Cause-Specific Conditional Survival In 2603 Consecutive Patients Undergoing Autologous Hematopoietic Cell Transplantation (aHCT) Over a 20-Year Period
Authors: Walde Ari M. Vander , Sun Can-Lan , Francisco Liton , Armenian Saro , Teh Jennifer Berano , Wong F. Lennie , Kogut Neal , Krishnan Amrita , Nademanee Auayporn , Popplewell Leslie , Stein Anthony Selwyn , Forman Stephen J. , Bhatia Smita 
Published: October 2019

Abstract
Abstract 933

Background:
aHCT is offered with curative intent to patients with hematologic malignancies. However, survival estimates are conventionally computed from time of transplantation. These estimates provide initial prognosis, but do not reflect how prognosis changes with changing hazard rates over time. Conditional survival accounts for elapsed time since diagnosis, describing the probability of survival after having already survived a certain period of time after aHCT. We describe cause-specific conditional survival, providing clinically relevant information to inform preventive and interventional strategies for patients alive for differing lengths of time from aHCT.

Methods:
From 1986 to 2006, a total of 2,603 consecutive patients received aHCT at City of Hope at a median age of 48 yrs (NHL: n=1063; MM: n=625; HL: n=475; AML: n=330; other: n=110). Information regarding vital status and cause of death were determined using National Death Index Plus and medical records. Survival probabilities and standardized mortality ratios (SMRs) were calculated for the entire cohort as well as by diagnosis, conditional on survival for 1, 2, 5, and 10 yrs after aHCT.

Results:
A total of 1135 deaths (representing 44% of the cohort) were observed by December, 2007; 79% of deaths were attributed to recurrent disease (range: 88% after MM to 71% after HL); 8% to subsequent neoplasm (SMN: range: 4% after MM to 13% after HL); 6% to cardiopulmonary disease (range: 2% after MM to 10% after HL); and 7% to other causes. Using conventional survival estimates, overall survival (OS) was 60% at 5 yr and 48% at 10 yr from aHCT; and the cohort was at a 15.6-fold increased risk of premature death compared with the general population (95%CI=14.7-16.6). Females were at a higher risk of premature death (SMR=19.1) than males (SMR=12.3). The cohort was at a 4.9-fold (95%CI=3.9-5.9) increased risk of death due to SMNs, and at a 2.3-fold (1.5-3.2) increased risk of deaths due to late cardiac complications. Conditional survival estimates demonstrated that every additional yr survived was associated with an increase in the probability of surviving the subsequent 5 yrs. Thus, the 5-yr survival rate was 68% after surviving 1 yr, 73% after surviving 2 yr, 80% after 5 yr; and approaching 88% after having survived 10 yrs from aHCT (Figure). Cause-specific conditional survival rates and SMRs by primary diagnosis are summarized in the Table. The risk of premature death (due to any cause) was comparable to the general population for 10-yr survivors, with the exception of HL survivors (2.6-fold increased). With the exception of MM, individuals who had survived 10 years were projected to have a <5% risk of relapse-related mortality over the next 5 yrs (range: AML – 0% to HL: 5%). However, non-relapse mortality remained elevated long-term, indicating a need for extended surveillance.

Conclusion:
This study demonstrates that the projected 5-yr survival rates improve conditional on previous time survived from aHCT, and that the 10-year survivors of aHCT for AML, NHL, and MM have mortality rates that are comparable to the general population. HL survivors continue to experience a 2.6-fold increased risk of premature death, primarily because of the excess risk of non-relapse mortality (due to SMN and cardiac causes). Conditional survival estimates provide clinically relevant prognostic information and an accurate estimate of cause-specific survival, helping inform preventive and interventional strategies.

Disclosures:
Nademanee: Genzyme: Consultancy, Research Funding; Allos Therapeutics: Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.