SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion.

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

Relevance of CD20 antigen expression among paediatric patients with B-lineage acute lymphoblastic leukaemia.

Literature regarding prognostic relevance of CD20 antigen expression among paediatric B-lineage acute lymphoblastic leukaemia (B-ALL) patients is sparse and contradictory. We analysed clinical laboratory parameters and survival characteristics pertinent to CD20 expression among 224 treatment-naïve paediatric B-ALL patients. 50% patients had CD20 expression (CD20+ B-ALL). There was no difference in the clinical & laboratory presentation and end of induction measurable residual disease (EOI-MRD) status according to CD20 expression. As compared to CD20- B-ALL patients, CD20+ B-ALL patients had two times more relapse (16% vs. 29%, p = 0.034), inferior relapse-free survival (79% vs. 66%, p = 0.025) but no difference in overall survival (75% vs. 69%, p = 0.126). Similar to high-risk NCI status and EOI-MRD positivity, CD20 expression was an independent predictor for inferior relapse-free survival (HR: 1.860, 95% CI: 1.008-3.432, p = 0.047). Compared to baseline, there was a significant increase in CD20-expressing EOI-residual blasts among CD20- B-ALL patients (5% vs. 13%, p = 0.001). EOI residual blasts of both CD20+ and CD20- patients had three times increased normalized CD20 expression intensity (nCD20), with the intensity among CD20- B-ALL patients reaching the pretreatment nCD20 of CD20+ B-ALL patients (4.9 vs. 3.6, p = 0.666). Rituximab can be considered in managing EOI-MRD-positive CD20- B-ALL patients as the residual blasts of these patients have quantitative and qualitative increases in CD20 expression.

Spatio-temporal dynamics of intra-host variability in SARS-CoV-2 genomes.

During the course of the COVID-19 pandemic, large-scale genome sequencing of SARS-CoV-2 has been useful in tracking its spread and in identifying variants of concern (VOC). Viral and host factors could contribute to variability within a host that can be captured in next-generation sequencing reads as intra-host single nucleotide variations (iSNVs). Analysing 1347 samples collected till June 2020, we recorded 16 410 iSNV sites throughout the SARS-CoV-2 genome. We found ∼42% of the iSNV sites to be reported as SNVs by 30 September 2020 in consensus sequences submitted to GISAID, which increased to ∼80% by 30th June 2021. Following this, analysis of another set of 1774 samples sequenced in India between November 2020 and May 2021 revealed that majority of the Delta (B.1.617.2) and Kappa (B.1.617.1) lineage-defining variations appeared as iSNVs before getting fixed in the population. Besides, mutations in RdRp as well as RNA-editing by APOBEC and ADAR deaminases seem to contribute to the differential prevalence of iSNVs in hosts. We also observe hyper-variability at functionally critical residues in Spike protein that could alter the antigenicity and may contribute to immune escape. Thus, tracking and functional annotation of iSNVs in ongoing genome surveillance programs could be important for early identification of potential variants of concern and actionable interventions.

Sex disparity in childhood cancer in India: a multi-centre, individual patient data analysis.

