Publications by authors named "Nirmalya Roy Moulik"

30 Publications

  • Page 1 of 1

Importance of conventional cytogenetics in the identification of ins(19;X)(q13.1;p11.2q28) and t(1;11)(q10;p10), both, novel cytogenetic abnormalities in a pediatric AML case.

Cancer Genet 2021 Mar 21;256-257:17-20. Epub 2021 Mar 21.

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

Acute Myeloid Leukemia (AML) is a heterogeneous disease with respect to morphology, immunophenotype, chromosomal abnormalities and genetic lesions. While a majority of AML cases harbour recurrent chromosomal abnormalities, several rare, apparently unique or novel aberrations may be identified by conventional cytogenetics. In fact, with the prognostic relevance of chromosomal abnormalities, and with the advent of new-age, target-specific therapy, identifying such aberrations becomes vital. In this study, we present a case of pediatric AML with ins(19;X)(q13.1;p11.2q28) and t(1;11)(q10;p10), both, novel, previously unreported chromosomal abnormalities in AML. Post induction, both these clonal cytogenetic abnormalities persisted. The documentation of this case will help determine the significance of these cytogenetic abnormalities. Also, this case exemplifies the importance of cytogenetics in the complete characterization and risk stratification of AML patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cancergen.2021.03.002DOI Listing
March 2021

A novel case of intrachromosomal amplification and insertion of RUNX1 on derivative chromosome 2 in pediatric AML.

Cancer Genet 2021 Jun 15;254-255:65-69. Epub 2021 Feb 15.

Department of Pediatric Oncology, Tata Memorial Hospital, Dr. E. Borges Road, Parel. Mumbai 400012, India; Cancer Cytogenetics Department, Room No. 6, CCE building, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Sector-22, Kharghar, Navi Mumbai 410210 India. Electronic address:

Intrachromosomal amplification of RUNX1 gene on chromosome 21 (iAMP21) is a rare occurrence in acute myeloid leukemia (AML). Herein, we describe a case of AML with amplification of RUNX1 and its insertion on chromosome 2 detected by conventional karyotyping and confirmed by metaphase FISH. A six-year-old female was diagnosed as acute myeloid leukemia with monocytic differentiation. The patient's bone marrow revealed 74% blasts which were MPO negative. Conventional karyotyping revealed a complex karyotype, with rearrangements in chromosomes 1, 2, 7, 8 and hsr(21). FISH on interphase cells with LSI RUNX1-RUNX1T1 dual colour dual fusion translocation probe showed 6-7 copies of RUNX1 signal. Metaphase FISH with LSI RUNX1-RUNX1T1 probe confirmed amplification of RUNX1 and insertion of amplified RUNX1 sequences on long arm of chromosome 2. Induction chemotherapy was initiated, however, the patient died within one month of diagnosis suggesting poor outcome associated with this novel finding. Insertion of amplified RUNX1 on another chromosome has not yet been reported so far.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cancergen.2021.02.004DOI Listing
June 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724305PMC
December 2020

Defibrotide treatment but not prophylaxis is useful in hepatic sinusoidal obstruction syndrome in children undergoing autologous stem cell transplant following high-dose chemotherapy: A single-center experience from the Royal Marsden Hospital, UK.

Pediatr Blood Cancer 2020 11 31;67(11):e28677. Epub 2020 Aug 31.

Children and Young People's Unit, The Royal Marsden Hospital, Sutton, United Kingdom.

Background: Hepatic sinusoidal obstruction syndrome (SOS) is a serious complication of autologous stem cell transplant (ASCT) in children with historically high mortality rates. Defibrotide has shown proven benefit in its treatment and may have a modest role in prevention. We report our experience with SOS in children undergoing autologous transplant.

Methods: Case records of 82 consecutive patients undergoing ASCT following high-dose chemotherapy between 2010 and 2017 were reviewed. Defibrotide was used for treatment of all with SOS and prophylactically in patients receiving busulfan-based conditioning until 2014.

