Publications by authors named "Maya Prasad"

58 Publications

FDG PETCT for assessing marrow involvement at staging pediatric nonhematological round cell malignancies.

Nucl Med Commun 2021 Oct 7. Epub 2021 Oct 7.

Department of Nuclear medicine and Molecular Imaging, Tata Memorial Hospital, Parel Homi Bhabha National Institute (HBNI), Mumbai, India Mackay base Hospital, Mackay, Australia Department of Surgery Department of Pediatric Medical Oncology, Tata Memorial Hospital, Parel, Mumbai, India.

Background And Hypothesis: Bone and lung are the common sites of metastasis in pediatric round cell tumors and its presence indicates poor outcomes. Staging workup for these malignancies thus includes bone marrow biopsy (BMB) along with evaluation of thorax, and tissue analysis for N MYCN status in neuroblastoma. BMB is an invasive procedure requiring general anesthesia with known disadvantages.With an aim of avoiding an invasive BMB a study was taken up to evaluate efficacy of FDG PET CT in detecting marrow involvement in neuroblastoma and rhabdomyosarcoma at staging.

Materials And Method: Prospective observational study evaluated 83 newly diagnosed treatment naïve patients of neuroblastoma (n = 43) and rhabdomyosarcoma (n = 42) who underwent conventional imaging of PETCT with CECT of local region along with a CT thorax and BMB (both iliac crest) done within 1 week. Findings of FDG PETCT were compared with bone marrow histology and accuracy parameters were calculated.

Result: The overall sensitivity, specificity, accuracy, positive-predictive value (PPV), negative-predictive value (NPV) of FDG PETCT for detection of marrow disease was 100%, 86.1%, 89.4%. 68.9% and 100%, respectively. Subset analysis showed sensitivity, specificity, PPV and NPV of 100%, 66%, 71.4% and 100%, respectively, for neuroblastoma, with rhabdomyosarcoma patients having few events NPV of 100% accuracy of 97.6%.

Conclusion: FDG PETCT with sensitivity and NPV of 100% can be considered as a first stop imaging and biopsy can be avoided in patients with a negative scan.
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http://dx.doi.org/10.1097/MNM.0000000000001491DOI Listing
October 2021

Atypical imaging presentation of herpes simplex virus encephalitis in paediatric immunocompromised oncology patients.

J Med Imaging Radiat Oncol 2021 Sep 14. Epub 2021 Sep 14.

Tata Memorial Centre, Mumbai, India.

Introduction: We aim to assess the imaging manifestations of brain involvement in paediatric immunocompromised patients with haematological malignancies on chemotherapy presenting with encephalitis and positive HSV CSF PCR. We also aim to determine whether our findings are similar or different to those described in literature for paediatric patients in general.

Methods: A retrospective study was performed in paediatric ALL/lymphoma patients on chemotherapy, and cases with positive CSF HSV-PCR with at least one head MRI scan were included. On imaging, location(typical/atypical), post-contrast enhancement and haemorrhage/diffusivity/gliosis were evaluated.

Result: A total of 28 scans were included in study from 16 patients fulfilling inclusion criteria, 12 (75%) HSV-1 and 4 (25%) HSV-2. Of the 16 initial scans (CT n = 10, MRI n = 6), 11 were normal (CT = 7, MRI = 4). Fourteen patients had follow-up MRI, of which two had normal scans. On the abnormal initial scan (5/16), only 20% had typical medial temporal/inferomedial frontal/cingulate involvement. Most had frontal (80%), parietal (60%) and non-medial temporal (40%) lesions. Abnormal diffusivity/haemorrhage was absent in all, and postcontrast enhancement was seen in 20%. On follow-up, more patients (33%) had typical medial temporal/inferomedial frontal/cingulate involvement. Widespread atypical site involvement of frontoparietal (75%), thalamus (58%), non-medial temporal (50%), occipital/basal ganglia (33%) and cerebellum (8%) was noted. Most lesions were cortical (91%)/subcortical (75%) with few periventricular lesions (58%). Few showed abnormal diffusivity (16%), post-contrast parenchymal enhancement/haemorrhage (8%), post-contrast meningeal enhancement (25%) and gliosis (16%).

Conclusion: Immunocompromised paediatric patients with haematological malignancies have widespread atypical brain involvement in herpes simplex encephalitis with lack of diffusion restriction and post-contrast enhancement, likely due to haematogenous spread of HSV across the blood-brain barrier, lack of cellular immunity and limited inflammatory cytokine response.
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http://dx.doi.org/10.1111/1754-9485.13326DOI Listing
September 2021

Assessment of outcomes of elective cancer surgeries in children during coronavirus disease 2019 pandemic: Retrospective cohort study from a tertiary cancer center in India.

Medicine (Baltimore) 2021 Sep;100(35):e26752

Homi Bhabha National Institute (HBNI), Mumbai, India.

Abstract: To describe the outcomes of elective cancer surgeries and adverse consequences on the patients and medical staff due to the surgical interventions in children during the Coronavirus Disease 2019 (COVID-19) pandemic.The study included children younger than 15 years who underwent elective cancer surgeries from March 4, 2020 and December 3, 2020.A total of 121 patients (62% male; median age, 3 years) underwent surgery. The surgical procedures included nephrectomies (n = 18), neuroblastoma (n = 26) and soft tissue tumor resections (n = 24) and complex surgical procedures like extended liver resections (n = 2), intra-atrial thrombectomy under cardiopulmonary bypass (n = 2), pancreatoduodenectomy (n = 1), and free microvascular flaps (n = 7). Clavien-Dindo Grade III complications were 5% (n = 6), and there were no postoperative deaths. Preoperative COVID-19 testing was performed in 82% of children, and only 2% showed severe acute respiratory syndrome coronavirus 2 positivity. Postoperatively, 26 children were tested because of specific symptoms and, 6 tested positive for severe acute respiratory syndrome coronavirus 2. Except for a median delay of 23 days in treatment, none of the patients with COVID-19 required critical hospital management. None of the surgical residents or faculty acquired COVID-19, while 4 each medical and support staff were tested positive in the study period.COVID-19 was not a deterrent for continued cancer care, and surgeries could be safely performed adopting universal preventive measures without any added morbidity from COVID-19. Caregivers and centers dealing with childhood cancers can be encouraged to sustain or seek early healthcare.
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http://dx.doi.org/10.1097/MD.0000000000026752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415926PMC
September 2021

Psychological distress in primary caregivers of children with cancer during COVID-19 pandemic-A single tertiary care center experience.

