Abstract
Background
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of HL for which optimal treatment is controversial. We retrospectively reviewed the files of patients with NLPHL diagnosed and followed up at our institution and describe clinical characteristics and outcome and explore prognostic factors for progression-free survival (PFS) and overall survival (OS).
Methods
We included consecutive patients diagnosed with NLPHL and followed at King Fahad Specialist Hospital, Damamm (KFSH-D), a referral center for the Eastern Province of Saudi Arabia. Primary aim of this study was to determine clinical outcomes (PFS and OS) according to treatment strategy, i.e. radiotherapy (+/- Rituximab) (RT) only, chemotherapy (+/- Rituximab) (CT), combined modality (+/- Rituximab) (CMT), Rituximab monotherapy (R), and active surveillance (AS). Secondary aim was an exploratory analysis of candidate prognostic factors for PFS and OS. PFS was defined as time (months) from date of diagnosis to disease progression or death from any cause. Event time distributions were estimated using the method of Kaplan-Meier and groups were compared using the log-rank test. We used univariable and multivariable PFS analyses for candidate prognostic factors.
Results
From 1/2006 to 12/2017 data on 49 patients treated at KFSH-D, aged 16 years (y) or older, with a diagnosis of NLPHL and with sufficient treatment and follow-up (F/U) were analyzed. Median age at diagnosis was 29y (range, 16-56), 76% were male. Histology was typical in 86% (n=42), variant in 8% (n=4), and with transformed histology at diagnosis in 6% (n=3) of cases. Disease characteristics: 63% (n=31) of patients were stage I/II and 37% (n=18) stage III/IV, B-symptoms 12%, extranodal disease 10%, splenic involvement 8%, bulky disease (≥5 cm) 12%, and bone marrow involvement 4% of patients. The German Hodgkin Study Group (GHSG) score was intermediate-risk and high-risk in 53% (n=26) and 24% (n=12) of patients, respectively. Management strategy (MS), depending on physician's preference, was RT (16%, n=8), CT (43%, n=21), CMT (27%, n=13), R (6%, n=3), and AS (8%, n=4). For patients induced with chemotherapy +/- RT, ABVD-like (+/- Rituximab) (n=25) or CHOP (+/- Rituximab) (n=9) were used in all cases.
The overall response rate (ORR) for 45 patients who received treatment was 91% (complete responses (CR), 69%), 98% ORR when cases with transformed histology at diagnosis were excluded. Median F/U was 36 months (m), (range, 8-127). Overall, outcome was excellent, with 3- and 5-y PFS estimates of 80% and 75%, respectively (Figure). Overall survival was 100% with no deaths observed (Figure). The current PFS is 98%. Transformation at relapse/progression was observed in 2 patients at 36m and 45m, respectively, and remain disease free at 24m and 35m, respectively, following salvage treatment and auto-SCT. The 5-y cumulative risk of transformation (excluding cases with transformed histology at diagnosis) was 6%. Two secondary cancers were observed.
Exploratory univariate analysis revealed high-risk GHLG score (P=0.001), bulky disease (P=0.001), splenic involvement (P=0.01), transformed histology at diagnosis (P=0.02), and non-RT MS (P=0.001) as risk factors for shorter PFS. In the final multivariate model, the GHLG score (P=0.01) and non-RT MS (P=0.004) were the only a risk factor for shorter PFS. In pairwise comparison, excluding patients with transformed histology at diagnosis and patients on AS, for patients with stage I/II disease, RT-based therapy was associated with improved 5-y PFS rates compared to CT-based therapy, (P = 0.02). For patients with stage III/IV disease 5-year PFS rates did not differ between RT-based and CT-based therapy (P= 0.4). For patients treated with CT, ABVD +/- Rituximab (n=13) vs CHOP +/- Rituximab (n=8) induction produced similar PFS rates at 5-years (P=0.9).
Conclusion
In this single center retrospective study, NLPHL had an excellent outcome. MS had an impact on PFS but not OS. High-risk GHLG score and omission of upfront RT were adversely prognostic factors for PFS. Large prospective trials are warranted to determine the optimal treatment approach for this rare B-cell lymphoma.
No relevant conflicts of interest to declare.
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