Results: Fourteen of the 82 children (17%) were diagnosed with SOS. The incidence was higher in those receiving busulfan-based conditioning (13/42 vs 1/40, P = 0.008). Mean (±SD) time to diagnosis of SOS was 19 (±5.6) days following stem cell rescue. Bilirubin levels and ultrasound were normal in 7/14 and 3/14 patients. Coagulopathy was noted in 10/14; one child developed multiorgan involvement. Nine children had mild SOS, whereas two and three had moderate and severe SOS, respectively. Intensive care was required for four of five non-mild cases. Patients with SOS had significantly delayed platelet recovery, higher transfusion requirement, and longer hospital stay. Unavailability of defibrotide prophylaxis for 17/42 receiving busulfan did not change the incidence of SOS (7/25 with defibrotide vs 6 /17 without defibrotide, P = 0.74). There was no significant difference in the severity of SOS between these groups.

Conclusion: Hepatic SOS was more commonly seen in children receiving busulfan-based conditioning. Stopping the use of prophylactic defibrotide did not increase incidence or severity of SOS. Overall outcome was excellent with supportive care and timely treatment with defibrotide.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.28677DOI 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.28682DOI Listing
November 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2020.1798951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116445PMC
December 2020

Assessment of tumor Epstein-Barr Virus status and its impact on outcomes in intermediate and high-risk childhood classic Hodgkin Lymphoma treated at a tertiary cancer center in India.

Leuk Lymphoma 2020 12 30;61(13):3217-3225. Epub 2020 Jul 30.

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

Indian studies on EBV in childhood classic Hodgkin Lymphoma (cHL) have mainly analyzed the epidemiology of EBV-positive [EBV(+)HL] or negative HL [EBV(-)HL], with limited data on outcomes. We studied a large cohort of children with intermediate and high-Risk cHL for tumor EBV status and its impact on outcomes retrospectively. Of evaluable 189 patients, 84.7% had EBV(+)HL. Positive status was significantly associated with age ≤ 10 years ( < .001), males ( = .015), non-Nodular Sclerosis (NS) histology ( = .004) and inversely with bulky-mediastinal disease ( < .001). At a median follow-up of 29-months (range1-75), 3-year Event-Free Survival (EFS) for EBV(+)HL and EBV(-)HL was 93.6%(95%CI:89.8%-97.5%), 81.1%(95%CI:67.2%-97.9%), ( = .048) and Overall Survival (OS) was 94.9%(95%CI:91.6%-98.4%), 84.6%(95%CI:71.5%-100%), ( = .075) respectively. Three-year EFS was better in males (HR-0.267,95%CI:0.078-0.916,  = .036) in EBV(+)HL and in patients with serum-albumin > 3g/dL (HR-0.117,95%CI:0.019-0.705,  = .019) in EBV(-)HL. EBV is associated with most of intermediate and high-risk childhood cHL, occurs in younger male patients with non-NS histology, with reduced incidence of bulky-mediastinal disease and favorable survival in childhood cHL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2020.1800005DOI Listing
December 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.

View Article and Find Full Text PDF

Download full-text PDF

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

Cytogenetic profile and outcome of a pediatric acute promyelocytic leukemia patient presenting with isolated isochromosome 17q in absence of RARA rearrangement.

Blood Cells Mol Dis 2021 May 3;88:102443. Epub 2020 May 3.

Department of Pediatric Oncology, Tata Memorial Hospital, Dr. E. Borges Road, Parel, Mumbai 400012, India; Homi Bhabha National Institute (HBNI), Anushaktinagar, Mumbai 400094, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bcmd.2020.102443DOI Listing
May 2021

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcp.14216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256116PMC
June 2020

Immunization of Children with Cancer in India Treated with Chemotherapy - Consensus Guideline from the Pediatric Hematology-Oncology Chapter and the Advisory Committee on Vaccination and Immunization Practices of the Indian Academy of Pediatrics.

Indian Pediatr 2019 12;56(12):1041-1048

Max Super Speciality Hospital, Saket, New Delhi, India.

