Outcomes of autologous hematopoietic stem cell transplantation in nodular lymphocyte-predominant Hodgkin lymphoma: A registry-based study from the EBMT-LWP

Abstract

Abstract INTRODUCTION Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma (HL), accounting for approximately 5–6% of cases. While long-term survival is favorable compared to classical HL, disease relapse and transformation to aggressive non-Hodgkin lymphoma (NHL) can occur. Most patients achieve excellent outcomes, with 10-year progression-free survival (PFS) rates of 70–75% and overall survival (OS) around 90%. However, approximately 20% relapse, typically within 3–4 years of diagnosis. Relapsed NLPHL generally follows an indolent course, with therapeutic options including observation, anti-CD20 monoclonal antibodies, radiotherapy, or chemotherapy. A subset of patients with high-risk features—such as refractory disease, early relapse (<24 months), or liver/bone marrow involvement—may benefit from intensified therapy, including autologous stem cell transplantation (ASCT), although the role of ASCT in NLPHL is not well established. This study aimed to evaluate outcomes of ASCT in patients with relapsed or refractory (R/R) NLPHL. METHODS We included adult patients (>18 years) with a diagnosis of NLPHL who underwent first ASCT between January 2010 and December 2021, more than one year after initial diagnosis, and were reported to the EBMT registry. Patients with untreated NLPHL before ASCT were excluded. Patients were selected based on the initial diagnosis of NLPHL; however, due to the limitations of the registry, we could not ascertain whether any had experienced histological transformation to aggressive NHL prior to ASCT. The primary endpoint was 3-year PFS post-ASCT. Secondary endpoints included 3-year OS, cumulative incidence of relapse, and non-relapse mortality (NRM). RESULTS A total of 789 patients (31% female, 69% male) met inclusion criteria. ASCTs were performed in 45% of cases between 2010–2014, 32% in 2015–2018, and 24% in 2019–2021. The median age at ASCT was 42 years (range 18–76), and the median time from diagnosis to ASCT was 30 months (IQR 18–66). Prior to ASCT, 6.3% received one line of therapy, 55% two lines, and 39% three or more. Rituximab (alone or in combination) was used before ASCT in 21% of patients. At transplant, 58% were in complete remission (CR), 28% in partial remission (PR), and 13% had refractory/stable disease. BEAM-based conditioning was used in 67% of cases. With a median follow-up of 2.6 years (range 2.1–3.0), the 1- and 3-year PFS rates were 82.3% and 71.9%, respectively. The 1- and 3-year OS rates were 93.7% and 87.6%. The cumulative incidence of relapse was 14.3% at 1 year and 23.3% at 3 years. One-year NRM was 3.4%. Patients in CR had higher 3-year PFS and lower relapse rates compared to those with PR or refractory disease (PFS: 77.9% vs. 60.8% and 64.3%; relapse: 18.2% vs. 31.8% and 32.5%, respectively). In multivariable analysis, factors included age at ASCT, sex, period of transplant, time from diagnosis to ASCT (< vs. >24 months), disease status at ASCT, conditioning regimen (BEAM vs. others), and prior rituximab use. PR at ASCT was associated with worse PFS compared to CR (HR 1.8, 95% CI 1.29–2.50, p<0.001) and a higher relapse rate (HR 1.86, 95% CI 1.28–2.71, p=0.001). Higher age at ASCT was associated with increased NRM (HR per 5-year increase 1.28, 95% CI 1.12–1.47, p<0.001) and lower OS (HR 1.13, 95% CI 1.04–1.22, p=0.003). CONCLUSIONS This is the largest reported cohort of patients with NLPHL undergoing ASCT. ASCT was associated with effective disease control and favorable survival, particularly in patients achieving CR before transplantation. While PR and refractory disease at ASCT were independently associated with higher relapse risk and inferior survival, the 3-year PFS rates of 60.8% and 64.3%, respectively, suggest that ASCT can still provide meaningful long-term benefit in these subgroups.