Hasmukh Jain

Background: Adolescents with cancer face unique psychological, social, and developmental challenges that are distinct from those faced by children and adults. While coping strategies influence psychological outcomes, the evidence is limited to high‐income countries. Minimal longitudinal data exist in low‐ and middle‐income contexts, where sociocultural factors may shape coping strategies differently. Methods: We conducted a longitudinal qualitative study of adolescents newly diagnosed with Acute Lymphoblastic Leukaemia (ALL) at a tertiary cancer centre in India. Thirty participants were purposively sampled and interviewed at baseline,3‐ and 6‐months after treatment initiation. The interviews were transcribed, translated, and analysed using thematic analysis. Results: Among the 30 participants, 93% were male, with a median age of 16.5 years. Coping strategies evolved over time, initially dominated by maladaptive mechanisms such as avoidance, distancing, and blaming. At 3 months, participants employed a combination of strategies, including avoidance, humour, religious coping, and support‐seeking. By 6 months, there was an increase in adaptive strategies, including acceptance, meaning‐making, and post‐traumatic growth. Gender differences emerged: females favoured religious coping and reported concerns about body image, while males preferred humour and fatalistic attributions. Conclusion: Coping in adolescents with ALL evolved during treatment, with an early reliance on maladaptive responses and a subsequent shift towards adaptive strategies. Gendered patterns reflect cultural and developmental contexts. These findings underscore the importance of culturally sensitive and developmentally tailored psychosocial interventions, including structured psychoeducation, fertility counselling, and identity‐focused support, to enhance resilience and improve psychosocial outcomes.

Talicabtagene autoleucel (tali-cel) is the first humanized CD19-directed CAR-T cell therapy approved in India for relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and B-cell non-Hodgkin lymphoma (B-NHL). Here, we integrated clinical and manufacturing operations through a centralized coordination unit (CCU) and evaluated tali-cel implementation. Patients with r/r B-ALL (n = 105) and r/r B-NHL (n = 145) who underwent leukapheresis between 15 November 2023 and 31 January 2025 across 56 treatment centers were included. The CCU enabled timely delivery, with manufacturing slot allocation within one week of slot request and a median vein-to-vein time of 29 days (range, 16–102), independent of geographic location. In r/r B-ALL patients, the median follow-up was 14 months, and the median overall survival (OS) not reached, and progression-free survival (PFS) was 18 months (range: 9-NR). The 12-month OS and PFS were 64% (95% CI: 53–72) and 55% (95% CI: 45–65). In r/r B-NHL, the median follow-up was 13 months and the median PFS was 11 months (range:7–16) and OS was not reached. The 12-month OS and PFS were 63% (95% CI: 54–71) and 47% (95% CI: 38-56). No patients underwent consolidative stem cell transplantation. Grade 3/4 cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), and Immune Effector Cell-associated Hemophagocytic Lymphohistiocytosis-like Syndrome (IEC-HS) occurred in 6%, 4%, and 23% of r/r B-ALL and 6%, 3%, and 18% of r/r B-NHL patients, respectively. These findings demonstrate the successful implementation of tali-cel across multiple centers in a large cohort, which might contribute towards improving CAR-T access globally.

PURPOSE: Outcomes in adults age 40 years and older with ALL are inferior to younger patients, with limited real-world data. METHODS: This is a retrospective analysis of adults age 40 years and older with newly diagnosed ALL enrolled in the Hematology Cancer Consortium registry from January 2019 to January 2021. Baseline variables, treatment patterns, response rates, toxicities, and survival were assessed. Overall survival (OS) and event-free survival (EFS) were estimated using Kaplan-Meier methodology. RESULTS: Of 349 registered patients, 61.3% (n = 214/349) initiated therapy, while 38.6% (n = 135/349) refused therapy. B-ALL represented 81% of cases (n = 174/214). Berlin-Frankfurt-Münster was used in 61.6% (n = 132/214) and German ALL in 30.3% (n = 65/214). Induction mortality was 18.6% (n = 40/214), mainly infection-related. Complete remission rates were 59.8% among assessed patients (n = 128/214), with minimal residual disease negativity in 45.8% (n = 61/133). Treatment de-escalation due to intolerance occurred in 30.8% (n = 66/214), and 35% (n = 75/214) were lost to follow-up. 3.7% (n = 8) patients underwent allotransplantation. At a median follow-up of 34 months, 3-year OS and EFS rates for the entire cohort were 31% and 29.6%, respectively (n = 214). Median OS and EFS were 13 and 11 months, respectively. CONCLUSION: Adults age 40 years and older with ALL in India have poor outcomes, driven by early mortality, treatment intolerance, and limited access to advanced therapies.

Approximately 10% of all cancers worldwide have been attributed to an underlying viral infection [1]. Regarding lymphoid malignancies, viral infections have been linked to several of these cancers ...

