Risk Factors for Prolonged Length of Hospitalization in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

Prolonged hospitalization exposes patients (pts) undergoing allogeneic hematopoietic cell transplantation (HCT) to risks of iatrogenic complications and results in significant morbidity and mortality as well as expense, however, there are limited data on risk factors that contribute to length of stay (LOS) in HCT pts. 

663 pts underwent HCT from 1/1997 to 12/2011. Among 663 pts, 49 died in the hospital within 6 weeks (wks) of transplant and were excluded, leaving 614 pts, median age 44 (range 18-71 years), for analysis. Pts underwent HCT for acute myeloid leukemia (n=258), acute lymphoblastic leukemia (n=98), myelodysplastic syndrome (n=87), chronic myeloid leukemia (n=78), non Hodgkin lymphoma (n=55), aplastic anemia (n=20), Hodgkin disease, myeloproliferative neoplasm, and plasma cell disorders (remaining n=18). The majority of pts underwent myeloablative transplant (n=599, 97.6%); 15 (2.4%) had a reduced-intensity transplant. 317 (51.6%) pts received a transplant from a related donor, 250 from an unrelated donor (40.7%) and 47 (7.7%) received cord blood.

153 pts (25%) were identified to have a prolonged LOS, defined as ≥6 wks.  In univariable analyses, variables associated with LOS included: poor performance status (PS) (odds ratio [OR] 1.31 per 10 point decrease on Karnofsky scale, p=0.017), unrelated donor transplant (OR 3.45, p<0.001), cord blood transplant (OR 7.86, p<0.001), HLA mismatch (OR 4.45, p<0.001), and CD34+ cell dose (median 2.04x10⁶/kg, range 0.01-26), (OR 1.43 per 1x10⁶/kg decrease, p<0.001). Prior chemotherapy, lymphoid malignancies, longer interval from diagnosis to HCT, and positive CMV status were also associated with LOS, with a trend towards significance (p=0.06 for all). In multivariable, logistic regression analyses, poor PS (OR 1.31 per 10 point decrease, p=0.031), unrelated donor (OR 3.14 p<0.001), cord blood transplantation (OR 2.42, p=0.048), CMV positivity of either donor or recipient (OR 1.91, p=0.018), and CD34+ cell dose (OR 1.35 per 1x10⁶/kg decrease, p<0.001) were significantly associated with prolonged LOS. 5-year non-relapse mortality (NRM) for pts hospitalized ≥6 wks was significantly worse than for pts hospitalized <6 wks (60.2% vs. 31.8%, p<0.001), as was overall survival (OS) at 5 years, (16.6% vs. 42.8%, p<0.001). There were no differences in the incidence or degree of acute GVHD.

In conclusion, hospitalization ≥6 wks following HCT is associated with significantly worse NRM and OS. Poor PS, CMV positivity, decreased CD34+ cell dose, and unrelated and cord blood transplants have previously been identified as factors predictive of poor outcome and are also factors that contribute to prolonged LOS. Efforts should be made to optimize modifiable factors such as cell dose in HCT pts, especially those with other risk factors, such as having an unrelated or cord blood donor.