BLAST: A Globally Applicable and Molecularly Versatile Survival Model for Chronic Myelomonocytic Leukemia

We sought to develop a survival model in chronic myelomonocytic leukemia (CMML) that is primarily based on clinical variables and examine additional impact from mutations and karyotype. A total of 457 molecularly annotated patients were considered. Multivariable analysis identified circulating blasts ≥2% (1 point), leukocytes ≥13 × 109/L (1 point), and severe (2 points) or moderate (1 point) anemia as preferred risk variables in developing a clinical risk stratification tool for overall survival (OS), acronymized to "BLAST": low risk (0 points; median, 63 months); intermediate risk (1 point; median, 28 months; hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.6-3.0), and high risk (2-4 points; median, 13 months; HR, 5.4; 95% CI, 4.1-7.3); the corresponding 3/5-year OS rates were 68%/53%, 43%/18%, and 12%/1%. BLAST model performance (area under the receiver operating characteristic curve [AUC] 0.77/0.85 at 3/5 years) was shown to be comparable to that of the molecular CMML-specific prognostic scoring system (AUC 0.73/0.75) and the international prognostic scoring system-molecular (AUC 0.73/0.74). Multivariable analysis of mutations and karyotype identified PHF6MUT and TET2MUT as being "favorable" and DNMT3AMUT, U2AF1MUT, BCORMUT, SETBP1MUT, ASXL1MUT, NRASMUT, PTPN11MUT, RUNX1MUT, TP53MUT, and adverse karyotype, "unfavorable." Molecular information was subsequently encoded in a combined clinical-molecular risk model (BLAST-mol; AUC 0.80/0.86 at 3/5 years) that included the aforementioned BLAST clinical risk variables and a 3-tiered molecular risk score. BLAST and BLAST-mol were subsequently validated by 2 separate external cohorts. Independent risk factors for blast transformation included DNMT3AMUT, ASXL1MUT, PHF6WT, leukocytes ≥13 × 109/L, and ≥2% circulating or ≥10% bone marrow blasts. The current study proposes an easy-to-implement, globally applicable, and molecularly adaptive risk model for CMML.

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Journal
Blood
Published
2025-05-07
DOI
https://doi.org/10.1182/blood.2024027170
Citations
17
Primary Topic
Acute Myeloid Leukemia Research
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article
Field-Weighted Citation Impact
30.09
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article

BLAST: A Globally Applicable and Molecularly Versatile Survival Model for Chronic Myelomonocytic Leukemia

Farhad Ravandi, Naseema Gangat, Terra L. Lasho, Dirk R. Larson et al.
17 citations
Blood
Acute Myeloid Leukemia Research
30.09
article

BLAST: A Globally Applicable and Molecularly Versatile Survival Model for Chronic Myelomonocytic Leukemia

Farhad Ravandi, Naseema Gangat, Terra L. Lasho, Dirk R. Larson, Francesco Passamonti, Courtney Denton Dinardo, Abhishek Avinash Mangaonkar, Ayalew Tefferi, Maymona Abdelmagid, Tapan Mahendra Kadia, Animesh Dev Pardanani, Guillermo Montalban‐Bravo, Kelly Sharon Chien, Koji Sasaki, Naval Guastad Daver, Mahsa Rezasoltani, Ali Alsugair, Clifford Michael Csizmar, Gautam M. Borthakur, Sanam Loghavi, Rashmi Kanagal‐Shamanna, Alexandre Bazinet, Francesco Onida, Cinthya J. Zepeda‐Mendoza, Guillermo Garcia‐Manero, Mrinal M. Patnaik, Christy M. Finke, Anuya Natu, Rong Lucy He, Kaaren K. Reichard, Danielle Hammond, Mark E. Gurney, Saubia Fathima, Muhammad Yousuf, Fnu Aperna
article en
17 citations

Abstract

We sought to develop a survival model in chronic myelomonocytic leukemia (CMML) that is primarily based on clinical variables and examine additional impact from mutations and karyotype. A total of 457 molecularly annotated patients were considered. Multivariable analysis identified circulating blasts ≥2% (1 point), leukocytes ≥13 × 109/L (1 point), and severe (2 points) or moderate (1 point) anemia as preferred risk variables in developing a clinical risk stratification tool for overall survival (OS), acronymized to "BLAST": low risk (0 points; median, 63 months); intermediate risk (1 point; median, 28 months; hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.6-3.0), and high risk (2-4 points; median, 13 months; HR, 5.4; 95% CI, 4.1-7.3); the corresponding 3/5-year OS rates were 68%/53%, 43%/18%, and 12%/1%. BLAST model performance (area under the receiver operating characteristic curve [AUC] 0.77/0.85 at 3/5 years) was shown to be comparable to that of the molecular CMML-specific prognostic scoring system (AUC 0.73/0.75) and the international prognostic scoring system-molecular (AUC 0.73/0.74). Multivariable analysis of mutations and karyotype identified PHF6MUT and TET2MUT as being "favorable" and DNMT3AMUT, U2AF1MUT, BCORMUT, SETBP1MUT, ASXL1MUT, NRASMUT, PTPN11MUT, RUNX1MUT, TP53MUT, and adverse karyotype, "unfavorable." Molecular information was subsequently encoded in a combined clinical-molecular risk model (BLAST-mol; AUC 0.80/0.86 at 3/5 years) that included the aforementioned BLAST clinical risk variables and a 3-tiered molecular risk score. BLAST and BLAST-mol were subsequently validated by 2 separate external cohorts. Independent risk factors for blast transformation included DNMT3AMUT, ASXL1MUT, PHF6WT, leukocytes ≥13 × 109/L, and ≥2% circulating or ≥10% bone marrow blasts. The current study proposes an easy-to-implement, globally applicable, and molecularly adaptive risk model for CMML.

BloodVol. 146(7)
Mayo Clinic (US), The University of Texas MD Anderson Cancer Center (US), University of Milan (IT), WinnMed (US), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Mayo Clinic Hospital (US), ASST Fatebenefratelli Sacco (IT)
Openalex Percentile: Top 0%
Acute Myeloid Leukemia Research
30.09
DOIOpen Access PDFOpenAlex
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