Ram Kumar Marwaha

The molecular basis of β thalassaemia in Punjabi and Maharashtran Indians includes a multilocus aetiology involving triplicated α-globin loci

Summary We have analysed 201 β‐thalassaemia (β‐thal) genes from natives of the Punjab (156) and Maharashtra states of India and found the causative mutation in 200 of them. The most common β‐globin gene mutations differed significantly between these two groups and between these groups and Indian immigrants in the U.S.A. and the U.K. In the Punjabi Indians the IVS‐1, nt 1 (G–T) mutation accounted for nearly one‐quarter of β‐thal genes, whereas it was 5% or less in the other groups. Likewise, the cap+ 1 mutation was much more prevalent in the Punjabis, whereas the nonsense codon 15 allele had a higher frequency in the Maharashtrans of the Bombay region. The common IVS‐1, nt5 allele had a frequency of 60% of β‐thal genes in the Maharastrans, 35% in North American immigrants, and only 23% in the Punjabis. Two‐thirds of all β‐thal genes in Punjab were found in the merchant caste (Khatri‐Arora), whereas the menial caste (Shudra) was highly represented among those with β‐thal genes in Maharashtra. Two novel β‐globin alleles were each found once; a frameshift codon 55 (+ A) in Maharashtrans and a frameshift codons 47–48 (+ ATCT) in Punjabis.

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.

Survival outcome of childhood acute lymphoblastic leukemia in India: a resource-limited perspective of more than 40 years.

The outcome of childhood acute lymphoblastic leukemia in India has been inferior to more than 80% cure rates in developed nations. This study was done to analyze the outcome of acute lymphoblastic leukemia in India over 4 decades. There has been a gradual improvement in survival rates of up to >70% in some centers along with a decline in relapse and mortality. However, these results cannot be generalized to the entire nation. There is a crying need to address treatment abandonment, take quality improvement, educational and financial initiatives; cooperative research into risk factors and disease biology, and the implementation of risk stratification along with the assessment of response to therapy.

Growth failure in children with chronic myeloid leukemia receiving imatinib is due to disruption of GH/IGF‐1 axis

The frontline treatment for chronic myeloid leukemia (CML) is tyrosine kinase inhibitor therapy. There is increasing evidence that imatinib results in growth failure in children; etiology is unclear.

Psychosocial burden in thalassemia

ObjectiveTo study the psychosocial life aspects of Indian adolescents suffering from transfusion dependent β-thalassemia major. Earlier studies done in Italy, Greece and United Kingdom reported the presence of psychosocial burden associated with the disease. We aimed to determine the presence of disease burden in the psychosocial life aspects of Indian adolescents affected with thalassemia.MethodsStructured interviews were carried out with each of the subjects using a schedule which contained questions relating to perceived burden of thalassemia in the various psychosocial life aspects of affected adolescents.ResultsAdverse impact of thalassemia was perceived in the domains of education (70%) and sports (72%). Most thalassemics were not satisfied with their body image. Almost all the study subjects felt that the disease did not affect their family or social relationships. The adolescents were anxious about their future health and education. Majority of the subjects (80%) did not discuss about their disease and its related problems with their friends. They mainly depended on their parents for monetary and emotional support.ConclusionThere is tremendous psychosocial disease burden perceived by the affected adolescents, and hence it is imperative to ameliorate it by promoting a clear understanding of the disease and initiating intervention programs.

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.

Acute Febrile Neutrophilic Dermatosis (Sweet's Syndrome) in Myelodysplastic Syndrome

This is the first report of the rare association of acute febrile neutrophilic dermatosis (Sweets syndrome) and myelodysplastic syndrome (MDS) in a child. The skin lesions showed a dramatic response to colchicine.

Prevalence of the H63D mutation of the HFE in north India: its presence does not cause iron overload in beta thalassemia trait

Abstract:  Objectives: To determine the allele frequency in the north Indian population of the two mutations in the HFE gene, the C282Y and H63D, which are responsible for causing hereditary haemochromatosis particularly in Caucasians of north European descent. We also wanted to correlate these mutations with the iron status in beta thalassemia traits. Patients and Methods: Sixty normal subjects and 215 individuals with beta thalassemia trait from north India were screened for the C282Y and H63D by polymerase chain reaction‐restriction fragment‐length polymorphism (PCR‐RFLP). We studied the iron status in these subjects and correlated the same with the HFE gene mutations. Results: On screening for the C282Y gene mutation, all individuals were detected to be of the wild‐type. The overall allele frequency of H63D was 9.09% with three individuals being homozygous for 63D. No statistically significant difference in the iron status was detected between the individuals of the wild‐type and mutant for H63D. Haplotyping of the homozygous 63D alleles revealed the pattern to be identical to the Europeans. Conclusions: Our study shows that H63D is prevalent and C282Y is rare in north Indians and the presence of 63D mutation does not increase body iron as measured by serum ferritin in beta thalassemia traits. Haplotype of H63D gene mutation is of an European haplotype, indicating a common origin.

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.