Background: ABVD regimen for Hodgkin lymphoma (HL), disfavoured in high-income countries, is popular in low-middle-income countries (LMIC). The feasibility/safety data for ‘non-ABVD’ protocols from LMIC is limited. Procedure: The retrospective study was conducted in a single center in India. Euronet-PHL-C1-based protocol was administered during 2010-19. A PET-CT was performed at diagnosis and following OEPA-course-2. Radiotherapy was administered for inadequate PET-response. Results: During the 10-year-period, 143 patients with HL were treated. The mean-age was 7.8±2.5 years. Bulky-disease was observed in 82 (59%). Treatment-abandonment was recorded in 13 (9.1%). The median follow-up duration was 46.4 months. An inadequate PET-response was observed in 41/118 (34.7%). Radiotherapy was administered to 23/41 (56.1%). There was a protocol violation of replacing radiotherapy in 12 (29.3%) patients with 2-courses of COPDAC. Sixty-nine episodes of febrile-neutropenia were observed in 54 patients. TRM was observed in 7 (5.3%). The majority of episodes of febrile-neutropenia (61%) and TRM (86%) were following OEPA-course-1. The 4-year overall-survival (OS) and event-free survival (EFS) were 93.5±2.2% and 86.2±3.4%, respectively. Nine (6.3%) patients relapsed. The survival compared favorably with 5-year-EFS (77.7%) of patients who received ABVD/COPP in the center in the past. Bulky-disease lacked association with inadequate PET-response (p=0.800) or relapse (p=1.000). Conclusions: OEPA/COPDAC regimen and response assessment by PET-CT permitted therapy reduction, including radiotherapy. The survival (4-year OS: 93.5±2.2%) was excellent, with a low relapse (6.3%). Febrile neutropenia and resultant TRM (5.3%) are concerning and occurred frequently following OEPA-course-1. The support system for managing febrile neutropenia should be optimized for administering OEPA in LMIC.

Objective:  Anaplastic Lymphoma Kinase ( ALK) gene gain-of-function point mutation leading to its overexpression has recently been identified and targeted in neuroblastoma (NB). We evaluated ALK gene mutation and its protein expression in cases of NB on fine needle aspiration biopsy (FNAB). Material and Methods: FNAB diagnosed cases of NB (n=56) were evaluated with cell blocks for MYCN amplification and ALK protein expression by Fluorescence in-situ hybridization and immunocytochemistry respectively. MGG stained smears (n=22) were used for Next generation sequencing (NGS) analysis using the Cancer Hotspot panel (version2) on Ion Torrent S5 platform. Staging and risk assignment as per International Neuroblastoma Risk Group (INRG) was performed and managed. All the parameters were correlated with overall survival. Results: ALK protein showed cytoplasmic expression in 65% of cases and did not correlate with MYCN amplification (p=0.35), INRG groups (p=0.52), and overall survival (p=0.2); however, ALK+ poorly differentiated NB showed better prognosis (p=0.02). ALK negativity was associated with poor outcome by Cox proportional hazard model (hazard ratio=2.36). ALK gene, exon 23 missense mutations (F1174L) were seen in 2/21 cases with an allele frequency of 8% and 54%. Both these cases showed ALK protein expression and died of disease within 1 and 17 months respectively. A novel IDH1 exon 4 mutation was also detected. Conclusion:  ALK expression is a promising prognostic as well as a predictive marker in advanced NB along with traditional prognostic parameters. FNAB smears are suitable for NGS and ALK gene mutation confers a poor prognosis.

Background: The majority of patients with high-risk neuroblastoma (HR-NB) in low- and middle-income countries (LMIC) do not have access to autologous stem cell transplant (ASCT) and dinutuximab. Consolidation with non-myeloablative chemotherapy is not well-defined, and the outcomes are variable. We report a single-center outcome of patients with HR-NB, treated with non-myeloablative consolidation. A tabulated compilation of similar reports is included. Procedure: A retrospective chart review of patients with HR-NB was performed from January 2009 till June 2016. Patients were treated on the backbone of HR-NBL1/SIOPEN protocol. Treatment included induction with rapid-COJEC, surgery, consolidation, radiotherapy to the primary tumor, and differentiation therapy with isotretinoin. Consolidation included 4 cycles of topotecan, vincristine, and doxorubicin (TVD) instead of ASCT. Infusion of vincristine and doxorubicin were modified for ease and to enable administration in daycare. Results: Over 7-½ years, 28 patients with HR-NB were treated. Two (7%) patients had therapy-related mortality. A relapse or disease progression occurred in 11 (39%) patients at a median duration of 17 months (IQR: 5, 18). Treatment abandonment was observed in 4 (14%) patients. The 4-year event-free survival was 29.3%. The median follow up of disease-free patients is 49 months (IQR: 45, 79). Patients with relapse were not treated further. Conclusions: A 4-year EFS of 29.3% was observed when 4-cycles of TVD were administered instead of ASCT in patients with HR-NB. The study and the review will aid stakeholders in LMIC for decision-making while considering the options of treatment for HR-NB if access to ACST and dinutuximab is lacking.