The mutational landscape in chronic myelomonocytic leukemia and its impact on allogeneic hematopoietic cell transplantation outcomes: a Center for Blood and Marrow Transplantation Research (CIBMTR) analysis

被引：16

作者：

Mei, Matthew ^{[1
]}

Pillai, Raju ^{[2
]}

Kim, Soyoung ^{[3
,4
]}

Estrada-Merly, Noel ^{[4
]}

Afkhami, Michelle ^{[2
]}

Yang, Lixin ^{[2
]}

Meng, Zhuo ^{[5
]}

Abid, Muhammad Bilal ^{[6
]}

Aljurf, Mahmoud ^{[7
]}

Bacher, Ulrike ^{[8
]}

Beitinjaneh, Amer ^{[9
]}

Bredeson, Christopher ^{[10
]}

Cahn, Jean-Yves ^{[11
]}

Cerny, Jan ^{[12
]}

Copelan, Edward ^{[13
]}

Cutler, Corey ^{[14
]}

DeFilipp, Zachariah ^{[15
]}

Diaz Perez, Miguel Angel ^{[16
]}

Farhadfar, Nosha ^{[17
]}

Freytes, Cesar O. ^{[18
]}

Gadalla, Shahinaz M. ^{[19
]}

Ganguly, Siddhartha ^{[20
]}

Gale, Robert Peter ^{[21
]}

Gergis, Usama ^{[22
]}

Grunwald, Michael R. ^{[13
]}

Hamilton, Betty K. ^{[23
]}

Hashmi, Shahrukh ^{[24
,25
]}

Hildebrandt, Gerhard C. ^{[26
]}

Lazarus, Hillard M. ^{[27
]}

Litzow, Mark ^{[28
]}

Munker, Reinhold ^{[26
]}

Murthy, Hemant S. ^{[29
]}

Nathan, Sunita ^{[30
]}

Nishihori, Taiga ^{[31
]}

Patel, Sagar S. ^{[32
]}

Rizzieri, David ^{[33
]}

Seo, Sachiko ^{[34
]}

Shah, Mithun Vinod ^{[35
]}

Solh, Melhem ^{[36
]}

Verdonck, Leo F. ^{[37
]}

Vij, Ravi ^{[38
]}

Sobecks, Ronald M. ^{[39
]}

Oran, Betul ^{[40
]}

Scott, Bart L. ^{[41
]}

Saber, Wael ^{[4
]}

Nakamura, Ryotaro ^{[1
]}

机构：

[1] City Hope Natl Med Ctr, Dept Hematol HCT, Duarte, CA 91010 USA

[2] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA USA

[3] Med Coll Wisconsin, Inst Hlth & Equ, Div Biostat, Milwaukee, WI USA

[4] Med Coll Wisconsin, Dept Med, CIBMTR Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI USA

[5] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA

[6] Med Coll Wisconsin, Div Hematol Oncol Infect Dis, Dept Med, Milwaukee, WI USA

[7] King Faisal Specialist Hosp Ctr & Res, Dept Oncol, Riyadh, Saudi Arabia

[8] Univ Hosp Bern, Univ Bern, Dept Hematol, Inselspital, Bern, Switzerland

[9] Univ Miami Hosp & Clin, Div Transplantat & Cellular Therapy, Sylvester Comprehens Canc Ctr, Miami, FL USA

[10] Ottawa Hosp, Transplant & Cellular Therapy Program, Ottawa, ON, Canada

[11] Univ Grenoble Alpes, Dept Hematol, CHU Grenoble Alpes, Grenoble, France

[12] Univ Massachusetts, Div Hematol Oncol, Dept Med, Med Ctr, Worcester, MA USA

[13] Atrium Hlth, Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC USA

[14] Dana Farber Canc Inst, Stem Cell Transplantat & Cellular Therapy, Boston, MA USA

[15] Massachusetts Gen Hosp, Hematopoiet Cell Transplant & Cellular Therapy Pr, Boston, MA USA

[16] Hosp Infantil Univ Nino Jesus, Dept Hematol Oncol, Madrid, Spain

[17] Univ Florida, Div Hematol Oncol, Coll Med, Gainesville, FL USA

[18] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA

[19] NCI, Div Canc Epidemiol Genet, Clin Genet Branch, NIH, Rockville, MD USA

[20] Univ Kansas Hlth Syst, Div Hematol Malignancy & Cellular Therapeut, Kansas City, KS USA

[21] Imperial Coll London, Dept Immunol & Inflammat, Haematol Res Ctr, London, England

[22] Thomas Jefferson Univ, Div Hematol Malignancies, Dept Med Oncol, Philadelphia, PA USA

[23] Cleveland Clin, Taussig Canc Inst, Dept Hematol & Med Oncol, Blood & Marrow Transplant Program, Cleveland, OH USA

[24] Mayo Clin, Dept Internal Med, Rochester, MN USA

[25] Sheikh Shakhbout Med City, Dept Med, Abu Dhabi, U Arab Emirates

[26] Univ Kentucky, Markey Canc Ctr, Lexington, KY USA

[27] Case Western Reserve Univ, Univ Hosp Cleveland, Med Ctr, Cleveland, OH USA

[28] Mayo Clin Rochester, Div Hematol & Transplant Ctr, Rochester, MN USA

[29] Mayo Clin, Div Hematol Oncol, Blood & Marrow Transplantat Program, Jacksonville, FL USA

[30] Rush Univ, Sect Bone Marrow Transplant & Cell Therapy, Med Ctr, Chicago, IL USA

[31] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood Marrow Transplant & Cellular Immunothe, Tampa, FL USA

[32] Univ Utah, Huntsman Canc Inst, Blood & Marrow Transplant Program, Salt Lake City, UT USA

[33] Novant Hlth Canc Inst, Charlotte, NC USA

[34] Dokkyo Med Univ, Dept Hematol & Oncol, Mibu, Tochigi, Japan

[35] Mayo Clin, Rochester, MN USA

[36] Northside Hosp, Blood & Marrow Transplant Grp Georgia, Atlanta, GA USA

[37] Isala Clin, Dept Hematol Oncol, Zwolle, Netherlands

[38] Washington Univ, Div Med Oncol, Sch Med, St Louis, MO USA

[39] Cleveland Clin, Cleveland, OH USA

[40] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Stem Cell Transplantat, Houston, TX USA

[41] Fred Hutchinson Canc Res Ctr, Seattle, WA USA

来源：

HAEMATOLOGICA | 2023年 / 108卷 / 01期

关键词：

PROGNOSTIC SCORING SYSTEM; MYELODYSPLASTIC SYNDROMES; CLINICAL-FEATURES; RISK-ASSESSMENT; UNITED-STATES; DECITABINE; CLASSIFICATION; NEOPLASMS;

D O I：

10.3324/haematol.2021.280203

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：150 / 160

页数：11

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