The Outcome of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Experience from a Referral Center in South India.

Although improved survival in children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL) has been demonstrated in trials, the outcome appears to be inferior in low- and middle-income countries (LMIC). Methods A file review of children aged ≤ 15 years diagnosed with Ph-ALL from 2010 to 2019 was performed. Minimal residual disease (MRD) was assessed by flow-cytometry. Real-time polymerase chain reaction (qRT-PCR) was used to quantify the BCR::ABL1 transcripts during treatment. Results The mean age of the 20 patients in the study was 91 months. Of 19 patients in whom the BCR::ABL1 transcript was confirmed, 10(50%) had P210, 7(35%) had P190, and two showed dual expression. The mean dose of imatinib that was administered was 294 ± 41 mg/m2/day. qRT-PCR for BCR::ABL1 was < 0.01% in all patients who were in remission or had a late relapse and was ≥ 0.01% in patients who had an early relapse. Two patients underwent HSCT. The 3-year event-free survival (EFS) was 35.0 ± 10.7%. Patients with a good prednisolone response (GPR) and a negative end-of-induction MRD demonstrated a superior EFS to those who lacked either or both (80.0 ± 17.9% vs. 16.7 ± 15.2%, P = 0.034). Conclusion The 3-year EFS of 20 children with Ph-ALL treated with chemotherapy and TKI was < 50%. An unusually high proportion of patients with p210 transcript expression; sub-optimal TKI dosing and lesser intensity of chemotherapy, due to the concern of high treatment-related mortality in LMIC are possible reasons for the poor outcome. Conventional treatment response parameters such as GPR and MRD predict outcomes in Ph-ALL. qRT-PCR for BCR::ABL1 may have a role in predicting early relapse. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01684-9.

What happens to children with acute lymphoblastic leukemia in low- and middle-income countries after relapse? A single-center experience from India.

Managing a child with acute lymphoblastic leukemia (ALL) after relapse is arduous in low- and middle-income countries. A file review of children aged ≤15 years diagnosed with relapsed ALL from 2010 to 2019 was performed. Classification of relapse followed the Berlin-Frankfurt-Münster (BFM) scheme. The majority of patients were treated with a modified ALL-REZ-BFM protocol. Of 764 children treated for ALL in the study period, 163 (21.3%) relapsed. The median age at relapse was 101 months (range: 8-297). The immunophenotype was B-ALL and T-ALL in 140 (86%) and 23 (14%) patients. The site of relapse was extramedullary, combined, and medullary in 46 (28%), 45 (28%), and 72 (44%) patients. Very early, early, and late relapses were observed in 57 (35%), 66 (40%), and 40 (25%) patients. The proportions of extramedullary and medullary sites were greater among patients with early and late relapses, respectively (p = 0.039). Eighty-four (52%) patients were treated with palliative intent. The 2-year event-free survival (EFS) of patients treated with curative intent was 36.3 ± 6.3%. The 2-year EFS for very early/early and late relapses were 18.2 ± 6.2% and 67.6 ± 10.4% (p < 0.001). The 2-year EFS did not differ between extramedullary, combined, and medullary relapses. Treatment-related mortality occurred in 14 (20%) patients. More than 50% of the patients with relapse were treated with the intent of palliation. Extramedullary relapses were more likely to be early and did not have a better outcome than medullary relapses. Children with late relapse had a fair chance of survival with chemotherapy.

The Nutritional Trajectory of Children with Acute Lymphoblastic Leukemia: A 10-Year Follow up Study from a Referral Center in South India.