Psychooncology 2021 Aug 25. Epub 2021 Aug 25.

Department of Pediatric Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, India.

Objective: Families of children with cancer undergoing treatment during COVID-19 pandemic represent a vulnerable population for psychological distress and early identification and remedial measures are imperative for wellbeing of both the children and the caregivers. This article reports the results of assessment of psychological distress in primary caregivers of children with cancer undergoing treatment at a tertiary care center.

Methods: Primary caregivers of children with cancer (≤15 years) taking treatment at our institute during the period of July 2020 to August 2020 were prospectively evaluated for psychological distress using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) tools over a telephonic call. There were 2 cohorts, A and B (50 participants each) depending on whether child was diagnosed with COVID-19 or not respectively during the study period.

Results: The assessment tool, PHQ-9 showed a score of ≥10 in 13% (n = 13) participants (95%CI:7.1%-21.2%) in the entire cohort and in 16% (n = 8, 95%CI:5.8%-26.2%) and 10% (n = 5, 95%CI:1.7%-18.3%) participants in cohort A and cohort B respectively. GAD-7 showed a score of ≥8 in 18% (n = 18) participants (95%CI:11.0%-27.0%) in the entire cohort and in 20% (n = 10, 95%CI:8.9%-31.1%) and 16% (n = 8, 95%CI:5.8%-26.2%) participants in cohort A and cohort B respectively. All participants were assessed, and supportive psychotherapeutic interventions administered over telephonic call.

Conclusions: Primary caregivers should be assessed and followed up for psychological distress irrespective of other co-existing factors. Robust support systems built over time could help withstand the exceptional strain of a major surge during a pandemic.
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http://dx.doi.org/10.1002/pon.5793DOI Listing
August 2021

COVID-19 in Children with Cancer and Continuation of Cancer-Directed Therapy During the Infection.

Indian J Pediatr 2021 Aug 11. Epub 2021 Aug 11.

Department of Pediatric Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, 400012, India.

Objective: To report the experience with COVID-19 in children with cancer at the largest tertiary-cancer care and referral center in India.

Methods: This study is a single tertiary center experience on COVID-19 in children with cancer and continuation of cancer-directed therapy in them. Children ≤ 15 y on active cancer treatment detected with COVID-19 until September 15, 2020 were prospectively followed up in the study. Patients were managed in accordance with well-laid guidelines. Treatment was continued for children with COVID-19 who were clinically stable and on intensive treatment for various childhood cancers.

Results: One hundred twenty-two children (median age 8 y; range 1-15 y, male:female 1.7:1) with cancer were diagnosed with COVID-19. Of 118 children, 99 (83.9%), 60 (50.8%), 43 (36.4%), 26 (22.0%), and 6 (5.1%) had RT-PCR positivity at 14, 21, 28, 35, and 60 d from diagnosis of COVID-19, respectively. Scheduled risk-directed intravenous chemotherapy was delivered in 70 (90.9%) of 77 children on active systemic treatment with a median delay of 14 d (range 0-48 d) and no increased toxicities. All-cause mortality rate was 7.4% (n = 9) and COVID-19 related mortality rate was 4.9% (n = 6). One hundred-fifteen (94.2%) children with COVID-19 did not require any form of respiratory support during the course of infection.

Conclusions: COVID-19 was not a major deterrent for the continuation of active cancer treatment despite persistent RT-PCR positivity. The long-term assessment of treatment adaptations requires further prospective follow-up and real-time addressal.
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http://dx.doi.org/10.1007/s12098-021-03894-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354680PMC
August 2021

Reference centile curves for mid-upper arm circumference for assessment of under- and overnutrition in school-aged Indian children and adolescents.

Nutrition 2021 Nov-Dec;91-92:111401. Epub 2021 Jun 26.

Division of Pediatric Hematology/Oncology/Stem Cell Transplant, Columbia University Irving Medical Center, New York, New York, USA.

Objectives: Malnutrition is common in developing countries and is not restricted to young children. It has been suggested that measuring mid-upper arm circumference (MUAC) is an easy, accurate, and low-cost method of identifying malnutrition in the early stages. The aims of this study were to construct age- and sex-specific MUAC reference centiles, and to define and validate cutoffs for assessment of under- and overnutrition in Indian children 5 to 17 y of age.

Methods: This was a cross-sectional, multicentric, observational study conducted in seven schools in seven states from June 2018 to November 2019. The study included 6680 healthy 5- to17-y-old children. MUAC was measured using non-stretch tapes (UNICEF). Sex-specific MUAC percentiles were computed for age and height. Cutoffs for MUAC z-scores for thinness and overnutrition were defined and validated for healthy school children (n = 726) and children with cancer (n = 500).

Results: Reference centiles for MUAC for age (and height) for boys and girls are presented. Cutoffs defined for thinness and for obesity were -0.7 and +1.5 z-score, respectively (corresponding to 25th and 95th percentiles of the MUAC for age/height). For ease of use, rounded cutoffs for thinness were 16 and 18.5 cm from 5 to 9 and 10 to 14 y of age, respectively, in both sexes, and a cutoff of 22 cm in boys and 20 cm in girl from 15 to 17 y of age. For obesity, 20 and 25.5 cm from 5 to 9 and 10 to 14 y of age, respectively, in both girls and boys and a rounded cutoff of 29 cm in boys and 27 cm in girls from 15 to17 y are proposed.

Conclusions: We presented MUAC percentiles and cutoffs for screening for thinness and overnutrition in Indian children from 5 to 17 y of age. These data may also be used in children with cancer and other chronic disorders with growth failure.
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http://dx.doi.org/10.1016/j.nut.2021.111401DOI Listing
June 2021

Barriers to long-term follow-up in adolescent and young adult survivors of childhood cancer: Perspectives from a low-middle income setting.

Pediatr Blood Cancer 2021 Dec 19;68(12):e29248. Epub 2021 Jul 19.

Clinical Psychology, Tata Memorial Hospital, Mumbai, India.

