Abstract
Comorbidity after allogeneic hematopoietic stem cell transplantation (alloHSCT) impairs quality of life (QoL), physical functioning, and survival. We developed a new standardized measure to capture comorbidity after transplantation, the Post-transplant Multimorbidity Index (PTMI) in a cohort of 50 long term survivors. We subsequently evaluated the content validity and impact on survival and QoL within a multicenter trial, including 208 patients (pts) after alloHSCT, who were prospectively evaluated applying the FACT-BMT, the Human Activity Profile (HAP), the SF-36 v.2, PTMI and the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI). The most prevalent comorbidities were compensated arterial hypertension (28.4%), ambulatory infections (25.5%), iron overload (23%), mild renal function impairment (20%), and osteoporosis (13%). Applying the PTMI 13% of patients had no comorbidity, while 37.1% had 1–3 comorbidities, 27.4% had 4–6 comorbidities, and 13.5% had > 6 comorbidities. Chronic graft-versus-host disease (cGvHD) was significantly associated with the PTMI, while age and prior acute GvHD were not. In contrast, the HCT-CI was not associated with the presence of cGvHD. cGvHD was significantly associated with depression (r = 0.16), neurological disease (r = 0.21), osteoporosis (r = 0.18) and nonmelanoma skin cancer (r = 0.26). The PTMI demonstrated strong measurement properties and compared to the HCT-CI captured a wider range of comorbidities associated with cGvHD.
Highlights
Supplementary information The online version of this article contains supplementary material, which is available to authorized users.While transplant related mortality (TRM) after allogeneic hematopoietic stem cell transplantation significantly decreased during the past 25 years [1], long term morbidity and late mortality remain a challenge [1,2,3]
The conditions and definitions captured by the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) [19], the Charlson Comorbidity Index (CCI) [21], and Functional Comorbidity Index (FCI) [22] were included into the Posttransplant Multimorbidity Index (PTMI) including the original definitions
Applying the four comorbidity indices in our development cohort of 50 subjects with Chronic graft-versus-host disease (cGvHD), we found a mean of 5.2 (SD ± 2.3) (PTMI), 1.5 (SD ± 1.23) (HCT-CI), 1.39 (SD ± 0.78) (CCS), and 2.18 (SD ± 1.16) (FCI) co-occurring conditions
Summary
Chronic graft-versus-host disease (cGvHD) is a direct risk factor for late mortality [4] and it induces subsequent comorbidity due to irreversible organ damage and toxicity of the immunosuppressive treatment [5, 6] resulting in a significantly higher prevalence of comorbidities in patients experiencing cGvHD [6,7,8,9]. Due to the development of toxicity-reduced conditioning regimens patients with higher comorbidity burden at the time of transplant and advanced age represent a significant proportion of transplant survivors [10]. The toxicity of the cytostatic treatment for malignant diseases before transplantation and during the conditioning regimen results in an increased incidence of secondary malignancies with cGvHD being a relevant additional factor [11,12,13]. Risk factors of cGvHD like low platelets have been shown to modulate the impact of comorbidities on mortality [14]
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