Justification: Children with cancer need to be immunized against the common vaccine-preventable diseases after completion and sometimes during ongoing treatment of cancer. However, the immunization schedule for these children needs to be altered due to disease and treatment related immune-suppression. Consequently, there are many guidelines/practice statements from around the world to address this issue, however, there is no such comprehensive guideline from India catering to the need of Indian children with cancer.

Process: A guideline was drafted after reviewing the available literature. The draft guideline was discussed and modified in a meeting attended by pediatric oncologists from the PHO chapter and vaccine experts from the ACVIP of the IAP. Subsequently, the modified draft was reviewed and recommendations were finalized.

Objectives: To review the current evidence and generate a nationally relevant guideline for immunization of children receiving chemotherapy for cancer.

Recommendations: Live vaccines are contraindicated during and up to 6 months after end of chemotherapy. Non-live vaccines are also best given after 6 months from the end of treatment for durable immunity. Annual inactivated influenza vaccine is the only vaccine recommended for all children during chemotherapy whereas hepatitis B vaccine is recommended only for previously unimmunised children with risk of transfusion associated transmission of infection. Post-treatment re-immunization/catch-up schedule largely depends on the pre-chemotherapy immunization status. Sibling immunization should continue uninterrupted except for oral polio vaccine which needs to be substituted by the injectable vaccine. Inactivated influenza vaccine is recommended and varicella vaccine is encouraged for all contacts including siblings.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2019

Managing peritoneal involvement in children and young people with rhabdomyosarcoma: A single-center experience from the United Kingdom.

Pediatr Blood Cancer 2019 09 27;66(9):e27805. Epub 2019 May 27.

Children and Young People's Unit, Royal Marsden Hospital, Sutton, United Kingdom.

We describe our experience in managing nine children and adolescents with rhabdomyosarcoma (RMS) and peritoneal involvement. The radiological pattern of peritoneal involvement was diverse from only ascites to solid peritoneal mass/omental caking. Treatment included systemic chemotherapy in all, surgery in three, and radiotherapy in eight. Two patients with presumed nonmalignant ascites, no solid peritoneal metastasis, nonalveolar histology, near-complete resection of residual disease, and radiotherapy survived long term. One patient has just completed treatment, and the remaining six relapsed/progressed at the time of reporting. Five of six patients died after a median of 5 (3-7) months from relapse despite second-line chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.27805DOI Listing
September 2019

Folic acid, one-carbon metabolism & childhood cancer.

Indian J Med Res 2017 Aug;146(2):163-174

Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

Folate has been studied in relation to many diseases, especially cancer. Although it has been postulated to exert a dual effect on development of cancer, its role remains to be clearly defined. Its effect on cancer is the result of gene-nutrient interaction between the genes in folate metabolic pathway and dietary folate availability; mutations in genes of folate metabolism have been shown to alter individual susceptibility to certain childhood cancers as well as response to cancer chemotherapy. Although mandatory fortification of food items with folate has been initiated in some countries, many countries are yet to adopt this due to concerns about undesired adverse effects of high folate levels on health, especially cancer. However, initial reports suggest that folate fortification has led to reduction in incidence of certain childhood cancers such as neuroblastoma, wilms tumour and leukaemias. Despite studies showing folate depletion during antifolate chemotherapy and higher toxicity of chemotherapy in folate-depleted individuals, folate supplementation during cancer chemotherapy is not routinely recommended. Studies investigating the precise effect of folate supplementation during chemotherapy on both short- and long-term outcomes of cancer are needed to arrive at a consensus guideline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijmr.IJMR_275_15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761026PMC
August 2017

Folate deficiency in north Indian children undergoing maintenance chemotherapy for acute lymphoblastic leukemia-Implications and outcome.

Pediatr Blood Cancer 2018 Jan 2;65(1). Epub 2017 Aug 2.

Department of Biochemistry, King George's Medical University, Lucknow, Uttar Pradesh, India.

Background: Treatment-related toxicity and mortality are not uncommon during maintenance chemotherapy for childhood acute lymphoblastic leukemia (ALL), especially in the low- and middle-income countries (LMIC). Undernutrition and micronutrient deficiencies are commonly seen in children from LMICs undergoing treatment for ALL. The present study examines the prevalence and clinical implications of folate deficiency in north Indian children with ALL during the maintenance phase of treatment in view of prolonged antifolate treatment and high population prevalence of folate deficiency.

