Preconditioning Level of C-Reactive Protein and Disease Stage Are Key Prognostic Factors In Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Pavlu Jiri , Shah Rajvi , Auner Holger W. , Milojkovic Dragana , Marin David , Sargent Jeremy , Rahemtulla Amin , MacDonald Donald H. , Kanfer Edward J. , Rezvani Katayoun , Dazzi Francesco , Goldman John M. , Apperley Jane F. , Szydlo Richard M. 
Published: October 2019

Abstract
Abstract 3488
It is important to determine prognostic indicators which may predict outcome of hematopoietic stem cell transplantation (HCT). The European Group for Blood and Marrow Transplantation (EBMT) proposed a scoring system for CML which, after modification, also predicted outcomes for patients transplanted for other hematologic malignancies. The HCT comorbidity index (HCT-CI) developed by Sorror et al. enabled further selection of patients for HCT based on their comorbidities. We have recently shown that the level of C-reactive protein (CRP) measured shortly before transplantation is another important prognostic factor in patients transplanted for CML in first chronic phase. In this study we tested the value of CRP together with other known prognostic factors in an independent cohort of 263 patients transplanted in a single institution from 1992 through 2009 for ALL (N=38, 14%) AML (N=72, 27%), MDS (N=19, 7%), and advanced phase CML (N=134, 51%). For the 130 (49%) recipients of stem cells from matched siblings conditioning consisted of cyclophosphamide and TBI. For the 133 (51%) unrelated donor transplant recipients in vivo T-cell depletion with anti CD52 antibody (Campath) was used in addition. Serum CRP levels were measured at a median of 16 days before stem cell infusion using a standard latex immunoassay (normal range 0–9 mg/L) while the patients were well without infection and off antibiotics. Patients' comorbidities were defined and assigned different weights (1-3) by the HCT-CI and disease stage was assessed in accordance with EBMT criteria. Thus, patients transplanted for AML (N=32) or ALL (N=27) in first complete remission were classified as early stage (N=59). Those with CML in accelerated phase (N=70), CML in second (N=42) or third (N=5) chronic phase, AML (N=19) or ALL (N=6) in second complete remission and MDS (N=19) were classified as intermediate stage (N=161). Patients with CML in blast phase (N=17) and acute leukemia in >2nd complete remission (N=26) or in relapse were defined as late stage (N=43). In univariate analysis, factors associated with day 100 nonrelapse mortality (NRM) were recipient's age at HCT, disease stage and preconditioning CRP level whereas disease stage, CRP level, and EBMT score were associated with overall survival (OS). In multivariate analysis only two factors showed independent prognostic value: late disease stage and elevated CRP level (>9 mg/L). Both predicted for inferior NRM (RR: 3.83, CI 1.65–8.92, P=.002 and RR: 1.51, CI 1.51–4.26, P<.001 respectively) and OS (RR: 2.88, CI 1.80–4.62, P< 0.001 and RR: 1.56, CI 1.15–2.13, P= 0.005). The day 100 NRM was 41% for patients with CRP>9 mg/L, 17% for those with CRP 0–9 mg/L (figure) and 25% for the whole cohort. The 5-year OS was 31.5% for patients with CRP 0–9 mg/L, 22.2% for those with CRP >9 mg/L and 28% for the whole cohort. There was no association between elevated preconditioning CRP levels and infection, either as a comorbidity or as a cause of death. The HCT-CI did not have a prognostic role in this cohort. These results confirm the high prognostic value of disease stage. Importantly, they extend our findings in early phase CML to other hematologic malignancies and establish pretransplantation levels of CRP as an independent predictor of allogeneic HCT outcomes.

Disclosures:
No relevant conflicts of interest to declare.