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

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).

Significant male preponderance in childhood acute lymphoblastic leukemia in India and regional variation: tertiary care center experience, systematic review, and evaluation of population-based data.

Although, a slight male preponderance has been reported in childhood acute lymphoblastic leukemia (ALL) from several developed nations, several Indian studies suggest a skewed gender ratio in ALL. To assess the gender ratio at presentation in ALL in India, we used a three-prong approach: (i) center audit, (ii) systematic review of published studies on ALL in India, and (iii) assessment of population based registry data. Data on gender at presentation in ALL were extracted from these multiple sources. In our center audit, we observed a significantly higher of male:female (M:F) ratio of 3.16:1 (P = .046) in ALL as compared to world literature. In the systematic review of all ALL studies from India, 367 articles were identified and reviewed. A total of 4230 and 1843 boys and girls in these studies were assessed and the M:F ratio was 2.503:1; much higher than the world ratio but not significantly different (P = .10). Population-based data obtained from the National Cancer Registry Program also depicted a male preponderance, especially from large cities in India in a consistent manner since 1984. There is also significant (P = .025) interregional variation in the gender ratio in India. Our study clearly demonstrates a consistent male preponderance in childhood ALL in India along with significant interregional variations over the last three decades. There is a clear need of prospective nationwide multicenter assessment of high-resolution data to confirm this important observation and assess its implications, especially on the health care system.

Outcome of neuroblastoma in India.

OBJECTIVES: To assess the outcome of childhood neuroblastoma in India over the last 2 decades, identify management lacunae and suggest remedial measures. METHODS: A comprehensive search to identify literature addressing outcome of childhood neuroblastoma from India was performed. International Society of Paediatric Oncology and American Society of Clinical Oncology Annual-Meeting abstracts were hand searched to identify unpublished data. Clinico-demographic and outcome data was extracted. RESULTS: Outcome of approximately 700 patients has been published over the last 2 decades with predominantly small to moderate single center series from 6 cities. Primarily non-myeloablative multiagent chemotherapy protocols alongwith surgery, have been used for treatment. A large majority of patients had stage III/IV neuroblastoma. Limited diagnostic facilities were available at most centers. Survival outcome of 8.7 to 80 % has been reported with high death and relapse rates alongwith high incomplete control/disease progression and treatment abandonment. Few series have identified prognostic parameters. Few patients with high-risk disease have been adequately treated and cured. CONCLUSIONS: There is a clear need for replicating neuroblastoma outcomes at centers of excellence in other cancer centers, improving diagnostic and laboratory facilities, administering adequate and appropriate contemporary therapy, assessing disease response and improving supportive care. National data management infrastructure along with better financial and social support initiatives are key factors.

Management of lower limb deformities in children with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) often leads to severe lower limb (LL) deformities due to recurrent fractures that significantly hamper ambulation. We describe our management experience of correction of LL deformities in four children with OI. Medical management consisted of peri and postoperative pamidronate therapy, calcium supplementation and rehabilitative care. Deformities were corrected with multiple osteotomies and intramedullary fixation by titanium elastic nails. At a mean follow-up of 30 months, all children have significantly reduced fracture incidence and have no evidence of recurrence of deformities with improved ambulatory status. We emphasize the importance of combined medical and surgical therapy for these patients.

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.

Childhood acute myeloid leukemia: an Indian perspective.

Cure rates of childhood malignancies are inferior in India as compared to developed nations. There is paucity of data addressing outcome of childhood acute myeloid leukemia (AML) from India. Hence, this study was designed to assess the outcome of childhood AML in India over the last 2 decades, identify shortcomings and suggest remedial measures. A comprehensive search to identify studies addressing outcome of childhood AML from India was carried out. International Society of Paediatric Oncology annual meeting abstracts were searched to identify unpublished data. Clinicodemographic and outcome data were extracted from these abstracts. Outcomes of <500 patients have been published to date, with predominantly small single-center series from 5 cities. Several AML protocols with modifications to suit the logistics in India have been used. Administration of chemotherapy (standard as well as oral and outpatient based) with manageable toxicity has been deemed feasible. Survival outcomes are modest (23% to 53.8%) except for AML M3 (over 80%), with high early-death rates, relapse, along with abandonment. Few series have identified prognostic parameters and disease burden at diagnosis, and used cytogenetics (for risk stratification) or bone marrow transplant (BMT). There is a need for assessment of risk factors in Indian patients; administration of adequate and appropriate therapy, both upfront and after relapse; improvement in supportive care; and national data management infrastructure with updating/monitoring of registries along with better financial and social support initiatives. These multimodal and additive remedial measures could significantly improve outcome of childhood AML in India by reducing mortality, relapse, and abandonment.

