Clinical Oncology,Pediatric Hematology/Oncology

Maintenance Therapy in Metastatic Solid Tumors: Innovative Strategy or Simple Second-line Treatment? Managing metastatic diseases involves defining the best strategy that is supposed to take into account both efficacy and quality of life. To this end, clinicians use stop and go or maintenance strategies. As a matter of fact, 2 maintenance strategies can be distinguished: continuation maintenance using a drug already present in induction treatment and switch maintenance with a newly introduced drug. Several drugs have been approved as maintenance therapy with several current indications in solid tumors. Questions remain concerning such strategies, notably duration, cost, tolerability, and shortcut between switch maintenance and early second line. If the concept of maintenance strategy remains trendy with numerous trials ongoing, several issues are still pending. The aims of this review were to accurately define and describe the various facets of maintenance therapy through its several indications in real life and then to discuss the future challenges of maintenance therapy in oncology.

Exceptional Responders in Oncology: A Systematic Review and Meta-Analysis of Patient Level Data Purpose: We aim to systematically review and analyze the available literature on "exceptional responders" in oncology. We hypothesize that survival or patients with an exceptional response may be predicted based on clinical factors. Materials and Methods: A PICOS/PRISMA/MOOSE selection protocol was used to find studies that reported oncology patients with an exceptional response. A total of 333 initial articles were screened, and 76 articles were included, accounting for 85 patients. The primary outcome was survival after exceptional response therapy (ERT). The secondary outcome was survival since diagnosis. Univariate and multivariate analyses were conducted for both outcomes with 17 covariates. Results: The median age was 52 years (interquartile range, 35-66 y), 51.8% were male individuals, 18 (21.2%) had lung cancer, and 1 patient (1%) met all National Cancer Institute criteria for exceptional response. The most common treatment resulting in exceptional response was a form of chemotherapy (49.2%) followed by targeted therapy (26.8%) and radiation therapy (7.7%). The median time from diagnosis to initiation of ERT was 7.92 months (interquartile range, 0-24.72 mo). On multivariate analysis of survival after initiation of ERT, there were no predictors of exceptional response. On multivariate analysis of survival since diagnosis, predictors of prolonged survival included time between diagnosis and ERT initiation (hazard ratio, 0.52; 95% confidence interval, 0.32-0.87; P=0.0124) and single prior surgery versus none (0.08; 95% confidence interval, 0.01-0.98; P=0.04853). Conclusions: There were no clinically apparent patient or treatment factors that predicted favorable survival following ERT; instead, reporting of exceptional response appears to be biased.

The Effect of Time to Postoperative Radiation Therapy on Survival in Resected Merkel Cell Carcinoma Objectives: Delays from surgery to adjuvant radiation therapy (aRT) are associated with poorer prognosis in multiple neoplasms. Presently, no data exist for Merkel cell carcinoma (MCC). The authors sought to assess the time interval from surgery to aRT and effect on outcomes in MCC. Materials and Methods: The National Cancer Database was queried for histologically confirmed nonmetastatic MCC status post resection and aRT diagnosed between 2004 and 2015 who received aRT within 24 weeks of surgery. Kaplan-Meier analysis assessed univariate overall survival (OS); multivariable Cox proportional hazards modeling assessed multivariate OS; χ2 and logistic regression assessed differences in baseline characteristics and predictors of delayed aRT. Results: Of 5952 patients meeting criteria, 13% commenced aRT within 4 weeks, 48% between 4 and 7 weeks, 23% between 8 and 11 weeks, 11% between 12 and 15 weeks, and 6% between 16 and 24 weeks. There were no differences in OS on the basis of the surgery-aRT interval (P=0.99). Predictors of worse OS on the multivariate analysis included advanced age, greater comorbidities, male sex, lower regional income, earlier year of diagnosis, more advanced tumor and nodal staging, positive margins, head and neck location, and treatment at community facilities (P<0.05 for all). Factors predictive of delayed aRT were identified. Subset analyses on these factors, such as receipt of chemotherapy or positive lymph nodes, did not demonstrate that the timing of aRT affected survival (P≥0.37). Conclusion: This study of a contemporary national database revealed that delays from resection to aRT were not associated with survival in MCC, somewhat discordant from other malignancies such as squamous cell carcinoma.

