Impact of minimal residual disease on relapse in childhood acute lymphoblastic leukemia: Lessons learnt from a tertiary cancer center in India.

Prognostic predictive value of end of induction minimal residual disease (EOI-MRD) is well established in acute lymphoblastic leukemia (ALL). We evaluated the factors likely to affect EOI-MRD positivity (>0.01%) by flow cytometry and relapse in different BFM-95 (Berlin-Frankfurt-Munich) risk groups among children and adolescents. In this retrospective study, data of 223 newly diagnosed patients with ALL was analyzed. Association between demographic and pretreatment characteristics with EOI-MRD was assessed. Risk factors for relapse were analyzed using univariate and multivariate Cox regression. Proportion of the SR (standard risk), MR (moderate risk), and HR (high risk) patients was 18.8%, 60.9%, 20.3%, respectively. Positive EOI-MRD among these risk groups was observed in 11.9%, 18.3%, and 55.5% patients respectively (p value <.01%). MRD positivity was more likely to be associated with older age (>10 years) and BFM-HR patients (p value .0008 and <.0001). Thirty-four (15.2%) patients relapsed in the whole cohort. On univariate analysis, statistically significant factors for RFS (relapse-free survival) included hyperleukocytosis, high-risk cytogenetics, NCI (National Cancer Institute) high risk, poor day-8 prednisolone response, BFM-HR and positive EOI-MRD status. Of all these only EOI-MRD retained its impact by multivariate analysis. Positive EOI-MRD significantly predicted relapse in BFM-MR with 5-year RFS of 88.0% and 68.4% (p value .02). Five-year RFS of EOI-MRD negative and positive groups were 86.4% and 65.5%, respectively (p value .004). EOI-MRD is a powerful tool to predict relapse in children and adolescent with ALL especially in BFM-MR. Application of MRD in HR patients needs to be redefined in conjunction with other variables.

Metabolic syndrome in childhood cancer survivors: delta BMI a risk factor in lower-middle-income countries.

PURPOSE: Metabolic syndrome (MetSyn) is an important late effect of childhood cancer. The combination of rising obesity and high prevalence of under-nutrition at diagnosis makes this a unique population to study in LMIC (lower middle-income countries). METHODS: Children ≤ 18 years of age at cancer diagnosis, in a single center in a LMIC, who were disease free and had completed treatment at least 2 years prior to study were included. MetSyn was defined using International Federation for Diabetes criteria for Asian Indians. Logistic regression analyses were carried out to evaluate the influence of various risk factors, including delta BMI (increase in body mass index from diagnosis to evaluation), on MetSyn. RESULTS: A high prevalence of MetSyn (12.2%), central obesity (33%), and dyslipidemia (61.8%) were found in a cohort of 500 Asian Indian childhood cancer survivors (CCS) at a median follow-up age of 17 years. Multivariable analysis revealed older age at diagnosis ≥ 10 years, OR 2.9 (1.6-5); longer survival duration ≥ 10 years, OR 2.2 (1.3-3.8); high BMI at diagnosis, OR 3.2 (1.5-6.9); and large delta BMI ≥ 50, OR 3.15(1.7-5.9) to be independent predictors of MetSyn. Patients who were underweight or normal at diagnosis with large delta BMI ≥ 50 had very high odds (OR, 12.5, 1.7-92) of developing MetSyn compared to those with lower delta BMI. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: A high prevalence of MetSyn was observed in CCS with early age at onset. Timely screening and early intervention are proven to be beneficial and delta BMI could be a useful screening tool for LMIC.

Symptomatic Cerebral Sinovenous Thrombosis Associated With L-Asparaginase In Children With Acute Lymphoblastic Leukemia: A Single Institution Experience Over 17 Years.

