Outcomes of pediatric mixed phenotype acute leukemia treated with lymphoid directed therapy: Analysis of an institutional series from India.

There is limited data regarding pediatric mixed phenotype acute leukemia (MPAL) and there is no global consensus on its management yet. In this retrospective study, we analyzed the outcomes of children diagnosed with MPAL at our institute. This study included children ≤ 14 years with MPAL who presented to a tertiary cancer center in India from January 1st 2009 to December 31st 2015. Over a seven-year period, 1390 patients with leukemia presented to our institute of which 22 patients (1.5%) had MPAL. Sixteen patients (72.7%) had B/myeloid leukemia, while 4 (18.1%) and 2 (9%) patients had T/myeloid and B/T leukemia respectively. Twenty-one patients were treated with a modified BFM ALL 95 protocol. 76.1% (n = 16) of patients had a good prednisolone response (GPR) on day 8 and end-of-induction (EOI) marrow was in remission in 90.5% (n = 19). A poor prednisolone response (PPR) on day 8 correlated with an inferior relapse-free survival (25% vs 79.5%, P=.025). The 4-year event-free survival (EFS) and overall survival (OS) for the entire group was 60.8% and 64.9% respectively while the EFS for patients who had a GPR and remission at the EOI (n = 15) was 80% as compared to 16.7% in patients with PPR or induction failure. Lymphoid directed chemotherapy is seen to have good survival outcomes in pediatric MPAL. However, a PPR on day 8 or a positive EOI marrow may be an indication for more aggressive treatment.

Higher incidence of syndrome of inappropriate antidiuretic hormone secretion during induction chemotherapy of acute lymphoblastic leukemia in indian children.

BACKGROUND: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a well-known adverse effect of vincristine (VCR). Literature suggests that Asians are predisposed to develop SIADH following VCR administration. However, data regarding the occurrence of SIADH in children with malignancy are limited. This study aims to analyze the incidence, clinical picture, risk factors, management, and outcome of SIADH during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A prospective study was conducted among the 166 newly diagnosed pediatric ALL patients who were treated at a tertiary cancer center in India between January 2015 and December 2015. Patients who developed hyponatremia during induction chemotherapy were further investigated for SIADH. RESULTS: The incidence of SIADH was 10.8% (n = 18) with a mean sodium level of 125 mEq/L (114-129 mEq/L). In the preceding 2 weeks, 72% of episodes were associated with the administration of two (n = 6) or three (n = 7) doses of VCR. One child presented with seizures. All the patients were managed with fluid restriction and only two patients required sodium correction with 3% saline. Girls older than 10 years of age showed a marginally significant correlation to develop SIADH (P-value = 0.059). CONCLUSION: We report a higher incidence of SIADH (10.8%) in Indian children, compared to that described in the literature, during induction chemotherapy for ALL. Regular monitoring of sodium levels during this period of chemotherapy is hence essential for the timely diagnosis and appropriate management of SIADH, which in turn will avert complications, including neurological symptoms secondary to SIADH.

Effect of imatinib on growth in children with chronic myeloid leukemia.

Imatinib is a preferred drug for pediatric Chronic Myeloid Leukemia (CML). Long-term use has inhibitory effects on other tyrosine kinase pathways causing off-target complications such as growth impairment. Our aim was to evaluate impact of long-term use on longitudinal growth in children with CML in Kerala. We hypothesized that the impact would be lesser compared to Northern India as Kerala has the lowest rates of underweight and stunting, with a high literacy rate and per capita income. Children ≤14 years of age, diagnosed with CML and received imatinib for at least 1 year were included. Girls >9 years of age and boys >11 years were considered pubertal. Height Z scores were derived using WHO AnthroPlus. Paired t test compared difference of Z scores in prepubertal and postpubertal age groups. Height Z scores were compared with mid-parental height and sibling height Z scores. Thirty-six children were included (M = 21; F = 15). Median duration of imatinib exposure was 84 months. Decrease in longitudinal growth affected children in both prepubertal and postpubertal age groups. Decrease in height Z scores was more in prepubertal age group when imatinib therapy was initiated (p = .0018). Of 10 patients currently above 19 years (of whom 8 were in pubertal age and 2 in prepubertal age at start of imatinib) none are stunted. Patient's height Z scores was lesser compared to sibling height Z scores (p = .027). Children on continuous imatinib showed a significant stunting when treatment was initiated during prepubertal age. There is a catch-up of growth as the final height reached is within normal limits of WHO reference values.

Risk-based management strategy and outcomes of tumor lysis syndrome in children with leukemia/lymphoma: Analysis from a resource-limited setting.

BACKGROUND: Data from low- and middle-income countries on tumor lysis syndrome (TLS) in the pediatric population are limited. This study aims to analyze the clinical and biochemical characteristics and treatment outcomes of TLS in children with leukemia/lymphomas in a resource-limited setting. PROCEDURE: Children with intermediate risk (IRD) and high risk (HRD) for developing TLS were retrospectively studied at a tertiary cancer center in India. RESULTS: Over a three-year period, 224 children with acute leukemia/lymphoma having IRD (21.8%, n = 49) and HRD (78.1%, n = 175) were identified. TLS developed in 53.6% (n = 120) cases, of which 75% (n = 90) had laboratory TLS alone. Thirteen children had clinical TLS (C-TLS) at presentation while 17 patients progressed to develop C-TLS. TLS developed in 51% (n = 25) and 54.5% (n = 95) of children with IRD and HRD, respectively. Rasburicase was used in 8.5% (n = 19) cases and five children required hemodialysis. Two children (0.8%) expired during the course of TLS management. Multivariate analysis identified the presence of hyperuricemia as the single significant risk factor for developing TLS. When children in whom a 25% change in biochemical values from the baseline that falls within the normal range were excluded, 21.4% (48/224) cases were identified to have clinically relevant TLS (8% in IRD and 25% in HRD). CONCLUSION: With hydration, supportive care and judicious use of rasburicase, it is feasible to manage TLS efficiently in resource-limited settings. A modification of the TLS definition criteria would help to identify clinically relevant TLS.

Treatment of tumor lysis syndrome in children with leukemia/lymphoma in resource-limited settings-Efficacy of a fixed low-dose rasburicase.

Rasburicase is a novel drug used during the management of tumor lysis syndrome. In countries with limited resources, it is frequently given at a lower dose and only for the treatment of established tumor lysis syndrome and not as prophylaxis. A retrospective study was conducted in the department of pediatric oncology at a tertiary referral oncology center in south India to analyze the use of rasburicase over the past 3 years. Data of all the 18 children (< 14 years of age) who were given rasburicase for the management of hyperuricemia were collected and analyzed. With a mean rasburicase dose of 0.085 mg/kg, hyperuricemia was managed efficiently without the need for a hemodialysis in 16 children (88.8 %). The fall in mean serum uric acid levels after the administration of a single dose of rasburicase at 4, 24, and 48 hours was 31.18 %, 64.8 %, and 74.5 %, respectively. Rasburicase efficiently decreases the uric acid levels to a normal level within a short period. In resource-limited settings, rasburicase at a lower dose is a promising option for managing hyperuricemia in the event of a tumor lysis syndrome.