A Break from Steroids May Save More Children with Leukaemia Without Compromising Treatment Outcomes (INPHOG-ALL-15-01)
While leukaemia survival rates reach 90% in high-income countries, children in India faced high treatment-related mortality with nearly half of these deaths occurring during the initial 4-to-6-week induction phase due to severe infections. While corticosteroid drugs (like prednisolone) are essential for killing leukaemia cells, taking them continuously for 4–5 weeks severely suppresses the immune system and increases vulnerability to fatal infections. In relapsed ALL, pulsed corticosteroid regimens have been effective, suggesting that continuous corticosteroid exposure may not be essential for therapeutic efficacy. Hence, the ICiCLe-ALL-14 phase 3 randomized trial aimed to determine whether giving prednisolone in a pulsed schedule (two 2-week bursts with a 1-week break) rather than continuous 4-week dosing would reduce early treatment deaths and severe
toxicity without lowering remission or long-term survival rates in children with non–high-risk B-cell precursor (BCP) ALL. 1246 randomised (623 per group). Induction deaths dropped from 3.5% in the continuous steroid group down to 1.3% in the pulsed steroid group (p=0.0149), largely by preventing fatal infections. Continuous prednisolone carried a 2.75-times higher risk of induction death. Both groups achieved nearly identical complete remission rates 98.8% and 98.0% (594/606); MRD ≥ 0.01% at EoI was 26.2% and 27.9%; 3-year EFS 72.7% (95% CI 68.2–76.7) and 72.2% (67.6–76.3); OS 85.0% (81.5–87.8) and 87.0% (83.6–89.3) in R1A and R1B respectively. The study concludes, Pulsed prednisolone during induction significantly reduced treatment-related deaths, particularly early deaths from infections compared to continuous dosing, without compromising CR rates, MRD clearance, EFS, or OS.
DOI:10.1016/j.lansea.2026.100788.
Two Drugs May Be Enough: Trial Finds No Benefit from Adding an extra drug (Etoposide) in Childhood AML (InPOG-AML-16-01)
Chemotherapy remains the backbone for treating AML. While a two-drug regimen (DA: daunorubicin + ara-C) is standard in adults, paediatric protocols have been heterogenous, often add a third drug despite a lack of randomized controlled trials proving its additional benefit. Therefore, a randomized controlled trial was conducted to compare a two-drug (DA) with a three-drug ara-C, daunorubicin, and etoposide (ADE). A total of 149 patients were randomized to the DA (n = 77) or ADE (n = 72) arm and followed for a median of 50.9 months. The cCR rate in the DA and ADE arm was 82% and 79% (p = 0.68) after the second induction. There were 13 (17%) induction deaths in the DA arm and 12 (17%) in the ADE arm (p = 0.97). The 5-year EFS in the DA and ADE arm was 34.4% and 34.5%, respectively (p = 0.66). The 5-year OS in the DA and ADE arms was 41.4% and 42.09%,
respectively (p = 0.74). There were no significant differences in toxicities between the regimens. Adding etoposide to standard induction chemotherapy provided no statistically significant improvement in remission rates, event-free survival, overall survival, or toxicity reduction in paediatric AML patients.
https://doi.org/10.1038/s41408-022-00726-1
A Better Scan Helps Reduce Radiation Exposure: PET-CT More Accurately Assesses Early Treatment Response Than CECT (InPOG HL-15-01)
While chemotherapy and radiation therapy (RT) are highly effective in curing paediatric Hodgkin lymphoma, RT is associated with significant long-term toxicities, including secondary malignancies, endocrine dysfunction, and cardiovascular disease. Therefore, modern paediatric oncology focuses on a response-adapted treatment approach, in which the need for RT is determined by the tumour's early response to chemotherapy, RT was delivered to children with suboptimal response at early response assessment (ERA) or those with bulky disease. Early response assessment (ERA) was done by CECT or PET-CT as per center practice and availability of resources. Therefore, this study aimed to compare the impact of CECT and PET-CT on treatment decisions and clinical outcomes. The study showed that using PET-CT instead of CECT for early response assessment (ERA) after
two cycles of chemotherapy identifies satisfactory treatment responses much more accurately (81.2% vs. 64.3%) in children and adolescents with HL. By using PET-CT to guide treatment decisions, clinicians were able to significantly reduce the proportion of patients needing radiation therapy—particularly among those with non-bulky disease (84.2% vs. 68.5%)—without compromising clinical outcomes. Long-term efficacy remained equivalent across both groups for 5-year overall survival (94.1% vs. 91.8%) and event-free survival (85.5% vs. 86.7%), confirming that PET-CT-adapted therapy safely reduces radiation exposure and its associated late-onset toxicities in paediatric patients in low- and middle-income countries.