Hemophagocytosis associated with hepatitis a and e coinfection in a young child.

We report and discuss a unique case of hemophagocytosis associated with hepatitis A and E coinfection in a young child which has never been reported earlier in children. Its varied presentation is emphasized and possible management options and outcome are discussed.

Cushing disease presenting as arthritis.

Cushing's syndrome is an endocrine disorder caused by hypercortisolism. Despite its varied clinical spectrum of presentation, Cushing's disease has not been reported to present as arthritis. Moreover, keratilysis exfolitiva has not been described in Cushing disease. We report a 12 year old male child with pituitary micro adenoma initially presenting as arthritis and developing keratilysis exfolitiva.

Myelofibrosis in children: experience at a single tertiary care center in India.

The authors describe 10 cases of myelofibrosis diagnosed and managed at their center over 16 years. There were 2 and 8 cases, respectively, of primary and secondary myelofibrosis. All patients presented with fever, pallor, hepatosplenomegaly, and/or lymphadenopathy. Hodgkin's lymphoma (n = 4), neuroblastoma (n = 1), thrombasthenic thrombopathy (n = 1), and retroperitoneal-mass (n = 1) were causal in 7 patients, whereas the diagnosis could not be established in a sole case of secondary myelofibrosis. Patients were managed with chemotherapy and appropriate care. However, outcome was poor. The authors emphasize variable clinical-laboratory spectrum of myelofibrosis, highlight management concerns, and demonstrate that prognosis/outcome depends upon appropriate management of the underlying condition.

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.

Acute lymphoblastic leukemia masquerading as juvenile rheumatoid arthritis: diagnostic pitfall and association with survival.

Acute lymphoblastic leukemia (ALL) often presents with osteoarthritic manifestations which may lead to misdiagnosis with juvenile rheumatoid arthritis (JRA). This study was designed to identify ALL patients with initial diagnosis of JRA, compare their clinicolaboratory characteristics and outcome with other ALL patients treated at our center. Case records of 762 patients with ALL were analyzed. Information regarding the clinical-demographic profile, therapy and outcome were recorded. Of the children, 49 (6.4%) had initial presentation mimicking JRA. Asymmetric oligoarthritis was the most common pattern of joint involvement. Majority presented with fever, pallor, arthritis, night pain, and bone pain. None of the routine prognostic factors including age, gender, lymphadenopathy, hepatosplenomegaly, total leukocytes count (TLC), and platelet count were significantly associated with relapse/death. The mean symptom-presentation interval (SPI), hemoglobin was significantly higher whilst the TLC was significantly lower in these patients compared to other ALL patients. The 5 year overall-survival was better than other patients with ALL (p = 0.06, by logrank test). Significantly longer SPI in these patients underscores the need for prompt and early investigations to rule out ALL in patients of JRA with atypical features and pointers of ALL. Children with ALL-mimicking JRA may belong to a subgroup of ALL with a better prognosis.

Pediatric disorders of sex development.

The management of disorders of sexual differentiation (DSD) involves a multidisciplinary approach. The main aim of analysis was to study the phenotype-karyotype correlation in North Indian children with DSD. The records of pediatric DSD were retrieved and characteristics noted. Of total of 58 children, 43 (74.1%) and 10 (17.2%) were raised as males and females respectively. The mean age at presentation was 31.3+/-9 months. The karyotype was 46XY in 45 (77.6%) and 46XX in 12 (20.7%). CAH was commonest cause of DSD (36.2%), followed by gonadal dysgenesis. Of the 15 patients of 46 XY CAH, there were 5 with 17-alpha hydroxylase deficiency, 2 with 3-beta HSD deficiency and one case of lipoid adrenal hyperplasia. There was an excess of genetic males, possibly due to prevalent socio-cultural factors and gender bias favoring males. There is a need to improve the diagnostic facilities and incorporate a team approach in management of DSD.