BACKGROUND: Sex disparity and its determinants in childhood cancer in India remain unexplored, with scarce information available through summary statistics of cancer registries. This study analysed the degree of sex bias in childhood cancer in India and its clinical and demographical associations. METHODS: In this retrospective, multicentre cohort study, we collected individual data of children (aged 0-19 years) with cancer extracted from the hospital-based records of three cancer centres in India between Jan 1, 2005, and Dec 31, 2019, and two population-based cancer registries (PBCRs; Delhi [between Jan 1, 2005, and Dec 31, 2014] and Madras Metropolitan Tumour Registry [between Jan 1, 2005, and Dec 31, 2017]). We extracted data on age, sex, and confirmed diagnosis of malignancy (according to the International Classification of Diseases-10 coding),and excluded participants if they were without a recorded diagnosis, had a benign diagnosis, had missing sex information, resided outside of India, or were a donor for haematopoietic stem cell transplantation (HSCT). The primary outcome was the male-to-female incidence rate ratio (MF-IRR) in the two PBCRs and the male-to-female ratios (MFR) from the hospital-based and the HSCT data. For PBCR data, MF-IRR was estimated by dividing the MFR by the total population at risk. MFR was analysed for patients seeking treatment at the cancer centres and for those undergoing HSCT. Logistic regression analyses were done to explore the association of clinical and demographical variables with sex of the patients seeking treatment and those undergoing HSCT in hospital-based data and multivariable analyses were done to determine independent sociodemographic predictors of sex bias. Annual time trends of MFR and MF-IRR during the 15-year study period were ascertained by time series regression analyses. FINDINGS: We included 11 375 children from PBCRs in the study. 26 891 children from hospital-based records were screened, and data from 22 893 (85·1%) were included (including 514 who underwent HSCT). Residence details were missing for 257 (1·1%) of 22 893 patients from hospital-based records. The crude MFR of children at diagnosis was in favour of boys: 2·00 (95% CI 1·92-2·09) in the Delhi PBCR and 1·44 (1·32-1·57) in Madras Metropolitan Tumour Registry. The MF-IRRs for cancer diagnosis were also skewed in favour of boys in both PBCRs (Delhi 1·69 [95% CI 1·61-1·76]; Madras Metropolitan Tumour Registry 1·37 [1·26-1·49]). The MFR for children seeking treatment from hospital-based records was 2·06 (95% CI 2·00-2·12) in favour of boys. In subgroup analyses, the proportion of boys seeking treatment was higher in northern India than southern India (p<0·0001); in private centres than in centres providing subsidised treatment (p<0·0001); in patients with haematological malignancies than those with solid malignancies (p<0·0001); in those residing 100 km or further from the hospital than those within 100 km of a hospital (p<0·0001); and those living in rural areas than those living in urban areas (p=0·0006). The MFR of 514 children who underwent HSCT was 2·81 (95% CI 2·32-3·43) in favour of boys. Time trend analysis showed that MFR did not show any significant annual change in either the overall cohort or in any of the individual centres for hospital-based data; however, the analysis did show a declining MF-IRR in the Delhi PBCR from 2005 to 2014 (p=0·031). INTERPRETATION: The sex ratio for childhood cancer in India has a bias towards boys at the level of diagnosis, which is more pronounced in northern India and in situations demanding greater financial commitment. Addressing societal sex bias and enhancing affordable health care for girls should be pursued simultaneously in India. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

A National Cancer Grid pooled procurement initiative, India.

In health systems with little public funding and decentralized procurement processes, the pricing and quality of anti-cancer medicines directly affects access to effective anti-cancer therapy. Factors such as differential pricing, volume-dependent negotiation and reliance on low-priced generics without any evaluation of their quality can lead to supply and demand lags, high out-of-pocket expenditures for patients and poor treatment outcomes. While pooled procurement of medicines can help address some of these challenges, monitoring of the procurement process requires considerable administrative investment. Group negotiation to fix prices, issuing of uniform contracts with standardized terms and conditions, and procurement by individual hospitals also reduce costs and improve quality without significant investment. The National Cancer Grid, a network of more than 250 cancer centres in India, piloted pooled procurement to improve negotiability of high-value oncology and supportive care medicines. A total of 40 drugs were included in this pilot. The pooled demand for the drugs from 23 centres was equivalent to 15.6 billion Indian rupees (197 million United States dollars (US$)) based on maximum retail prices. The process included technical and financial evaluation followed by contracts between individual centres and the selected vendors. Savings of 13.2 billion Indian Rupees (US$ 166.7million) were made compared to the maximum retail prices. The savings ranged from 23% to 99% (median: 82%) and were more with generics than innovator and newly patented medicines. This study reveals the advantages of group negotiation in pooled procurement for high-value medicines, an approach that can be applied to other health systems.

