Trend Analysis of 5-Year All-Cause Mortality After Autologous Stem Cell Transplantation in Patients with Lymphoma and Multiple Myeloma
Authors: Akhtari Mojtaba , Armitage James O. , Bierman Philip , Bociek R. Gregory , Faber Edward Anthony , Maness Lori , Vose Julie M , Loberiza Fausto R. 
Published: October 2019

Abstract
Abstract 842

Background.
Autologous stem cell transplantation (ASCT) is a common treatment modality for patients (pts) with lymphoma and myeloma and in certain settings appears to be associated with improved survival. We evaluated the risk of death and its attributable causes in three sequential cohorts of patients undergoing ASCT between 1983 and 2010 to look for possible changes in outcome over time.

Methods.
Adults ≥ 18 years of age with lymphoma or multiple myeloma who received ASCT between 1983 and 2010 at a university medical center were identified and divided into three cohorts based on time of transplantation: 1983–1990 (I), 1991–2000 (II) and 2001–2010 (III). The primary cause of death (COD) was determined and verified by the attending physician. The risk of dying from a particular cause (relapse, infection, secondary malignancy, organ failure) was compared across time periods using Cox proportional hazards regression while adjusting for age, gender, disease type, stage at transplant, and time from diagnosis to transplant.

Results.
A total of 2284 pts with lymphoma and myeloma were analyzed, and there were 1215 deaths (with 972 occurring within 5 years of ASCT). Pts transplanted in the more recent time period were older and more likely to be transplanted < 1 year from diagnosis. There was a significant improvement in the 5-year probability of overall survival (OS) over time: 36% vs. 55% vs. 60% (p <0.001) in cohort I, II and III respectively. The most frequent COD was: relapse, organ failure, infection, secondary malignancy and interstitial pneumonitis. The adjusted risk of death from relapse vs. all other causes did not significantly change over time: II vs. I [hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.69–1.04], III vs. I [HR 0.86, 95% CI 0.67–1.10]. The risk of death from infection vs. all other causes significantly improved over time: II vs. I [HR 0.20, 95% CI 0.09–0.44, p<0.0001], III vs. I [HR 0.24, 95% CI 0.06–0.09, p 0.003]. The risk of death from organ failure vs. all other causes was not significantly improved: II vs. I [HR 0.78, 95% CI 0.42–1.48)], III vs. I [HR 0.73, 95% CI 0.34–1.54]. The risk of death from second malignancy vs. all other causes was not significantly different across time periods: II vs. I [HR 0.59, 95% CI 0.21–1.66], III vs. I [HR 1.29, 95% CI 0.41–4.04].

Conclusion.
The OS of patients undergoing ASCT in our institution has improved significantly over the past three decades as assessed in three sequential cohorts. This improvement is related to a measurable decrease in infectious mortality. The reasons for this are likely multifactorial and could include improved supportive care, use of growth factors, cumulative transplant center experience, introduction of peripheral stem cell transplantation vs. bone marrow transplantation, selection of regimens with less toxicity, improved salvage therapies, and patient selection factors. Relapse continues to be the most common cause of death in this patient population with no appreciable change over time. These results suggest that better strategies to improve outcomes are needed which could include better preparative regimens and/or post transplant therapies.

Disclosures:
Vose: GSK: Research Funding; Millenium: Research Funding; Celgene: Research Funding; BMS: Research Funding; Exelixis: Research Funding; SBio: Research Funding; Pharmacyclics: Research Funding; Genentech: Research Funding.