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http://dx.doi.org/10.1002/pbc.29248DOI Listing
December 2021

Efficacy of ready-to-use therapeutic food in malnourished children with cancer: Results of a randomized, open-label phase 3 trial.

Pediatr Blood Cancer 2021 Sep 1;68(9):e29197. Epub 2021 Jul 1.

Division of Hematology/Oncology/Stem Cell Transplant, Department of Pediatrics, Columbia University Medical Center, New York, New York, USA.

Background: The adverse influence of undernutrition in children with cancer may be remediated by early nutritional intervention. This study assessed the efficacy of ready-to-use therapeutic food (RUTF) in improving nutritional status and reducing treatment-related toxicities (TRTs) in such children.

Methods: In a randomized controlled phase-3 open-label trial, severely and moderately undernourished children with cancer were randomized 1:1 to receive standard nutritional therapy (SNT) or SNT+RUTF for 6 weeks. The primary outcome (weight gain >10%) and secondary outcomes (improved/maintained nutritional status, improved body composition) were assessed after 6 weeks. TRTs were assessed over 6 months.

Results: Between July 2015 and March 2018, 260 subjects were enrolled, 126 were analyzable in both arms at 6 weeks. More children on RUTF had weight gain (98 [77.8%] vs. 81 [64.2%], p = .025) with a greater increase in fat mass as a percentage of body mass (median 2% [IQR -0.12 to 4.9] vs. 0.5% [IQR -1.45 to 2.27, p = .005]) but a greater loss of lean mass (median -1.86% [IQR -4.4 to 0.50] vs. -0.4% [IQR -2.4 to 1.4, p = .007]) compared to the SNT arm. Fewer subjects on the RUTF arm had episodes of severe infection (10.6% vs. 31%, p < .0001), treatment delays (17.7% vs. 39%, p < .0001), and severe mucositis (11% vs. 23.8%, p = .006) compared to the SNT arm. The odds of developing TRTs on the RUTF arm were lower even after adjusting for improvement in nutritional status.

Conclusions: RUTF is efficacious in improving weight gain and nutritional status in undernourished children with cancer and decreases TRTs. Incorporating RUTF into a healthy, balanced diet should be considered in undernourished children with cancer.
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http://dx.doi.org/10.1002/pbc.29197DOI Listing
September 2021

Nutritional Management of Diencephalic Syndrome: A Case Series.

Neurol India 2021 Mar-Apr;69(2):524-525

Division of Pediatric Oncology, Department of Medical Oncology, Tata Memorial Hospital; Department of Medical Oncology, Homi Bhabha National Institute, Mumbai, Maharashtra, India.

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http://dx.doi.org/10.4103/0028-3886.314587DOI Listing
June 2021

Safety and efficacy of concurrent carboplatin during full-dose craniospinal irradiation for high-risk/metastatic medulloblastoma in a resource-limited setting.

Pediatr Blood Cancer 2021 05 3;68(5):e28925. Epub 2021 Feb 3.

Department of Pediatric Oncology, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India.

Purpose: To assess the safety and efficacy of concurrent carboplatin during craniospinal irradiation (CSI) in high-risk/metastatic medulloblastoma defined as either residual tumor >1.5 cm or leptomeningeal metastases.

Methods: This single-arm combined prospective (2005-2011) and retrospective (2011-2019) study was undertaken at a tertiary care cancer center in India. Following surgery, patients with newly diagnosed high-risk/metastatic medulloblastoma received concurrent carboplatin (35 mg/m ) for 15 days (day 1 to day 15) during CSI plus posterior fossa/tumor bed boost, followed by six cycles of standard adjuvant chemotherapy.

Results: All 97 patients completed their planned course of radiotherapy without interruptions, except for two (2.1%) patients who had brief gaps due to treatment-related toxicity. Grade 3-4 anemia, neutropenia, thrombocytopenia, and febrile neutropenia were seen in four (4.1%), 41 (42.2%) 21 (21.6%), and 18 (18.6%) patients, necessitating packed cell transfusion, granulocyte colony-stimulating factor, and platelet support in five (5.1%), 41 (42.2%), and five (5.1%) patients, respectively, during the concurrent phase. Following myelorecovery, 92 (94.9%) patients completed the planned six cycles of standard adjuvant systemic chemotherapy. There were no treatment-related deaths during the concurrent chemo-radiotherapy phase, while three (3.1%) toxic deaths were ascribed to adjuvant chemotherapy-related complications. At a median follow-up of 82 months, the 5-year Kaplan-Meier estimates of progression-free survival and overall survival were 60.2% and 62.1%, respectively. On univariate analysis, leptomeningeal metastases (M0/M1 vs. M2/M3) and histological subtype (large cell/anaplastic vs. others) emerged as significant prognostic factors for survival.

Conclusion: Addition of concurrent carboplatin to RT as radiosensitizing chemotherapy is a simple and effective way of treatment intensification in high-risk/metastatic medulloblastoma.
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http://dx.doi.org/10.1002/pbc.28925DOI Listing
May 2021

COVID-19 in cancer patients on active systemic therapy - Outcomes from LMIC scenario with an emphasis on need for active treatment.

Cancer Med 2020 12 31;9(23):8747-8753. Epub 2020 Oct 31.

Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, India.

Background: There is limited data on outcomes in cancer patients with coronavirus disease 2019 (COVID-19) from lower middle-income countries (LMICs).

Patients And Methods: This was an observational study, conducted between 12 April and 10 June 2020 at Tata Memorial centre, Mumbai, in cancer patients undergoing systemic therapy with laboratory confirmed COVID-19. The objectives were to evaluate cumulative 30-day all-cause mortality, COVID-19 attributable mortality, factors predicting mortality, and time to viral negativity after initial diagnosis.