Procedures: Pre-cycle folate levels/deficiency as well as weight for age z-score and serum albumin level were determined and correlated with complications of treatment and mortality encountered during the maintenance phase of treatment.

Results: Twenty-nine of 52 children enrolled in the study had folate deficiency at some point during maintenance chemotherapy. Neutropenia (18 of 29 vs. 4 of 23; P = 0.002), thrombocytopenia (17 of 29 vs. 4 of 23; P = 0.005), febrile neutropenia (17 of 29 vs. 4 of 23; P = 0.005), and need for chemotherapy dose reduction (20 of 29 vs. 7 of 21; P = 0.01) were more common in folate-deficient children. Maintenance deaths were higher (8 of 29 vs. 1 of 23; P = 0.03) and survival lower (P = 0.02) in deficient children. In multivariate analysis, hypoalbuminemia (P = 0.02) and folate deficiency (P = 0.01) were associated with febrile neutropenia, and folate deficiency with maintenance deaths (P = 0.03).

Conclusions: Folate deficiency was associated with treatment-related complications and adverse outcome in our patients. The risks and benefits of folate supplementation in deficient children during maintenance chemotherapy need to be explored with properly designed randomized studies in similar settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.26730DOI Listing
January 2018

Long-term risk of portal hypertension and related complications in children treated with 6-thioguanine for acute lymphoblastic leukemia: A single-center experience.

Pediatr Blood Cancer 2017 Oct 24;64(10). Epub 2017 Feb 24.

Department of Paediatrics, The Royal Marsden Hospital, Sutton, SM2 5PT, UK.

Long-term follow-up of 11 children with 6-thioguanine-induced hepatoportal toxicity is described. Features of persistent portal hypertension in eight patients after 9.7 ± 3.4 years (mean ± SD) of treatment were more common in late presenters. Splenomegaly, thrombocytopenia and altered hepatic echotexture were seen in six, eight and seven patients, respectively. One of the thrombocytopenic patients had heavy menstrual bleeding and pregnancy loss. Five of six patients who underwent upper gastrointestinal endoscopy had esophageal varices and four underwent banding. Late presentation in a subset of patients mandates long-term surveillance and follow-up for all patients treated with 6-thioguanine for early detection and management of hepatoportal complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.26495DOI Listing
October 2017

Tracking children with acute lymphoblastic leukemia who abandoned therapy: Experience, challenges, parental perspectives, and impact of treatment subsidies and intensified counseling.

Pediatr Hematol Oncol 2016 Aug 19;33(5):327-337. Epub 2016 Sep 19.

c Division of Pediatric Hematology-Oncology , Department of Pediatrics , King George's Medical University , Lucknow , India.

Refusal for treatment and therapy abandonment are important reasons for unfavorable outcome of childhood acute lymphoblastic leukemia (ALL) in resource-poor countries. The present study, conducted on children with ALL whose treatment was abandoned, attempted to track all these children to ascertain the causes and outcome of therapy abandonment/refusal. In order to improve outcome of ALL, measures to prevent abandonment were introduced in the form of treatment subsidies and intensified multistage counseling. Of the 77 (of 418) children abandoning therapy, 17 (22%) refused upfront, whereas the rest abandoned during various phases of chemotherapy. Only 39 (50.6%) of these 77 families could be subsequently contacted. Financial problems, too many dependents at home, and wrong perceptions about cancer led to abandonment in majority. Children abandoning treatment before completion of induction had a significantly shorter survival than who abandoned post induction (P < .0001). Intensified preabandonment counseling and subsidized treatment led to significant reduction in abandonment rates (P < .0001).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08880018.2016.1212956DOI Listing
August 2016

Effect of folate status and methylenetetrahydrofolate reductase genotypes on the complications and outcome of high dose methotrexate chemotherapy in north Indian children with acute lymphoblastic leukemia.