Lorsque les systèmes de santé reçoivent peu de fonds publics et que leurs processus d'achat sont décentralisés, le prix et la qualité des médicaments contre le cancer ont un impact direct sur l'accès aux traitements efficaces contre la maladie. Des facteurs tels que l'application de prix différenciés, les négociations en fonction des volumes ainsi que la confiance placée dans des génériques bon marché dont la qualité n'a pas été évaluée peuvent entraîner des décalages entre l'offre et la demande, d'énormes dépenses non remboursables pour les patients et de piètres résultats thérapeutiques. Bien que les acquisitions groupées de médicaments puissent contribuer à résoudre certains de ces problèmes, le suivi du processus d'achat requiert un engagement considérable au niveau administratif. Les négociations collectives en vue de fixer les tarifs, l'établissement de contrats types assortis de conditions générales standardisées, mais aussi les achats effectués par des hôpitaux en particulier peuvent également faire baisser les coûts et améliorer la qualité sans nécessiter d'importants investissements. Le National Cancer Grid, un réseau réunissant plus de 250 centres d'oncologie en Inde, a testé un dispositif d'achat groupé visant à assurer une meilleure négociabilité pour des médicaments et soins de soutien essentiels contre le cancer. Au total, 40 substances ont été prises en compte dans ce projet pilote. La demande groupée en médicaments émise par 23 centres équivalait à 15,6 milliards de roupies indiennes (197 millions de dollars américains) d'après le prix maximal de vente au détail. Ce processus prévoyait une évaluation technique et financière, puis des contrats entre chaque centre et les distributeurs sélectionnés. Des économies de 13,2 milliards de roupies indiennes (166,7 millions de dollars américains) ont pu être réalisées par rapport au prix maximal de vente au détail. Ces économies étaient comprises entre 23 et 99% (médiane: 82%) et concernaient davantage les médicaments génériques que les marques et les médicaments récemment brevetés. La présente étude révèle les avantages que représentent les négociations collectives lors des achats groupés de médicaments essentiels, une approche applicable à d'autres systèmes de santé.

En los sistemas sanitarios con escasa financiación pública y procesos de adquisición descentralizados, el sistema de fijación de precios y la calidad de los medicamentos contra el cáncer afectan directamente al acceso a una terapia eficaz contra dicha enfermedad. Factores como los diferentes sistemas de determinación de precios, la negociación en función del volumen y la dependencia de genéricos de bajo precio sin evaluación de su calidad pueden generar retrasos en la oferta y la demanda, elevados gastos para los pacientes y malos resultados en el tratamiento. Aunque la adquisición conjunta de medicamentos puede ayudar a abordar algunos de estos retos, el seguimiento del proceso de adquisición requiere una inversión administrativa considerable. La negociación colectiva a la hora de determinar los precios, la emisión de contratos unificados con términos y condiciones estandarizados y la adquisición por parte de algunos hospitales también reducen los costes y mejoran la calidad sin necesidad de realizar una gran inversión. La Red Nacional de Cáncer, una red que cuenta con más de 250 centros oncológicos en la India, puso a prueba la adquisición conjunta con el fin de mejorar la negociabilidad de medicamentos oncológicos y de tratamiento complementario que resultaban costosos. En esta prueba piloto se incluyó un total de 40 medicamentos. La demanda conjunta de medicamentos por parte de 23 centros fue equivalente a 15 600 millones de rupias indias (197 millones USD) según los precios minoristas máximos. El proceso incluyó una evaluación técnica y financiera, así como contratos entre centros independientes y proveedores seleccionados. Se logró un ahorro de 13 200 millones de rupias indias (166,7 millones USD) en comparación con los precios minoristas máximos. El ahorro osciló entre el 23 y el 99% (media: 82%) y fue más alto con los medicamentos genéricos que con los de marca y los recién patentados. Este estudio pone de manifiesto las ventajas de la negociación colectiva en lo que respecta a la adquisición conjunta de medicamentos costosos, un enfoque que se puede aplicar a otros sistemas sanitarios.

Prevalence and prognostic significance of IKZF1 deletion in paediatric acute lymphoblastic leukemia: A systematic review and meta-analysis.