OBJECTIVE: Survivors of childhood acute lymphoblastic leukemia (ALL) are vulnerable to late adverse events such as obesity and an associated metabolic syndrome. METHODS: Children treated for ALL from 2002 to 2012 were included. BMI was calculated at diagnosis, end of treatment, and 5, 8, and 10-years from diagnosis. BMI-centiles were used to categorize the patients: underweight (<5th-percentile), normal (5th-85th percentile), overweight (85th-95th percentile), and obese (≥95th centile). RESULTS: The study included 179 children with ALL (median age: 59-months). The proportions of patients who were underweight, normal, overweight/obese, were 37%, 56% and 7%, respectively, at diagnosis; and 15%, 51% and 34%, respectively, at 5-years from diagnosis. The median (IQR) BMI Z-score at diagnosis was -1.12(-2.40, -0.26). The median (IQR) BMI z-score of the cohort was higher after 5 [0.22(-0.83,1.24), P < 0.001] and 10-years of diagnosis [0.30(-0.69,0.99), P < 0.001], respectively. The proportion of overweight/obese individuals was higher after 5 (34%, P < 0.001) and 10 (26%, P = 0.001) years. There was a significant correlation between the baseline BMI Z-score and that observed after 5-years (ρ = 0.49, P < 0.001), and 10-years (ρ = 0.55, P < 0.001). CONCLUSION: At 10-years of follow-up, >25% of children with ALL were overweight/obese. The BMI Z-score at the time of diagnosis continued to correlate with the Z-score after 10-years.

Postchemotherapy tumor volume as a prognostic indicator in Wilms tumor: A single-center experience from South India.

BACKGROUND: Optimal risk stratification is the key to minimizing relapse and toxicity in children with Wilms tumor (WT). The study evaluated poor tumor volume response to chemotherapy as a risk factor that predicts relapse. PROCEDURE: Children with WT who were treated between 2005 and 2020 at the center were analyzed. Tumor volumes at the time of diagnosis and after preoperative chemotherapy were calculated from cross-sectional imaging. The International Society of Paediatric Oncology (SIOP)-WT-2001 protocol was used for treatment. The area under a receiver operating characteristic curve was estimated to ascertain the ability of tumor volume to predict relapse. RESULTS: Ninety-five patients with a median age of 40 months were included. A postchemotherapy tumor volume cutoff of 270 ml was ascertained to have the best predictive value for relapse. Patients with a tumor volume of <270 ml following preoperative chemotherapy had a better 3-year event-free survival (EFS) than those with a tumor volume of ≥270 ml (89.8% ± 4.0% vs. 57.4% ± 12.5%, p = .001). The data demonstrated that a tumor volume of ≥270 ml after chemotherapy was associated with an increased risk of relapse (hazard ratio [HR]: 5.3, p = .006). The EFS in patients with an epithelial or stromal type of histopathology was not affected by the tumor volume response (p = .437). Conversely, patients with other types of intermediate-risk histopathology who had a poor tumor volume response had an inferior survival (3-year EFS 51.4% ± 18.7%, p = .001). CONCLUSION: A postchemotherapy tumor volume cutoff of ≥270 ml emerged as a strong predictor of relapse in a low- and middle-income country (LMIC) center study of WT treated with the SIOP protocol.

A single assessment of methotrexate levels at 42 hours permits safe administration and early discharge in children with lymphoblastic lymphoma and leukemia receiving high-dose methotrexate.

High-dose methotrexate (HDMTX) is an important component of treatment in pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). Optimal rescue therapy is essential for the safe administration of HDMTX. A cost-effective strategy that does not compromise safety is necessary for low- and middle-income countries. Consecutive admissions for HDMTX in children with ALL and LL over 12 months were analyzed. The dose of HDMTX was 3 g/m2 in B-ALL and B-LL and 5 g/m2 in T-ALL and T-LL. A methotrexate level was measured at 42 hours of starting HDMTX infusion (T42-MTX). Three doses of folinic acid at T42, T48, and T54 and alkalinized hydration till T54 were administered if T42-MTX <1 µM. A total of 282 cycles of HDMTX that were administered in 71 patients were analyzed. T42-MTX was <1 µM in 266 (94.3%) cycles. T42-MTX was ≥1 µM in 12% and 3% of cycles of HDMTX administered at a dose of 5 g/m2 and 3 g/m2, respectively (p = .074). The median duration of hospitalization for HDM was three days and did not differ with the dose of HDMTX administered (p = .427). Mucositis, delayed recovery of blood counts, and hospitalization for reversible toxicity occurred after 21 (7.4%), 28 (9.9%), and 19 (6.7%) cycles of HDMTX, respectively. Mucositis was greater following the administration of 5 g/m2 of HDMTX. A single T42-MTX measurement permits the safe administration of HDMTX and an expedited discharge from the hospital within three days in more than 90% of children with ALL/LL.