Comorbidity, History of Alcohol Disorders, and LDH Predict Non-Relapse Mortality (NRM) Among Recipients of Autologous Hematopoietic Cell Transplantation (HCT) for Lymphoma

Little is known about the impact of patient (pt)-specific variables in risk-stratification prior to autologous HCT for lymphoma. We investigated the extent to which pt-related factors other than age, namely comorbidities, alcohol use disorders, and other demographics impact non-relapse (NRM) after autologous HCT for lymphoma.

We retrospectively analyzed data from 322 pts treated with autologous HCT for lymphoma between 2000 and 2005 at the FHCRC (n=264) and VAPSHCS (n=58). Comorbidities were assessed per the HCT comorbidity index (CI). Alcohol use disorders included self-identification as a current or past alcoholic, engaging in current or prior “heavy” or “binge” drinking, convictions for alcohol related crimes, or history of rehabilitation for alcoholism.

Pre-transplant pt characteristics (Table) were assessed for associations with NRM in univariate analysis. Factors with a p-value of <0.1 entered Cox proportional hazard models. In these models, HCT-CI scores of ≥3 (HR=4.52, p=.004), elevated LDH (HR=2.24, p=.02), and alcohol use disorders (HR=2.21, p=.05) were associated with increases risks for NRM. Age, histology, center, chemo-sensitivity, smoking, and drug use were not. Hence, a simple model including none (36% of pts), 1 (48%), or ≥2 (16%) significant risk factors was created.

Overall, NRM incidences were 8% at 1 year and 15% at 5 years. Pts with 0, 1, or ≥2 of the significant risk factors had NRM incidences of 2%, 8% and 20% at 1-year and 6%, 16% and 28% at 5-years, respectively (Figure 1). Leading causes of death (COD) among those dying of NRM within 1 year (n=24) were infection (33%), alveolar damage (25%) and multi-organ failure (17%). Among those dying beyond 1-year (n=21), leading COD were secondary malignancy (43%), infection (14%) and chronic comorbidities (14%).

In summary, pre-transplant LDH and history of alcohol use disorders adds to the prognostic role of the HCT-CI in risk-assessment prior to autologous HCT for lymphomas. Age, cigarette smoking, and other demographics do not. Our simple risk model could aid in decision-making in the clinic and highlights areas of potential intervention to reduce NRM following auto HCT.

TABLE 1: PATIENT CHARACTERISTICS
				N
Total eligible for analysis				322
Center
FHCRC				264
VAPSHCC				58
				Median	Range
Age (years)				50	20-75
Distant Traveled to Transplant Center (miles)
				144.95	0-2719
# Prior Chemo Regimens
				2	0-9
					%
Marital Status
Married					68.3
Other					31.7
Histology
Aggressive NHL					61.8
Indolent NHL					13.8
HD					23.6
Unknown					<1
Conditioning Regimen
TBI-based					40
Chemotherapy-based					45
Radio-immunotherapy based					15
Chemosensitive disease?
Y					46.6
N					53.4
HCT-CI score
0					30.2
1 or 2					34.5
>3					35.4
LDH elevated?
Y					54
N					44
Unknown					2
Tobacco Use (pack years)
Never					45.3
<15					13
15-29					11
>30					14.6
Unknown					16.1
Alcohol Disorder History
Y					12.4
N					87.6
History of Drug Use
Y					20
N					80