Indian J Med Paediatr Oncol 2016 Apr-Jun;37(2):85-9

Department of Hematopathology, King George's Medical University, Lucknow, Uttar Pradesh, India.

Purpose: The genes of the folate metabolic pathway have been associated with toxicities during high dose methotrexate therapy for childhood ALL, however, the importance of intrinsic folate status in this regard is unclear.

Methods: In the present study the effect of precourse folate levels and MTHFR genotypes on the complications during high dose methotrexate chemotherapy in children with ALL were examined.

Results: Twenty-one children were studied. Folate deficiency was associated with higher incidence of neutropenia (P = 0.03) and longer duration of chemotherapy interruption (P = 0.009). Children with MTHFR1298 mutations needed more red cell transfusion (P = 0.03). All 3 deaths encountered were seen in folate deficient children.

Conclusions: Folate deficiency was associated with higher complications during high dose methotrexate therapy, the implications of which are important especially in resource poor settings with high prevalence of folate deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/0971-5851.180144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854052PMC
May 2016

Genetic associations of killer immunoglobulin like receptors and class I human leukocyte antigens on childhood acute lymphoblastic leukemia among north Indians.

Hum Immunol 2016 Jan 21;77(1):41-46. Epub 2015 Oct 21.

Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India. Electronic address:

Background: Molecular interactions between KIRs and their cognate HLA class-I ligands, play a central role in the regulation of natural killer (NK) cell responses in malignancies. We aimed to determine the role of KIR genes and their HLA ligands in genetic predisposition of childhood acute lymphoblastic leukemia (ALL).

Methods: Genotyping of 16 KIR genes, along with HLA class-I groups C1/C2 and Bw4 super-type ligands, was carried-out in 137 childhood ALL cases and 274 healthy controls.

Results: We observed an increased incidence of activating KIRs namely; 2DS2 (OR=2.23, p=<0.001), 2DS3 (OR=1.74, p=0.011), 3DS1 (OR=2.22, p=<0.001), 2DS5 (OR=2.10, p=0.001), 2DS1 (OR=4.42, p=<0.001) and 2DS4 (OR=2.88, p=<0.001) genes in childhood ALL cases compared to controls. Frequency of BB genotype that possess 2-6 activating KIR genes was predominant in cases compared to controls (OR=2.55, p=<0.001). KIR-receptor/HLA-ligand combinations analysis revealed a moderate risk of almost 2-fold for activating KIR-ligand combinations namely; KIR2DS1-HLAC2, KIR2DS2-HLAC1 and KIR3DS1-HLABw4 in childhood ALL cases.

Conclusion: Our data suggests the role for KIR genes and their HLA ligands in aetiology of childhood ALL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humimm.2015.10.009DOI Listing
January 2016

Effect of Pre-treatment Nutritional Status, Folate and Vitamin B12 Levels on Induction Chemotherapy in Children with Acute Lymphoblastic Leukemia.

Indian Pediatr 2015 May;52(5):385-9

Departments of Pediatrics, Biochemistry and Hemato-pathology; King Georges University, Lucknow, India. Correspondence to: Dr Archana Kumar, Professor and In-charge, Division of Pediatric Hematology-Oncology, Department of Pediatrics, King Georges University, Lucknow, Uttar Pradesh, India.

Objective: To evaluate pre-treatment undernutrition, and folate and B12 deficiency in children with acute lymphoblastic leukemia, and their correlation with complications and outcome of induction chemotherapy.

Design: Observational study.

Setting: Tertiary care teaching hospital in Northern India.

Participants: 50 children with acute lymphoblastic leukemia.

Procedure: Children were assessed for nutritional status (Weight for age Z-score, serum albumin, folate and B12) at presentation, and were followed-up during induction for bone marrow response, counts and outcome. Folate and B12 were repeated twice at monthly intervals after induction. Univariate and multivariate analyses were done to determine the association of nutritional parameters with the outcome variables.