Results: Of the 24 660 footfalls and 7043 patients evaluated, 230 patients on active systemic therapy with a median age of 42 (1-75) years were included. COVID-19 infection severity, as per WHO criteria, was mild, moderate, and severe in 195 (85%), 11 (5%), and 24 (11%) patients, respectively. Twenty-three patients (10%) expired during follow-up, with COVID-19 attributable mortality seen in 15 patients (6.5%). There were no mortalities in the pediatric cohort of 31 (14%) patients. Advanced stage cancer being treated with palliative intent vs others [30-day mortality 24%% vs 5%, odds ratio (OR) 5.6, 95% CI 2.28-13.78, P < .001], uncontrolled cancer status vs controlled cancer (30-day mortality37.5%% vs 4%%, OR 14, 95% CI 4.46-44.16, P < .001) and severe COVID-19 vs mild COVID-19 (30-day mortality 71% vs 3%, OR 92.29, 95% CI 26.43-322.21, P < .001) were significantly associated with mortality. The median time to SARS-CoV-2 RT-PCR negativity was 17 days [interquartile range (IQR)17-28) in the cohort.

Conclusions: The mortality rates in cancer patients with COVID-19 who are receiving systemic anti-cancer therapy in LMICSs are marginally higher than that reported in unselected COVID-19 cohorts with prolonged time to viral negativity in a substantial number of patients. The pediatric cancer patients tended to have favorable outcomes.
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http://dx.doi.org/10.1002/cam4.3423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724305PMC
December 2020

Intravascular extension of Wilms tumor: Characteristics of tumor thrombus and their impact on outcomes.

J Pediatr Urol 2021 02 8;17(1):69.e1-69.e8. Epub 2020 Oct 8.

Homi Bhabha National Institute (HBNI), Mumbai, India; Department of Biostatistics, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India.

Background: Studies describing intravascular involvement in Wilms tumor have focused on illustrating individual institutional experience and the elements of surgical management. Thrombus characteristics like extent, patterns of regression, and correlation with the surgical findings, intraluminal adhesion, and viable tumor in the thrombus, and patency of the inferior vena cava (IVC) have not been systematically described.

Objectives: The aim of this study is to evaluate these thrombus characteristics and explore their impact on the overall outcomes.

Methods: All patients with histologically confirmed Wilms tumors with intravascular thrombus diagnosed in the pediatric oncology unit of Tata Memorial Hospital registered from 2006 to 2019 were included. Data regarding clinical, radiological, and surgical particulars were retrieved from the prospectively maintained institutional database. Specific data for the thrombus included: distal extent before and after neoadjuvant chemotherapy, correlation of extent with the surgical findings, completeness of thrombectomy, the presence of a viable tumor in the thrombus, and the patency of the IVC. Survival analysis was performed utilizing the Kaplan-Meier method on SPSS software version 25.

Results: The study included 43 (9.9%) of the 432 patients with Wilms tumor having intravascular extension. Retrohepatic IVC (33.3%) followed by atrioventricular (26%) formed the frequent levels of thrombus with maximum regression occurring after chemotherapy in the latter (Summary figure). The overall concordance rate between computed tomography (CT) scan and surgical findings for the presence of thrombus was 86% and 4 patients had the thrombus limited to a lower level than the preoperative scan. At a median follow-up of 5-years, the 5-year event-free and overall survival was 81% and 82.2% respectively. Atrioventricular thrombus (p = 0.003) and postoperative patency of IVC (p = 0.02) were significantly associated with inferior survival, while the extent of regression, thrombus fracture, and viability was not significant.

Discussion: The findings of this study bring forth the characteristics of intravascular tumor thrombus affecting the outcomes which can be validated in future prospective studies. Although the ideal method for radiological assessment of the intravascular thrombus is elusive, CT scan provided adequate information for the presence and level of the intravascular thrombus with reasonable accuracy in this study. Study limitations include small sample size, the limited number of events, and lack of multivariate analysis to rule out confounding factors that could influence the observed findings.

Conclusion: Atrioventricular thrombus and occlusion of IVC represent adverse prognostic factors. The extent of regression, fracture, and viability of thrombus did not affect survival in this study.
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http://dx.doi.org/10.1016/j.jpurol.2020.10.003DOI Listing
February 2021

Clinicoepidemiologic Profile and Outcome Predicted by Minimal Residual Disease in Children With Mixed-phenotype Acute Leukemia Treated on a Modified MCP-841 Protocol at a Tertiary Cancer Institute in India.

J Pediatr Hematol Oncol 2020 10;42(7):415-419

Departments of Pediatric Oncology.

Introduction: Mixed-phenotype acute leukemia (MPAL) accounts for 1.2% to 5% of acute leukemia across age groups with intermediate prognosis. We evaluated clinicoepidemiologic profiles and outcomes of MPAL.

Methods: Records of children younger than 15 years of age with acute leukemia from January 2010 to December 2016 were reviewed on the basis of the MPAL WHO 2008 criteria. Treatment was uniform with a modified MCP-841 protocol. Descriptive analysis tools were used. Outcomes were measured by the Kaplan-Meier method on MedCalc, version 14.8.1.

Results: Among 3830 children with acute leukemia in the study period, 2892 received treatment from our center, of whom 24 (0.83%) had MPAL, median age 9 years, with a male:female ratio of 3:1, and median white blood cell of 13.4×10/L. Common immunophenotypes were B/myeloid-12 (50%), T/myeloid-9 (37.5%), and B/T-lymphoid-3 (12.5%). Some B/myeloid cases had abnormal cytogenetics. Seventeen patients were evaluable for outcome. Sixteen patients underwent postinduction bone marrow and 13 (81%) achieved morphologic remission. Thirteen patients underwent flow cytometry-based minimal residual disease evaluation; 9 (69%) were <0.01% (4 postinduction, 5 postconsolidation), and 67% of these had sustained remission till the last follow-up. None underwent bone marrow transplant. The projected 3-year event-free and overall survival rates were 40% and 48%, respectively (median follow-up: 22 mo).

Conclusion: MPAL represented <1% of childhood acute leukemia. acute lymphoblastic leukemia-type chemotherapy that incorporated high-dose cytarabine was effective in achieving an minimal residual disease-negativity rate of 69% in evaluated patients, which was also predictive of better outcome.
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http://dx.doi.org/10.1097/MPH.0000000000001880DOI Listing
October 2020

The importance of enteral nutrition to prevent or treat undernutrition in children undergoing treatment for cancer.

Pediatr Blood Cancer 2021 03 23;68(3):e28724. Epub 2020 Sep 23.

Division of Pediatric Oncology, Tata Memorial Hospital, Mumbai, India.

