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.

Common queries in managing rhabdomyosarcoma in low- and middle-income countries: An Indo-North American collaboration.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma among children and adolescents. The management of RMS involves risk stratification of the patients based on various clinicopathological characteristics. The multimodality treatment approach requires chemotherapy, surgery, and/or radiation. The treatment of RMS necessitates the involvement of multiple disciplines, such as pathology, pediatric oncology, surgery, and radiation oncology. The disease heterogeneity, molecular testing, evolving treatment regimens, and limited resources are some of the challenges faced by clinicians while treating a patient with RMS in low- and middle-income countries (LMICs). In this review, we endeavor to bring experts from varying fields to address clinicians' common questions while managing a child or adolescent with RMS in LMICs. This review is most applicable to level 2 centers in LMICs as per the levels of services described by the Adapted Treatment Regimens Working Group of the Pediatric Oncology in Developing Countries committee of the International Society of Pediatric Oncology.

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.

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.

The Unique Balancing Act of Managing Children With Cancer and COVID-19 Infection: A Single Center Experience From South India.

Children with cancer are vulnerable to severe infections. Balancing the intensive treatment of cancer, with the potential risk of coronavirus disease-2019 (COVID-19) related morbidity and mortality is a unique challenge. Children with cancer testing positive for severe acute respiratory syndrome coronavirus 2 virus by reverse-transcription polymerase chain reaction at our center were studied. Thirty-seven children tested positive for COVID-19 during the study period. The severity of the illness was mild, moderate, severe, and critical in 10 (27%), 13 (35%), 12 (32%), and 2 (5%) patients, respectively. Of the 14 patients with a severe/critical illness, 2 had oncological emergencies, 4 had dengue co-infection, and 1 had an inguinal bacterial abscess. All patients were discharged in a stable condition. Modification of the treatment protocol was performed in 11 (33%) of 33 patients who were on active treatment for cancer. There was a median delay of 32.5 days to administer the next cycle of chemotherapy in patients who acquired COVID-19 during cancer treatment. Six of 7 patients who were retested after 14 days remained positive by reverse-transcription polymerase chain reaction. Children with cancer with COVID-19 recover with good supportive care. Curative chemotherapy can be administered safely with appropriate modifications in children with cancer with COVID-19.

A Case of Novel GATA-1 Mutation-positive Transient Abnormal Myelopoiesis With Life-threatening Complications in a Neonate With Down Syndrome.

Transient abnormal myelopoiesis is a transient myeloproliferative disorder seen in ∼15% to 20% of infants with Down syndrome. These infants are usually asymptomatic, requiring only monitoring, but they can have variable severity of symptoms up to multisystemic dysfunction requiring chemotherapy. GATA-1 somatic mutations acquired in utero are pathognomic of this entity and present nearly in all cases. Herein, we present a case of Down syndrome in a neonate who presented within her first week of life with life-threatening features of transient abnormal myelopoiesis requiring chemotherapy support. In addition, next-generation sequencing revealed a small mutant clone (8%) positive for a novel frameshift GATA-1 mutation.

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.

PEST domain NOTCH mutations confer a poor relapse free survival in pediatric T-ALL: Data from a tertiary care centre in India.

A comprehensive genotype-phenotype analysis of pediatric T-ALL data was performed. 33 confirmed pediatric (≤12 y) T-ALL samples were evaluated for oncogenic transcripts: TLX-1, TLX-3, common fusion of STIL-TAL1, NOTCH1 mutations and copy number variations (CNVs). Mean WBC was 235.69 × 103/µL. TLX1 and TLX-3 overexpression detected in 1 (3%) and 7 (21%) patients and STIL-TAL1 in 8 (27%). NOTCH1 mutations were noted in 17 (52%), of which 12 (71%) in HD domain and 6 (35%) in PEST domain (including one case with mutations in all three domains). Commonest CNVs were CDKN2A (85%) and CDKN2B (75%). Relapse occurred in 8 (24%) patients. The median follow-up was 15 months (range: 0.5-36). Bulky liver (p = 0.025), day 35 marrow (p = 0.004) and NOTCH mutation (p = 0.046) were predictive of time to an event. RFS was significantly poor for cases with PEST Vs. HD domain mutations (50% Vs. 85%) (p = 0.0009). Though cases with PEST domain NOTCH mutations had poor RFS, the OS was not influenced by NOTCH mutation positivity.

Autologous stem cell transplant for high-risk neuroblastoma: Achieving cure with low-cost adaptations.