We assessed the overall survival (OS) impact of time to relapse (TTR) in multinational cohorts with independent observational and randomized validation. Patients with nMTCL with frontline complete response were assigned to TTR12 (≤12 months) or without TTR12 based on time to progression or next therapy. OS analyses included modified landmark (m-LM), standard landmark (s-LM), and time-dependent Cox (td-Cox), adjusting for age, histology, and prognostic index for T-cell lymphoma (PIT) score. Across 452 patients, 165 (36.5%) had TTR12, 181 (40%) relapsed at ≥12 months, and 106 (23.5%) remained relapse-free. TTR12 conferred worse OS using m-LM (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.58-2.90; P< .001), s-LM (HR, 1.92; 95% CI, 1.39-2.66; P< .001); and td-Cox (HR, 5.81; 95% CI, 2.94-11.46; P< .001). Results were consistent in the independent validation cohorts. TTR12 consistently conferred worse OS irrespective of frontline stem cell transplantation or PIT score, in peripheral T-cell lymphoma, not otherwise specified (m-LM: HR, 2.32; 95% CI, 1.51-3.55; P< .001; s-LM: HR, 2.10; 95% CI, 1.33-3.31; P = .001), anaplastic large cell lymphoma (m-LM: HR, 3.34; 95% CI, 1.18-9.50; P = .023; s-LM: HR, 2.96; 95% CI, 1.02-8.81; P = .046), and angioimmunoblastic T-cell/T follicular helper cell lymphoma (m-LM only: HR, 1.92; 95% CI, 1.15-3.21; P = .013). Second-line novel therapies improved OS (second-line start to death) vs chemotherapy in TTR12 only (HR, 0.60; 95% CI, 0.37-0.97; P = .038; without TTR12: HR, 0.82; 95% CI, 0.51-1.32; P = .407). TTR12 serves as a prognostic and potential OS surrogate marker, supporting stratification of new risk groups and need for their differential treatment.

PURPOSE: The 2022 European LeukemiaNet (ELN22) genetic risk stratification for AML makes critical changes, including removal of FLT3- internal tandem duplications (ITD) allelic ratio and inclusion of mutations in myelodysplasia-related (MR) genes and in-frame bZIP CEBPA mutations. We evaluated the applicability of ELN22 in a uniformly treated younger AML cohort and explored refinements to improve risk prediction. METHODS: We retrospectively analyzed 473 adult patients with AML treated with intensive therapy. A combination of cytogenetics and next-generation sequencing was used to stratify patients into the ELN17 and ELN22 risk. In addition, we also evaluated leukemic stem cell (LSC) burden at diagnosis and postinduction measurable residual disease by multiparametric flow cytometry. RESULTS: A total of 77 cases (16.3%) were reclassified from ELN17, primarily because of changes associated with FLT3 -ITD, CEBPA , and MR gene mutations. As per ELN22, 56.7% of patients were classified as favorable, 28.3% intermediate, and 15.0% adverse risk. ELN22 adverse-risk patients had significantly inferior overall survival and relapse-free survival compared with intermediate- and favorable-risk patients. High LSC burden at diagnosis, presence of WT1 mutations, and DNMT3A-FLT3 -ITD comutated NPM 1 dichotomized the ELN22 intermediate-risk group. CONCLUSION: We conclude that ELN22 is prognostically valid in intensively treated younger patients with AML. Incorporation of WT1 mutation status, triple-mutated NPM1 , and LSC burden may improve risk stratification, particularly within the heterogeneous intermediate-risk category.

PURPOSE: Anticancer therapy increases the risk of hepatitis B virus (HBV) reactivation in patients with occult hepatitis B infection (OHBI), particularly in those who receive rituximab or stem-cell transplantation. However, the exact risk of HBV reactivation in patients with ALL/lymphoblastic lymphoma (LBL) receiving prolonged, intensive myelosuppressive chemotherapy is not known and thus the role of antiviral prophylaxis is not clearly established. PATIENTS AND METHODS: This prospective observational study was conducted at a single tertiary cancer center in India (October 2017 to August 2021). Patients age 15 years and older with ALL/LBL were screened for OHBI and enrolled. Liver function tests and HBV DNA levels were monitored at baseline, during treatment, and throughout follow-up phase. During episodes of hepatitis, extended serology panel was performed. The primary end point was the incidence of HBV reactivation. RESULTS: OHBI was identified in 30.4% (172/566) of patients treated at our center during the study period. In the prospective cohort, 65 patients with ALL/LBL and OHBI, treated on a pediatric-inspired protocol, were enrolled. HBV reactivation occurred in six patients (9.2%; 95% CI, 4.3 to 18.7), none of whom developed HBV-related hepatitis. Seventeen patients experienced at least one episode of grade ≥3 hepatitis, with a median AST of 401 U/L (range, 192-3,490) and ALT of 430 U/L (range, 255-1,950). Hepatitis led to chemotherapy delays in five patients, with a median delay of 15.5 days (range, 7-39). CONCLUSION: Our findings indicate a moderate to high risk of HBV reactivation in ALL/LBL patients with OHBI treated with pediatric-inspired protocols, particularly during maintenance, supporting prophylactic antiviral therapy as standard practice in regions with high or intermediate HBV endemicity.