Results: Baseline undernutrition was observed in 66%, hypo-albuminemia in 32.6%, folate deficiency in 41.3% and B12 deficiency in 36.9% of included children. Significant decline in folate levels was noted on serial assays during chemotherapy (P=0.001). Folate deficient children had higher risk for delayed marrow recovery and counts on day 14 (P=0.007 and P=0.001). Hypoalbuminemia (P=0.04), B12 deficiency (P=0.001) and folate (P=0.03) deficiency were associated with toxic deaths during induction.

Conclusions: Baseline nutritional deficiencies negatively influence the outcome and occurrence of complications during induction chemotherapy in children with acute lymphoblastic leukemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13312-015-0642-xDOI Listing
May 2015

Successful prevention of varicella outbreak in an overcrowded paediatric oncology ward using oral acyclovir prophylaxis.

J Trop Pediatr 2015 Apr 21;61(2):151. Epub 2015 Mar 21.

Department of Pediatrics, King George's Medical University, Lucknow, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/tropej/fmv008DOI Listing
April 2015

Are concerns about folic acid supplementation in children with acute lymphoblastic leukemia justified?

Indian Pediatr 2014 Sep;51(9):754-5

Division of Pediatric Hematology-Oncology, Department of Pediatrics, King George's Medical University, Lucknow, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
September 2014

Glutathione-S-transferase polymorphism and acute lymphoblastic leukemia (ALL) in north Indian children: a case-control study and meta-analysis.

J Hum Genet 2014 Sep 7;59(9):529-35. Epub 2014 Aug 7.

Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

Various studies on association of glutathione S-transferase (GST) polymorphisms and childhood acute lymphoblastic leukemia (ALL) have yielded conflicting results. We examined this association among north Indian children and conducted an updated meta-analysis to overcome sample size-related limitations. GSTM1, GSTP1 and GSTT1 genotypes in 100 children with ALL and 300 healthy controls were compared. GSTT1 null mutation (odds ratio (OR) 2.54, 95% confidence interval (CI) 1.50-4.32) and GSTP1 homozygous mutation (OR 3.13, 95%CI 1.48-6.59) were found to increase the risk of childhood ALL, while GSTM1 did not alter the risk. Meta-analysis included 22, 10 and 20 studies examining the association of childhood ALL with GSTM1, GSTP1 and GSTT1 genotypes, respectively. Only GSTM1 genotype (OR 1.29, 95%CI 1.10-1.62) was associated with increased risk in the overall analysis. However, both GSTM1 (OR 1.54, 95%CI 1.12-2.10) and GSTT1 (OR 1.63, 95%CI 1.32-1.99) null genotypes were associated with increased risk in Asian subjects. The risk of developing childhood ALL was not associated with GSTP1 genotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/jhg.2014.66DOI Listing
September 2014

Role of folate status and methylenetetrahydrofolate reductase genotype on the toxicity and outcome of induction chemotherapy in children with acute lymphoblastic leukemia.

Leuk Lymphoma 2015 May 19;56(5):1379-84. Epub 2014 Aug 19.

Division of Pediatric Hematology-Oncology, Department of Pediatrics, King George's Medical University , Lucknow , India.

The effect of serum folate levels and methylenetetrahydrofolate reductase (MTHFR) genotype on complications and outcome of induction chemotherapy in 150 children with acute lymphoblastic leukemia (ALL) was studied. Folate deficiency in 26% at baseline was more common in children with MTHFR 677 mutations. Folate deficient children had a higher incidence of neutropenia (p = 0.03), thrombocytopenia (p = 0.02) and febrile neutropenia (p = 0.01) and higher transfusion requirement during induction compared to folate sufficient children. Sepsis related induction deaths were more frequent in folate deficient children (p = 0.02) during induction. Children with 677 and 1298 mutations had a higher incidence of cytopenias (p = 0.01) and mucositis (p = 0.007), the risks of which increased with concomitant folate deficiency. A significant fall in folate levels was observed post-induction (p = 0.02), most markedly in mutant 677 genotypes. Multivariate analysis revealed associations of baseline folate deficiency with low counts at day 14 (p = 0.001) and MTHFR 1298 mutations with mucositis (p = 0.02).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/10428194.2014.947608DOI Listing
May 2015

MTHFR gene polymorphism in acute lymphoblastic leukemia among North Indian children: a case-control study and meta-analysis updated from 2011.