IKZF1 (IKAROS family Zinc Finger 1) alteration is an essential regulator of both T- and B-cell lineage specification with leukemogenic potential. IKZF1 deletion have been described in childhood acute lymphoblastic leukemia (ALL) with varying prevalence often influenced by underlying cytogenetics and also shown to have diverse prognostic significance. We aimed to evaluate the prevalence and prognostic significance of IKZF1 deletion among childhood ALL. Electronic databases of MEDLINE, EMBASE and SCOPUS were searched and 32 studies found eligible. Estimated prevalence of IKZF1 deletion among BCR::ABL1 negative and BCR::ABL1 positive ALL patients was 14% (95%CI:13-16%, I2 = 79%; 26 studies) and 63% (95%CI:59-68% I2 = 42%; 10 studies) respectively. Most common site of IKZF1 deletion was whole chromosome (exon1-8) deletion in 32.3% (95%CI: 23.8-40.7%) followed by exon 4-7 deletion in 28.6% (95%CI: 19.7-37.5%). A positive minimal residual disease at the end of induction was more common among patients with IKZF1 deletion, odds ratio: 3.09 (95%CI:2.3-4.16, I2 = 54%; 15 studies). Event-free survival and overall survival were significantly worse for IKZF1 deletion, hazard ratio (HR): 2.10 (95%CI:1.90-2.32, I2 = 28%; 31 studies) and HR: 2.38 (95%CI:1.93-2.93, I2 = 40; 15 studies) respectively. In summary, the current meta-analysis highlights the frequency of IKZF1 deletion and its negative impact on survival in childhood ALL. Further studies exploring the influence of IKZF1 deletion in the presence of classical cytogenetic and other copy number alterations would further help in characterising its prognostic role.

Reducing chemotherapy dose intensity by 25% and adding rituximab improves survival in pediatric mature B-cell non-Hodgkin lymphoma in LMIC setting.

BACKGROUND AND OBJECTIVES: Pediatric B-cell non-Hodgkin lymphomas (NHL) in low- and middle-income countries (LMICs) have historically had inferior outcomes due to higher treatment-related mortality (TRM) and relapses. To address this issue, we evaluated the impact of reducing chemotherapy dose intensity by 25% and adding rituximab on outcomes in pediatric B-NHL. PATIENTS AND METHODS: Patients, less than 18 years of age with group B and C disease as per the Lymphome Malin de Burkitt (LMB) risk stratification were enrolled between September 2017 and October 2022. The LMB-89 protocol, with a 25% reduction in all chemotherapy doses and the addition of rituximab, was administered. The response was assessed using positron emission tomography with computed tomography (PET/CT) after four cycles of chemotherapy (interim) and at the end of treatment. RESULTS: The study included 25 patients with a median age of 6.9 years, among whom 20 (80%) were males. Twenty patients had group B and five had group C disease. Complete metabolic response (CMR) was achieved by 22/25 (88%) patients, and three (12%) achieved partial metabolic response (PMR) in the interim PET/CT. At the end of treatment, 22/24 (92%) patients achieved CMR, one had PMR, and one had progressive disease. The median follow-up was 45 months (range: 3-71 months). The 4-year event-free survival and overall survival were 88% and 92%, respectively. There were two deaths, one due to disease progression and the other due to sepsis. CONCLUSION: Our study demonstrates a significant improvement in outcomes in pediatric B-NHL compared to previous reports from LMICs, achieved through a 25% reduction in chemotherapy dose intensity and the addition of rituximab.

2023 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting.

PURPOSE: This review is an update of the MASCC/ESMO 2015 recommendations for the prophylaxis of acute and delayed nausea and vomiting induced by multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting. METHODS: A systematic literature search was conducted using PubMed from June 1, 2015, through February 1, 2023. RESULTS: We identified 56 references (16 were duplications or invalid), leaving 40 manuscripts for this search. The panel classified level I evidence (three manuscripts) and level II evidence (14 manuscripts). High-dose chemotherapy and stem cell transplant were discussed in four of these manuscripts, and multiple-day chemotherapy treatment in 15. Some manuscripts covered both topics. Additionally, a search for breakthrough nausea and vomiting resulted in 12 "hits." No new relevant studies were identified. CONCLUSIONS: The recommendations for patients receiving high-dose chemotherapy with stem cell transplants and patients undergoing multiple-day cisplatin were updated. For patients receiving high-dose chemotherapy for stem cell transplant, a combination of a 5-HT3 receptor antagonist with dexamethasone and aprepitant is recommended. Olanzapine could be considered part of the antiemetic regimen. Patients receiving multiple-day cisplatin should receive a 5-HT3 receptor antagonist plus dexamethasone plus aprepitant plus olanzapine. For patients experiencing breakthrough nausea and vomiting, the available evidence suggests using a single dose of olanzapine daily for 3 days.

