Validation of the Revised Pretransplant Assessment of Mortality Score in Patients with Acute Myelogenous Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Despite recent advances, allogeneic hematopoietic stem cell transplantation (allo-HSCT) continues to be accompanied by a high rate of morbidity and mortality. Several scores have been developed to predict outcome after allo-HSCT. The recently revised Pretransplant Assessment of Mortality (PAM) score is based on patient age, donor type, disease risk, cytomegalovirus (CMV) serostatus of patient and donor, and forced expiratory volume in 1 second (FEV). The aim of this study was to analyze the predictive power of the PAM score in an independent large cohort of patients with acute myelogenous leukemia (AML). We selected adult patients with AML who underwent a first allo-HSCT at the University Hospital of Dresden, a tertiary care hospital with a large transplantation program. All adult patients treated between January 1, 2003, and July 1, 2015, were included. The PAM score was calculated as described previously. Overall survival (OS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) after allo-HSCT were analyzed. Age, AML type, sex match, CMV match, donor type, European Leukemia Net risk classification, type of conditioning, disease stage, and PAM score as a continuous variable were selected a priori for multivariate Cox regression analyses. A total of 544 patients met the inclusion criteria. The median patient age was 57 years. With a median follow-up of 47 months (range, 1 to 161 months), the estimated OS for the whole cohort at 4 years was 43%, with a CIR of 30% and an NRM of 31%. The probability of OS at 4 years was 65% for patients with a PAM score of 0, 52% in those with a PAM score of 1, 33% in those with a PAM score of 2, and 22% in those with a PAM score of 3 (P < .001, log-rank test). Both the CIR and NRM increased with higher PAM scores (P = .005 and P < .001, respectively, Gray test). In multivariate analysis, age (hazard ratio [HR], 1.02 per year; P = .004), disease stage (primary induction failure versus first complete remission (CR1); HR, 1.5; P = .03), and the PAM score (HR 1.04; P = .03) had a significant impact on OS. This is the first independent validation of the revised PAM score allowing for simple and valid estimation of transplantation outcomes. It can serve as an important tool in counseling patients with AML, as well as in designing future trials.

External Validation of the Revised Pretransplant Assessment of Mortality Score in Allogeneic Hematopoietic Cell Transplantation: A Cohort Study

“… 13 The PAM score was originally developed to predict OS, but an external validation of the rPAM score for outcomes such as NRM or CIR has not been performed in detail. 14 , 21 The results of our study support the use of the rPAM score in clinical practice for pretransplant risk stratification in allo-HCT.…”

“…To address these challenges, several prognostic models and scores were developed. 14 , 20 , 21 Due to the variability of analyzed outcomes, some prognostic scores include disease-related factors to predict relapse (eg, DRI), whereas other integrate patient-related risk factors (eg, HCT-CI) reflecting comorbid conditions predicting transplant-related mortality. 16 , 21 A more universal approach pursues the EBMT score, which incorporates transplant- and disease-related risk factors 22 and the rPAM score with the integrated patient-, disease-, and donor-specific features.…”

“…The revised PAM (rPAM) score has been validated in a cohort of patients with acute myelogenous leukemia receiving allo-HCT where it was associated with all-cause mortality, cumulative incidence of relapse (CIR), and NRM. 14 However, since the rPAM score has not been validated externally in allo-HCT cohorts covering a wider spectrum of diseases, we aimed to validate the rPAM score in a real-world cohort of patients with an extended follow-up.…”

External validation and comparison of multiple prognostic scores in allogeneic hematopoietic stem cell transplantation

“…Validation studies of each of these scores have been published, [19][20][21][22][23] however, few direct comparisons on the same population have rarely been performed, and mostly include 2 or 3 scores (HCT-CI and EBMT or PAM). 6,14,[24][25][26][27] Furthermore, methodologies have varied; Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) guidelines, 17,28 which outline best practices for model development and validation, are inconsistently followed.…”

Comparison of Risk Scoring Systems in HLA-Matched Related Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study

“…The EBMT score of the patients was evaluated in 4 risk groups as 0-2, 3, 4, and >5 [ 23 ]. The rPAM score was evaluated in four categories of <17, 17-21, 21-30, and >30 [ 24 ]. The HCT-CI-Age score was evaluated in 3 groups as scores of 0, 1-2, and >3 [ 25 ].…”