J Hum Genet 2014 Jul 12;59(7):397-404. Epub 2014 Jun 12.

Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.

Studies on the association of methylenetetrahydrofolate reductase (MTHFR) genotype in childhood acute lymphoblastic leukemia (ALL) have yielded conflicting results. The present study examines this association in north Indian children with ALL and includes an updated meta-analysis. MTHFR (677 and 1298) genotype of children with ALL and healthy adult controls were done by the PCR-restriction fragment length polymorphism (PCR-RFLP) method and were compared using various models of inheritance. A total of 150 patients and 300 controls were included. The 677T allele was found protective (odds ratio (OR) 0.21, 95% confidence interval (CI) 0.04-0.94), whereas 1298C allele led to an increase in risk (OR 4.44, 95% CI 2.19-8.99) of childhood ALL. Meta-analysis included 31 and 27 studies examining the association of 677 and 1298 genotypes, respectively. The 677 C -> T polymorphism was protective (OR 0.90, 95% CI 0.82-0.99). Protection was more pronounced in folate-sufficient populations as compared with those not covered by folate fortification guidelines. The 1298A->C polymorphism was associated with a marginal increase in risk (OR 1.19, 95% CI 1.01-1.40).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/jhg.2014.44DOI Listing
July 2014

Measles outbreak in a pediatric oncology unit and the role of ribavirin in prevention of complications and containment of the outbreak.

Pediatr Blood Cancer 2013 Oct 29;60(10):E122-4. Epub 2013 Apr 29.

Division of Pediatric Hematology-Oncology, Department of Pediatrics, King George's Medical University, Lucknow, India.

The role of oral ribavirin in treatment and containment of a measles outbreak in 15 children in an oncology unit is presented. Measles was diagnosed on clinical features and history of contact. Measles specific IgM ELISA and RNA were positive in 7 of 15 and 2 of 7 tested children, respectively. Duration of illness was longer in unimmunized as compared to immunized children (P = 0.02). Complications were higher in hematological malignancies (P = 0.025). Delay in starting ribavirin was associated with fatal complications (2 of 2 vs. 0 of 13, P = 0.009). Ribavirin prevented measles in all (21 of 21) patients exposed to the cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.24575DOI Listing
October 2013

The authors reply to Dr. Prashanth.

Pediatr Crit Care Med 2013 Mar;14(3):339-40

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PCC.0b013e31827d152aDOI Listing
March 2013

Causes, outcome and prevention of abandonment in retinoblastoma in India.

Pediatr Blood Cancer 2013 May 9;60(5):771-5. Epub 2013 Jan 9.

Division of Paediatric Haematology-Oncology, Department of Paediatrics, King George's Medical University Lucknow, Uttar Pradesh, India.

Background: The high-cure rates of 90% in retinoblastoma are not replicated in developing countries due to late presentation and poor compliance to treatment. The present study takes a closer look at causes of abandonment of therapy and effectiveness of counselling in reducing abandonment.

Procedure: A retrospective study of children with retinoblastoma registered at our centre from March 2008 through August 2011.

Results: Fifty (49.50%) of 101 children registered for treatment abandoned therapy. Abandonment rates were significantly higher in rural as compared to urban children (P = 0.02). There was no significant difference in rate of abandonment between stages or laterality of disease and other socio-demographic factors. Telephone calls were more effective than letters in tracing patients (31.2% vs. 2.4%). Major reasons cited behind abandonment were financial problems (30%) and unwillingness to enucleate (20%). Of the 12 children who returned and were retreated 6 (50%) died of progressive disease. Nineteen (73%) of those who did not return died at home. Abandonment rates steadily declined from 71.42% in 2008 to 16.66% in 2011 (P = 0.01) due to effective pre-abandonment counselling by a support team under the National Retinoblastoma Registry of India from 2009.