The impact of COVID-19 pandemic on access to treatment for children with cancer in India and treating center practices.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led the Indian government to announce a nationwide lockdown on March 23, 2020. This study aimed to explore the impact of the pandemic on the accessibility of care for children with cancer and to view strategies adopted by hospitals for service delivery. METHODS: Weekly average of childhood cancer (≤18 years) patient registrations during pre-lockdown period (January 1 to March 23, 2020) were compared with post-lockdown period (March 24 to May 31, 2020). The effect on the scheduled treatment was investigated for post-lockdown period. A survey of health care providers was conducted to determine centers' adopted strategies. RESULTS: In 30 participating centers, 1146 patients with childhood cancer (797 pre-lockdown period and 349 post-lockdown period) were registered. The weekly average registration was 67.3 and 35.5 patients during pre-lockdown and post-lockdown respectively (decline of 47.9%). Although most centers experienced this decline, there were 4 that saw an increase in patient registrations. The distribution of patients registered post-lockdown was found significantly different by age (lesser older age, P = .010) and distance (lesser travel distance, P = .001). 36.1% of patients, who were scheduled for any of the treatment modalities (chemotherapy, surgery, radiotherapy, and hematopoietic stem cell transplantation) during the post-lockdown period, experienced delays. Centers adopted several strategies including modifications to treatment protocols, increased use of growth factors, and increased support from social organizations. CONCLUSIONS: This multicenter study from India suggests that the COVID-19 pandemic and the lockdown impacted 2 out of 3 children with cancer. The effect of this on survival is yet to be established.

Hodgkin Lymphoma in Children Under 5 Years: Do They Behave Differently?

The median age of presentation for Hodgkin lymphoma (HL) is lower in developing countries with a higher proportion under 5 years of age possibly attributable to the high prevalence of Epstein-Barr virus-driven disease. It is unclear whether the clinical presentation and outcomes of this cohort are different with concern regarding late effects being most pronounced in this age group. We report the outcome of children under 5 years of age enrolled in the InPOG-HL-15-01, the first multicentric collaborative study for newly diagnosed children and adolescents with HL from India. Thirty-five (9%) of the study population was younger than 5 years with a striking male preponderance of 34:1. They were less likely to have bulky disease, mediastinal or splenic involvement. The outcomes appear to be at least as favorable as in the older patient group. Efforts need to be made to evolve treatment strategies that spare this very young cohort from potential late effects.

Symposium report: breast cancer in India-trends, environmental exposures and clinical implications.

PURPOSE: Incidence of breast cancer (BC), particularly in young women, are rising in India. Without population-based mammography screening, rising rates cannot be attributed to screening. Investigations are needed to understand the potential drivers of this trend. METHODS: An international team of experts convened to discuss the trends, environmental exposures, and clinical implications associated with BC in India and outlined recommendations for its management. RESULTS: Panels were structured across three major BC themes (n = 10 presentations). The symposium concluded with a semi-structured Think Tank designed to elicit short-term and long-term goals that could address the challenges of BC in India. CONCLUSION: There was consensus that the prevalence of late-stage BC and the high BC mortality rates are associated with the practice of detection, which is primarily through clinical and self-breast exams, as opposed to mammography. Triple-Negative BC (TNBC) was extensively discussed, including TNBC etiology and potential risk factors, the limited treatment options, and if reported TNBC rates are supported by rigorous scientific evidence. The Think Tank session yielded long-term and short-term goals to further BC reduction in India and included more regional etiological studies on environmental exposures using existing India-based cohorts and case-control studies, standardization for molecular subtyping of BC cases, and improving the public's awareness of breast health.

Treating early-stage Hodgkin lymphoma in resource-limited settings: InPOG-HL-15-01 experience.

