Megan Melody1, Najla Al Ali1, Ling Zhang2, Hanadi Ramadan1, Eric Padron1, David Sallman1, Kendra Sweet1, Jeffrey Lancet1, Alan List1, John M Bennett3, Rami Komrokji4. 1. Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. 2. Department of Hematopathology and Laboratory Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. 3. Hematopathology Division, Department of Pathology, University of Rochester Medical Center, Rochester, NY. 4. Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. Electronic address: Rami.komrokji@moffitt.org.
Abstract
BACKGROUND: Bone marrow fibrosis (BMF), a poor prognostic factor in myelodysplastic syndromes (MDS), in the context of new risk stratifications of MDS has not been fully explored. We examined the relationship between BMF in MDS and survival outcomes, and explored the landscape of somatic gene mutations in the setting of BMF. PATIENTS AND METHODS: We retrospectively evaluated 2624 MDS patients for BMF who were divided into 2 groups: grade 0-2 BMF (96%) and severe/grade 3 BMF (4%) based on analysis presented. Commonly MDS tested acquired somatic mutations were also compared between those 2 groups of patients with available next-generation sequencing data. RESULTS: Only grade 3 BMF was associated with worse overall survival independent from the Revised International Prognostic Scoring System (IPSS-R) (hazard ratio = 1.6; 95% confidence interval, 1.2-1.9; P < .005). More patients with severe BMF were classified as MDS-EB1 and -EB2 by the World Health Organization 2016 classification, a higher-risk International Prognostic Scoring System score, and a high/very high IPSS-R risk category than patients with grade 0-2 BMF. A complex karyotype, higher bone marrow myeloblasts, lower platelets, and higher rate of elevated lactate dehydrogenase were observed more often in patients with severe BMF. No differences in response to hypomethylating agents or lenalidomide were observed. Among somatic gene mutations tested in MDS, TP53 mutation and SETBP1 were more frequent in patients with grade 3 BMF. CONCLUSION: The presence of grade 3 BMF is associated with reduced overall survival independent from IPSS-R; however, BMF grade did not affect response to hypomethylating agent or lenalidomide treatment. TP53 and SETBP1 mutations occurred with greater frequency among patients with severe fibrosis.
BACKGROUND: Bone marrow fibrosis (BMF), a poor prognostic factor in myelodysplastic syndromes (MDS), in the context of new risk stratifications of MDS has not been fully explored. We examined the relationship between BMF in MDS and survival outcomes, and explored the landscape of somatic gene mutations in the setting of BMF. PATIENTS AND METHODS: We retrospectively evaluated 2624 MDSpatients for BMF who were divided into 2 groups: grade 0-2 BMF (96%) and severe/grade 3 BMF (4%) based on analysis presented. Commonly MDS tested acquired somatic mutations were also compared between those 2 groups of patients with available next-generation sequencing data. RESULTS: Only grade 3 BMF was associated with worse overall survival independent from the Revised International Prognostic Scoring System (IPSS-R) (hazard ratio = 1.6; 95% confidence interval, 1.2-1.9; P < .005). More patients with severe BMF were classified as MDS-EB1 and -EB2 by the World Health Organization 2016 classification, a higher-risk International Prognostic Scoring System score, and a high/very high IPSS-R risk category than patients with grade 0-2 BMF. A complex karyotype, higher bone marrow myeloblasts, lower platelets, and higher rate of elevated lactate dehydrogenase were observed more often in patients with severe BMF. No differences in response to hypomethylating agents or lenalidomide were observed. Among somatic gene mutations tested in MDS, TP53 mutation and SETBP1 were more frequent in patients with grade 3 BMF. CONCLUSION: The presence of grade 3 BMF is associated with reduced overall survival independent from IPSS-R; however, BMF grade did not affect response to hypomethylating agent or lenalidomide treatment. TP53 and SETBP1 mutations occurred with greater frequency among patients with severe fibrosis.
Authors: Amer M Zeidan; Jan Philipp Bewersdorf; Rena Buckstein; Mikkael A Sekeres; David P Steensma; Uwe Platzbecker; Sanam Loghavi; Jacqueline Boultwood; Rafael Bejar; John M Bennett; Uma Borate; Andrew M Brunner; Hetty Carraway; Jane E Churpek; Naval G Daver; Matteo Della Porta; Amy E DeZern; Fabio Efficace; Pierre Fenaux; Maria E Figueroa; Peter Greenberg; Elizabeth A Griffiths; Stephanie Halene; Robert P Hasserjian; Christopher S Hourigan; Nina Kim; Tae Kon Kim; Rami S Komrokji; Vijay Kutchroo; Alan F List; Richard F Little; Ravi Majeti; Aziz Nazha; Stephen D Nimer; Olatoyosi Odenike; Eric Padron; Mrinal M Patnaik; Gail J Roboz; David A Sallman; Guillermo Sanz; Maximilian Stahl; Daniel T Starczynowski; Justin Taylor; Zhuoer Xie; Mina Xu; Michael R Savona; Andrew H Wei; Omar Abdel-Wahab; Valeria Santini Journal: Leukemia Date: 2022-10-20 Impact factor: 12.883