Early-stage nodular lymphocyte predominant Hodgkin lymphoma: Disease characteristics, treatment pattern, and long-term outcomes from a tertiary care cancer institute in India

Abstract

Abstract Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare & distinct subtype of Hodgkin lymphoma (HL), accounting for approximately 5% of all HL cases. While outcomes are favorable in early-stage disease with lymphoma specific deaths in less than 5% at 10 years, treatment remains heterogenous & deaths unrelated to lymphoma outnumber lymphoma specific deaths. Furthermore, data on real-world outcomes in resource-limited settings such as India remain scarce. Objectives: To report the clinical characteristics, treatment patterns, & long-term outcomes of patients with early-stage NLPHL treated at a tertiary cancer center in India. Method: We included all consecutive patients diagnosed with Stage I–II NLPHL between 2010 & 2022. Clinical data were extracted from electronic medical records. Immunoarchitectural patterns (IAP) were categorized as either typical (patterns A–B) or variant (patterns D–F). Treatment modalities were categorised as radiotherapy (RT) alone, chemotherapy alone, combined modality treatment (CMT), or observation. Survival outcomes were estimated using the Kaplan–Meier method. The prognostic scoring systems, including GHSG prognostic score (based on variant IAP, male gender & serum albumine less than 4 gm/dl) described by Hartmann et al. (Blood, 2013) & the NLPHL-International Prognostic Score (LP-IPS, using age ≥45 years, stage III-IV, hemoglobin <10.5 g/dL, & splenic involvement) by GLOW group was also evaluated. Results: A total of 112 patients with early-stage NLPHL were included. The median age was 31 years (IQR 24-39), & 84 (75%) were male. Stage I & II disease were seen in 49% &51% of patients respectively with 24 (21.5%) having bulky disease. The majority presented with peripheral lymphadenopathy & only 3 (2.7%) had extranodal disease; B-symptoms were noted in only 6 (5.4%) patients, 25 (22%) had more than 2 sites of involvement & five patients (5%) having serum albumin less than 4 gm/dL. Variant IAP were observed in 19 (28%) of 68 evaluable cases. GHSG prognostic score were available for 68 patients with 37 (54%) patients in intermediate risk group with a score of 2, while 17 (25%) and 14 (21%) in low risk group (score 0) and 14 (21%) in high risk group (risk score of 3-4). However as per the GLOW LP-IPS score, the majority 93 (83%) were in the low risk group with no risk factors while 17(15%) had one risk factor & only 2 (1.8%) had 2 risk factors. Treatment included RT alone in 57(51%), CMT in 48 (43%), chemotherapyal alone in 4 patients & observation in 3 patients. Amongst 48 patients receiving CMT, ABVD based chemotherapy was used in 34(70%) followed by CHOP based in 9(18%) while rituximab was combined with chemotherapy in 15(31.25%) patients only. So as to understand factors influencing treatment decision, we compared the RT and CMT group for baseline characteristics & CMT group had significantly higher proportion of patient having stage II disease (85.4 vs 22.8%), bulky disease (40.4 vs 8.9%), more than 2 site involvement (47 vs 8%), SUVmax more than 10 (66.6% vs 29.8%), variant IAP (29.2 Vs 8.8%) and GHSG high risk (31.3 vs 11.1%) however they did not differ in terms of age, gender, ECOG status, B symptoms and LP-IPS risk groups. A total of eight patients have relapsed, 2 locally & 6 at distant sites. Progression free & overall survival at 8 years is 91 & 98% respectively. Six patients received salvage chemotherapy and one patient underwent consolidation ASCT. Three patients have died with only one lymphoma related death while remaining 2 were unrelated (1-concurrent second malignancy, 1-cause unknown). Though absolute number of relapses and deaths were small in numbers, they did not differ significantly in CMT vs RT group ( 8.4 vs 5.3% and 1.8 vs 4.2% respectively). Simillarly, type of chemotherapy, use of rituximan, LP-IPS or GHSG prognostic score were not associatd with either relapse or death. Conclusions: Patients with early-stage NLPHL treated in a real-world LMIC setting achieve excellent long-term survival, comparable to international cohorts. Stage II disease, bulk nodes, variant IAP & more than 2 site disease influence treatment decision in favour of CMT & leads to comparable outcomes with RT and CMT in overall patient population. Disease control is excellant with non lymphoma related deaths outnumbering the lymphoma related deaths suggesting personalized treatment strategies based on prognostic factors & long-term surveillance are crucial to optimize outcomes.