014e9c012a6a825d7388e111f23d3b7b 270504.pdf 93d72f688c91639f04d8075ddabe665f490aded3 270504.pdf 59471f889b466fd9ebd1549406bfa8a65bf64da5ef8f25a20ff8618a7f1a46fc 270504.pdf Title: Real-World Data on Chronic Myelomonocytic Leukemia: Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes Subject: Despite emerging molecular information on chronic myelomonocytic leukemia (CMML), patient outcome remains unsatisfactory and little is known about the transformation to acute myeloid leukemia (AML). In a single-center cohort of 219 CMML patients, we explored the potential correlation between clinical features, gene mutations, and treatment regimens with overall survival (OS) and clonal evolution into AML. The most commonly detected mutations were TET2, SRSF2, ASXL1, and RUNX1. Median OS was 34 months and varied according to age, cytogenetic risk, FAB, CPSS and CPSS-Mol categories, and number of gene mutations. Hypomethylating agents were administered to 37 patients, 18 of whom responded. Allogeneic stem cell transplantation (alloSCT) was performed in 22 patients. Two-year OS after alloSCT was 60.6%. Six patients received targeted therapy with IDH or FLT3 inhibitors, three of whom attained a long-lasting response. AML transformation occurred in 53 patients and the analysis of paired samples showed changes in gene mutation status. Our real-world data emphasize that the outcome of CMML patients is still unsatisfactory and alloSCT remains the only potentially curative treatment. However, targeted therapies show promise in patients with specific gene mutations. Complete molecular characterization can help to improve risk stratification, understand transformation, and personalize therapy. Keywords: chronic myelomonocytic leukemia; CMML; AML transformation; clonal evolution; prognosis; treatment; hypomethylating agents; targeted therapy; gene mutations; survival Author: Sandra Castaño-Díez, Mónica López-Guerra, Cristina Bosch-Castañeda, Alex Bataller, Paola Charry, Daniel Esteban, Francesca Guijarro, Carlos Jiménez-Vicente, Carlos Castillo-Girón, Albert Cortes, Alexandra Martínez-Roca, Ana Triguero, José Ramón Álamo, Silvia Beà, Dolors Costa, Dolors Colomer, María Rozman, Jordi Esteve and Marina Díaz-Beyá Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Aug 25 09:35:59 2022 CEST ModDate: Thu Aug 25 09:40:53 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 21 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3303262 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- 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edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4923ab24 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Children: Item: Title: Patients Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Item: Title: Cytogenetics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Gene Mutations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Treatment and Response Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Patient Characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Gene Mutations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Overall Survival Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Response to Treatment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: AlloSCT Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Targeted Therapies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: AML Transformation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Info: Title: Real-World Data on Chronic Myelomonocytic Leukemia: Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes Author: Sandra Castaño-Díez, Mónica López-Guerra, Cristina Bosch-Castañeda, Alex Bataller, Paola Charry, Daniel Esteban, Francesca Guijarro, Carlos Jiménez-Vicente, Carlos Castillo-Girón, Albert Cortes, Alexandra Martínez-Roca, Ana Triguero, José Ramón Álamo, Silvia Beà, Dolors Costa, Dolors Colomer, María Rozman, Jordi Esteve and Marina Díaz-Beyá Subject: Despite emerging molecular information on chronic myelomonocytic leukemia (CMML), patient outcome remains unsatisfactory and little is known about the transformation to acute myeloid leukemia (AML). In a single-center cohort of 219 CMML patients, we explored the potential correlation between clinical features, gene mutations, and treatment regimens with overall survival (OS) and clonal evolution into AML. The most commonly detected mutations were TET2, SRSF2, ASXL1, and RUNX1. Median OS was 34 months and varied according to age, cytogenetic risk, FAB, CPSS and CPSS-Mol categories, and number of gene mutations. Hypomethylating agents were administered to 37 patients, 18 of whom responded. Allogeneic stem cell transplantation (alloSCT) was performed in 22 patients. Two-year OS after alloSCT was 60.6%. Six patients received targeted therapy with IDH or FLT3 inhibitors, three of whom attained a long-lasting response. AML transformation occurred in 53 patients and the analysis of paired samples showed changes in gene mutation status. Our real-world data emphasize that the outcome of CMML patients is still unsatisfactory and alloSCT remains the only potentially curative treatment. However, targeted therapies show promise in patients with specific gene mutations. Complete molecular characterization can help to improve risk stratification, understand transformation, and personalize therapy. 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504, 95, 514 Annotation: Subtype: Link Rect: 473, 480, 511, 491 Annotation: Subtype: Link Rect: 517, 480, 553, 491 Annotation: Subtype: Link Rect: 452, 445, 490, 456 Annotation: Subtype: Link Rect: 207, 411, 245, 422 Annotation: Subtype: Link Rect: 251, 411, 287, 422 Annotation: Subtype: Link Rect: 176, 377, 214, 387 Annotation: Subtype: Link Rect: 520, 353, 557, 364 Annotation: Subtype: Link Rect: 441, 319, 479, 330 Annotation: Subtype: Link Rect: 95, 285, 133, 295 Annotation: Subtype: Link Rect: 287, 250, 324, 261 Annotation: Subtype: Link Rect: 269, 215, 306, 226 Annotation: Subtype: Link Rect: 316, 181, 354, 192 Annotation: Subtype: Link Rect: 95, 147, 133, 157 Annotation: Subtype: Link Rect: 266, 123, 304, 134 Annotation: Subtype: Link Rect: 231, 100, 269, 111 Checksum: f43dbcb6 Type: CRC32 Checksum: 014e9c012a6a825d7388e111f23d3b7b Type: MD5 Checksum: 93d72f688c91639f04d8075ddabe665f490aded3 Type: SHA-1