Artificial Intelligence Estimates the Importance of Baseline Factors in Predicting Response to Anti-PD1 in Metastatic Melanoma Objective: Prognosis of patients with metastatic melanoma has dramatically improved over recent years because of the advent of antibodies targeting programmed cell death protein-1 (PD1). However, the response rate is ~40% and baseline biomarkers for the outcome are yet to be identified. Here, we aimed to determine whether artificial intelligence might be useful in weighting the importance of baseline variables in predicting response to anti-PD1. Methods: This is a retrospective study evaluating 173 patients receiving anti-PD1 for melanoma. Using an artificial neuronal network analysis, the importance of different variables was estimated and used in predicting response rate and overall survival. Results: After a mean follow-up of 12.8 (±11.9) months, disease control rate was 51%. Using artificial neuronal network, we observed that 3 factors predicted response to anti-PD1: neutrophil-to-lymphocyte ratio (NLR) (importance: 0.195), presence of ≥3 metastatic sites (importance: 0.156), and baseline lactate dehydrogenase (LDH) > upper limit of normal (importance: 0.154). Looking at connections between different covariates and overall survival, the most important variables influencing survival were: presence of ≥3 metastatic sites (importance: 0.202), age (importance: 0.189), NLR (importance: 0.164), site of primary melanoma (cutaneous vs. noncutaneous) (importance: 0.112), and LDH > upper limit of normal (importance: 0.108). Conclusions: NLR, presence of ≥3 metastatic sites, LDH levels, age, and site of primary melanoma are important baseline factors influencing response and survival. Further studies are warranted to estimate a model to drive the choice to administered anti-PD1 treatments in patients with melanoma.

Phase I Study of Sorafenib and Vorinostat in Advanced Hepatocellular Carcinoma Objectives: Preclinical data suggest histone deacetylase inhibitors improve the therapeutic index of sorafenib. A phase I study was initiated to establish the recommended phase 2 dose of sorafenib combined with vorinostat in patients with unresectable hepatocellular carcinoma. Materials and Methods: Patients received vorinostat (200 to 400 mg by mouth once daily, 5 of 7 d) and sorafenib at standard or reduced doses (400 mg [cohort A] or 200 mg [cohort B] by mouth twice daily). Patients who received 14 days of vorinostat in cycle 1 were evaluable for dose-limiting toxicity (DLT). Results: Sixteen patients were treated. Thirteen patients were evaluable for response. Three patients experienced DLTs, 2 in cohort A (grade [gr] 3 hypokalemia; gr 3 maculopapular rash) and 1 in cohort B (gr 3 hepatic failure; gr 3 hypophosphatemia; gr 4 thrombocytopenia). Eleven patients required dose reductions or omissions for non-DLTtoxicity. Ten patients (77%) had stable disease (SD). The median treatment duration was 4.7 months for response-evaluable patients. One patient with SD was on treatment for 29.9 months, and another patient, also with SD, was on treatment for 18.7 months. Another patient electively stopped therapy after 15 months and remains without evidence of progression 3 years later. Conclusions: Although some patients had durable disease control, the addition of vorinostat to sorafenib led to toxicities in most patients, requiring dose modifications that prevented determination of the recommended phase 2 dose. The combination is not recommended for further exploration with this vorinostat schedule in this patient population.

ENvironmental Dynamics Underlying Responsive Extreme Survivors (ENDURES) of Glioblastoma: A Multidisciplinary Team-based, Multifactorial Analytical Approach Although glioblastoma (GBM) is a fatal primary brain cancer with short median survival of 15 months, a small number of patients survive >5 years after diagnosis; they are known as extreme survivors (ES). Because of their rarity, very little is known about what differentiates these outliers from other patients with GBM. For the purpose of identifying unknown drivers of extreme survivorship in GBM, the ENDURES consortium (ENvironmental Dynamics Underlying Responsive Extreme Survivors of GBM) was developed. This consortium is a multicenter collaborative network of investigators focused on the integration of multiple types of clinical data and the creation of patient-specific models of tumor growth informed by radiographic and histologic parameters. Leveraging our combined resources, the goals of the ENDURES consortium are 2-fold: (1) to build a curated, searchable, multilayered repository housing clinical and outcome data on a large cohort of ES patients with GBM; and (2) to leverage the ENDURES repository for new insights into tumor behavior and novel targets for prolonging survival for all patients with GBM. In this article, the authors review the available literature and discuss what is already known about ES. The authors then describe the creation of their consortium and some preliminary results.

