Consolidative Radiation Therapy Following Autologous Transplantation in Relapsed or Refractory Hodgkin Lymphoma
Authors: Jauhari Shekeab , Plastaras John , Lukens John , Maity Amit , Schuster Stephen J. , Dwivedy Nasta Sunita 
Published: October 2019

Abstract
Radiation therapy (RT) is an important treatment modality in relapsed or refractory Hodgkin lymphoma (HL), providing local control and potentially durable responses when used as salvage therapy. For decades, RT has also been administered before and after autologous stem cell transplantation (ASCT) for consolidation, but no consensus exists regarding the efficacy or optimal timing of peri-transplant RT. Data is especially lacking on post-transplant consolidative RT, which may be associated with reduced toxicity and improved disease control compared with pre-transplant RT. We provide here a single-institution retrospective analysis comparing survival outcomes and toxicities according to receipt of post-transplant consolidative RT.
Sixty-four patients with relapsed or refractory HL received ASCTs at our institution between 2006 and 2013. Seventeen patients received post-transplant consolidative RT, defined as completing RT within 5 months of ASCT, whereas 47 received no RT. All patients received staging PET/CT scans prior to ASCT and had at least 1 year of follow-up after ASCT. Primary outcomes included progression-free survival (PFS), overall survival (OS), and local control (LC), defined as the absence of relapse at previous sites of PET-avid disease. The log rank test was used to compare survival measures. Radiation-associated toxicities, including pulmonary and hematologic complications, were reviewed.
For the entire cohort, median age at ASCT was 41 years and median follow-up after ASCT was 40 months. In the post-transplant RT group, there were more cases of disease limited to one side of the diaphragm, as shown in Table 1. There were also more cases of refractory HL, defined as persistent disease following frontline therapy, and a trend towards younger age and absence of prior RT. Median dose of post-transplant RT was 3540 cGy (Range: 1500 - 4050 cGy) and median time from ASCT to RT was 4 months (Range: 2 - 5 months). 16/17 (94%) patients received RT to supra-diaphragmatic sites only.
For the entire cohort, OS was 84% and PFS was 50% at 36 months following ASCT. There was no significant difference in OS₃₆ among patients who received post-transplant RT (87% v. 83% for no RT, p = 0.68). There was also no significant difference in PFS₃₆ among post-transplant RT patients (55% v. 47% for no RT, p = 0.33). There was significant improvement in LC₃₆ among patients who received post-transplant RT (78% v. 48%, p = 0.02). There were also non-significant trends toward improved PFS₃₆ among patients who received post-transplant RT and had relapsed (rather than refractory) disease (75% v. 48%, p = 0.13) or had no prior RT (53% v. 35%, p = 0.14).
3/17 (18%) post-transplant RT patients died during the follow-up period, all secondary to disease progression. 9/47 (20%) patients with no post-transplant RT died during the follow-up period, of which 7 deaths were secondary to disease progression and 1 was a complication of ASCT. One patient developed grade III anemia and thrombocytopenia as an early complication of post-transplant RT, but no other acute or late RT-associated toxicities were observed.
Patients receiving post-transplant consolidative RT have improved LC and limited RT-associated toxicity. While there was no significant improvement in PFS or OS in this group, patients who have not received radiation previously or who have relapsed disease may preferentially benefit from post-transplant RT. Our study was limited by small numbers. Selection bias may influence which patients are referred for post-transplant RT. For these reasons, analyses of larger patient populations and prospective study are warranted.
Table 1. Baseline Patient Characteristics Characteristics With Post-Transplant RT (n = 17) Without Post-Transplant RT (n = 47) p-Value Median Age at ASCT (y) 37 43 0.06 Male Gender - n (%) 10 (59) 23 (49) 0.58 Stage Category - n (%) I / II 11 (65) 22 (47) 0.26 III / IV 6 (35) 25 (53) Bulky Mediastinal Adenopathy - n (%) 5 (29) 7 (15) 0.28 Presence of B Symptoms - n (%) 10 (59) 24 (51) 0.77 Prior Radiation - n (%) 3 (18) 18 (38) 0.14 Relapsed v. Refractory Disease - n (%) Relapsed 6 (35) 31 (66) 0.04 Refractory 11 (65) 16 (34) Disease Burden at Relapse - n (%) One Side of Diaphragm 16 (94) 28 (60) 0.01 Both Sides of Diaphragm 1 (6) 19 (40) Disease Status at Transplant - n (%) Complete Response 8 (47) 28 (60) 0.40 Partial Response 9 (53) 19 (40)

Disclosures
Schuster: Genentech: Consultancy; Pharmacyclics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Hoffman-LaRoche: Research Funding; Janssen: Research Funding; Gilead: Research Funding; Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding.