High-Dose Therapy and Autologous Stem Cell Transplantation for Chemoresistant Diffuse Large B Cell Lymphoma: The Seattle Experience.
Authors: Gutman Jonathan A. , Gooley Ted A. , Nourigat Jacob , Pagel John M. , Press Oliver W. , Holmberg Leona A. , Bensinger William I. , Petersdorf Stephen H. , Gopal Ajay K. 
Published: October 2019

Abstract
High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is the standard treatment for patients with chemosensitive relapsed or refractory diffuse large B cell lymphoma (DLBCL). Unfortunately, there are few established options for DLBCL patients with chemoresistant disease and data regarding the efficacy of ASCT in this setting are limited. We conducted a retrospective review of patients with chemoresistant DLCBL undergoing ASCT at our Center with the goal of identifying variables associated with better outcomes. Between March 1990 and September 2004, 40 pts underwent ASCT for chemoresistant DLBCL, defined as < 50% reduction in the size of the tumor with the chemotherapy regimen immediately preceding ASCT. The median age of these pts was 44 years (range 17–69). The number of prior chemotherapies was 2 (n=21), 3 (n=15), or 4 (n=4). Twenty-two (55%) patients had progressive disease (PD) following their pre-transplant salvage therapy and 18 (45%) patients had stable disease (SD). Sixteen patients (40%) had never achieved at least a partial response (PR) to any previous chemotherapy. Median time from diagnosis to ASCT was 13 months (range 6–98). The international prognostic index (IPI) at time of ASCT was available for 33 patients and was 0–1 for 10 patients and 2–4 for 23 patients. Twenty-four patients (60%) underwent conditioning with combined chemotherapy and radiation and 16 patients (40%) received chemotherapy only. All patients received mobilized peripheral blood stem cells. Thirty-three patients have died as of last contact, with an estimated 3-year overall survival (OS) of 21% and a median follow-up of 4.0 years among the 7 survivors. Among 34 patients who did not have refractory disease following transplant, estimated 3-year progression free survival (PFS) was 12%. Causes of death include PD (n=24), ASCT toxicity (n=3), and late infection (n=2). After adjusting for year of transplant, patients with a remission duration of less than one year following initial treatment and patients whose remission duration exceeded one year had a reduced, but not statistically significant, hazard of mortality compared to patients that never responded (remission <1 year: HR=0.28, p=0.21; > 1 year: HR=0.14, p=0.08) (Figure 1). The hazard of death decreased with transplants performed more recently (p=0.03). There was no statistically significant association between outcomes and age at transplant, number of prior chemotherapy regimens, conditioning regimen (radiation vs non-radiation based), disease status at ASCT (progressive vs stable), or pre-ASCT IPI (available for 33 patients). Though outcomes following ASCT for chemoresistant DLBCL are poor, a minority of patients with prolonged remission prior to initial relapse may achieve long term survival following HDT. Additional strategies are needed to treat this disease.
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