Cardiac Toxicity in Operable Esophageal Cancer Patients Treated With or Without Chemoradiation Purpose: The purpose of this study was to evaluate predictors of cardiac events in esophageal cancer patients treated with neoadjuvant chemoradiotherapy (NA CRT) followed by surgery compared with surgery alone. Materials and Methods: We retrospectively identified patients treated for esophageal cancer between 2006 and 2016. A total of 123 patients were identified; 70 were treated with surgery alone, and 53 were treated with NA CRT. Cardiac events were scored based on Common Terminology Criteria for Adverse Events (version 4.03), and dosimetric data was compiled for all patients who received radiation. Univariate analysis and multivariable analysis (MVA) were performed to identify predictors of cardiac events. Competing risk of death regression was performed to a model the cumulative incidence of cardiac events. Results: The overall rates of grade ≥3 cardiac events were 24.5% in the NA CRT group versus 10% in the surgery group (P=0.04). On MVA, use of NA CRT (P<0.01, hazard ratio [HR]: 3.45, 95% confidence interval [CI]: 1.35-9.09) predicted for grade ≥3 cardiac events, though no dosimetric variable predicted for grade ≥3 cardiac events or overall survival. On MVA, NA CRT predicted for pericardial effusions of any grade (P<0.01, HR: 3.70, 95% CI: 1.67-8.33). The V45 Gy was the most significant predictor of pericardial effusions (P=0.012, HR: 1.03, 95% CI: 1.01-1.06) Conclusions: NA CRT significantly increased the rate of grade ≥3 cardiac events compared with patients treated with surgery alone. Although no dosimetric parameter predicted for grade ≥3 cardiac events or survival, the V45 Gy predicted for pericardial effusions.

Competing Mortality in Patients With Neuroendocrine Tumors Objectives: Patients with neuroendocrine tumors (NETs) are at increased risk of mortality from competing causes in light of the improvement in overall survival over recent decades. The purpose of this study was to explore the competing causes of deaths and the risk factors associated with competing mortality. Materials and Methods: The Surveillance, Epidemiology, and End Results database was used to identify patients diagnosed with NETs between 1973 and 2015. Risk of competing mortality was estimated by the standardized mortality ratios (SMRs) and by using the Fine and Gray multivariate regression model. Results: Of the 29,981 NET patients, 42.5% of the deaths that occurred during follow-up were attributed to competing causes (83.9% from noncancer causes and 16.1% from second primary neoplasms). Overall SMR of competing mortality was 2.50 (95% confidence interval [CI]: 2.43-2.56). The SMR of noncancer causes was 2.65 (95% CI: 2.58-2.73), with the highest risk present within the first year of diagnosis. The SMR of second primary neoplasms was 1.91 (95% CI: 1.79-2.04), with the highest risk observed after 10-year postdiagnosis. A drastic rise in competing mortality was observed in the last decade between 2005 and 2015. Advanced age, black race, small intestinal and gastric NETs, and surgery were significantly associated with competing mortality. Female, pancreatic and recto-anal NETs, distant and regional spread, chemotherapy and radiotherapy were significantly associated with lower competing mortality. Conclusions: Competing mortality plays an increasingly significant role over the years and may hamper efforts made to improve survival outcomes in NET patients.

