Chronic Graft-Versus-Host Disease Risk Score: A CIBMTR Analysis
Authors: Arora Mukta , Klein John P. , Antin Joseph H. , Bolwell Brian J. , Boyiadzis Michael , Cahn Jean-Yves , Cairo Mitchell S. , Cutler Corey S. , Flowers Mary E.D. , Gale Robert P. , Hassebroek Anna , Herzig Roger H. , Horowitz Mary M. , Isola Luis , Jacobsohn David A. , Klumpp Thomas R. , Lee Stephanie J. , Petersdorf Effie W. , Santarone Stella , Schouten Harry C. , Spellman Stephen , Urbano Alvaro , Weisdorf Daniel J. , Wingard John R. , Pavletic Steven Z. 
Published: October 2019

Abstract 898

Chronic graft-versus-host disease (cGvHD) remains a major barrier to allogeneic (allo) hematopoietic cell transplant (HCT). Previous studies have identified several variables associated with high mortality in persons with cGvHD. The most consistent risk-factors for mortality are thrombocytopenia and the progressive type of cGvHD onset. We evaluated subject-, disease-, and transplant related variables at diagnosis of cGvHD to develop a risk score in 5343 patients with cGvHD. All patients received first allo-transplant for acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML) and myelodysplastic syndrome (MDS) between 1995 and 2004 and reported to CIBMTR. 10 variables were significantly correlated with cGvHD in multivariate analysis of overall survival and non-relapse mortality (NRM) and were used to build the risk score (Table 1). Variable-specific risk scores (VSRC) were constructed for each factor based on the relative risk (RR) of overall or NRM associated with each factor category. Scores were summed for each subject to assign an overall risk score (ORS). Risk groups (RG) of 1–6 were assigned based on the overall risk score. RG1: ORS 0–2, RG2: ORS 3–6, RG3: ORS 7–8, RG4: ORS 9–10, RG5: ORS: 11, RG6: ORS ≥ 12. Survival and NRM were significantly different between RGs (Figure 1 and Figure 2). Although this cGvHD risk score requires independent validation, knowledge of the above HCT factors and cGvHD-specific factors at the time of initial diagnosis provides important prognostic information for clinical care and clinical trial planning. Future analysis will validate this risk score in a more recent allo-transplant cohort assembled after 2005.

Table 1: Variable Overall Survival NRM VSRC RR P RR P Recipient age (baseline: <10 years) <0.0001 <0.0001 Age < 30: 0; 30–59: 1; > 60: 2 10–19 1.35 0.0026 1.41 0.008 20–29 1.31 0.0057 1.46 0.003 30–39 1.41 0.0003 1.66 <0.0001 40–49 1.53 <0.0001 1.90 <0.0001 50–59 1.73 <0.0001 2.17 <0.0001 > 60 2.18 <0.0001 2.75 <0.0001 Prior Acute GVHD (baseline: no AGVHD) <0.0001 <0.0001 No acute GVHD: 0; Prior acute GVHD: 1 Grade I-II 1.23 0.0003 1.31 0.0001 Grade III-IV 1.55 <0.0001 1.71 <0.0001 Time from HCT to cGvHD (baseline: <5 mo) > 5 mo: 0; < 5 mo: 1 > 5mo 0.79 <0.0001 0.84 0.0016 S. Bilirubin at cGvHD (baseline: < 1mg/dl) <0.0001 <0.0001 Bilirubin ≤ 2: 0; Bilirubin > 2: 2 1–2 mg/dl 1.11 0.0557 1.22 0.0035 > 2 mg/dl 1.65 <0.0001 1.88 <0.0001 KPS (cGvHD onset) (baseline: < 80) KPS ≥ 80: 0 KPS <80: 1 80–100 0.57 <0.0001 0.47 <0.0001 Platelet count(cGvH onset) (baseline: < 100) Platelets ≥ 100:0; Platelets < 100: 1 > 100 × 10^9/L 0.64 <0.0001 0.53 <0.0001 HLA group (baseline: HLA-identical sib) <0.0001 <0.0001 HLA –identical sib, well-matched or partially matched URD:0; Other related or mismatched URD: 1 Other related 1.38 0.0019 1.37 0.0137 Well matched URD 1.03 0.6405 1.0 0.9863 Partially matched URD 1.11 0.0931 1.17 0.0360 Mismatched URD 1.37 <0.0001 1.51 <0.0001 Disease status at HCT (Baseline: Early) <0.0001 <0.0001 Early: 0; Intermediate: 1; Advanced: 2 Intermediate 1.22 0.0001 0.99 0.0137 Advanced 1.86 <0.0001 1.83 <0.0001 GvHD prophylaxis (Baseline: T-cell depletion) <0.0001 <0.0001 CSA + methotrexate +/− other: 0; Other categories: 1 CSA + methotrexate+/− other 0.81 <0.0001 0.77 <0.0001 Tacrolimus + methotrexate +/− other 1.12 0.1108 1.07 0.4099 Sex match (Baseline: male to male) 1.94 <0.0001 <0.0001 Male to male, male to female, female to female: 0; Femal to male: 2 Male to female 0.91 0.1096 0.89 0.1087 Female to male 1.94 0.0009 1.25 0.0006 Female to female 1.10 0.1203 1.15 0.0428

Figure 1 Overall survival by cGvHD risk score Figure 1. Overall survival by cGvHD risk score

Figure 2 NRM by cGvHD risk score Figure 2. NRM by cGvHD risk score

Disclosures:

No relevant conflicts of interest to declare.