A prognostic model predicting autologous transplantation outcomes in children, adolescents and young adults with Hodgkin lymphoma

Abstract

Autologous hematopoietic cell transplantation (AutoHCT) is a potentially curative treatment modality for relapsed/refractory Hodgkin lymphoma (HL). However, no large studies have evaluated pre-transplant factors predictive of outcomes of AutoHCT in children, adolescents and young adults (CAYA, age <30 years). In a retrospective study, we analyzed 606 CAYA patients (median age 23 years) with relapsed/refractory HL who underwent AutoHCT between 1995–2010. The probabilities of progression free survival (PFS) at 1, 5 and 10 years were 66% (95% CI: 62–70), 52% (95% CI: 48–57) and 47% (95% CI: 42–51), respectively. Multivariate analysis for PFS demonstrated that at the time of AutoHCT patients with Karnofsky/Lansky score ≥90, no extranodal involvement and chemosensitive disease had significantly improved PFS. Patients with time from diagnosis to first relapse of <1 year had a significantly inferior PFS. A prognostic model for PFS was developed that stratified patients into low, intermediate and high-risk groups, predicting for 5-year PFS probabilities of 72% (95% CI: 64–80), 53% (95% CI: 47–59) and 23% (95% CI: 9–36), respectively. This large study identifies a group of CAYA patients with relapsed/refractory HL who are at high risk for progression after AutoHCT. Such patients should be targeted for novel therapeutic and/or maintenance approaches post-AutoHCT.

Long‐term outcomes among 2‐year survivors of autologous hematopoietic cell transplantation for Hodgkin and diffuse large b‐cell lymphoma

“…High‐dose chemotherapy followed by autologous hematopoietic cell transplantation (auto‐HCT) remains the standard treatment for medically fit patients with relapsed or refractory aggressive lymphomas . Reported survival rates 3 to 5 years after auto‐HCT for classic Hodgkin lymphoma (cHL) and diffuse large B‐cell lymphoma (DLBCL) range from 40% to 70% . Treatment failure is most commonly due to relapse or progression of the underlying disease, which primarily occurs within the first 2 years after auto‐HCT .…”

“…1,2 Reported survival rates 3 to 5 years after auto-HCT for classic Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) range from 40% to 70%. [2][3][4][5][6][7][8] Treatment failure is most commonly due to relapse or progression of the underlying disease, which primarily occurs within the first 2 years after auto-HCT. 1 For those patients who survive the initial post-auto-HCT period, long-term outcomes are not well described.…”

Hodgkin lymphoma in children and adolescents: improving the therapeutic index

“…With the observation that complete response by PET/CT is associated with higher survival following AHSCT, 16 evaluation of novel combinations to improve CR rates would be of value, perhaps in conjunction with adult cooperative groups as part of an AYA initiative. Given that the median age at relapse is in mid adolescence, consideration for lowering the age for eligibility for trials would greatly improve access to novel agents for adolescents with HL.…”

“…A recent CIBMTR analysis of 671 patients ,30 years who underwent AHSCT for relapsed/ refractory HL reported progression free survival and overall survival rates of 56% and 73%, respectively. 16 Clinical risk factors including first remission ,12 months, poor performance status, chemoresistance, extranodal disease at relapse, and receipt of regimens other than ABVD/ABVD-like for first line therapy predict reduced survival post AHSCT. In contrast, patients with late relapse of low-stage disease are predicted to have excellent outcomes with conventional chemotherapy or chemoradiotherapy, and thus may be able to avoid the acute and long-term toxicity associated with AHSCT.…”

Ifosfamide, gemcitabine, and vinorelbine is an effective salvage regimen with excellent stem cell mobilization in relapsed or refractory pediatric Hodgkin lymphoma

“…Multiple factors have been identified that correlate with outcome to salvage therapy, including advanced stage, extranodal disease, B symptoms, time to relapse, and extent of prior therapy . The high ORR in our cohort may be a reflection of patient characteristics: all of our patients were at first relapse or progression, only one had prior radiotherapy, and none had B symptoms.…”