Patterns of Postdiagnosis Depression Among Late-Stage Cancer Patients: Do Racial/Ethnic and Sex Disparities Exist? Objectives: The incidence of depression after a late-stage cancer diagnosis is poorly understood and has not been the subject of intense investigation. We used population-based data to examine trends in postdiagnosis depression incidence among racial/ethnic and sexual groups. Methods: We identified 123,066 patients diagnosed with late-stage breast, prostate, lung, or colorectal cancer from 2001 to 2013 in the Surveillance Epidemiology and End Results Medicare-linked database. The primary outcome was the incidence of postdiagnosis depression after a late-stage cancer diagnosis. Trend analysis was performed using the Cochran-Armitage test. Stratified incidence rates were calculated for the racial/ethnic and sexual groups. Results: The incidence of depression after cancer diagnosis increased from 15.3% in 2001 to 24.1% in 2013, Ptrend<0.0001. About 50% of depression was reported in the first 3 months of stage IV cancer diagnosis. A total of 19,775 (20.0%) non-Hispanic whites, 1937 (15.9%) non-Hispanic blacks, and 657 (12.7%) Hispanics were diagnosed with depression during a mean follow-up of 2.7 months (interquartile range: 0.9 to 10.2 mo). The incidence of depression is significantly higher among females than males, 22.7% versus 16.3%, P<0.0001. In the multivariable logistic regression, non-Hispanic whites and females were still independent predictors of higher risk of postdiagnosis depression. Conclusions: There are significant differences in the incidence of postdiagnosis depression among racial/ethnic and sexual groups in the United States. The consideration of racial/ethnic in depression prevention and diagnosis among cancer patients should be discussed as a matter of importance to ensure that there is no diagnosis bias among non-Hispanic blacks and Hispanics.

Surveillance Mammography After Breast Conservation Therapy: Is Tomosynthesis Worth It? Introduction: We investigated the downstream workup and costs associated with digital breast tomosynthesis (DBT) compared with 2-dimensional full field digital mammogram (FFDM) when employed as initial follow-up imaging in breast conservation therapy. Methods: Between the years 2015 and 2017, 450 consecutive breast conservation therapy patients, ages 32 to 89, with a follow-up DBT (n=162) or FFDM (n=288) were retrospectively reviewed. The primary endpoints were further workup after follow-up mammogram and associated health care costs at 1 year. A single DBT costs an estimated $149 compared with $111 for FFDM, based on Centers for Medicare claims data from the Oncology Care Model. Results: The first posttreatment mammogram was received within 3 (20%), 3 to 6 (32%), or after 6 months (48%) following radiation. Younger patients and those undergoing hypofractionated radiation were more likely to get DBT. There were no differences in stage, receptor status, or mammogram timing between those in the FFDM and DBT groups. The following downstream workup ensued for DBT compared with FFDM imaging: 18% versus 29% short-interval (6-mo) mammogram (odds ratio=1.83, P=0.01), 6% versus 11% breast magnetic resonance imaging (odds ratio=1.90, P=0.08), 4% ultrasound for each, and 3% biopsy for each (1 positive in the FFDM group). Including downstream workup, the estimated cost per patient in the DBT group was $216.14 compared with $237.83 in the FFDM group. Independent predictors for reduced downstream workup per multivariable analysis were the use of DBT and first follow-up mammogram at least 6 months after radiation (P<0.05). Discussion: Excess workup was reduced with DBT compared with FFDM in the posttreatment setting, which translated to an improvement in cost efficiency in this study.

Impact of IgG Monitoring and IVIG Supplementation on the Frequency of Febrile Illnesses in Pediatric Acute Lymphoblastic Leukemia Patients Undergoing Maintenance Chemotherapy Monitoring serum immunoglobulin G (IgG) levels in pediatric oncology patients and treating subtherapeutic levels with intravenous immunoglobulin (IVIG) may prevent infections; however, evidence is limited. This retrospective study assessed pediatric acute lymphoblastic leukemia patients diagnosed 2006 to 2011 to evaluate if monitoring/supplementing IgG would reduce febrile illnesses during maintenance chemotherapy. A subject was categorized as "ever IgG monitored" if they had ≥1 IgG levels checked and their risk days were stratified into not IgG monitored days and IgG monitored days. IgG monitored days were further stratified into IgG monitored with IVIG supplementation, monitored with no IVIG supplementation (IgG level >500 mg/dL) and monitored with no IVIG supplementation days (IgG level <500 mg/dL). Generalized linear mixed effects poisson models were used to compare events (febrile episode, positive blood culture, and febrile upper respiratory infection rates among these groups. In 136 patients, the febrile episode rate was higher in the ever IgG monitored cohort than the never monitored cohort (5.26 vs. 3.78 episodes/1000 d). Among monitored patients, IVIG monitoring and supplementation did not significantly impact the febrile episode, febrile upper respiratory infection, or the positive blood culture rates. These data suggest that monitoring/supplementing low IgG is not indicated for infection prophylaxis in acute lymphoblastic leukemia patients during maintenance chemotherapy.