BACKGROUND: The majority of patients in low- and middle-income countries (LMIC) are unable to receive optimal therapy, including autologous stem cell transplant (ASCT) for high-risk neuroblastoma. Management is intensive and multidisciplinary; survival is often poor. We report a single-center outcome of high-risk neuroblastoma, with adaptations optimized for LMIC. PROCEDURE: The study was retrospective. Patients were treated on the backbone of the high-risk neuroblastoma study-1 of SIOP-Europe (HR-NBL1/SIOPEN) protocol with ASCT. Adaptations incorporated to decrease cost, requirement for inpatient admission, infections, and faster engraftment included (a) optional outpatient administration for rapid-COJEC, (b) two sessions of stem-cell apheresis, (c) storing stem cells at 2-6°C without cryopreservation for up to 7 days, (d) no central lines, (e) no antibacterial/antifungal/antiviral prophylaxis, (f) omitting formal assessment of cardiac/renal/pulmonary functions before ASCT, and (g) administration of pegylated granulocyte colony-stimulating factor on Day +4. RESULTS: Over 5 years 9 months, 35 patients with high-risk neuroblastoma were treated. Rapid-COJEC was administered over a median duration of 80 days (interquartile range: 77, 83). Conditioning regimen included melphalan (n = 7), oral busulfan-melphalan (Bu/Mel; n = 6), or intravenous Bu/Mel (n = 22). The median viability of stem cells stored for 6 days (n = 28) was 93% (range: 88-99). Two (5.7%) patients had ASCT-related mortality. The 3-year overall and event-free survival was 41% and 39%, respectively. A relapse occurred in 20 (57%) patients. Treatment abandonment was observed in one (3%) patient. CONCLUSIONS: Administration of therapy in a disciplined time frame along with low-cost adaptations enables to manage high-risk neuroblastoma with low abandonment and an encouraging survival in LMIC. Stem cells can be stored safely without cryopreservation for up to 7 days.

Imatinib-Induced Hypogammaglobulinemia in Children and Adolescents with Chronic Myeloid Leukemia.

Imatinib-induced tyrosine kinase inhibition extends beyond the BCR-ABL mutation, resulting in adverse effects. We evaluated hypogammaglobulinemia as a potential 'off-target' action of imatinib in children with CML. A cross-sectional, observational study was performed. Patients with CML in chronic phase, age <18-years at diagnosis, receiving imatinib for a duration exceeding 6-months were enrolled. Serum immunoglobulin G, A, and M were measured by end-point nephelometry. Thirty patients were enrolled. The mean age at diagnosis was 10.4 ± 3.1 years (range: 5-18). The mean age at enrollment was 16.4 ± 4.1 years (range: 9-23). The median dose of imatinib was 287.5 mg/m2 (IQR: 267.3, 345.0). The median duration of imatinib-therapy was 6-years (IQR: 3.0, 10.3). The median (IQR) normalized levels of IgG, IgA, and IgM were 33.0% (IQR: -12.8, 58.7), 28.1% (IQR: -17.0, 90.1) and 15.9% (IQR: -9.3, 40.5), respectively. The IgG, IgA, and IgM levels were reduced in 9 (30%), 8 (27%), and 10 (33%) patients, respectively. Five (17%) patients had pan-hypogammaglobulinemia. We suggest checking immunoglobulin levels in patients with CML receiving imatinib with recurrent/unusual infections.

Challenges in the management of localized Ewing sarcoma in a developing country.

Survival in pediatric Ewing sarcoma (ES) lags in low- and middle-income countries (LMICs). This study analyzed factors contributing to a lower outcome in an LMIC center. A retrospective case review of children with localized ES treated from January 2011 till December 2017 was performed. Neoadjuvant chemotherapy with alternating cycles of vincristine, doxorubicin, cyclophosphamide; and ifosfamide, etoposide was administered 3-weekly for 48 weeks. Reassessment was planned for week 12, followed by local therapy (surgery/radiotherapy or both) tailed by adjuvant chemotherapy. Forty-eight patients with mean age 8 years (range: 0.7-14) were evaluated. Extremity and central axis tumors were seen in 25 (52%) and 23 (48%) patients. Three patients died of neutropenic sepsis and five abandoned therapy. Local therapy included primary surgery, radiotherapy and a combination of surgery and radiotherapy in 7 (16%), 20 (45%) and 17 (39%) patients. The 3-year event-free survival (EFS) and disease-free survival (DFS) for the cohort were 47.7 ± 11% and 57.6 ± 11.2%. Time to local therapy >16 weeks was associated with inferior DFS vs. local therapy administered within 16 weeks [46.6 ± 12.4 vs. 63.9 ± 19.4, p=.046]. Older age, axial site, large size and incomplete surgical resection did not predict relapse/progression. Patients who received wide local excision, as local therapy, had 100% DFS. Coordinated efforts to ensure timely therapy can improve outcome in pediatric ES. Abandonment and treatment-related mortality (TRM) are additional challenges that need to be tackled in LMICs.

