TY - JOUR
T1 - A Personalized Prediction Model for Outcomes after Allogeneic Hematopoietic Cell Transplant in Patients with Myelodysplastic Syndromes
AU - Nazha, Aziz
AU - Hu, Zhen Huan
AU - Wang, Tao
AU - Lindsley, R. Coleman
AU - Abdel-Azim, Hisham
AU - Aljurf, Mahmoud
AU - Bacher, Ulrike
AU - Bashey, Asad
AU - Cahn, Jean Yves
AU - Cerny, Jan
AU - Copelan, Edward
AU - DeFilipp, Zachariah
AU - Diaz, Miguel Angel
AU - Farhadfar, Nosha
AU - Gadalla, Shahinaz M.
AU - Gale, Robert Peter
AU - George, Biju
AU - Gergis, Usama
AU - Grunwald, Michael R.
AU - Hamilton, Betty
AU - Hashmi, Shahrukh
AU - Hildebrandt, Gerhard C.
AU - Inamoto, Yoshihiro
AU - Kalaycio, Matt
AU - Kamble, Rammurti T.
AU - Kharfan-Dabaja, Mohamed A.
AU - Lazarus, Hillard M.
AU - Liesveld, Jane L.
AU - Litzow, Mark R.
AU - Majhail, Navneet S.
AU - Murthy, Hemant S.
AU - Nathan, Sunita
AU - Nishihori, Taiga
AU - Pawarode, Attaphol
AU - Rizzieri, David
AU - Sabloff, Mitchell
AU - Savani, Bipin N.
AU - Schachter, Levanto
AU - Schouten, Harry C.
AU - Seo, Sachiko
AU - Shah, Nirav N.
AU - Solh, Melhem
AU - Valcárcel, David
AU - Vij, Ravi
AU - Warlick, Erica
AU - Wirk, Baldeep
AU - Wood, William A.
AU - Yared, Jean A.
AU - Alyea, Edwin
AU - Popat, Uday
AU - Sobecks, Ronald M.
AU - Scott, Bart L.
AU - Nakamura, Ryotaro
AU - Saber, Wael
N1 - Publisher Copyright:
© 2020 American Society for Transplantation and Cellular Therapy
PY - 2020/11
Y1 - 2020/11
N2 - Allogeneic hematopoietic stem cell transplantation (HCT) remains the only potentially curative option for myelodysplastic syndromes (MDS). Mortality after HCT is high, with deaths related to relapse or transplant-related complications. Thus, identifying patients who may or may not benefit from HCT is clinically important. We identified 1514 patients with MDS enrolled in the Center for International Blood and Marrow Transplant Research Registry and had their peripheral blood samples sequenced for the presence of 129 commonly mutated genes in myeloid malignancies. A random survival forest algorithm was used to build the model, and the accuracy of the proposed model was assessed by concordance index. The median age of the entire cohort was 59 years. The most commonly mutated genes were ASXL1(20%), TP53 (19%), DNMT3A (15%), and TET2 (12%). The algorithm identified the following variables prior to HCT that impacted overall survival: age, TP53 mutations, absolute neutrophils count, cytogenetics per International Prognostic Scoring System–Revised, Karnofsky performance status, conditioning regimen, donor age, WBC count, hemoglobin, diagnosis of therapy-related MDS, peripheral blast percentage, mutations in RAS pathway, JAK2 mutation, number of mutations/sample, ZRSR2, and CUX1 mutations. Different variables impacted the risk of relapse post-transplant. The new model can provide survival probability at different time points that are specific (personalized) for a given patient based on the clinical and mutational variables that are listed above. The outcomes’ probability at different time points may aid physicians and patients in their decision regarding HCT.
AB - Allogeneic hematopoietic stem cell transplantation (HCT) remains the only potentially curative option for myelodysplastic syndromes (MDS). Mortality after HCT is high, with deaths related to relapse or transplant-related complications. Thus, identifying patients who may or may not benefit from HCT is clinically important. We identified 1514 patients with MDS enrolled in the Center for International Blood and Marrow Transplant Research Registry and had their peripheral blood samples sequenced for the presence of 129 commonly mutated genes in myeloid malignancies. A random survival forest algorithm was used to build the model, and the accuracy of the proposed model was assessed by concordance index. The median age of the entire cohort was 59 years. The most commonly mutated genes were ASXL1(20%), TP53 (19%), DNMT3A (15%), and TET2 (12%). The algorithm identified the following variables prior to HCT that impacted overall survival: age, TP53 mutations, absolute neutrophils count, cytogenetics per International Prognostic Scoring System–Revised, Karnofsky performance status, conditioning regimen, donor age, WBC count, hemoglobin, diagnosis of therapy-related MDS, peripheral blast percentage, mutations in RAS pathway, JAK2 mutation, number of mutations/sample, ZRSR2, and CUX1 mutations. Different variables impacted the risk of relapse post-transplant. The new model can provide survival probability at different time points that are specific (personalized) for a given patient based on the clinical and mutational variables that are listed above. The outcomes’ probability at different time points may aid physicians and patients in their decision regarding HCT.
KW - Genomic biomarkers
KW - MDS
KW - Mutations
UR - http://www.scopus.com/inward/record.url?scp=85090061841&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85090061841&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2020.08.003
DO - 10.1016/j.bbmt.2020.08.003
M3 - Article
C2 - 32781289
AN - SCOPUS:85090061841
SN - 1083-8791
VL - 26
SP - 2139
EP - 2146
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 11
ER -