Conclusions: Abandonment rates for children with retinoblastoma continue to be unacceptably high. Rural background, financial constraints and hesitancy to enucleate were important causes behind abandonment. Outcome of patients who abandoned treatment was uniformly dismal. Inclusion of support team and intensified initial counselling helped in improving compliance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.24454DOI Listing
May 2013

Nutritional status and complications in children with diabetic ketoacidosis.

Pediatr Crit Care Med 2012 Jul;13(4):e227-33

Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Objective: Diabetic ketoacidosis in children continues to be an important cause of morbidity and mortality, especially in developing economies as a result of malnutrition, a high rate of infections, and delay in seeking timely medical care. Malnutrition also increases the risk of diabetic ketoacidosis-related complications. The objective of this study was to assess the nutritional status of patients presenting with diabetic ketoacidosis and correlate it with the incidence of complications at presentation and those encountered during the course of illness.

Design: Prospective study.

Setting: Pediatric emergency and intensive care units, Advanced Pediatrics Centre, PGIMER, Chandigarh, India.

Patients: Thirty-three children between 1 month and 12 yrs of age presenting with diabetic ketoacidosis between July 2008 and June 2009 were enrolled consecutively and assessed for nutritional status by anthropometric parameters (body weight, crown-heel length/height, mid-upper arm circumference, triceps and subscapular skin fold thicknesses), biochemical parameters (serum albumin, zinc, magnesium, vitamin A levels), and preillness dietary history (by pretested Food Frequency Questionnaire). Patients were classified as malnourished or normally nourished based on the weight for age criteria matched for Indian standards. The incidence of complications (electrolyte imbalances, hypoglycemia, sepsis, cerebral edema, etc.) and outcome in terms of survival or death in both the groups were compared with Student's t-test for parametric data, Mann-Whitney U test for nonparametric data, and chi-square test for categorical variables.

Interventions: None.

Measurements And Main Results: Anthropometric assessment showed that 11 of 33 (33.3%) were malnourished. Preillness dietary history revealed that 16 (48.5%) were calorie- and protein-deficient (known diabetic n = 7; new onset n = 9), whereas 11 (33.3%) were only calorie-deficient (known diabetic n = 2). Hypoalbuminemia was seen in 21 (63.6%), hypovitaminosis A in eight (24.2%), and low zinc levels in three (9%). The malnourished and normally nourished groups were similar with respect to demographics, precipitating factors, severity of diabetic ketoacidosis, treatment received, and outcome. However, the incidence and severity of therapy-related hypokalemia (100% vs. 72.7%; p = .05) and hypoglycemia (63.6 vs. 13.6%; p = .004) were significantly higher in the former as compared with the latter. The mean ± SD admission serum potassium levels were similar in both the groups (3.4 ± 0.8 mEq/L in the malnourished vs. 3.5 ± 0.7 mEq/L in the normally nourished) with the malnourished group showing a significant fall at 6 hrs after start the of diabetic ketoacidosis protocol (2.8 ± 0.8 mEq/L vs. 3.6 ± 0.7 mEq/L; p = .033), although the mean rate and dose of insulin infusion were similar. The fall in blood glucose (mean ± SD mg/dL) at 12, 24, and 36 hrs after onset of the diabetic ketoacidosis protocol was also significantly greater in the malnourished group as compared with the normally nourished diabetic ketoacidosis (195 ± 69.1 and 272.61 ± 96.3, p = .02; 171 ± 58.5 and 257 ± 96.3, p = .05; and 153.75 ± 49.6 and 241.71 ± 76.3, p = .04, respectively). The incidence of hypophosphatemia, hypomagnesemia, cerebral edema, renal failure, sepsis, and septic shock was similar in both the groups. There were two deaths, both resulting from complicating cerebral edema and renal failure and unrelated to the nutritional status of the patients.

Conclusions: The incidence and severity of therapy-related hypokalemia and hypoglycemia were significantly higher in the malnourished as compared to the normally nourished diabetic ketoacidosis. Other diabetic ketoacidosis-related complications and outcome were similar in both the groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PCC.0b013e31823c9a11DOI Listing
July 2012