BACKGROUND: Cerebral sinovenous thrombosis (CSVT) is a rare, yet important complication of acute lymphoblastic leukemia (ALL) therapy, associated with significant morbidity and mortality. Paucity of data from India prompted us to report our experience with CSVT over a period of 17 years. MATERIALS AND METHODS: This is a retrospective analysis of 500 consecutive ALL patients, below 18 year of age, treated between January 1998 and December 2014, who developed symptomatic CVST. RESULTS: Seven of the 467 eligible patients developed symptomatic CVST with an incidence of 1.5% (7/467). Six of the CVST events, occurred during induction and 1 during reinduction. Median time to symptoms was 21 days (range, 2 to 27 d) from first exposure to L-asparaginase therapy. Management included low-molecular-weight heparin (enoxaparin sodium) at a dose of 1 mg/kg twice a day for at least 3 months along with supportive care. There were 2 thrombosis-attributable deaths. The remaining patients tolerated rechallenge with L-asparaginase uneventfully during reinduction, under cover of heparin prophylaxis. Complete neurological recovery was observed in all surviving patients. CONCLUSIONS: Incidence of symptomatic L-asparaginase associated CSVT during ALL treatment was 1.5% with high case fatality rate (28%). It is noteworthy that full neurological recovery is likely in surviving patients, and rechallenge with L-asparaginase is safe with heparin prophylaxis. Currently available screening methods are not practically implementable in resource-limited settings.

Profile of Childhood Cancers From Hospital-Based Cancer Registries in India, 2012-19.

OBJECTIVE: To describe the clinical pattern of childhood and adolescent cancers across India using hospital-based data in the National Cancer Registry Program. METHODS: Records of 60720 cancer cases in the 0-19 year age group for the period 2012-2019 from 96 hospital-based cancer registries were reviewed. Childhood cancers were classified based on the International Classification of Childhood Cancer (ICCC). Descriptive analysis was used to examine the distribution of cancer by five-year age groups, sex and ICCC diagnostic groups and subgroups. Data were analysed using IBM SPSS software and visualised using R software. RESULTS: 3.2% and 4.6% of all cancer cases in India were among children in the 0-14 year and 0-19 year age groups respectively. The male-to-female ratio for all cancers was 1.72 for 0-14 years and 1.73 for 0-19 years. The four leading groups of cancers among 0-14 year olds were leukemia (40%), lymphoma (12%), central nervous system tumor (11%) and bone cancer (8%). The four leading cancers among the 0-19 year age group were leukemia (36%), lymphoma (12%), bone (11%) and central nervous system tumor (10%). CONCLUSION: Cancers in the 0-14 and 0-19 age groups accounted for a considerable proportion of all cancers with significant male preponderance. Such information helps to fine-tune research and planning strategies.

Primary orbital yolk sac tumor in an infant: A rare entity.

We report a case of pure orbital yolk sac tumor (YST) in an 11-month-old infant, which is a rare entity. The child presented with progressive painless swelling of the right eye and on examination had proptosis, chemosis, and lid edema. Systemic examination was within normal limits. Magnetic resonance imaging (MRI) orbit revealed a lobulated heterogeneously enhancing right retroocular mass extending up to the orbital apex, displacing the optic nerve and eroding the medial orbital wall. Biopsy of the lesion revealed pure YST histology. Serum alpha-fetoprotein (AFP) was markedly raised at 76900 ng/mL. She was started on infant bleomycin etoposide cisplatin (BEP) chemotherapy protocol. There was a good clinical and radiological response. A high index of malignancy is required in young children presenting with orbital proptosis. A multidisciplinary approach and early intervention are essential to save both vision and life.

Incidence and Prognostic Impact of TCF3-PBX1 Fusion in Childhood Acute Lymphoblastic Leukemia: A Single Centre Experience.

Molecular abnormalities in leukemic cells are important determinants of risk stratification in Pediatric acute lymphoblastic leukemia (ALL). TCF3-PBX1 fusion is one of the common aberrations in ALL with doubtful prognostic significance. Therefore, aim of our study is to revisit the clinical characteristics and outcome of this abnormality in children with ALL treated at our institute.Demographic, Clinical and treatment related characteristics of 539 newly diagnosed ALL patients from January 2009 and December 2018, < 18 years of age treated on BFM-95 protocol, was abstracted from the medical records. Clinical characteristics and outcome of children with and without TCF3-PBX1 fusion was compared.Incidence of TCF3-PBX1 fusion was observed in 24/539(4.4%) patients with a median age of 4 years (range 1-17). None of the patients in TCF3-PBX1 group had CNS or testicular disease at presentation. Day -8 prednisolone response and morphological remission at the end of induction was similar in both study groups. 5-year overall and event free survival for those with and without fusion was 75%, 70.1% and 79.5%, 69.5% respectively.The incidence of TCF3-PBX1 fusion in the present study was 4.4% and it does not have an independent prognostic significance.