Methotrexate Polyglutamate Values in Children and Adolescents With Acute Lymphoblastic Leukemia During Maintenance Therapy Inadequate adherence to maintenance therapy is a major cause of relapse in patients with acute lymphoblastic leukemia (ALL). Therapeutic monitoring of mercaptopurine (thiopurine) red cell metabolites to assess adherence has been available for many years. Recently a clinical laboratory improvement amendments of 1988-approved test for methotrexate with three polyglutamate residues (MTXPG3) measured in peripheral blood red cells was approved. MTXPG3 is the primary intracellular metabolite of methotrexate, and like thiopurine metabolites, is retained for the life of the red cell giving an estimate of drug exposure over time. Normative values for MTXPG3 are available for adults and children with rheumatoid arthritis on methotrexate monotherapy, which are not applicable for patients with ALL on maintenance. Older literature on the MTXPG3 fraction in children with ALL is limited. We examined the MTXPG3 levels from 123 samples in 76 patients with ALL on maintenance oral methotrexate and mercaptopurine that were collected for clinical care. Male individuals had significantly higher MTXPG3 levels than female individuals which was unrelated to absolute neutrophil count, age, serum creatinine, and average doses of methotrexate or mercaptopurine. The MTXPG3 5th, 10th, 90th, and 95th percentile values are 0, 8.4, 53, and 64, respectively with a median of 24.7 nmol/L. The low 5th percentile MTXPG3 reflects 6 samples from 3 patients, age 16 to 21 years that were considered poorly adherent before collecting the specimen. As with red cell thiopurine (mercaptopurine) metabolites, MTXPG3 normative values may provide useful information to monitor for poor patient adherence or methotrexate toxicity during maintenance chemotherapy in ALL.

Impact of Race and Socioeconomic Status on Psychologic Outcomes in Childhood Cancer Patients and Caregivers Complex relationships between race and socioeconomic status have a poorly understood influence on psychologic outcomes in pediatric oncology. The Family Symptom Inventory was used to assess symptoms of depression and anxiety in pediatric patients with cancer and their caregivers. Separate hierarchical linear regression models examined the relationship between demographic variables, cancer characteristics, socioeconomic status, and access to care and patient or caregiver depression/anxiety. Participants included 196 pediatric patients with cancer (mean age, 11.21 y; 49% African American) and their caregivers. On average, caregivers reported low levels of depression/anxiety. Symptoms of depression and anxiety in patients were correlated with poorer mental health in caregivers (r=0.62; P<0.01). Self-reported financial difficulty (β=0.49; P<0.001) and brain cancer diagnosis for their child (β=0.42; P=0.008) were significantly associated with depression and anxiety in caregivers. Analysis did not reveal significant associations between race, household income, or access to care and patient or caregiver depression/anxiety. Perception of financial hardship can adversely impact mental health in caregivers of children with cancer. Psychosocial assessment and interventions may be especially important for caregivers of patients with brain tumors and caregivers who report feeling financial difficulty.

The Value of 18F-FDG PET/CT in Detecting Bone Marrow Involvement in Childhood Cancers Background: The aim of this study was to assess the utility of 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing bone marrow involvement (BMI) compared with bone marrow biopsy (BMB) in the initial staging of pediatric patients with non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), Ewing sarcoma (ES), and neuroblastoma (NB). Procedure: A total of 94 patients (57 boys, 37 girls, median age 7 y, range 1 to 18 y) with newly diagnosed NHL, HL, ES, and NB between July 2014 and December 2017, who underwent BMB and 18F-FDG PET/CT before chemotherapy were included in this study. There were 36 patients with NHL, 27 HL, 16 ES, and 15 NB. 18F-FDG PET/CT and BMB results were reviewed and compared retrospectively. Findings: Retrospective analysis of data from 94 pediatric patients (57 boys, 37 girls, median age 7 y, range 1 to 18 y) was performed. Of the 94 patients, 29 had BMI on 18F-FDG PET/CT. BMB was positive in 14, negative in 13, and insufficient in 2 of these 29 patients. In 65 patients negative on 18F-FDG PET/CT, BMB was also negative in 54 and insufficient in 7. For the whole group, sensitivity, specificity, and positive and negative predictive values of 18F-FDG PET/CT in detecting bone marrow metastasis at the time of diagnosis were 90.6%, 100%, 100%, and 95.4% and those of BMB were 53.1%, 87.1%, 94.4%, and 80.6%, respectively. Conclusion: Our study demonstrates that 18F-FDG PET/CT predicts BMI better than BMB. 18F-FDG PET/CT may be used at initial staging of pediatric patients with NHL, HL, ES, and NB.