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http://dx.doi.org/10.1002/pbc.28724DOI Listing
March 2021

Focused nutrition clinic for severely malnourished children with cancer is feasible and effective in high-volume, resource-constrained settings.

Expert Rev Anticancer Ther 2020 11 23;20(11):919-920. Epub 2020 Sep 23.

Division of Pediatric Oncology, Tata Memorial Hospital , Mumbai, India.

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http://dx.doi.org/10.1080/14737140.2020.1823225DOI Listing
November 2020

Increased toxicities in children with Burkitt lymphoma treated with rituximab: Experience from a tertiary cancer center in India.

Pediatr Blood Cancer 2020 11 31;67(11):e28682. Epub 2020 Aug 31.

Department of Pediatric Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India.

Background: Even though rituximab has emerged as standard of care for the management of high-risk pediatric Burkitt lymphoma (BL), its safety in children from the low-middle-income countries (LMICs) remains to be proven. We herein report our experience of using rituximab in children with BL.

Methods: All patients diagnosed with BL between January 2015 and December 2017 were treated in a risk-stratified manner with either the modified MCP-842 or modified LMB protocol. Patients with poor response to MCP-842 were switched to the LMB-salvage regimen. In addition, rituximab was given to selected high-risk patients.

Result: Forty-two (49.4%) of 85 patients with BL received rituximab. The incidence of febrile neutropenia (90.5% vs 67.4%; P = 0.02), pneumonia (38.1% vs 11.6%; P = 0.005), intensive care unit admissions (54.5% vs 17.6%; P = 0.002), and toxic deaths (26.2% vs 9.3%; P = 0.04) was higher among BL patients who received rituximab. Pneumonia was fatal in 11 of 16 (69%) patients who received rituximab. On multivariate analysis, rituximab continued to be significantly associated with toxic deaths ( OR: 11.45 [95% CI: 1.87-70.07; P = 0.008]). The addition of rituximab to intensive chemotherapy resulted in an inferior one-year event-free survival (49.4% ± 8.1% vs 79.3% ± 6.5%; P = 0.025) and one-year overall survival (63.1% ± 8.5% vs 91.8% ± 4.5%; P = 0.007) with no improvement in one-year relapse-free survival (78.3% ± 7.3% vs 83.9% ± 6.0%; P = 0.817).

Conclusion: Rituximab was associated with increased toxicities and toxic deaths in our patients. The potential immunomodulatory effect of rituximab and increased susceptibility to infections in patients from LMICs have to be carefully considered while choosing this drug in the treatment of BL in resource-constrained settings.
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http://dx.doi.org/10.1002/pbc.28682DOI Listing
November 2020

Standardizing lymph nodal sampling for Wilms tumor: A feasibility study with outcomes.

J Pediatr Surg 2020 Dec 1;55(12):2668-2675. Epub 2020 Aug 1.

Homi Bhabha National Institute (HBNI), Mumbai, India; Department of Biostatistics, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India.

Background: Despite being mandated by cooperative groups, omission of nodal sampling is the most frequent protocol deviation in surgery for Wilms tumor. The stations as well as the number of nodes that should be sampled are not clearly defined resulting in a marked variation in practices among surgeons. We propose a systematic method for nodal sampling intending to reduce interoperator variation. In this study, we have assessed the feasibility and yield of systematic lymph node sampling and also evaluated the factors influencing nodal metastasis.

Methods: Prospective evaluation of 113 Wilms tumor patients operated at a single tertiary cancer center between 2015 and 2019. All these patients underwent a systematic 5-station nodal sampling.

Results: Median lymph node yield was 8 and 13.2% (15/113) patients harbored a histologically positive nodal disease. Of the patients with positive nodal disease, interaortocaval nodes had metastasis in 46.7% (n = 7). They represented isolated sites of nodal disease (skip metastases) in 28.6% (n = 4) of patients. Right-sided tumors had more frequent involvement of interaortocaval nodes and skip disease. Tumors with high-risk histology had 12.5 times more odds of harboring nodal disease as compared to low and intermediate-risk histology Wilms tumor.

Conclusions: The proposed method of systematic station wise sampling provides a template to guide surgeons in performing lymph node harvesting. Interaortocaval nodes sampling should be performed routinely as the incidence of disease at this station is sufficiently high and metastasis may skip hilar nodes.

Study Of Diagnostic Test: Level III evidence.
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http://dx.doi.org/10.1016/j.jpedsurg.2020.07.026DOI Listing
December 2020

Machine learning derived genomics driven prognostication for acute myeloid leukemia with .

Leuk Lymphoma 2020 12 5;61(13):3154-3160. Epub 2020 Aug 5.

Haematopathology Laboratory, ACTREC, Tata Memorial Centre, Navi Mumbai, India.

Panel based next generation sequencing was performed on a discovery cohort of AML with . Supervised machine learning identified mutation and absence of mutations in and genes as well as a low mutation to be associated with favorable outcome. Based on this data patients were classified into favorable and poor genetic risk classes. Patients classified as poor genetic risk had a significantly lower overall survival (OS) and relapse free survival (RFS). We could validate these findings independently on a validation cohort ( = 61). Patients in the poor genetic risk group were more likely to harbor measurable residual disease. Poor genetic risk emerged as an independent risk factor predictive of inferior outcome. Using an unbiased computational approach based we provide evidence for gene panel-based testing in AML with and a framework for integration of genomic markers toward clinical decision making in this heterogeneous disease entity.
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http://dx.doi.org/10.1080/10428194.2020.1798951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116445PMC
December 2020

High Response Rates and Promising Outcomes of Patients with Relapsed Ewing Sarcoma, Especially in Adolescents and Young Adults Treated on a Novel Hybrid Salvage Chemotherapy Regimen.

J Adolesc Young Adult Oncol 2021 04 20;10(2):185-192. Epub 2020 Jul 20.

Bone and Soft Tissue Disease Management Group and Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India.

