Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients withCMML

Abstract

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post‐transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0–1), intermediate risk (2, 3), and high risk (4–6) three groups and the 3‐year overall survival (OS) were 93.3% (95%CI, 61%–99%), 78.9% (95%CI, 60%–90%), and 51.6% (95%CI, 32%–68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776–0.902) and 0.749 (95% CI, 0.684–0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo‐HSCT.

Chronic GvHD in a prognostic model: Graft versus leukemia predictor or immortal time bias?

“…This resulted in a lower but significant HR Both this and previous studies hypothesize that the presence of cGvHD may improve survival by reducing relapse rate through an increased Graft vs Leukemia effect. However, in this study, overall survival is remarkably similar to non-relapse mortality for all risk groups in the derivation cohort (their figure 1B,C), 1 which indicates relapse of disease has a minor impact on overall survival. This indicates that most likely the majority of the prognostic effect of cGvHD on overall survival is not related to a reduced incidence of relapse but attributable to immortal time bias.…”

“…chronic myelomonocytic leukemia (CMML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) in this journal. 1 This score consisted of five items: Age, Blasts, Leukocytes, Anemia, and chronic Graft vs Host Disease (ABLAG). The strongest predictor in this score was the absence of chronic Graft vs Host Disease (cGvHD), with a univariate HR of 3.0, and a multivariate HR of 4.8, with cGvHD occurring in 40% of patients.…”