Intensity of Therapy for Malignancy and Risk for Recurrent and Complicated Clostridium difficile Infection in Children Clostridium difficile infection (CDI) is common in pediatric oncology patients and is often associated with recurrences and complications. We hypothesized that higher intensity of chemotherapy would be associated with these outcomes. We conducted a retrospective cohort study including all cases of primary CDI in children with malignancy in our institution for over 7 years. Intensity of chemotherapy was measured by the Intensity of Treatment Rating Scale, third edition, ranging from level 1 (minimal) to 4 (highest). Outcomes included recurrence within both 56 and 180 days, CDI-associated complications, and primary treatment failure (PTF). Risk of recurrence was compared using Cox proportional hazards regression. Among 192 patients with CDI and malignancy, 122 met inclusion criteria. CDI recurred in 27% (31/115) of patients followed for 56 days and 46% (48/104) of patients followed for 180 days. Fourteen patients (11.4%) had a CDI-associated complication, including 4 intensive care unit admissions and 3 surgical procedures, but no deaths. Ten patients (8.2%) had PTF. Although PTF and severe complications were infrequent, recurrence was common in our cohort. None of these outcomes were associated with level of treatment intensity. More research is required to assess oncologic and nononcologic risk factors for CDI recurrence, PTF, and severe CDI-associated complications.

Metabolic Changes in Children that Received Chemotherapy Cancer treatments are associated with short and long-effects. Epidemiological reports have revealed clinical features of metabolic syndrome (MS), obesity or overweight in young cancer survivors. The aim of the study was to examine the prevalence of unhealthy weight status and risk factors associated with MS related to chemotherapy. We study 52 pediatric cancer patients and analyze cholesterol, triglycerides, glycosylated hemoglobin, body mass index, waist circumference (WC), FINDRISC test. All the parameters were analyzed according to the percentile corresponding to sex and age of each child. The data show an important modification in weight, body mass index, and WC as in triglycerides, and cholesterol that could be associated with the development of MS. The variance analysis showed that the WC, triglycerides, and cholesterol are statistically correlated in our population. A follow-up for MS in children cancer survivor should be considered necessary.

Characteristics and Survival Outcomes of Children With Hodgkin Lymphoma Treated Primarily With Chemotherapy Background: Hodgkin disease is a malignant tumor of the lymphatic system that comprises ∼6% of childhood cancers. In developing countries, efforts are made to ensure adherence to standard protocol/regimens, study patients' outcomes, and compare with that in developed world. Materials and Methods: We conducted a retrospective medical records' review of 212 children younger than 20 years presenting to The Indus Hospital in Pakistan with previously untreated Hodgkin lymphoma between August 2000 and December 2012. We collected demographic and other epidemiologic variables such as age, sex, stage, subtype of disease, and survival outcomes. Results: The mean±SD age of patients at time of diagnosis was 9.0±3.8 years with a male to female ratio of ∼4.7:1. In total, 44 (20.8%) patients were 5 years of age or above at presentation. Overall, 131 (61.8%) patients presented with B-symptoms and mixed cellularity was the most frequently diagnosed subtype in 65.1% of cases. In total, 170 (80.2%) achieved full remission after completion of chemotherapy. Patients were treated with alternating cycles of ABVD (Adriamycin, Bleomycin, Vincristine, and Dacarbazine) and COPDAC (Cyclophosphamide, Vincristine, Prednisolone, and Dacarbazine). The majority (n=114, 59.1%) received 6 cycles of chemotherapy, 44 (22.8%) received ≤4 cycles followed by 24 (12.4%) receiving 8 cycles. Radiotherapy was administered only to those patients with significant residual disease at the end of chemotherapy (n=20, 10%). The 5-year overall survival and event-free survival in our cohort was 89.6% and 82.1%, respectively. Conclusion: Our findings suggest that treatment with 4 to 8 alternating cycles of ABVD/COPDAC has an excellent outcome in childhood Hodgkin disease.