About 30%-35% of nonmetastatic and 60%-80% of metastatic Ewing Sarcoma (ES) will relapse post-treatment and outcomes after relapse continue to be poor over last several decades. Prognostic factors affecting survival after relapse of ES are also not robustly known. We present outcomes using a novel hybrid salvage protocol of four active chemotherapeutic agents in our cohort of patients after relapse of ES. This is a retrospective analysis of all consecutive relapsed ES patients treated with curative intent over 4 years (January 2012 to December 2015). All received 12-cycles of hybrid chemotherapy regimen with surgery/radiotherapy done after first 4 cycles. Event-free survival (EFS)/overall survival (OS) estimates were analyzed by Kaplan-Meier product-limit estimator. Cox regression analysis was performed to identify prognostic factors predicting outcome in relapsed ES. Salvage regimen was given to 53/108 relapsed ES patients with the rest having opted for palliation upfront. Median age of the treated patients was 19 years (range: 4-40); male:female ratio was 2.7:1. Median time to first relapse was 18.8 months (range: 2.2-91). While 41/53 patients (77%) completed salvage therapy, 6 (11.3%) progressed and 6 (11.3%) abandoned treatment. Median follow-up of the study cohort is 31 months (range: 4-81). Of the analyzable cohort ( = 47), 30 (64%) had a second relapse or progression on salvage treatment. At last follow-up, 31 patients had died (including one due to toxicity and rest due to disease) and 16 patients were alive (14 with no active disease and 2 with disease). The 4-year EFS and OS are 28% and 37%, respectively, for the entire cohort. While adolescents and young adult patients (AYA) had a better survival (-0.041), relapsed ES patients with shorter disease-free interval (DFI) (<24 months) had a poorer survival (-0.004). The type of relapse (local or metastatic or combined) after primary treatment did not affect outcome after salvage therapy. We have used a novel hybrid chemotherapy protocol using four active agents in relapsed ES, which is well tolerated and shows promising results. Older age (≥15 years) and longer DFI (>24 months) portend better survival post-relapse. In our cohort of relapsed ES, AYAs fared better than others and type of relapse after primary treatment did not affect outcome after salvage therapy.
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http://dx.doi.org/10.1089/jayao.2020.0016DOI Listing
April 2021

Outcomes with nondose-dense chemotherapy for Ewing sarcoma: A practical approach for the developing world.

Pediatr Blood Cancer 2020 11 24;67(11):e28604. Epub 2020 Jul 24.

Department of Pediatric Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, Maharashtra, India.

Background: The current multidisciplinary approach in the treatment of Ewing sarcoma has improved cure rates, with contemporary dose-dense chemotherapy attaining 5-year event-free survival (EFS) of 73% in localized cases. Dose-intense and dose-dense chemotherapy is difficult in the majority of resource-limited settings with limited access to optimal supportive care. We report on patients with Ewing sarcoma treated on EFT-2001, a nondose-dense chemotherapy protocol.

Procedure: A retrospective analysis was conducted of patients (<15 years) with Ewing sarcoma treated with curative intent during January 2013-June 2017 with an institutional ethics committee-approved nondose-dense protocol (EFT-2001). Local therapy was planned after 9-12 weeks of chemotherapy with metastatic sites addressed with radiotherapy. The study assessed outcomes and prognostic factors.

Results: We analysed 200 patients with M:F ratio of 1.27:1 and metastases in 41 patients (20.5%). At a median follow up of 41.5 months (range 4.5-81.8 months), respective 3-year EFS and overall survival (OS) of the whole cohort is 65.3% (95% confidence interval [CI]: 58.1-71.7%) and 79.3% (95% CI: 72.8-84.5%); for localized and metastatic cohort, 70.9% (95% CI: 62.9-77.5%) and 82.8% (95% CI: 75.7-89.0%); and for metastatic cohort, 42.8% (95% CI: 28.0-58.6%) and 65.3% (95% CI: 47.7-78.3%). Presence of residual disease (morphologic/metabolic) on positron emission tomography-computed tomography scan done 3 months post definitive radiotherapy (hazard ratio [HR] 7.92 [95% CI: 3.46-18.14]) and delay in any form of local control >4 months (HR 3.42 [95% CI: 1.32-8.89]) affected outcomes. Nonrelapse mortality during treatment was 6.5%, mainly due to cardiomyopathy (3.0%) and bacterial sepsis (1.5%). Cardiotoxicity was seen in 11.5% of patients.

Conclusions: Nondose-dense chemotherapy provides good outcomes with manageable toxicities in a multidisciplinary treatment approach, while reducing cumulative drug exposures in the developing world where dose-intense or dose-dense chemotherapy could potentially increase toxicity, and hence seems a feasible approach in resource-limited settings. Presence of any residual disease post definitive radiotherapy or delay in local control portends poor outcome.
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http://dx.doi.org/10.1002/pbc.28604DOI Listing
November 2020

Comment on: The COVID-19 pandemic: A rapid global response for children with cancer from SIOP, COG, SIOP-E, SIOP-PODC, IPSO, PROS, CCI, and St Jude Global.

Pediatr Blood Cancer 2020 09 10;67(9):e28462. Epub 2020 Jul 10.

Pediatric Oncology Division, Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India.

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http://dx.doi.org/10.1002/pbc.28462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404379PMC
September 2020

Childhood cancer survivorship and late effects: The landscape in India in 2020.

Pediatr Blood Cancer 2020 09 10;67(9):e28556. Epub 2020 Jul 10.

Tata Memorial Hospital, Mumbai, India.

Survivorship care is a major area of focus in the holistic management of childhood cancer with current knowledge and information almost exclusively from high-income countries. In this review, we summarize the state of scientific knowledge, service delivery, advocacy initiatives, and research efforts in this field in India. Twenty-one single-center studies published until today (20 in the last decade) confirm some of the well-documented issues in childhood cancer survivors and highlight the high prevalence of hepatitis B and hepatitis C infection in our survivors. Heterogeneity in methodology, outcome metrics, and quality precludes drawing further conclusions, and the ongoing multicenter Indian Pediatric Oncology Group study would address this. Besides the usual model of follow-up clinics in hospital settings, innovative models of service delivery led by not-for-profit organizations are being developed. Advocacy initiatives driven by survivors and support groups are also under way. All of these portend a promising future.
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http://dx.doi.org/10.1002/pbc.28556DOI Listing
September 2020

Incidence, treatment, and outcomes of primary and recurrent Non-Wilms renal tumors in children: Report of 109 patients treated at a single institution.

