Development and Validation of a Novel Acute Myeloid Leukemia–Composite Model to Estimate Risks of Mortality

Sorror, Mohamed L.; Storer, Barry E.; Fathi, Amir T.; Gerds, Aaron T.; Medeiros, Bruno C.; Shami, Paul J.; Brunner, Andrew M.; Sekeres, Mikkael A.; Mukherjee, Sudipto; Peña, Esteban Gilberto Ramos; Elsawy, Mahmoud; Wardyn, Shylo E.; Whitten, J. L.; Moore, Rachelle; Becker, Pamela S.; McCune, Jeannine S.; Appelbaum, Frederick R.; Estey, Elihu H.

doi:10.1001/jamaoncol.2017.2714

Cited by 142 publications

(120 citation statements)

References 28 publications

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“…Adding the biomarkers resulted in a slight improvement of the c-statistic (.58 to .61; P < .001). This augmentation of the HCT-CI score also proved to improve prediction of 1-year mortality after initial therapy of AML [44]. In another multicenter retrospective study, on 3,033 allo-HSCT patients, Sorror et al have developed and validated the HCT-CI/age score; for patients 40 years of age or older, 1 additional point was added to the original HCT-CI score [45].…”

Section: Discussionmentioning

confidence: 99%

Baseline Renal Function and Albumin are Powerful Predictors for Allogeneic Transplantation-Related Mortality

Shouval

Jong

Fein

et al. 2018

Biology of Blood and Marrow Transplantation

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Biomarkers measured in blood chemistry before allogeneic hematopoietic stem cell transplantation (HSCT) may reflect patients' physiological status. We hypothesized that selected markers are predictive for nonrelapse mortality (NRM) following transplantation and could contribute to risk assessment. We investigated the value of pre-HSCT albumin, estimated glomerular filtration rate (eGFR), and alkaline phosphatase (AlkP) in predicting NRM. We retrospectively analyzed clinical and laboratory data from 1217 patients receiving a first HSCT in 2 European centers between 2003 and 2015. Transplantation indications and conditioning regimens were diverse. Patients had a median age of 55 years and hematopoietic cell transplantation comorbidity index (HCT-CI) scores of 0 (24%), 1 to 2 (39%), and ≥3 (37%). Cutoffs of eGFR <60 mL/min, albumin <3.5 g/dL, and AlkP >180 IU/L corresponded with 8.8%, 8.3%, and 6.5% of the patients, respectively. eGFR and albumin were associated with increased risk and higher cumulative incidence of day-100, 1-year, and 2-year NRM, both as continuous or categorized variables. A similar pattern was observed for AlkP, except for day-100 NRM. In multivariable analyses, eGFR and albumin were consistently among the top risk factors for early and late-term NRM, abrogating the role of age. Prediction models for day-100, 1-year, and 2-year NRM based only on HCT-CI resulted in c-statistics of .565, .575, and .577, respectively. Addition of both biomarkers increased c-statistics for day-100, 1-year, and 2-year NRM to .651, .633, and .624, respectively. Albumin and eGFR are prognostic biomarkers for NRM after HSCT and improve the discriminative power of the HCT-CI.

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Section: Discussionmentioning

confidence: 99%

Baseline Renal Function and Albumin are Powerful Predictors for Allogeneic Transplantation-Related Mortality

Shouval

Jong

Fein

et al. 2018

Biology of Blood and Marrow Transplantation

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“…Nonetheless, the HCT-CI cannot be validated for some subgroups, for example, in some cohorts of patients with AML [8,9]. Recently, a composite model including an augmented HCT-CI was found to be predictive even in patients with AML undergoing nontransplantation therapy [3]. Overall, the HCT-CI remains a standard scoring system of comorbidity, which allows for comparisons of patient cohorts in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…Initially, the EBMT score was used only for chronic myelogenous leukemia (CML), but it was subsequently validated for hematologic diseases in general. Recently, Sorror et al [3] published a cohort study in patients with AML that investigated the influence of comorbidities, age, and disease-specific risks factors on overall survival (OS) after various treatment strategies. This "AML composite model" is predictive for early and late mortality.…”

Section: Introductionmentioning

confidence: 99%

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

Middeke

Kollinger

Baldauf

et al. 2018

Biology of Blood and Marrow Transplantation

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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.

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“…1,2 These benefits are observed even among older patients or those with comorbidities, 3,4 who can be treated with low-intensity chemotherapy, such as hypomethylating agent or low-dose cytarabine, when appropriate. Without chemotherapy, many patients succumb to AML within a few months.…”

Section: Introductionmentioning

confidence: 99%

Utilization of initial chemotherapy for newly diagnosed acute myeloid leukemia in the United States

Bhatt¹,

Shostrom

Gundabolu³

et al. 2018

Blood Advances

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Development and Validation of a Novel Acute Myeloid Leukemia–Composite Model to Estimate Risks of Mortality

Cited by 142 publications

References 28 publications

Baseline Renal Function and Albumin are Powerful Predictors for Allogeneic Transplantation-Related Mortality

Baseline Renal Function and Albumin are Powerful Predictors for Allogeneic Transplantation-Related Mortality

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

Utilization of initial chemotherapy for newly diagnosed acute myeloid leukemia in the United States

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