BACKGROUND: Hodgkin lymphoma (HL) in childhood is an eminently curable disease. Excellent outcomes can be achieved even in resource-limited settings and increasingly, the focus is on limiting long-term toxicity. Contemporary treatment incorporates a risk-stratified, response-adapted approach using multiagent chemotherapy with or without low-dose radiotherapy (RT). Many developing countries continue to use ABVD (adriamycin, bleomycin, vinblastin, and dacarbazine)-based regimen owing to limited acute toxicity, cost, and ease of delivery. We report outcomes of children with early-stage HL using limited cycles of ABVD-based treatment in the first prospective multicentric collaborative study from India InPOG-HL-15-01. METHODS: Children <18 years with biopsy-proven HL were enrolled. Patients with stages I and IIA with or without bulky disease were classified as having early-stage disease. Patients were planned to receive four cycles of ABVD subject to satisfactory early response assessment (ERA) scheduled after two cycles of chemotherapy. RT was limited to patients with bulky disease or those with suboptimal ERA. RESULTS: Four hundred ten patients were enrolled over 30 months from 27 centers. One hundred thirty-four were classified as having early-stage disease. Fifty-three (40%) of these had bulky disease. One hundred ten (83%) of this cohort achieved complete or very good partial ERA. Fifty-four (40%) received RT. At a median of 52 months since diagnosis, 5-year event-free survival (EFS) and overall survival (OS) is 94% and 95.5%, respectively. Treatment-related mortality and abandonment were <1%. CONCLUSION: Limited cycles of ABVD with RT to selected patients is a very effective option for patients with early-stage disease in resource-limited settings.

COVID19 in children with cancer in low- and middle-income countries: Experience from a cancer center in Chennai, India.

Crowded outpatient clinics and common wards in many hospitals in low and middle-income countries predispose children, caregivers, and health care workers to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report on the clinical features and outcomes of 15 children with cancer at our center who tested positive for SARS-CoV-2. Five out of 15 patients were symptomatic, and one patient required intensive care and respiratory support. All the patients in the study have recovered from the SARS-CoV-2 infection without any sequelae and have resumed their cancer treatment.

Olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced vomiting in children: An open-label, randomized phase 3 trial.

BACKGROUND: Breakthrough chemotherapy-induced vomiting (CIV) is defined as CIV occurring after adequate antiemetic prophylaxis. Olanzapine and metoclopramide are two drugs recommended for the treatment of breakthrough CIV in children, without adequate evidence. We conducted an open-label, single-center, phase 3 randomized controlled trial comparing the safety and efficacy of olanzapine and metoclopramide for treating breakthrough CIV. PROCEDURE: Children aged 5-18 years who developed breakthrough CIV after receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy were randomly assigned to the metoclopramide or olanzapine arm. The primary objective of the study was to compare the complete response (CR) rates between patients receiving olanzapine or metoclopramide for treating breakthrough CIV during 72 hours after the administration of the study drug. Secondary objectives were to compare CR rates for nausea and toxicities between the two arms. RESULTS: Eighty patients were analyzed (39 in the olanzapine arm and 41 in the metoclopramide arm). CR rates were significantly higher in the olanzapine arm compared with the metoclopramide arm for vomiting (72% vs 39%, P = 0.003) and nausea (59% vs 34%, P = 0.026). Seven patients in the metoclopramide arm crossed over to the olanzapine arm and none crossed over in the olanzapine arm (P < 0.001). The mean nausea score in the olanzapine arm was significantly lower than the metoclopramide arm after the initiation of the rescue antiemetic (P = 0.01). Hyperglycemia and drowsiness were more commonly seen in the olanzapine arm. CONCLUSION: Olanzapine is superior to metoclopramide for the treatment of breakthrough CIV in children. Drowsiness and hyperglycemia need to be monitored closely in children receiving olanzapine for breakthrough CIV.

A retrospective analysis of patients undergoing postchemotherapy retroperitoneal lymph node dissection and metastasectomy in advanced nonseminomatous germ cell tumors.

INTRODUCTION: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) and metastasectomy play an important role in the management of advanced-stage nonseminomatous germ cell tumors (NSGCT). We aimed to analyze preoperative parameters that could predict postoperative histology. MATERIALS AND METHODS: We analyzed the data of 72 patients who underwent PC-RPLND and 14 patients who underwent metastasectomy after receiving cisplatin- or carboplatin-based chemotherapy for advanced stage NSGCT at our institute from 1994 to 2015. Clinical and pathological parameters such as the histology of orchidectomy, RPLND and metastasectomy, serum tumor markers, and the pre and post chemotherapy retroperitoneal lymph node size were recorded. RESULTS: Seventy-two patients with a mean age of 28 years underwent PC-RPLND. Of the various variables evaluated, only percentage change in nodal size was found to be statistically significant in predicting necrosis (P = 0.004). A decrease of 75% was found to predict the necrosis with a specificity of 100%. There was 84.6% concordance between the histology of RPLND and that of metastasectomy. CONCLUSION: A 75% reduction in tumor size is highly predictive of absence of viable tumor or teratoma, however larger series are required to confirm these findings. RPLND histopathologies have a high concordance with metastasectomy histology and thus can be used as a guide to tailor further management.

