Evaluation of All Cause of Death after High Dose Chemotherapy and Autologous Stem Cell Transplant in Hodgkin Lymphoma and Non-Hodgkin Lymphoma
Authors: Roberts Danielle , Goyal Subir , Chang Zhao , Flowers Christopher R , Lechowicz Mary Jo , Langston Amelia , Waller Edmund K. , Lonial Sagar , Allen Pamela , Blum Kristie A. , Koff Jean L. , Kaufman Jonathan L , Nooka Ajay K , Graiser Michael , Rosand Cecilia , Palmer Alexandra , Bumpers Nassoma , Fenner Catherine , Andrews Joel O , Raine Caleb J. , Cohen Jonathon B. 
Published: October 2019

Abstract
Background
High dose chemotherapy and autologous stem cell transplant (ASCT) results in cure for up to 50% of patients with Hodgkin (HL) and aggressive non-Hodgkin lymphoma (NHL) that relapse after initial treatment with chemo-immunotherapy. Despite improvements in supportive care and patient selection, death after ASCT remains a concern due to progressive disease, infection, and other treatment- and non-treatment-related causes. We evaluated causes and predictors of death in patients undergoing ASCT for HL and NHL.
Methods
We conducted a single-institution, retrospective study of all patients with HL and NHL including diffuse large B-cell lymphoma, high grade B-cell lymphoma NOS, follicular lymphoma, Burkitt lymphoma, marginal zone lymphoma, and T-Cell lymphoma who underwent ASCT at Emory University between January 1, 2006 and June 1, 2017. We evaluated each patient with regards to pre-transplant disease and other baseline characteristics, treatment response after ASCT, occurrence of relapse post-ASCT, post-ASCT death and cause of death. Among patients who died, we compared baseline characteristics of interest between groups based on the documented cause of death using Fisher's Exact tests and t-tests. The association between cause of death and time to death from ASCT was evaluated by the Kruskal-Wallis test. Box plots were used to describe time to death post-transplant.
Results
Of 642 patients completing ASCT, 192 died during the period of observation after a median follow-up of 24 months. Among patients who died, the leading causes of death were relapsed disease (n=136, 71%), infection (n=18, 9%), organ dysfunction (n=16, 8%), secondary malignancy (n=8, 4%), and other/unspecified (n-14, 7%). When the group was divided into disease-related (n=136) vs non-disease-related death (n=56), none of the pre-specified variables of interest including age, gender, disease status at transplant, stage, induction or salvage therapy, conditioning regimen, or KPS were significantly associated with disease- vs non-disease-related death. Of the 18 deaths due to infection 7 were due to bacterial sepsis (including 5 prior to day +30 post ASCT), 3 were due to fungal infections, 3 were due to pneumonia, 1 death each was due to hepatitis C, nocardia, pneumocystis jirovecii, cytomegalovirus, and C. Difficile. The median time to death for patients experiencing infection or organ dysfunction was 0.5 years each compared to 1 year for patients dying of disease relapse and 4 years for patients experiencing a secondary malignancy (p<0.001; See Figure).
Conclusions
Among patients completing ASCT for HL or NHL, most deaths occurred due to relapse of the primary disease. There were no significant associations with baseline or treatment-related variables with the cause of death. The median time to death for patients with infection or organ dysfunction was 0.5 years, suggesting that continued monitoring and supportive care of patients completing ASCT is required beyond the initial engraftment period. Our findings support the role of intensive follow-up during the first year post- ASCT and continued monitoring for long-term toxicities for subsequent years of follow-up.
Figure Figure.

Disclosures
Roberts: AstraZeneca: Consultancy. Flowers:Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; Gilead: Research Funding; Burroughs Wellcome Fund: Research Funding; V Foundation: Research Funding; OptumRx: Consultancy; Genentech/Roche: Research Funding; Janssen Pharmaceutical: Research Funding; Celgene: Research Funding; Millennium/Takeda: Research Funding; Pharmacyclics: Research Funding; Abbvie: Consultancy, Research Funding; Gilead: Consultancy; Karyopharm: Consultancy; Pharmacyclics/ Janssen: Consultancy; TG Therapeutics: Research Funding; BeiGene: Research Funding; Acerta: Research Funding; Abbvie: Research Funding; Spectrum: Consultancy; Genentech/Roche: Consultancy; Denovo Biopharma: Consultancy; Bayer: Consultancy. Waller:Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celldex: Research Funding; Kalytera: Consultancy; Pharmacyclics: Other: Travel Expenses, EHA, Research Funding; Cambium Medical Technologies: Consultancy, Equity Ownership. Lonial:Amgen: Research Funding. Allen:Merck: Research Funding; Bayer: Consultancy. Blum:Morphosys: Research Funding; Novartis: Research Funding; Seattle Genetics: Research Funding; Celgene: Research Funding. Kaufman:Roche: Consultancy; Karyopharm: Other: data monitoring committee; Abbvie: Consultancy; Janssen: Consultancy; BMS: Consultancy. Nooka:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive technologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cohen:Bristol-Myers Squibb: Research Funding; Janssen: Research Funding; Bristol-Myers Squibb: Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Takeda: Research Funding; BioInvent: Consultancy; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.