Obesity and Sarcopenia in Survivors of Childhood Acute Lymphoblastic Leukemia.

OBJECTIVE: To describe the prevalence of obesity and sarcopenia among survivors of childhood acute lymphoblastic leukemia (ALL) using DEXA scan, and study associated risk factors. METHODS: This case control study was conducted between July, 2013 and June, 2014 at a tertiary care cancer centre in India. Study participants included 65 survivors of childhood ALL who were <18 years of age at diagnosis, treated between years 1996 and 2008, and were at least two years since completion of therapy. The controls included 50 matched siblings. Dual energy X-ray absorptiometry (DEXA) was used to study the body composition (body fat percentage, BF% and lean body mass, LBM) of the participants and controls. McCarthy's body fat reference data were applied and logistic regression analysis was used to study various risk factors. RESULTS: At a median (range) follow-up of 5 (7.2-17.2) years, BF% (DEXA) identified a significantly higher prevalence of obesity of 21.5% (14/65) and sarcopenic obesity (14%) among survivors as compared to the controls (0/50, P<0.001), while the prevalence of sarcopenia as detected by LBM was similar at 60% (39/65) and 56% (28/50), respectively. On multivariate analysis, age at evaluation, high-risk disease and cranial irradiation were independently associated with high likelihood of obesity, while none of the factors predicted sarcopenia. CONCLUSIONS: High prevalence of obesity and sarcopenic obesity were observed among survivors of childhood ALL.

Incidence and Risk Factors for Hypertension During Childhood Acute Lymphoblastic Leukemia Therapy.

OBJECTIVE: To determine the incidence of hypertension among children during the induction and re-induction phases of acute lymphoblastic leukemia (ALL) therapy and association with possible risk factors. METHODS: A retrospective analysis of 208 consecutive pediatric (age <18 y) ALL patients, treated per BFM-95 protocol between January 2009 and December 2013. Data were analyzed to determine the incidence of hypertension and risk factors for its development. RESULTS: Incidence of hypertension requiring antihypertensive medication, was 29% (61/208) during induction and 17% (33/198) during re-induction (P=0.003). Median (range) age of patients developing hypertension was 4 y (4 mo to 8 y). Age <10 y and presence of constipation were independently predictive of hypertension by multivariate analysis. CONCLUSIONS: The present study reports a high incidence of hypertension among children undergoing ALL induction therapy.

Umbilical Cord Blood Banking: Consensus Statement of the Indian Academy of Pediatrics.

JUSTIFICATION: Practitioners and people need information about the therapeutic potential of umbilical cord blood stem cells and pros and cons of storing cord blood in public versus private banks. PROCESS: Indian Academy of Pediatrics conducted a consultative meeting on umbilical cord blood banking on 25th June 2016 in Pune, attended by experts in the field of hematopoietic stem cell transplantation working across India. Review of scientific literature was also performed. All expert committee members reviewed the final manuscript. OBJECTIVE: To bring out consensus guidelines for umbilical cord banking in India. RECOMMENDATIONS: Umbilical cord blood stem cell transplantation has been used to cure many malignant disorders, hematological conditions, immune deficiency disorders and inherited metabolic disorders, even when it's partially HLA mismatched. Collection procedure is safe for mother and baby in an otherwise uncomplicated delivery. Public cord blood banking should be promoted over private banking. Private cord blood banking is highly recommended when an existing family member (sibling or biological parent) is suffering from diseases approved to be cured by allogenic stem cell transplantation. Otherwise, private cord blood banking is not a 'biological insurance', and should be discouraged. At present, autologous cord stem cells cannot be used for treating diseases of genetic origin, metabolic disorders and hematological cancers. Advertisements for private banking are often misleading. Legislative measures are required to regularize the marketing strategies of cord blood banking.