Switching to Bortezomib may Improve Recovery From Severe Vincristine Neuropathy in Pediatric Acute Lymphoblastic Leukemia Purpose: The purpose of this study was to evaluate the impact of switching patients being treated for acute lymphoblastic leukemia (ALL) from vincristine to bortezomib. Patients and Methods: A total of 20 patients with ALL were switched from vincristine to bortezomib (1.3 mg/m2/dose) because of worsening neuropathy despite physical therapy interventions (n=18) or at increased risk of neuropathy (n=2). Relapse rates were compared with 56 vincristine-only patients matched by prognostic factors. Maintenance blood counts in bortezomib patients were compared with cooperative group data using vincristine during maintenance. In addition, 6 evaluable patients were assessed for neuropathy using the pediatric-modified total neuropathy score. Neuropathy scores were collected during treatment with vincristine and after switching to bortezomib. Results: After a median follow-up of 3.5 years the relapse rate in patients switched to bortezomib was nonsignificantly different than those remaining on vincristine. Patients on monthly bortezomib had statistically significantly lower platelet counts that did not require transfusions or dose adjustment. Total neuropathy for all 6 cases decreased significantly when switched to bortezomib from vincristine (P=0.015), with motor neuropathy declines in 5 of 6 subjects. Conclusions: Bortezomib substitution for vincristine in ALL treatment is a potential strategy to mitigate severe vincristine neuropathy. These findings should be confirmed in a randomized clinical trial to further assess benefits and risks of this approach.

Investigation of Dynamic Thiol/Disulfide Homeostasis in Children With Acute Immune Thrombocytopenia Oxidative stress may play a role in the pathogenesis of immune thrombocytopenia (ITP), but the role of dynamic thiol/disulfide homeostasis has not been studied. The objective of this study was to assess whether there is a change in thiol/disulfide homeostasis in children with acute ITP. A total of 40 children with acute ITP and 50 healthy age-matched and sex-matched controls were included in this study. Serum total thiol and native thiol levels have been measured with a novel automatic spectrophotometric method. The amount of dynamic disulfide bonds and related ratios were calculated from these values. The average total thiol and native thiol levels of the patient group were found to be significantly lower than those levels of controls (P<0.01). However, intravenous immunoglobulin (IVIG) treatment with 1 g/kg/d prevented these reductions. disulfide level was slightly, but not significantly, depressed in ITP patients, but it recovered following IVIG treatment. We detected no marked changes in disulfide/total thiol, disulfide/native thiol, and native thiol/total thiol ratios between groups. These results are the first to demonstrate that thiol/disulfide homeostasis plays a role in ITP pathogenesis, and IVIG treatment can prevent the reduced thiol levels in children.

Probiotic Supplementation Decreases Chemotherapy-induced Gastrointestinal Side Effects in Patients With Acute Leukemia Introduction: In children with acute leukemia, gut microbiota is modified secondary to chemotherapy administration, leading to gastrointestinal side effects. Probiotics are microorganisms that can restore gut microbiota and may help alleviate gastrointestinal symptoms. The aim of this pilot study was to assess the effects of probiotic supplementation on chemotherapy-induced gastrointestinal side effects in children with acute leukemia (AL). Methods: In this randomized pilot study, patients under 17 years of age diagnosed with AL who were on remission induction or remission reinduction chemotherapy were randomly assigned to receive probiotic supplementation (a concentration of 5×109 CFU per sachet was administered at a standard dose twice daily, by mouth) or no probiotic supplementation. The primary endpoint was the prevalence of gastrointestinal side effects. Vomiting, nausea, flatulence, dyspepsia, diarrhea, constipation, abdominal pain, and abdominal distention were assessed in both groups. Results: Gastrointestinal side effects were less prevalent in the probiotic group, and 3 of the 8 gastrointestinal side effects (nausea, vomiting, and abdominal distension) significantly decreased in the probiotic group (P<0.05). We found for diarrhea a relative risk of 0.5 (95% confidence interval [CI], 0.2-1.2; P=0.04); for nausea an RR of 0.5 (95% CI, 0.4-0.8; P=0.04) and for vomiting an RR of 0.4 (95% CI, 0.2-0.9; P=0.04). Conclusions: Daily supplementation with Lactobacillus rhamnosus reduced chemotherapy-induced gastrointestinal side effects in children with AL.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com