TY - JOUR
T1 - The mutational landscape in chronic myelomonocytic leukemia and its impact on allogeneic hematopoietic cell transplantation outcomes
T2 - a Center for Blood and Marrow Transplantation Research (CIBMTR) analysis
AU - Mei, Matthew
AU - Pillai, Raju
AU - Kim, Soyoung
AU - Estrada-Merly, Noel
AU - Afkhami, Michelle
AU - Yang, Lixin
AU - Meng, Zhuo
AU - Abid, Muhammad Bilal
AU - Aljurf, Mahmoud
AU - Bacher, Ulrike
AU - Beitinjaneh, Amer
AU - Bredeson, Christopher
AU - Cahn, Jean Yves
AU - Cerny, Jan
AU - Copelan, Edward
AU - Cutler, Corey
AU - DeFilipp, Zachariah
AU - Perez, Miguel Angel Diaz
AU - Farhadfar, Nosha
AU - Freytes, César O.
AU - Gadalla, Shahinaz M.
AU - Ganguly, Siddhartha
AU - Gale, Robert Peter
AU - Gergis, Usama
AU - Grunwald, Michael R.
AU - Hamilton, Betty K.
AU - Hashmi, Shahrukh
AU - Hildebrandt, Gerhard C.
AU - Lazarus, Hillard M.
AU - Litzow, Mark
AU - Munker, Reinhold
AU - Murthy, Hemant S.
AU - Nathan, Sunita
AU - Nishihori, Taiga
AU - Patel, Sagar S.
AU - Rizzieri, David
AU - Seo, Sachiko
AU - Shah, Mithun Vinod
AU - Solh, Melhem
AU - Verdonck, Leo F.
AU - Vij, Ravi
AU - Sobecks, Ronald M.
AU - Oran, Betul
AU - Scott, Bart L.
AU - Saber, Wael
AU - Nakamura, Ryotaro
N1 - Publisher Copyright:
©2023 Ferrata Storti Foundation.
PY - 2023/1
Y1 - 2023/1
N2 - Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28-77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of intermediate-2 (HR=1.46, P=0.049) or high (HR=3.22, P=0.0004) correlated significantly with overall survival. When the molecularly informed CPSS-Mol prognostic model was applied, a high CPSS-Mol score (HR=2 P=0.0079) correlated significantly with overall survival. The most common somatic mutations were in ASXL1 (62%), TET2 (35%), KRAS/NRAS (33% combined), and SRSF2 (31%). DNMT3A and TP53 mutations were associated with decreased overall survival (HR=1.70 [95% CI: 1.11-2.60], P=0.0147 and HR=2.72 [95% CI: 1.37-5.39], P=0.0042, respectively) while DNMT3A, JAK2, and TP53 mutations were associated with decreased disease-free survival (HR=1.66 [95% CI: 1.11-2.49], P=0.0138, HR=1.79 [95% CI: 1.06-3.03], P=0.0293, and HR=2.94 [95% CI: 1.50-5.79], P=0.0018, respectively). The only mutation associated with increased relapse was TP53 (HR=2.94, P=0.0201). Nonetheless, the impact of TP53 mutations specifically should be interpreted cautiously given their rarity in CMML. We calculated the goodness of fit measured by Harrell’s C-index for both the CPSS and CPSS-Mol, which were very similar. In summary, via registry data we have determined the mutational landscape in patients with CMML who underwent allogeneic HCT, and demonstrated an association between CPSS-Mol and transplant outcomes although without major improvement in the risk prediction beyond that provided by the CPSS.
AB - Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28-77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of intermediate-2 (HR=1.46, P=0.049) or high (HR=3.22, P=0.0004) correlated significantly with overall survival. When the molecularly informed CPSS-Mol prognostic model was applied, a high CPSS-Mol score (HR=2 P=0.0079) correlated significantly with overall survival. The most common somatic mutations were in ASXL1 (62%), TET2 (35%), KRAS/NRAS (33% combined), and SRSF2 (31%). DNMT3A and TP53 mutations were associated with decreased overall survival (HR=1.70 [95% CI: 1.11-2.60], P=0.0147 and HR=2.72 [95% CI: 1.37-5.39], P=0.0042, respectively) while DNMT3A, JAK2, and TP53 mutations were associated with decreased disease-free survival (HR=1.66 [95% CI: 1.11-2.49], P=0.0138, HR=1.79 [95% CI: 1.06-3.03], P=0.0293, and HR=2.94 [95% CI: 1.50-5.79], P=0.0018, respectively). The only mutation associated with increased relapse was TP53 (HR=2.94, P=0.0201). Nonetheless, the impact of TP53 mutations specifically should be interpreted cautiously given their rarity in CMML. We calculated the goodness of fit measured by Harrell’s C-index for both the CPSS and CPSS-Mol, which were very similar. In summary, via registry data we have determined the mutational landscape in patients with CMML who underwent allogeneic HCT, and demonstrated an association between CPSS-Mol and transplant outcomes although without major improvement in the risk prediction beyond that provided by the CPSS.
UR - http://www.scopus.com/inward/record.url?scp=85145425537&partnerID=8YFLogxK
U2 - 10.3324/haematol.2021.280203
DO - 10.3324/haematol.2021.280203
M3 - Article
C2 - 35443559
AN - SCOPUS:85145425537
SN - 0390-6078
VL - 108
SP - 150
EP - 160
JO - Haematologica
JF - Haematologica
IS - 1
ER -