBPC) harvest in 27 pediatric solid tumor patients weighing less than 20 Kg
Authors: Fernández Sasso D. , López O. , García Lombardi M. , Chantada G. , Figueroa M. , Diez B. , Dengra C. , Koziner B. 
Published: March 2020

9061 While PBPC collection has become a safe and common procedure in adults, fewer reports exist about its efficacy and safety in low weight pediatric patients. PBPC harvest might be difficult in this patient population and extracorporeal separator line priming with red blood cells is usually required to improve hemodynamic stability and effectiveness of the collection. We present our experience in 27 children (11 females, 16 males) weighing less than 20 kg and autografted between May 2001 and December 2005. Median age and weight at the time of apheresis were 2.7 years (0.7 to 8) and 14.3 kg (9.7 to 20), respectively. Diagnosis were neuroblastoma in 15, brain tumor in 10, and others in 2. Harvest of PBPC started after mobilization with G-CSF 10 ug/kg/day SC for 4 days. A double lumen (Arrow 7Fr) central venous catheter was surgically placed under sedation in the OR. Collections were performed using a COBE Spectra separator primed with irradiated, white cell-depleted and CMV-negative packed red cells. A median of 2 (1 to 7) procedures were performed, resulting in the harvest of 12.9 (3.6–33.1) × 108/kg mononuclear cells and 4.98 (2.33–12.69) × 106/kg CD34 (+) cells. The apheresis were performed in the presence of the parents and did not require sedation. Only 1 patient had as side-effect perioral paresthesias with normal serum calcium. No patient had vasovagal reactions. A median platelet count reduction of 66% was observed, comparing pre and post apheresis values. All patients completed the procedure with a median of 71.800 platelets (25.000 to 152.000) and a median hemoglobin of 10.8 g/dl (8.2 to13.6). All children were successfully transplanted with myeloid engraftment (ANC >500 × 109/L) at a median of 11 days (9 to 14) and independence from platelet transfusions (> 20,000x × 109/L) at a median of 17 days (8 to 39) after PBPC infusion. Median of hospitalization days was 23 (18 to 42). We conclude that PBPC harvesting using large volume continuous flow cell separation was safe, even in this low-weight pediatric population. This procedure shortens the total number of apheresis, providing an adequate number of CD34 + cells, resulting in satisfactory hematological recovery and duration of hospitalization. No significant financial relationships to disclose.