Validation of an algorithmic nutritional approach in children undergoing chemotherapy for cancer.

BACKGROUND: Undernutrition impacts clinical outcome adversely in children with cancer. This study aimed to validate a nutritional algorithm with specific application to the low- and middle-income country (LMIC) setting. PROCEDURE: Fifty children with a new diagnosis of cancer were enrolled in this randomized interventional study. Weight, height/length, and mid-upper-arm circumference (MUAC) were measured at baseline. The study arm was administered nutritional care as per the algorithm and the control arm received the institutional standard of care. Weight was monitored regularly and MUAC was repeated after 3 months. Children were classified based on weight for height if <2 years of age or body mass index if ≥2 years, as normal, wasted, and severely wasted. The algorithmic approach comprised administration of oral supplements, nasogastric feeds, and/or parenteral nutrition based on objective assessment of the nutritional status. RESULTS: Fifty patients were analyzed (study: 25, control: 25). Four in the study arm (16%) and six in the control arm (24%) had wasting at baseline. MUAC was <5th percentile in 15 (60%) and 13 (52%) patients in the study and control arms, respectively. At the end of 3 months, the median increment in weight was 0.8 kg (interquartile range [IQR]: -0.02; 2.00) and 0.0 kg (IQR: -0.70; 1.25) in the study and control arms, respectively (P = .153). The median increment in MUAC was 1.20 cm (IQR: 0.10; 2.30) and 0.00 cm (IQR: -0.50; 1.10) in the study and control arms, respectively (P = .020). CONCLUSIONS: The application of an algorithm designed for use in LMICs resulted in significant improvement in nutritional status, as measured by MUAC.

Effect of socio-economic status & proximity of patient residence to hospital on survival in childhood acute lymphoblastic leukaemia.

BACKGROUND & OBJECTIVES: : Survival in paediatric acute lymphoblastic leukaemia (ALL) in lower/middle income countries continues to lag behind outcomes seen in high-income countries. Socio-economic factors and distance of their residence from the hospital may contribute to this disparity. This study was aimed at identifying the impact of these factors on outcome in childhood ALL. METHODS: : In this retrospective study, file review of children with ALL was performed. Patients were treated with the modified United Kingdom (UK) ALL-2003 protocol. Details of socio-economic/demographic factors were noted from a web-based patients' database. Modified Kuppuswamy scale was used to classify socio-economic status. RESULTS: : A total of 308 patients with a median age of five years (range: 1-13 yr) were studied. Patients belonging to upper, middle and lower SE strata numbered 85 (28%), 68 (22%) and 155 (50%). Nearly one-third of the patients were underweight. There was no treatment abandonment among children whose mothers were graduates. Neutropenic deaths during maintenance therapy were lower in mothers who had passed high school. In patients who survived induction therapy, the five year event-free survival (EFS) of upper SE stratum was significantly better 78.7±4.9 vs. 59±7.2 and 58.1±4.6 per cent in middle and lower strata (P =0.026). Five year overall survival was higher in the higher SE group; being 91.2±3.5, 78.3±5.6 and 78.8±3.9 per cent (P =0.055) in the three strata. Survival was unaffected by a distance of residence from treating centre or rural/urban residence. High-risk and undernourished children had a greater hazard of mortality [1.80 (P =0.015); 1.98 (P =0.027)]. INTERPRETATION & CONCLUSIONS: : Our findings showed that higher socio-economic status contributed to superior EFS in children with ALL who achieved remission. Undernutrition increased the risk of mortality.

The 5-Year EFS of Multisystem LCH With Risk-Organ Involvement Is Suboptimal: A Single-center Experience From India.

