Late Altered Organ Function in Long Term Survivors after Allogeneic HSCT: A Paired Comparison with Their Identical Sibling Donor
Authors: Rovo Alicia , Daikeler Thomas , Halter Joerg , Heim Dominik , Studt Jan Dirk , Medinger Michael , Arber Caroline , Stern Martin , Tsakiris Dimitrios , Tyndall Alan , Gratwohl Alois , Tichelli Andre 
Published: April 2020

Abstract
Long term prognosis following allogeneic hematopoetic cell transplantation (HSCT) has greatly improved over the last decades. Therefore, interest of the general health status has become a major topic in the surveillance of long term survivors. To assess health status in very long term survivors (&gt;10 years follow-up) we conducted a prospective, single center cross-sectional study, evaluating simultaneously 44 recipients and their respective sibling donors. A comprehensive clinical and biological examination was performed. We compared here in a paired analysis the results of routine clinical chemistry tests between recipients and their respective donor (table 1). At the time of this study, recipients and donors had a median age of 44.3 (24–63) and 43.4 (22–61) years respectively, and a median time of 17.5 (11–26) years since HSCT; 22/44 (50%) recipients had chronic graft-versus-host disease (cGVHD). Performance status demonstrated that 81/88 (92%) participants had a Karnofsky Score of 100%, reflecting the overall good clinical condition of both, recipients and donors (p&gt;0.10). However, clinical chemistry tests of the recipients were systematically abnormal, with increased C-reactive protein (CRP), liver tests, lipids, von Willebrand factor antigen (vWF), creatinine, and decreased albumin, and glomerular filtration rate (GFR), compared with the donors (p&lt;0.05; table 1). In the recipients, increased CRP, creatinine, vWF and decreased GFR were associated with chronic GvHD (p&lt;0.05). For the other parameters no correlation with transplant related factors were found. Furthermore, we defined a scoring system to detect organ dysfunctions. All values out of range were allocated with one point. Included parameters were: high CRP, decreased GFR, low albumin, increased vWF, abnormal liver tests and dyslipidemia We compared recipients/donors with a score of ≥2 to those with a score below this value. An abnormal score was observed in 28/44 (64%), recipients, and in 7/44 (16%) donors (p&lt;0.0001). More recipients with cGVHD had an abnormal score (13/22; 59%) compared to recipients without (5/22; 23%; p= 0.014). In conclusion, using a unique design comparing recipients with their respective donor, we demonstrate that an altered organ function may exist in clinically healthy very long term survivors. In part, this altered organ function is attributed to cGVHD reflected by an ongoing inflammatory process even in patients off immunosuppression. The clinical significance of the altered organ function not explained by cGVHD needs to be further investigated.
Table 1: Clinical chemistry parameters: comparison between long-term survivors and their respective donor (with and without GvHD).
Parameter Donors N 44 Recipients P-values donors versus recipients All N 44 with GVHD N 22 without GVHD N 22 All recipients with/without GVHD C-Reactive Protein (CRP) 1.0 (0.5–38.1) 3.7 (0.5–79.2) 4.5 (0.9–79.2) 1.2 (0.5–11.0) 0.034 0.001/0.125 Creatinine 66 (45–93) 79 (44–206) 88 (55–206) 77 (44–103) 0.0001 &lt;0.0001/0.007 Glomerular Filtration Rate (GFR) 107 (72–144) 82 (30–141) 77 (30–124) 95 (66–141) &lt;0.0001 &lt;0.0001/0.034 Albumin 41 (29–46) 40 (31–45) 38 (31–43) 40 (32–45) 0.009 0.021/0.361 Bilirubine 9.5 (5–29) 8.0 (5–20) 8.0 (5–17) 7.0 (5–20) 0.020 0.213/0.053 ASAT 22 (16–64) 27.5 (15–65) 26 (20–65) 28 (15–44) 0.0004 0.002/0.013 ALAT 22 (10–101) 25.5 (12–72) 27 (12–70) 23 (12–72) 0.037 0.030/0.161 Gamma-GT 18 (9–140) 31 (10–319) 30 (11–319) 32 (10–91) 0.0003 0.002/0.005 Alkaline Phosphatase 56 (32–155) 69 (39–222) 70 (39–222) 68 (41–120) 0.003 0.016/0.034 Triglicerides 1.0 (0.45–3.9) 1.5 (0.53–8.9) 1.5 (0.53–8.9) 1.6 (0.69–3.7) 0.011 0.208/0.007 Cholesterol 4.7 (3.1–9.3) 5.1 (2.7–7.8) 5.0 (2.7–7.8) 5.3 (3.7–6.4) 0.118 0.407/0.058 HDL-cholesterol 1.6 (1.0–3.2) 1.5 (0.6–2.5) 1.5 (0.6–2.5) 1.5 (1.0–2.2) 0.037 0.213/0.124 Chol/HDL-chol. Ratio 2.9 (1.7–8.6) 3.2 (1.8–8.7) 3.1 (1.8–8.7) 3.4 (1.8–5.7) 0.022 0.094/0.047 LDL-cholesterol 2.4 (1.4–7.7) 2.8 (1.07–4.8) 2.7 (1.1–4.8) 2.9 (1.1–3.9) 0.126 0.284/0.145 Von Willebrand factor Antigen (vWF) 97.5 (55–188) 126 (51–296) 139 (51–296) 108 (51–235) 0.006 0.002/0.173