J Pediatr Urol 2020 Aug 5;16(4):475.e1-475.e9. Epub 2020 Jun 5.

Homi Bhabha National Institute (HBNI), Mumbai, India; Department of Nuclear Medicine, Tata Memorial Centre, Bombay, India.

Introduction: Non-Wilms renal tumors represent a compelling subset of childhood renal tumors. However, their relative rarity renders accurate diagnosis, and therapy challenging which in some instance is inferred from their adult counterparts.

Objective: To describe the incidence and analyze the diagnostic challenges, therapies and, outcomes of non-Wilms renal tumors at the largest tertiary cancer centre in India.

Methods: All patients with histologically confirmed non-Wilms renal tumours diagnosed in the paediatric oncology unit of Tata Memorial Hospital between 2006 and 2019 were included. Data regarding clinical and radiological features and treatment outcomes were retrieved from the prospectively maintained institutional database. At the outset, histological types were categorised into a high and low-risk group depending on anticipated survival. Survival analysis was performed utilising the Kaplan-Meier method on SPSS software version 24.0.

Results: Of the 569 patients with renal tumors, 109 (19%) patients with primary (n = 97) or recurrent (n = 12) non-Wilms renal tumors were included. Histological high-risk group included clear cell sarcoma (CCSK) (39.4%), renal cell carcinoma (RCC) (19.3%), malignant rhabdoid tumor (MRTK) (12.8%), Ewing's sarcoma (rES) (15.6%), synovial sarcoma (2%), and undifferentiated sarcoma (2%). The low-risk group comprised of congenital mesoblastic nephroma (CMN) (4.6%), cystic partially differentiated nephroblastoma (2%), and other rare tumors (3%). Diagnostic error occurred in 2 patients in the high-risk group. All low-risk tumours were treated with surgery alone and most (97%) high-risk tumors were operated either upfront (61.5%) or after preoperative chemotherapy (38.4%). Adjuvant therapy based on histology was offered to 70%. The recurrent tumors received various salvage treatments including chemotherapy; radiotherapy; surgery and immunotherapy, however, only 2 patients could be salvaged. The 3-year overall survival for the entire cohort with primary tumors was 59%, and the survival rates were 76.7%, 77.9%, 0.0%, and 52% for CCSK, RCC, MRTK, and rES (summary figure). Low-risk tumors had 100% survival while the recurrent tumors had a median survival of 10.5 months.

Conclusions: Non-Wilms renal tumors constitute a heterogeneous group of tumors, accounting for less than 20% of all renal tumors. Low-risk tumors are associated with excellent outcomes following surgery alone while the high-risk tumours have a variable outcome. MRTK and recurrent non-Wilms tumour have the worst survival. Favourable outcomes for CCSK and RCC and worst outcomes for MRTK were observed in this study. Renal ES have higher incidence of treatment failure and unsatisfactory outcomes. Recurrent non-Wilms tumours have an extremely poor outcome and more alternative or innovative approaches are needed for their treatment.
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http://dx.doi.org/10.1016/j.jpurol.2020.05.168DOI Listing
August 2020

Feasibility of Nonanatomical Liver Resection in Diligently Selected Patients with Hepatoblastoma and Comparison of Outcomes with Anatomic Resection.

Eur J Pediatr Surg 2021 Jun 18;31(3):236-244. Epub 2020 May 18.

Homi Bhabha National Institute, Mumbai, India.

Introduction:  Treatment guidelines for hepatoblastoma discourage nonanatomic liver resections. However, the evidence for this is inadequate and comes from a study performed almost two decades ago which additionally contained inherent limitations. This study aimed to assess the feasibility and oncologic outcomes of nonanatomic resections (NAR) performed in diligently selected patients and compare the results with anatomic resections (AR).

Materials And Methods:  A total of 120 patients who underwent liver resections for hepatoblastoma between January 2008 and July 2019 were reviewed. Feasibility of NAR was based on postchemotherapy relations to vessels, site of the lesion, and possibility of achieving negative resection margins.

Results:  AR was performed in 95 patients and 25 had NAR. The NAR cohort had similar International Childhood Liver Tumors Strategy Group (SIOPEL) risk group distribution. Blood loss and operative times were lower in patients undergoing NAR. No differences were noted between the two groups concerning postoperative morbidity and hospitalization. There were no pathologic positive margins or local recurrences in the NAR patients. Relapse free (RFS) and overall survival (OS) was similar in the two groups ( = 0.54 and 0.96, respectively). Subgroup analysis of only posttreatment extent of tumor (POSTTEXT) I and II patients also showed no difference in RFS or OS for the two groups with a persistent significant difference in operative times and blood loss.

Conclusion:  NAR is feasible with clear margins in carefully selected patients. It is not associated with more complications and outcomes are not inferior to AR. NAR is associated with lesser blood loss and operative time.
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http://dx.doi.org/10.1055/s-0040-1710328DOI Listing
June 2021

Post-induction Measurable Residual Disease Using Multicolor Flow Cytometry Is Strongly Predictive of Inferior Clinical Outcome in the Real-Life Management of Childhood T-Cell Acute Lymphoblastic Leukemia: A Study of 256 Patients.

Front Oncol 2020 24;10:577. Epub 2020 Apr 24.

Hematopathology Laboratory, ACTREC, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India.