The study describes an 8-year experience of a single center in managing patients with langerhans cell histiocytosis on the basis of the langerhans cell histiocytosis-III platform. A retrospective case-file review of children diagnosed during 2006 to 2013 was performed. Group 1 (multisystem with risk-organ involvement) patients received an initial treatment of 6 to 12 weeks, followed by continuation treatment to complete 12 months. Drugs included vinblastine, prednisolone, and 6-mercaptopurine. Group 2 (multisystem without risk-organ involvement) patients received a similar treatment, except for 6-mercaptopurine. Group 3 (single-system/multifocal bone disease) patients were treated for a duration of 6 months. Forty-nine patients were treated: 24 (49%), 14 (28.6%), and 11 (22.4%) in groups 1, 2, and 3, respectively. The mean age at diagnosis was 31.6 ± 28.4 months (range, 4 to 120 mo). Five patients abandoned treatment. There were 7 deaths, all in group 1. All patients who died had either a partial response or progressive disease after induction (P=0.000). Among patients with liver involvement, those with sclerosing cholangitis had a greater mortality (P=0.007). A relapse was observed in 12 (24.5%) patients. The frequency of relapse was not different in the 3 groups (P=0.833). The 5-year event-free survival in groups 1, 2, and 3 was 29.3 ± 10%, 58.9 ± 14.6%, and 69.3 ± 15%, respectively (P=0.019). The 5-year overall survival was 100% in groups 2/3 and 68.9 ± 9.8% in group 1 (P=0.011).

The deferiprone and deferasirox combination is efficacious in iron overloaded patients with ß-thalassemia major: A prospective, single center, open-label study.

BACKGROUND: The high cost, coupled with the need for continuous infusion, renders Desferrioxamine (DFO), a non-feasible option for iron-chelation in a large majority of patients with ß-thalassemia major in developing countries. Monotherapy with deferiprone (DFP) or deferasirox (DFX) may not always attain optimal control, particularly in heavily iron-loaded patients. Combination of DFP and DFX is a potential alternative. PROCEDURE: A prospective, single-center, open-label, uncontrolled study was conducted to evaluate the safety and efficacy of the combination in patients with ß-thalassemia major. Patients who had received either DFP or DFX for >1 year and a serum ferritin >2,000 µg/L were enrolled. Blood counts, liver/renal functions, and serum ferritin were monitored during the 1-year study period. Facilities for cardiac T2*-MRI were unavailable. RESULTS: Thirty-six patients with a mean age of 13 ± 6.9 years (range: 4-29) and a ferritin of 6,768 ± 4,145 µg/L formed the study cohort. Eight (22%) patients had transient gastrointestinal adverse effects. DFX was discontinued in one patient for persistent abdominal pain/diarrhea. Eight (22%) had joint symptoms; DFP was discontinued in two. Four (11%) patients had elevation in AST/ALT levels, managed with temporary interruption of DFX. Nine (25%) had an inconsistent elevation of creatinine to >33% of baseline; no intervention was done. One had transient proteinuria. None had neutropenia. At the end of 1 year, the serum ferritin reduced by a mean value of 3,275.3 ± 618.2 µg/L (P < 0.001). CONCLUSIONS: The oral combination was found to be safe, efficacious, and a feasible option in patients with suboptimal response to monotherapy.

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.

Complete Peripheral Blast Clearance is Superior to the Conventional Cut-Off of 1000/µL in Predicting Relapse in Pediatric Pre-B Acute Lymphoblastic Leukemia.

Risk-stratification has contributed to a dramatic improvement in survival in pediatric acute lymphoblastic leukemia (ALL). This study evaluated the utility of prephase response and day 15 bone marrow when a minimal residual disease (MRD) assessment was available. A file review of children aged ≤ 15 years diagnosed with precursor-B ALL from 2014 to 2019 was performed. The protocol used for risk stratification and treatment was based on a UKALL-2003 backbone. All patients received one week of prephase therapy comprised of intravenous dexamethasone in the first 48 h followed by oral prednisolone. The median age of the 255 patients in the study was 5 years. Following the prephase, the peripheral blood absolute blast count was 0 and ≥ 1000/µL blasts in 141 (56%) and 29 (11%), respectively. Ten of 199 (5%) patients with an evaluable day 15 bone marrow had M3 status. At the end of induction, 30 (12%), 127 (50%) and 98 (38%) patients belonged to the standard-risk, intermediate-risk and high-risk (HR) groups, respectively. An M3 day15 bone marrow was the sole reason for escalation in three (3%) of the patients in the HR group. A lack of complete clearance of peripheral blood blasts post-prephase [HR: 2.45 (1.04-5.75), p = 0.040] and a positive MRD [HR: 3.00 (1.28-7.02), p = 0.011] independently predicted risk of relapse. Complete blast clearance is superior to the traditional cut-off of 1000/µL in predicting relapse. The role of a day 15 bone marrow morphology is diminished when an end of induction MRD is available.