In-Hospital Complications and Mortality after Autologous Peripheral Blood Stem Cell Transplantation in Older Vs. Younger Multiple Myeloma Patients: An Analysis of the National Inpatient Sample

Background:   Autologous hematopoietic stem cell transplantation (Auto HSCT) has improved survival in patients (pts) with multiple myeloma (MM).  Based upon clinical trials, auto HSCT is preferred for patients under the age of 65, as older pts are thought to be at higher risk for transplant complications and mortality.  The aim of this population based study was to evaluate in-hospital complications and mortality after autologous peripheral blood stem cell transplantation (auto PBSCT) in younger (< age 65) vs. older (> or equal to age 65) MM pts utilizing the Nationwide Inpatient Sample (NIS).

Methods: Data for the study were drawn from the NIS, a component of the Healthcare Cost and Utilization Project sponsored by the Agency for Healthcare Research and Quality. The NIS database was used to identify all MM pts admitted to US Hospitals for auto PBSCT over a three-year period (2008-2010). Patient characteristics were extracted from the NIS and adverse outcomes were identified by ICD-9-CM codes.  We analyzed the relationship of age to in-hospital mortality, length of stay (LOS), total hospital costs, and adverse outcomes. We then performed multivariate logistic regression to determine predictors of in-hospital mortality.  Data was analyzed with SPSS v 22.

Results: We identified 2209 pts. The median (M) age was 59 yrs, with 1650 pts (74.7%) < age 65 and 559 pts (25.3%) ≥ to age 65. Pt demographics included: 1262 pts (57.1%) male, 1246 (56.4%) Caucasian, 280 (12.7%) African-American, 157 (7.1%) Hispanic, 37 (1.7%) Asian Pacific Islander, and 489 (22%) unknown race. Overall in-hospital mortality following auto PBSCT was 1.5% and 2.3% in older pts vs. 1.2% in younger pts (p=0.061). Mean LOS was 18.6 ± 10.8 days (standard deviation) in older pts vs. 16.8 ± 7.2 days in younger pts (p < 0.001).   Mean total hospital charges were $161,117 ± $105,008 in older pts vs. $151,192 ± $78,342 in younger pts (p < 0.001). There was no significant difference in hematologic toxicities such as neutropenia between older and younger pts.  In-hospital complications that were more likely to occur in older vs. younger pts were severe sepsis (23 (4.1%) vs. 22 (1.3%), p <0.001), septic shock (18 (3.2%) vs. 15 (0.9%), p <0.001), acute kidney injury (44 (7.9%) vs. 61 (3.7%), p <0.001), pneumonia (36 (6.4%) vs. 67 (4.1%), p = 0.021), acute respiratory failure (22 (3.9%) vs. 18 (1.1%), p <0.001), and endotracheal intubation requiring prolonged mechanical ventilation (18 (3.2%) vs. 21 (1.3%), p = 0.003).  Interestingly, stomatitis/mucositis occurred less often in older pts (183 (32.7%) vs. 659 (39.9%), p = 0.002). In univariate analysis for risk factors for in-hospital mortality, neutropenia (OR 0.369, 95% CI: 0.15 – 0.89, p = 0.028), febrile neutropenia (OR 0.24, 95% CI: 0.06 – 0.99, p=0.05), sepsis (OR 19.57, 95% CI: 9.64 – 39.75, p <0.001), Clostridium difficile infection (OR 4.91, 95% CI: 2.09 – 11.56, p < 0.001), acute kidney injury (OR 8.12, 95% CI: 3.67 – 17.95, p < 0.001), pneumonia (OR 11.32, 95% CI: 5.33 – 24.05, p <0.001), and acute respiratory failure (OR 71.67, 95% CI: 32.51 – 157.99, p < 0.001) were predictors of in-hospital mortality. In a multivariate analysis accounting for age and gender, sepsis (OR 0.12, 95% CI: 0.05 – 0.29, p < 0.001), Clostridium difficile infection (OR 0.32, 95% CI: 0.11 – 0.92, p = 0.03), acute kidney injury (OR 0.31, 95% CI: 0.11 – 0.90, p = 0.03), and acute respiratory failure (OR 0.03, 95% CI: 0.01 – 0.09, p < 0.001) remained independent predictors of in-hospital mortality.

Conclusions: Overall, in-hospital mortality in MM pts following auto PBSCT was rare (1.5%) and there was no significant difference in mortality between older vs. younger pts. This is consistent with other recent findings that chronological age does not increase mortality in recipients of ASCT, which is possibly the result of advances in auto PBSCT, such as less toxic conditioning regimens and improvements in supportive care.  Older pts did have significantly increased LOS and total hospital charges compared to younger pts, and were at increased risk for severe sepsis/septic shock and respiratory complications including pneumonia and acute respiratory failure.  Such in-hospital complications in older MM pts undergoing auto PBSCT should be of particular attention to physicians caring for this pt population. Further research is needed in other populations and datasets to confirm these findings.