Amita Trehan

Survival outcome in childhood ALL: Experience from a tertiary care centre in North India

Survival of children with ALL, in developing nations has not kept pace with cure rates in developed countries. Our study was designed to assess survival data and identify risk factors.

Outcome of chronic idiopathic thrombocytopenic purpura in children

There is paucity of data on long‐term probability of remission in chronic idiopathic thrombocytopenic purpura (ITP). Aim was to study the course and factors influencing remission of chronic ITP. Chronic ITP was defined as thrombocytopenia persisting >6 months following initial diagnosis.

Serum galactomannan assay for the diagnosis of invasive aspergillosis in children with haematological malignancies

Diagnostic efficacy of Galactomannan (GM) assay for invasive aspergillosis (IA) is variably reported. Data from developing countries are scant. Children with haematological malignancies and fever were enrolled prospectively. Blood sample for GM was drawn on the day of admission; levels were measured with Platellia Aspergillus enzyme immunoassay. Diagnostic criteria were adapted from EORTC‐MSG‐2002. Proven, probable and possible episodes were considered as the disease group. One hundred febrile episodes in 78 patients were evaluated. The mean age was 6.1 years. Majority (75%) episodes were in patients with acute lymphoblastic leukaemia. One episode each was diagnosed with proven and probable IA, while 23 were diagnosed with possible IA. Best results were obtained with a cut‐off value of 1.0, with sensitivity, specificity, positive and negative predictive value of 60%, 93%, 75 and 87 respectively. The sensitivity dropped to 40%, at cut‐off value of 1.5 and specificity was 38%, at a cut‐off of 0.5. A higher value of GM correlated with pulmonary nodules (P = 0.037) and mortality (P = 0.001). GM assay is adjunctive to clinical/radiological evidence. A negative GM assay may not reassure the physician against the use of amphotericin in patients with febrile neutropenia, as it does not exclude the diagnosis of clinically relevant other fungal infections, particular mucormycosis.

Methylenetetrahydrofolate reductase gene polymorphisms: association with risk for pediatric acute lymphoblastic leukemia in north Indians.

Genetic polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene have been associated with the development of acute leukemias and various malignancies. We conducted a case–control study in 95 north Indian children with acute lymphoblastic leukemia (ALL) and 255 controls, to investigate the role of MTHFR C677T and A1298C polymorphisms as risk factors in the development of ALL. PCR-RFLP on genomic DNA was carried out to determine C677T and A1298C genotypes. The frequency of MTHFR C677T for the T allele was found to be 23.2% among patients and 18.2% among controls. The frequency of the C allele in MTHFR A1298C was 44.2% among cases and 48.2% in controls. Patients showed a higher frequency of heterozygosity for the MTHFR C677T polymorphism as compared to controls (40% vs 27.8%; OR = 1.73, 95% CI 1.02–2.91, p = 0.02), and the A1298C polymorphism did not show any difference in genotype frequency between cases and controls. MTHFR 677CC/1298AC genotype frequencies showed a statistically significant difference between cases and controls (OR = 0.58, 95% CI 0.34–1.01, p = 0.04). In conclusion, our study in north Indian controls and patients with pediatric ALL showed increased frequency for MTHFR C677T in the heterozygous state and no significant difference in the frequency of A1298C genotype between the two groups.

Evaluation of the genetic basis of phenotypic heterogeneity in north Indian patients with thalassemia major.

Objectives: To assess the molecular basis of phenotypic heterogeneity in north Indian patients with thalassemia major (TM). Methods: To determine the clinical severity, 130 patients of TM were studied for the age of first presentation and frequency of blood transfusion. The type of beta mutations, Xmn–1Gγ polymorphism and G6PD Mediterranean mutation was characterized. Analysis of the phenotypic presentation and the genotype was performed. Results: Majority (83.8%) presented before 1 year of age (mean 8.8 months). The caste distribution showed 41.6% were Aroras and 32.3% were migrants from Pakistan. IVS1‐5(G→C) was commonest (32.7%) and the common five Indian mutations comprised of 88.4% of alleles. The mean age of presentation with IVS1‐5(G→C), Fr 8/9, (+G) 619‐bp del and IVS1‐1(G→T) homozygosity was 4.3, 6, 3.4 and 9.1 months respectively. Xmn–1Gγ status showed −/− in 66.9%, +/− in 26.1% and +/+ in 6.9% patients. Xmn–1Gγ−/− presented before 1 year of age. The mean age of presentation with +/+ was 18.3 months. Six hemizygous boys and one heterozygous girl with G6PD Mediterranean were found (prevalence 5.3%). Eight patients could be reclassified as thalassemia intermedia on follow up. Conclusions: This study showed that majority of TM in north India present before 1 year of age and homozygous 619‐bp deletion presents the earliest. The presence of Xmn‐1Gγ polymorphism delays the presentation, is associated with the IVS 1‐1 (G→T) and shows variable improvement with hydroxyurea therapy. Based on the results of genotyping, reevaluation of patients can improve the outcome in a few patients.

