Abstract
Relapsed or refractory Hodgkin lymphoma in younger patients is routinely treated with platinum-based salvage chemotherapy and response is consolidated with high-dose therapy and autologous stem cell transplant (HDT/ASCT). Age >45y has been associated with inferior outcomes with first-line therapy, attributable to more aggressive biology, comorbid illnesses, reduced physiologic reserve, and heightened sensitivity to toxicities of therapy. Optimal management of older patients with relapsed or refractory HL is uncertain, as the safety and efficacy of consolidative HDT/ASCT have not been well described in this population.
We systematically reviewed all patients age ≥50 who underwent HDT/ASCT between January 1995 and August 2013 at MSKCC for relapsed or refractory HL; age 50 was selected to enrich for higher-risk patients. All patients had achieved either a complete response (CR) or partial response (PR) to second-line therapy, defined by CT and either gallium or 18FDG-PET. Center standard routinely requires adequate hepatic, renal, and cardiopulmonary reserve (left ventricular ejection fraction >50%, hemoglobin-adjusted diffusion capacity >50% predicted). Overall survival (OS) and event free survival (EFS) were calculated with Kaplan-Meier curves, and toxicity through day 100 was assessed by chart abstraction. Toxicities were graded according to the CTCAE version 4.
42 patients age ≥50y were identified in a retrospective chart review of patients with relapsed or refractory HL treated with HDT/ASCT. Median age was 54.9y at transplant (range, 50.1-66.4 years old). Ten (24%) patients were ≥60y, 32 (76%) were 50-60y. At initial diagnosis, 24 patients (57%) had stage I-II disease and 18 patients (43%) had stage III-IV disease. All patients had classical HL histology. 38% of patients had primary refractory disease, 48% patients were in first relapse, and 14% had multiply relapsed disease. The most common second-line therapy was ifosfamide, carboplatin, and etoposide (78%). 32 patients (76%) had a CR to second-line therapy and proceeded to HDT/ASCT. 9 patients (21%) achieved a PR to second-line chemotherapy; of these, 2 converted to a CR with additional systemic therapy, 5 received definitive involved-field radiotherapy (IFRT), and 2 proceeded to HDT/ASCT in a PR. Patients required a mean of 2.4 days (range, 1-4) for peripheral blood stem cell mobilization. 18 (43%) of patients were conditioned with cyclophosphamide, etoposide, and carmustine (CBV), 17 (40%) with cyclophosphamide, etoposide, and total or subtotal lymphoid irradiation, 6 (14%) with carmustine, etoposide, cytarabine, and melphalan, and 1 (2%) with melphalan and etoposide. 55% of patients also received pre-transplant a hyperfractionated IFRT boost to the site of relapsed disease.
At a median follow up of 46 months post-transplant, OS and EFS were 71% and 66%, respectively. Mean transplant admission duration was 17 days with 22% of patients requiring readmission within 100 days post-transplant. Mean time to neutrophil engraftment was 10 days, and mean time to platelet engraftment was 24 days; 22% of patients had delayed platelet recovery beyond 30 days post-transplant. 4 patients (10%) required intensive care for sepsis. The most common toxicities were gastrointestinal, including a combination of grade 2-3 mucositis, nausea, vomiting, and diarrhea in 98% of patients. 17 pts (40%) experienced grade 3 or 4 hypoxia during the transplant admission, but persistent pneumonitis did not occur in any pt. Bacteremia occurred in 16 pts (38%), but there were no deaths due to sepsis. Transplant related mortality was 2%, with one death prior to day 100 from respiratory failure and thromboembolic stroke. Assessment of the subgroup of 10 pts >60y showed similar OS and EFS outcomes to the cohort as a whole (P=NS).
In our single center experience treating patients age ≥50y with relapsed or refractory HL, HDT/ASCT is adequately tolerated and achieves outcomes comparable to our prior published outcomes in younger patients with similar second-line therapy and conditioning regimens (patients of median age 27 experienced an OS of 83% and EFS of 68% following HDT/ASCR, at a median follow-up of 43 months). HDT/ASCT should be routinely offered to older patients with relapsed or refractory HL who are otherwise suitable candidates for autotransplantation.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
