High-Dose Therapy and Autologous Hematopoietic Progenitor Cell Transplantation for Recurrent or Refractory Hodgkin's Disease: Analysis of the Stanford University Results and Prognostic Indices

Abstract

One hundred nineteen patients with relapsed or refractory Hodgkin's disease (HD) received high-dose therapy followed by autologous hematopoietic progenitor cell transplantation. Three preparatory regimens, selected on the basis of prior therapy and pulmonary status, were employed. Twenty-six patients without a history of prior chest or pelvic irradiation were treated with fractionated total body irradiation, etoposide (VP) 60 mg/kg and cyclophosphamide (Cy) 100 mg/kg. Seventy-four patients received BCNU 15 mg/kg with identical doses of VP and Cy. A group of 19 patients with a limited diffusing capacity or history of pneumonitis received a novel high-dose regimen consisting of CCNU 15 mg/kg, VP 60 mg/kg and Cy 100 mg/kg. Twenty-nine patients (24%) had failed induction therapy and 35 (29%) had progressive HD within 1 year of initial chemotherapy. At 4 years actuarial survival was 52%, event-free survival was 48% and freedom from progression (FFP) was 62%. No significant differences were seen in survival data with the three preparatory regimens. Six patients died within 100 days of transplantation and 5 died at a later date of transplant-related complications. Secondary malignancies have developed in 6 patients, including myelodysplasia/leukemia in four patients and solid tumors in two patients. Regression analysis identified systemic symptoms at relapse, disseminated pulmonary or bone marrow disease at relapse and more than minimal disease at the time of transplantation as significant prognostic factors for overall and event-free survival and FFP. Patients with none of these factors enjoyed an 85% FFP at 4 years compared with 41% for patients with one or more unfavorable prognostic factors (P = .0001). Our results confirm the efficacy of high-dose therapy and autografting in recurrent or refractory HD. Although longer follow-up is necessary to address ultimate cure rates and toxicity, our data indicate that a desire to reduce late effects should drive future research efforts in favorable patients whereas new initiatives are needed for those with less favorable prognoses.

High‐dose chemo‐radiotherapy for relapsed or refractory Hodgkin lymphoma and the significance of pre‐transplant functional imaging

“…For the past two decades, we have incorporated accelerated fractionation radiotherapy (RT) either as total lymphoid irradiation (TLI) or as an involved field (IF-RT) into our transplant conditioning regimen. In an initial study conducted from 1986 to 1993, at Memorial Sloan-Kettering Cancer Center (MSKCC), chemosensitive disease was not required in order to be eligible for ASCT, and despite this, the 10-year survival following ASCT was 45%, with no relapses occurring >3 years following HDT (Moskowitz et al, 2001;Horning et al, 1997). Like others, we found a marked survival advantage for patients with chemosensitive disease, and required evidence of chemosensitivity in our subsequent protocols (Josting et al, 2002).…”

Brentuximab Vedotin in Transplant-Naïve Relapsed/Refractory Hodgkin Lymphoma: Experience in 30 Patients

“…Namely, the quality of response to salvage chemotherapy remains one of the strongest predictors for long-term survival in patients with relapsed/refractory HL undergoing ASCT. Several studies showed that chemoresistance or suboptimal response to pretransplant salvage chemotherapy represents the major adverse prognostic factors affecting PFS [5,6,[9][10][11][12][13].…”

Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine‐based high‐dose chemotherapy regimen

“…Disease recurrence is the main cause of ASCT failure. Duration of response to upfront treatment, poor sensitivity to pre-transplant salvage chemotherapy and early disease progression after ASCT were shown to be the most important predictors of unfavourable outcome in HL patients undergoing ASCT (Crump et al, 1993;Horning et al, 1997;Lazarus et al, 2001;Moskowitz et al, 2001;Josting et al, 2002Josting et al, , 2005Sureda et al, 2005;Majhail et al, 2006;Smith et al, 2011;Mart ınez et al, 2013;Hertzberg, 2014). Accordingly, the persistence of metabolically active lymphoma lesions after salvage therapy and/or conditioning, as evidenced by 18F fluorodeoxyglucose positron emission tomography ( 18F FDG-PET), emerged as the strongest independent predictor for PFS and overall survival (OS) in patients with relapsed and refractory (RR) HL treated with ASCT (Hutchings, 2011;Smeltzer et al, 2011;Devillier et al, 2012;Moskowitz et al, 2012;von Tresckow & Engert, 2012;Akhtar et al, 2013;Hertzberg, 2014;Pinto et al, 2014).…”