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Abstract Background To evaluate the treatment cost and cost effectiveness of a risk‐stratified therapy to treat pediatric acute lymphoblastic leukemia (ALL) in India. Methods The cost of total treatment duration was calculated for a retrospective cohort of ALL children treated at a tertiary care facility. Children were risk stratified into standard (SR), intermediate (IR) and high (HR) for B‐cell precursor ALL, and T‐ALL. Cost of therapy was obtained from the hospital electronic billing systems and details of outpatient (OP) and inpatient (IP) from electronic medical records. Cost effectiveness was calculated in disability‐adjusted life years. Results One hundred and forty five patients, SR (50), IR (36), HR (39), and T‐ALL (20) were analyzed. Median cost of the entire treatment for SR, IR, HR, and T‐ALL was found to be $3900, $5500, $7400, and $8700, respectively, with chemotherapy contributing to 25%–35% of total cost. Out‐patient costs were significantly lower for SR (p

Background: To evaluate the treatment cost and cost effectiveness of a risk‐stratified therapy to treat pediatric acute lymphoblastic leukemia (ALL) in India. Methods: The cost of total treatment duration was calculated for a retrospective cohort of ALL children treated at a tertiary care facility. Children were risk stratified into standard (SR), intermediate (IR) and high (HR) for B‐cell precursor ALL, and T‐ALL. Cost of therapy was obtained from the hospital electronic billing systems and details of outpatient (OP) and inpatient (IP) from electronic medical records. Cost effectiveness was calculated in disability‐adjusted life years. Results: One hundred and forty five patients, SR (50), IR (36), HR (39), and T‐ALL (20) were analyzed. Median cost of the entire treatment for SR, IR, HR, and T‐ALL was found to be $3900, $5500, $7400, and $8700, respectively, with chemotherapy contributing to 25%–35% of total cost. Out‐patient costs were significantly lower for SR (p < 0.0001). OP costs were higher than in‐patient costs for SR and IR, while in‐patient costs were higher in T‐ALL. Costs for non‐therapy admissions were significantly higher in HR and T‐ALL (p < 0.0001), representing over 50% of costs of in‐patient therapy. HR and T‐ALL also had longer durations of non‐therapy admissions. Based on WHO‐CHOICE guidelines, the risk‐stratified approach was very cost effective for all categories of patients. Conclusions: Risk‐stratified approach to treat childhood ALL is very cost‐effective for all categories in our setting. The cost for SR and IR patients is significantly reduced through decreased IP admissions for both, chemotherapy and non‐chemotherapy reasons. [ABSTRACT FROM AUTHOR]

Classification of pediatric T‐cell acute lymphoblastic leukemia (T‐ALL) patients into CIMP (CpG Island Methylator Phenotype) subgroups has the potential to improve current risk stratification. To investigate the biology behind these CIMP subgroups, diagnostic samples from Nordic pediatric T‐ALL patients were characterized by genome‐wide methylation arrays, followed by targeted exome sequencing, telomere length measurement, and RNA sequencing. The CIMP subgroups did not correlate significantly with variations in epigenetic regulators. However, the CIMP+ subgroup, associated with better prognosis, showed indicators of longer replicative history, including shorter telomere length (P = 0.015) and older epigenetic (P < 0.001) and mitotic age (P < 0.001). Moreover, the CIMP+ subgroup had significantly higher expression of ANTP homeobox oncogenes, namely TLX3, HOXA9, HOXA10, and NKX2‐1, and novel genes in T‐ALL biology including PLCB4, PLXND1, and MYO18B. The CIMP− subgroup, with worse prognosis, was associated with higher expression of TAL1 along with frequent STIL‐TAL1 fusions (2/40 in CIMP+ vs 11/24 in CIMP−), as well as stronger expression of BEX1. Altogether, our findings suggest different routes for leukemogenic transformation in the T‐ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. These novel findings can lead to new therapeutic strategies. In this study, an integrated methylomic, transcriptomic, and genomic analysis was performed to investigate the biology behind prognostically relevant DNA methylation (CIMP) subgroups in pediatric T‐cell acute lymphoblastic leukemia. We identified differentially expressed genes in the CIMP subgroups including known oncogenic drivers as well as novel genes in T‐ALL biology. Altogether, our findings suggest different routes for leukemogenic transformation in the T‐ALL CIMP subgroups, indicated by different replicative histories and distinct methylomic and transcriptomic profiles. [ABSTRACT FROM AUTHOR]

This study reviewed the clinical characteristics of 112 pediatric B-cell precursor acute lymphoblastic leukemia ( BCP- ALL) patients with TCF3- PBX1 fusion treated according to the Japan Association of Childhood Leukemia Study ( JACLS) ALL02 protocol ( n = 82) and Children's Cancer and Leukemia Study Group ( CCLSG) ALL 2004 protocol ( n = 30). The 3-year event-free survival ( EFS) and overall survival ( OS) rates were 85.4 ± 3.9% and 89.0 ± 3.5% in JACLS cohort, and the 5-year EFS and OS were 82.8 ± 7.0% and 86.3 ± 6.4% in CCLSG cohort, respectively, which are comparable to those reported in western countries. Conventional prognostic factors such as age at onset, initial white blood cell count, and National Cancer Institute risk have also no impact on OS in both cohorts. Surprisingly, the pattern of relapse in JACLS cohort, 9 of 82 patients, was unique: eight of nine patients relapsed during the maintenance phase and one patient had primary induction failure. However, bone marrow status and assessment of minimal residual disease on days 15 and 33 did not identify those patients. Interestingly, the two patients with IKZF1 deletion eventually relapsed in JACLS cohort, as did one patient in CCLSG cohort. International collaborative study of larger cohort is warranted to clarify the impact of the IKZF1 deletion on the poor outcome of TCF3- PBX1 positive BCP- ALL. [ABSTRACT FROM AUTHOR]