Comorbidity Significantly Impairs Quality Of Life In Patients After Allogeneic Hematopoietic Stem Cell Transplantation – Results From The Prospective German Multicenter Validation Trial
Authors: Wolff Daniel , Herzberg Philipp Y. , Pavletic Steven Z. , Heussner Pia , Mumm Friederike , Balsiger Christina , Hilgendorf Inken , Hemmati Philipp , Holler Ernst , Greinix Hildegard T , Mitchell Sandra A. 
Published: October 2019

Abstract
Comorbidity after allogeneic hematopoietic stem cell transplantation (alloHSCT) significantly impairs quality of life (QoL), physical functioning (PF), and survival. Therefore, we evaluated a newly developed measure of comorbidity after transplantation, the Post-transplant Multimorbidity Index (PTMI) within a multicenter trial validating the NIH consensus criteria for severity assessment of chronic graft-versus-host disease (cGVHD).

Methods
189 patients (pts) (median age 44 years, range 18-72) after alloHSCT were prospectively evaluated using the NIH consensus criteria, including the NIH-cGVHD grading form, the FACT-BMT, the Human Activity Profile (HAP), and the SF-36 v.2. The PTMI and the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) (Sorror et al) was retrospectively documented by chart review. Enrolment occurred a median of 275 (range: 85–4003) days after alloHSCT. Based on NIH criteria, 121 pts had cGVHD (mild n=24, moderate n=59, severe n=38). Sixty eight pts without cGVHD were included as controls.

Results
The most prevalent comorbidities were infections treated as outpatient during the past 3 months (n=53; 28%) followed by mild renal function impairment (n=42; 22%), osteoporosis (DEXA t-score< -1.5) (n=27; 14%) and severe infections requiring hospitalization during the past 3 months (n=23; 12%). Applying the PTMI 47 (24%) pts had no comorbidity, while 107 (56%) pts. had 1-3 comorbidities, 24 (13%) pts 4-6 comorbidities, and 11 (6%) pts > 6 comorbidities. In the subgroup of pts with cGVHD (n=72) enroled after more than 1 year post alloHSCT 12.5% of pts had > 6 comorbidities detected by the PTMI. In contrast the HCT-CI classified only 4% of the 72 pts. as multimorbid with > 6 comorbidities. Chronic GVHD and time after transplant were significantly associated with PTMI, while age was not significant in a multivariate analysis. In contrast, the HCT-CI was not associated with the presence of cGVHD. None of the single comorbidities alone were significantly associated with having cGVHD, although osteoporosis (p=0.084) and moderate infections not requiring inpatient treatment during the last 3 months (p=0.07) approached significance. Examining the association between the PTMI sum score and QoL (FACT-BMT), physical and mental health (SF-36) and activity (HAP), a significant correlation was detected between PTMI sum score with all subscales of the FACT-BMT. Similarly, significant correlations were observed between the PTMI sum score and 6 of the 8 subscales of the SF-36 (physical functioning, role limitations due to emotional problems, mental health, vitality, general health perception and change in health), while comorbidity did not impair social functioning and role limitation due to physical problems. The PTMI sum score was also correlated with the HAP adjusted activity score (AAS) but not the maximal activity score (MAS). Osteoporosis was a significant independent predictor of impairments in QoL, physical and mental health, and activity. Infectious complications treated as outpatient during the past 3 months significantly impaired social/family and emotional wellbeing as captured by the FACT, a similar effect was detected by the social functioning and general health perception subscales of the SF36. The HCT-CI score was significantly associated with FACT-BMT and HAP-AAS, and with only 2 of the 8 SF-36 subscale scores (vitality and mental health).

Conclusions
Comorbidity burden in alloHSCT survivors is significant, and the summative score from a new measure of post-transplant comorbidity captured a wider range of comorbid conditions and was significantly associated with the presence of cGVHD, and with impairments in QoL, physical and mental health, and PF. The HCT-CI also demonstrated associations between comorbidity and QoL, although as a measure developed primarily to predict early post-transplant mortality it missed common long term comorbidities like metabolic bone diseases and does not cover a recent history of infectious complications. Our results provide preliminary support for a new measure of comorbidity developed specifically for the post-transplant population. A multicenter trial prospectively validating the PTMI is ongoing.

Disclosures:
No relevant conflicts of interest to declare.