DOI:10.1002/pbc.30091.
Low-Cost Oral Therapy Shows Promise for Children with Relapsed Langerhans Cell Histiocytosis (InPOG-HIST-19-03).
A prospective multicentric study undertaken in India to evaluate the efficacy, safety, and cost-effectiveness of outpatient oral lenalidomide plus dexamethasone (LENDEX) in 15 children with relapsed or refractory Langerhans cell histiocytosis. The regimen achieved an overall response rate of 73%, with complete remission increasing from 26% after six cycles to 53% after nine cycles, while only one patient experienced disease progression. Treatment was well tolerated on an outpatient basis, with no child requiring hospitalization, minimal toxicity (primarily mild anaemia and myalgia), and no treatment-related deaths during a median follow-up of 24 months. In addition, the regimen was highly cost-effective, with the average drug cost for a 20-kg child estimated at approximately ₹792 (US$9) for six cycles and ₹1,188 (US$13) for nine cycles. These findings
support further evaluation of a treatment strategy comprising nine cycles of LENDEX followed by 12 months of maintenance therapy with 6-mercaptopurine.
https://doi.org/10.1002/1545-5017.70217.
Dexamethasone Can Be Omitted from Antiemetic Treatment in Children Receiving Highly Emetogenic Chemotherapy: CIVIC POD trial (INPHOG-SUPP-22-03)
Chemotherapy-induced nausea and vomiting (CINV) is a major concern in children receiving highly emetogenic chemotherapy, while repeated dexamethasone exposure can cause clinically relevant toxicities. Olanzapine, a multireceptor antiemetic, has shown improved CINV control in paediatric oncology and was therefore explored as a potential steroid-sparing alternative to dexamethasone. Hence, a multicentre, phase III randomized noninferiority trial conducted at six tertiary oncology centres in India to determine whether dexamethasone could be omitted from antiemetic prophylaxis in children and adolescents receiving highly emetogenic chemotherapy. The study included 310 patients aged 4–18 years, with osteosarcoma, Ewing sarcoma, and Hodgkin lymphoma being the most common diagnoses. Patients were randomly assigned to receive either standard (dexamethasone
+ palonosetron + fosaprepitant) or dexamethasone-free regimen (olanzapine + palonosetron + fosaprepitant). The primary outcome was complete response to vomiting, defined as no vomiting and no need for rescue antiemetics during the overall from initiation of chemotherapy to 120-hr period. Olanzapine showed noninferior control of chemotherapy-induced vomiting, with complete response achieved in 63.5% of patients compared with 56.9% in the dexamethasone group (absolute difference, 6.6% [95% CI, 24.5 to 17.7]). Acute and delayed vomiting control were also comparable between the groups, and nausea outcomes were similar. Olanzapine was associated with more somnolence, fatigue, and constipation, but these adverse effects were predominantly grade 1–2, with no grade 3–4 clinical adverse events or treatment discontinuations attributed to olanzapine. Overall, the CIVIC POD trial shows that dexamethasone
can be omitted from antiemetic prophylaxis without compromising vomiting control when olanzapine is combined with palonosetron and fosaprepitant. These findings support a potential steroid-sparing approach to CINV prevention in children receiving highly emetogenic chemotherapy.
DOI - https://doi.org/10.1200/JCO-26-00677.
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