Rapid lung MRI - paradigm shift in evaluation of febrile neutropenia in children with leukemia: a pilot study

Immunocompromised children with hematological malignancies are at increased risk of developing potentially fatal pulmonary infections. Early detection and prompt treatment is critical to combat morbidity and mortality in these children. Twenty-six children with leukemia (age range: 5–13years) presenting with fever and neutropenia were included in this prospective study, which was approved by the institutional ethics committee. All patients underwent HRCT and MRI of the chest on the same day. The findings of HRCT and MRI were compared, with HRCT as the standard of reference. There was perfect agreement between MRI and CT examinations findings by kappa test (κ = 1). No significant difference was observed between the two modalities by the McNemar test (p > 0.05). Rapid lung MRI is technically feasible; has a high correlation, sensitivity and specificity to CT scan; and can emerge as the first line modality for the detection of pulmonary nodules in children with leukemia and persistent febrile neutropenia.

The deferiprone and deferasirox combination is efficacious in iron overloaded patients with β-thalassemia major: A prospective, single center, open-label study

The high cost, coupled with the need for continuous infusion, renders Desferrioxamine (DFO), a non‐feasible option for iron‐chelation in a large majority of patients with β‐thalassemia major in developing countries. Monotherapy with deferiprone (DFP) or deferasirox (DFX) may not always attain optimal control, particularly in heavily iron‐loaded patients. Combination of DFP and DFX is a potential alternative.

Chemotherapy related fatal neurotoxicity during induction in acute lymphoblastic leukemia

Neurotoxicity is a common complication during cancer chemotherapy. It is estimated that 3–10% of children with acute lymphoblastic leukemia (ALL) experience acute, transient neurotoxicity during induction chemotherapy. Fatal acute neurotoxicity is rarely encountered. Neurological evaluation of children with ALL at diagnosis and during treatment is of value in order to diagnose neurological complications early so that appropriate intervention can be adopted. This communication describes the profile of two children with unexpected, acute fatal neurologic toxicity during induction chemotherapy for ALL.

Cytomegalovirus Retinitis in an ALL child on exclusive chemotherapy treated successfully with intravitreal ganciclovir alone.

A child suffering from acute lymphoblastic leukemia on treatment with exclusive chemotherapy presented with vision-threatening cytomegalovirus (CMV) retinitis in 1 eye. Prompt diagnosis and treatment with 3 weekly doses of 2 mg/0.1 mL intravitreal ganciclovir resulted in successful healing of CMV retinitis with restoration of visual acuity. In children with acute lymphoblastic leukemia on exclusive chemotherapy without hematopoietic stem cell transplantation, CMV retinitis has been reported in only 1 case in literature. This child was treated successfully with intravenous ganciclovir. This report highlights the use of successful intravitreal ganciclovir in pediatric age group to avoid side effects of systemic ganciclovir.

Pattern of mortality in childhood acute lymphoblastic leukemia: experience from a single center in northern India.

The outcome of acute lymphoblastic leukemia (ALL) in developing countries is inferior compared with the resource-rich nations. This descriptive study was designed to determine the pattern of deaths in children with ALL treated at a single center and identify the problem areas in management. Case records of 532 patients with ALL were analyzed. Information regarding the clinical-demographic profile, therapy, and course of illness were recorded. One hundred twenty-eight (24.0%) deaths were recorded. Sepsis (53.3%) and bleeding (15.7%) were the most common causes of mortality. The mortality rate fell significantly during the induction and remission phases of the therapy in 2 consecutive time periods between 1990 to 1997 and 1998 to 2006. The factors associated with an increased risk of death were longer symptom diagnosis interval (P=0.049), bulk disease (P=0.008), mediastinal adenopathy (P=0.001), higher total leukocyte count (P=0.001), and lower platelet count (P=0.007) at presentation as compared with the survivors. Multivariate analysis showed that longer symptom diagnosis interval (P=0.001), mediastinal adenopathy (P=0.006), lower platelet count (P=0.001), and higher total leukocyte count significantly influenced death. The estimated median time to death for the induction and remission deaths were 0.5 and 17 months, respectively. A high mortality rate necessitates the reappraisal of our treatment protocols. Many deaths should be avoidable by the provision of adequate supportive care, close supervision during and after chemotherapy, and appropriate antibiotic and antifungal therapy.