Impact of Risk Factors and Long Term Survival Analysis of Patients With Primary Refractory Hodgkin Lymphoma Who Underwent High Dose Chemotherapy and Autologous Stem Cell Transplant

• Published in: Transplantation and cellular therapy Vol. 29; no. 7; pp. 451.e1 - 451.e12
• Main Authors: Akhtar, Saad, Rauf, M. Shahzad, Elhassan, Tusneem Ahmed M., Khan, Zubair Ali, Elshenawy, Mahmoud A., Maghfoor, Irfan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2023
• Subjects: Adolescent and young adults; Adult; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Autologous stem cell transplantation; Hematopoietic Stem Cell Transplantation - methods; Hodgkin Disease - drug therapy; Hodgkin lymphoma; Humans; Neoplasm Recurrence, Local - drug therapy; Prognostic model; Refractory Hodgkin lymphoma; Retrospective Studies; Risk Factors; Stem Cell Transplantation; Survival Analysis; Transplantation, Autologous - methods; Young Adult; Adolescent and young adults; Prognostic model; Autologous stem cell transplantation; Refractory Hodgkin lymphoma; Hodgkin lymphoma
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2023.04.002

•In a large cohort of primary refractory Hodgkin lymphoma who received high-dose chemotherapy and autologous stem cell transplantation (auto-SCT), numerous prognostic factors were analyzed for a risk factor-based survival model.•These patients had encouraging survival.•Post-auto-SCT failure and risk factors related to outcome were explored.•Newer treatment strategies are likely to improve survival.
Patients with primary refractory Hodgkin lymphoma (ref-HL) can still be salvaged with high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). Outcomes of patients with ref-HL is poorer than those with relapsed HL, but most studies have included patients with both relapsed and refractory diseases, and separate analyses or studies on patients with ref-HL are limited. This study aimed to evaluate the outcomes of HDC auto-SCT and impact of various prognostic factors in patients with ref-HL at the time of primary treatment failure and subsequent survival at the time of failure post-HDC auto-SCT. This retrospective single-institution cohort analysis using an HDC and auto-SCT database was approved by the Institutional Research Advisory Counsel and Ethics Committee for identifying patients. We used the Fine and Gray competing risk analysis method, a regression model for outcome analysis, and the Kaplan-Meier (KM) method for survival analysis. The study cohort comprised 200 consecutive ref-HL patients who underwent HDC auto-SCT between 1996 and 2019. The median patient age was 22.75 years, and median follow-up was 106 months. Post-auto-SCT disease status was complete remission (CR) in 122 patients (61%), partial remission in 22 (11%), and progressive disease in 47 (23.5%). KM median progression-free survival (PFS) after auto-SCT was 43.9 months (5 years, 49.3%; 10 years, 45.5%). Median overall survival (OS) was 168.6 months (5 years, 61.2%: 10 years, 56.2%). Eighty-five patients (44.5%) died, 69 (34.5%) due to disease. Multivariate analysis identified similar adverse factors for both PFS and OS. For PFS, these adverse factors included stage III-IV at relapse (hazard ratio [HR], 1.65; P = .045), mediastinal involvement (HR, 2.01; P = .009), and absence of CR after salvage chemotherapy (HR, 2.2; P = .001). PFS with 0 or 1 adverse factors (not reached), 2 adverse factors (40.8 months), and 3 adverse factors (5.4 months) was significant (P < .001). For OS, significant adverse factors included stage III-IV at relapse (HR, 1.68; P = .045), mediastinal involvement (HR, 2.52; P = .007), and no CR after salvage chemotherapy (HR, 2.15; P = .004) were significant. OS with 0 or 1 adverse factors (not reached), 2 adverse factors (148.5 months), and 3 adverse factors (34.4 months) was significant (P < .001). The median OS after auto-SCT failure was 23.6 months; patients received post auto-SCT brentuximab/second SCT (not reached), other treatments (22.5 months), and supportive care (8.4 months) (P < .001). OS with 5 risk factors present at HDC auto-SCT failure— stage III-IV, failure at <12 months, tumor >5 cm, B symptoms, and low serum albumin—was 152 months for 0 or 1 risk factors, 30.9 months with 2 risk factors, and 9.45 months with 3 to 5 risk factors (P < .001). Ref-HL patients have encouraging survival after HDC auto-SCT and can even be salvaged after auto-SCT failure. Based on prognostic factors, survival prediction is possible. Patients who fail to respond to HDC auto-SCT may benefit from newer treatments strategies and may qualify for enrollment in clinical trials.