Intravenous fosaprepitant for the prevention of chemotherapy-induced vomiting in children: A double-blind, placebo-controlled, phase III randomized trial.

BACKGROUND: Fosaprepitant is a neurokinin-1 receptor antagonist, approved for the prevention of chemotherapy-induced nausea and vomiting. The data on the use of fosaprepitant in children are limited and therefore we conducted a phase III randomized controlled trial. PROCEDURE: Children aged 1-12 years scheduled to receive moderately or highly emetogenic chemotherapy were randomly assigned to arm-A (fosaprepitant) or arm-B (placebo). Children recruited to arm-A received intravenous ondansetron plus dexamethasone followed by fosaprepitant infusion. Children recruited to arm-B received the same drugs as those given to children in arm-A, except that fosaprepitant was substituted with a placebo. Ondansetron and dexamethasone were continued for 48 hours after completion of chemotherapy. The primary end point of the study was to determine the proportion of patients who achieved a complete response (CR), defined as no vomiting, no retching, and no use of rescue medication, during the 24-120 hours (delayed phase) after administration of the last dose of chemotherapy. Secondary end points were the proportion of patients who achieved a CR during the acute phase (0-24 hours) and overall after administration of the last dose of chemotherapy. RESULTS: One-hundred-sixty-three patients were analyzed (81 in the fosaprepitant arm and 82 in the placebo arm). CR rates were significantly higher in the fosaprepitant arm compared to those in the placebo arm during the acute phase (86% vs 60%, P < 0.001), delayed phase (79% vs 51%, P < 0.001), and overall phase (70% vs 41%, P < 0.001). Three (4%) patients in the fosaprepitant arm and sixteen (20%) in the placebo arm required rescue anti-emetics (P = 0.0017). CONCLUSION: Addition of fosaprepitant to ondansetron and dexamethasone improved chemotherapy-induced vomiting control in children treated with moderately or highly emetogenic chemotherapy.

Prevalence of multi-drug resistant organisms in stool of paediatric patients with acute leukaemia and correlation with blood culture positivity: A single institution experience.

BACKGROUND: Multi-drug resistant (MDR) bacteria are associated with increased morbidity and mortality in children with acute leukaemia. The present study was conducted to assess the prevalence of MDR bacteria in stool cultures of patients with acute leukaemia at presentation to the hospital. The results were then correlated with blood cultures when patients developed septicaemia. PATIENTS AND METHODS: The study involved analysis of case records of patients with newly diagnosed acute leukaemia less than 18 years of age treated at our centre from January 2015 to December 2015. Stool cultures were sent within 72 hr of hospital admission and blood cultures were sent when clinically indicated. MDR was defined as resistance to at least one antibiotic in three or more following antimicrobial groups: cephalosporins, ß-lactam/ß-lactamase inhibitor, carbapenems, fluoroquinolones and aminoglycosides. RESULTS: The analysis included 85 patients with acute leukaemia, among whom 48 of 85 (56%) patients had positive stool cultures and 42 of 85 (50%) patients were positive for MDR bacteria. Blood cultures were positive in 13 of 48 patients (27%, seven MDR and six non-MDR) with positive stool cultures and three of 37 patients (8%, one MDR and two non-MDR) with negative stool cultures (P = 0.01). The concordance between stool and blood culture for similar organism was 61%. There were seven deaths in 48 stool culture positive patients and two deaths in 37 stool culture negative patients. CONCLUSION: This study shows the high prevalence of MDR bacteria in newly diagnosed children with acute leukaemia. Colonisation with MDR bacteria in stools is associated with increased positivity of blood cultures and mortality.