Atypical Chronic Myeloid Leukemia: Where Are We Now?
Abstract
:1. General Concepts
2. Clinical Case 1: aCML in Younger Patients
3. Clinical Case 2: aCML in the Elderly Patient/Unfit for Allogeneic Stem Cell Transplantation
4. Characteristics of aCML at Presentation and Prognosis
5. Diagnostic Tools in aCML
6. Cytogenetics in aCML
7. Molecular Landscape of aCML
8. Clinical Case 1: Treatment Choices in a Transplant Eligible Patient
9. Clinical Case 2: Treatment Approach in a Transplant Ineligible Patient
10. Treatment
10.1. Hematopoietic Stem Cell Transplant
10.2. Hypomethylating Agents
10.3. AML-Like Chemotherapy
10.4. Interferon-Alpha and Hydroxyurea
10.5. Target Therapy
11. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Clinical Case 1 | Clinical Case 2 | |
---|---|---|
Age (years) | 41 | 71 |
WBC | 32.12 × 109/L | 29.35 × 109/L |
Differential (PB) | hypogranulated neutrophils 46% band-cells 12% eosinophils 2% basophils - monocytes 6% lymphocytes 14% myeloblasts - promyelocytes 2% metamyelocytes 12% myelocites 6% | neutrophils with P-H abnormality 30% band-cells 17% eosinophils - basophils - monocytes 15% lymphocytes 9% myeloblasts 1% promyelocytes 14% metamyelocytes 6% myelocites 8% |
Hb | 13.5 g/dL | 14.9 g/dL |
Plts | 103 × 109/L | 239 × 109/L |
BM blasts | 2% | 4% |
Screening for mutations in JAK2, CALR and MPL | negative | negative |
BCR/ABL | negative | negative |
Gene mutations identified by NGS panel | TET2
p.Q635* (VAF 37.09%) TET2 p.C1221Y (VAF 42.23%) EZH2 p.R690H (VAF 82.89%) | SETBP1 p.D868N (VAF 47.1%) SRSF2 p.P95H (VAF 52.34%) TET2 p.Y1245Lfs*22 (VAF 52.8%) |
Screening for ETNK1 mutations | negative | ETNK1 p.H243P |
Karyotype | 46, XY (20) | 46, XY (20) |
Treatment | Decitabine 3cycles PR with residual thrombocytopenia HSCT | Peghilated IFN alpha PR |
Follow-up time (months after diagnosis) | 8 months | 10 months |
Status at last follow up | Alive in complete remission | Alive with stable disease and partial hematological response |
WHO 2016 Diagnostic Criteria for aCML |
---|
Peripheral blood leukocytosis (WBC count ≥ 13 × 109/L) because of increased numbers of neutrophils and their precursors with prominent dysgranulopoiesis |
Neutrophil precursors (promyelocytes, myelocytes, metamyelocytes) ≥ 10% of leukocytes |
No Ph chromosome or BCR-ABL1 fusion gene and not meeting criteria for PV, ET, or PMF * |
No evidence of PDGFRA, PDGFRB, FGFR1 rearrangement, or PCM1-JAK2 |
Minimal absolute basophilia; basophils usually < 2% of leukocytes |
No or minimal absolute monocytosis; monocytes usually < 10% of leukocytes |
Hypercellular bone marrow with granulocytic proliferation and granulocytic dysplasia, with or without dysplasia in the erythroid and megakaryocytic lineages |
Less than 20% blasts in the blood and bone marrow |
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Crisà, E.; Nicolosi, M.; Ferri, V.; Favini, C.; Gaidano, G.; Patriarca, A. Atypical Chronic Myeloid Leukemia: Where Are We Now? Int. J. Mol. Sci. 2020, 21, 6862. https://doi.org/10.3390/ijms21186862
Crisà E, Nicolosi M, Ferri V, Favini C, Gaidano G, Patriarca A. Atypical Chronic Myeloid Leukemia: Where Are We Now? International Journal of Molecular Sciences. 2020; 21(18):6862. https://doi.org/10.3390/ijms21186862
Chicago/Turabian StyleCrisà, Elena, Maura Nicolosi, Valentina Ferri, Chiara Favini, Gianluca Gaidano, and Andrea Patriarca. 2020. "Atypical Chronic Myeloid Leukemia: Where Are We Now?" International Journal of Molecular Sciences 21, no. 18: 6862. https://doi.org/10.3390/ijms21186862