Role of HSCT in children and adolescents with refractory or relapsed NHL

Abstract

Background: For Non-Hodgkin Lymphoma (NHL) in children and adolescents systematic treatment protocols resulted in improved event-free survival rates without transplant indications in first CR. However, so far no standard treatment approach could be established for relapsed or refractory NHL (r/r NHL). The aim of the current project was to gather international experiences on re-induction strategies in children and adolescents with r/r NHL and to identify factors predictive of outcome. Methods: Retrospective analysis of eligible cases collected on a common project specific CRF. Inclusion criteria were: a) NHL diagnosis, any subtype except ALCL, B) age at diagnosis < 18 years, c) diagnosis in/after Jan 2000, d) refractory disease, disease progression or relapse. The primary endpoint of the study was overall survival (pOS). Secondary endpoints were treatment-related mortality (TRM) and disease-related mortality (DOD). Results: A total of 695 eligible patients were reported by the following national groups: Germany (146), Italy (118), UK (67), France (66), Turkey (45), Sweden and Finland (35), Japan (33), Belarus (26), Moscow (23), Spain (23), Czech Republic (19), Austria (18), Hong Kong (18), Slovakia (11), Ukraine (9), Denmark (9), Poland (8), Belgium (6), Netherlands (5), Norway (5), Switzerland (4) and Chile (1). Median age at initial diagnosis was 10.8 years (0.3 to 17.9) and 499 (72%) of the patients were male. The distribution of histological subtypes was Burkitt 282, DLBCL 118, PMLBL 46, mature B-NHL not further specified 11, T-LBL 181, pB-LBL 37, PTCL 15 and other NHL subtypes 5. Eight-year pOS for the total cohort was 37±2% with highly significant differences according to NHL subtypes, with pOS of 30±3% in Burkitt, 51±5% in DLBCL, 47±8% in PMLBL, 35±2% in LBL and 41±10% in rare subtypes. Late relapses >9 months from diagnosis (n=233, pOS 47±4%) were associated with superior pOS compared to r/r NHL diagnosed 6 to < 9 months (n=107, pOS 35±5%), 3 to < 6 months (n=264, pOS 31±3%) and < 3 months (n=91, pOS 30±5%) after NHL onset. A total of 236 pts did not receive HSCT as it was not planned in one third of those pts and not achieved because of disease progression in the remaining two thirds. Outcome was poor for patients who did not receive high-dose treatment (n=236, pOS 11±2%) compared to autologous (n=197, pOS 55±4%) or allogeneic (n=243, pOS 49±3%) transplant. The 5-year cumulative incidences of TRM and DOD were 2+1% and 80±3% for patients without HSCT, 6±2% and 32±3% for autologous HSCT and 14+2% and 35±3% for allo HSCT. Among those patients who underwent HSCT, the remission status at HSCT was highly significant associated with outcome (pOS of 59±3% for CR, 60±9% for CRu and VGPR, 35±7% for PR, 20±10% for SD and 11±6% for progressive disease). Conclusions: International co-operative efforts provided by far the largest series of r/r NHL which allowed the identification of prognostic parameters in r/r NHL and may support transplantation strategies.