TY - JOUR
T1 - A multistate model of survival prediction and event monitoring in prefibrotic myelofibrosis
AU - Carobbio, Alessandra
AU - Guglielmelli, Paola
AU - Rumi, Elisa
AU - Cavalloni, Chiara
AU - De Stefano, Valerio
AU - Betti, Silvia
AU - Rambaldi, Alessandro
AU - Finazzi, Maria Chiara
AU - Thiele, Juergen
AU - Vannucchi, Alessandro M.
AU - Tefferi, Ayalew
AU - Barbui, Tiziano
N1 - Funding Information:
The study was sponsored by Fondazione per la Ricerca Ospedale di Bergamo (FROM) (ethical committee approval number: 208-18). This work was supported by AIRC 5 × 1000 call “Metastatic disease: the key unmet need in oncology” to MYNERVA project, #21267 (MYeloid NEoplasms Research Venture AIRC). A detailed description of the MYNERVA project is available at http:// www.progettoagimm.it. We acknowledge Alberto Ferrari for the support in writing the paper.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Among 382 patients with WHO-defined prefibrotic myelofibrosis (pre-PMF) followed for a median of 6.9 years, fibrotic or leukemic transformation or death accounts for 15, 7, and 27% of cases, respectively. A multistate model was applied to analyze survival data taking into account intermediate states that are part of the clinical course of pre-PMF, including overt PMF and acute myeloid leukemia (AML). Within this multistate framework, multivariable models disclosed older age (>65 years) and leukocytosis (>15 × 109/L) as predictors of death and leukemic transformation. The risk factors for fibrotic progression included anemia and grade 1 bone marrow fibrosis. The outcome was further affected by high molecular risk (HMR) but not driver mutations. Direct transition to overt PMF, AML, or death occurred in 15.2, 4.7, and 17.3% of patients, respectively. The risk of AML was the highest in the first 5 years (7%), but leveled off thereafter. Conversely, the probability of death from overt PMF or AML increased more rapidly over time, especially when compared to death in the pre-PMF state without disease progression. The probability of being alive with pre-PMF status decreased to 70 and 30% at 10 and 20 years, respectively. This study highlights the aspects of the clinical course and estimates of disease progression in pre-PMF.
AB - Among 382 patients with WHO-defined prefibrotic myelofibrosis (pre-PMF) followed for a median of 6.9 years, fibrotic or leukemic transformation or death accounts for 15, 7, and 27% of cases, respectively. A multistate model was applied to analyze survival data taking into account intermediate states that are part of the clinical course of pre-PMF, including overt PMF and acute myeloid leukemia (AML). Within this multistate framework, multivariable models disclosed older age (>65 years) and leukocytosis (>15 × 109/L) as predictors of death and leukemic transformation. The risk factors for fibrotic progression included anemia and grade 1 bone marrow fibrosis. The outcome was further affected by high molecular risk (HMR) but not driver mutations. Direct transition to overt PMF, AML, or death occurred in 15.2, 4.7, and 17.3% of patients, respectively. The risk of AML was the highest in the first 5 years (7%), but leveled off thereafter. Conversely, the probability of death from overt PMF or AML increased more rapidly over time, especially when compared to death in the pre-PMF state without disease progression. The probability of being alive with pre-PMF status decreased to 70 and 30% at 10 and 20 years, respectively. This study highlights the aspects of the clinical course and estimates of disease progression in pre-PMF.
UR - http://www.scopus.com/inward/record.url?scp=85092602100&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092602100&partnerID=8YFLogxK
U2 - 10.1038/s41408-020-00368-1
DO - 10.1038/s41408-020-00368-1
M3 - Article
C2 - 33056979
AN - SCOPUS:85092602100
VL - 10
JO - Blood Cancer Journal
JF - Blood Cancer Journal
SN - 2044-5385
IS - 10
M1 - 100
ER -