Measurable/minimal residual disease (MRD) status is suggested as a powerful indicator of clinical-outcome in T-cell lymphoblastic leukemia/lymphoma (T-ALL). Contrary to B-cell ALL, reports on T-ALL MRD are limited and mostly based on molecular methods, mainly from developed countries. Multicolor flow cytometry (MFC)-based T-ALL studies are very few. Clinically relevant cut-off levels and ideal time-point for MRD assessment are still inconclusive. In view of lack of T-ALL MRD data from the developing world, we evaluated the prognostic value of MFC-based post-induction (PI)-MRD assessment in T-ALL in the context of standard practice. We included 256 childhood-T-ALL patients (age < 15 years) treated with a modified-MCP841 protocol, which uses high-dose cytarabine during consolidation, as a part of standard hospital practice. MRD was studied using 10-color 11-antibody MFC with any level of detectable disease being considered positive. Post-induction (PI)-MRD was available in all patients, and post-consolidation (PC) MRD was available mostly in PI-MRD-positive patients ( = 88). Three years cumulative-incidence-of-relapse (3years-CIR) in PI-MRD-positive patients was inferior to negative patients (46.3% vs. 18.4%). The median relapse-free-survival (RFS), event-free-survival (EFS) and overall-survival (OS) with hazard ratio (HR) of PI-MRD-positive patients were 21.4 months vs not reached ( < 0.0001, HR-4.7), 21.6 months vs. not-reached ( = 0.0003, HR-2.01) and 37.3 months vs. not reached ( = 0.026, HR-1.64) respectively. RFS, EFS and OS of patients with PI-MRD<0.01% ( = 17) were as inferior as PI-MRD ≥ 0.01% in comparison with MRD-negative patients with HR of 4.7 ( < 0.0001), 2.45 ( = 0.0003), and 2.5 ( = 0.029), respectively. Three-years-CIR of patients with hyperleukocytosis (≥100 × 109/L) was also higher (50.5 vs. 27.6%) with inferior RFS, EFS, and OS. Among PI-MRD-positive patients, 3years-CIR, RFS, EFS, and OS of PC-MRD-positive were also inferior to that of negative patients. On multivariate analysis any-level detectable PI-MRD and hyperleukocytosis remained independently associated with inferior RFS, EFS, and OS. A combination of PI-MRD-positive status and hyperleukocytosis identified the patients with the worst clinical outcomes. Detectable PI-MRD using MFC was found to be the strong predictive factor of inferior clinical outcome in T-ALL patients. The combination of PI-MRD status and hyperleukocytosis provides the most influential tool for the management of T-ALL in resource constrained settings from developing world.
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http://dx.doi.org/10.3389/fonc.2020.00577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193086PMC
April 2020

Comment on: Nutritional concerns of survivors of childhood cancer: A "First World" perspective; perspective from a low/middle-income country.

Pediatr Blood Cancer 2020 07 9;67(7):e28362. Epub 2020 May 9.

Department of General Medicine, Tata Memorial Centre, Mumbai, India.

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http://dx.doi.org/10.1002/pbc.28362DOI Listing
July 2020

A Rare Association of Retinoblastoma With Incontinentia Pigmenti.

J Pediatr Hematol Oncol 2020 07;42(5):372-374

Department of Paediatric Oncology, Tata Memorial Hospital, Mumbai, India.

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http://dx.doi.org/10.1097/MPH.0000000000001797DOI Listing
July 2020

Prognostic Value of 18F-FDG PET/CT-Metabolic Parameters at Baseline and Interim Assessment in Pediatric Anaplastic Large Cell Lymphoma.

Clin Nucl Med 2020 Mar;45(3):182-186

From the Departments of Nuclear Medicine and Molecular Imaging.

Introduction: The event-free survival in pediatric anaplastic large cell lymphoma (ALCL) remains at 70% irrespective of the diverse chemotherapy regimens used. There is lack of valid prognostic factors identifying high-risk patients. We investigated the prognostic value of baseline metabolic parameters and interim response on F-FDG PET/CT in pediatric ALCL patients.

Methods: We retrospectively reviewed 40 pediatric ALCL patients with paired F-FDG PET/CT and treated uniformly on vinblastine-based institution protocol. The SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis of the lymphomatous lesion were measured. Continuous PET parameters were stratified by their median values. Deauville scoring system was used to assess response to chemotherapy in the interim scan. Prognostic factors for overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, log-rank test, and Cox proportional hazards model.

Results: At median follow-up of 52 months, 13 patients died and 13 had recurrence. On univariate analysis, higher whole-body MTV (WBMTV) and partial response on interim scan were statistically associated with OS. High-risk features, WBMTV, and partial response were statistically associated with DFS. On multivariate analysis combining baseline characteristics and interim response, interim response (hazard ratio, 3.56; P = 0.034) was statistically significant for OS. Multivariate analysis for DFS using only baseline characteristics revealed WBMTV as statistically significant (hazard ratio, 4.08; P = 0.035), but none of the parameters was statistically significant when baseline characteristics and interim response were evaluated together.

Conclusions: Whole-body tumor burden assessment with MTV and interim response may help to identify high-risk patients who might get benefitted from intensive therapy.
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http://dx.doi.org/10.1097/RLU.0000000000002927DOI Listing
March 2020

A comparison of asparaginase activity in generic formulations of E.coli derived L- asparaginase: In-vitro study and retrospective analysis of asparaginase monitoring in pediatric patients with leukemia.

Br J Clin Pharmacol 2020 06 18;86(6):1081-1088. Epub 2020 Feb 18.

Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Navi Mumbai, India.

Aims: L-asparaginase is an essential medicine in the treatment of pediatric acute lymphoblastic leukemia (ALL) and the quality of generic formulations is an area of concern. We compared nine generic formulations of L-asparaginase available in India with the innovator.

Methods: The quality of formulations was assessed by measuring 72-hour trough asparaginase activity in children with ALL during induction following administration of 10,000 IU/m of L-asparaginase. In-vitro analysis of the label claim was assessed by measuring activity of three generic formulations. Liquid chromatography-mass spectrometry (LC/MS) was used to determine the amount of host contaminant proteins (HCPs) in the formulations.

Results: Between March 2015 to June 2018, 240 samples from 195 patients were analyzed. The number of samples analyzed ranged from 7-66 per generic brand (median: 18) and seven of the innovator. The proportion of generic formulations that failed to achieve a predefined clinical threshold activity of 50 IU/L ranged from 16.7% (2/12) to 84.9% (28/33) in the highest activity to lowest activity generic respectively. On other hand, all innovator samples had activity greater than 50 IU/L. In-vitro asparaginase activity in the three generic formulations tested ranged from 71.4-74.6% of the label claim (10,000 IU) compared to 93.5% for the innovator. LC/MS analysis of generic 5 identified 25 HCPs with a relative peptide count of 27.1% of the total peptides.

Conclusions: Generic formulations had lower asparaginase activity which raises serious clinical concerns regarding their quality. Until stringent regulatory enforcement improves the quality of these generics, dose adaptive strategies coupled with therapeutic drug monitoring need to be considered.
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http://dx.doi.org/10.1111/bcp.14216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256116PMC
June 2020
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