Moleculair prognose van belang WHO proliferatief of dysplastisch cave mastocytose Mayo MDACC CPSS agressieve chronische leukemie weinig therapeutische mogelijkheden alleen allo beinvloedt natuurlijk beloop: small proportion cure allo tenzij Mayo / MDACC laag - afh leeftijd, comorbiditeit, risicoclassificatie, donor (indien sympt?) hydrea - forse myeloproliferatie - bij hoog kreat door lysozymurie - alternatieven 6-thiopurine indien intolerantie of evt. AML-therapie - 1x/week dosisaanpassing -- CMML: startdosis 1000 mg 1dd, op geleide van cytopenie (n >0,5 houden) hypomethylering - cytopenie - indien hydrea niet werkt pm, etoposide, LD ara-C, thioguanine WHO - monocytosis ≥1 × 109/L en ≥10%, persisterend - geen WHO criteria for BCR-ABL+ CML, PMF, PV, or ET ---- JAK2, CALR, or MPL pleit voor MPN ---- TET2, SRSF2, ASXL1, SETBP1 in the proper clinical contest can be used to support a diagnosis. It should be noted however, that many of these mutations can be age-related or be present in subclones. Therefore, caution would have to be used in the interpretation of these genetic results. - geen PDGFRA, PDGFRB, or FGFR1 rearrangement (or PCM1-JAK2, which should be specifically excluded in cases with eosinophilia) - <20% blasts in the blood and bone marrow - dysplasia in 1 or more myeloid lineages, anders: ---- An acquired clonal cytogenetic or molecular genetic abnormality is present in hemopoietic cellsΔ or ---- > 3 months * CMML-0: <2 percent blasts in the peripheral blood and <5 percent blasts in the marrow * CMML-1: 2-4 percent blasts in the peripheral blood and/or 5 to 9 percent blasts in the marrow * CMML-2: 5-19 percent blasts in the peripheral blood, 10 to 19 percent blasts in the marrow, or presence of one or more Auer rods Historically, CMML had been classified into "myelodysplastic syndrome (MDS)" or "myeloproliferative neoplasm (MPN)" subtypes, defined by a white blood count of <13 x 109/L or ≥13 x 109/L respectively, by the French-American-British (FAB) classification schema, S/ B-symptomen, pancytopenie, huidafwijkingen, splenomegalie kan: lever en klieren kan ook lysozymurie: hypokaliemie en factor X def en hoog kreat PROGNOSIS - The general prognosis of patients with CMML is poor, with an expected median overall survival (OS) of approximately 30 months. Historically, CMML had been classified into "myelodysplastic syndrome (MDS)" or "myeloproliferative neoplasm (MPN)" subtypes, defined by a white blood count of <13 x 109/L or ≥13 x 109/L respectively, by the French-American-British (FAB) classification schema, or as "CMML-0, CMML-1, or CMML-2" subtypes, defined by peripheral blood and marrow blast percentages by the World Health Organization (WHO) [16,35,48,49]. Although the latter distinction is highly prognostic, the former is less so. (See 'Diagnosis' above.) Mayo chronic myelomonocytic leukemia (CMML) prognostic model Absolute monocyte counts >10,000/microL [>10 x 109/L] one point Circulating immature cells, defined as: Myelo, myelo, metamyelo, and/or promyelo (1) Decreased hemoglobin (<10 g/dL [<100 g/L]) (1) Decreased platelets (<100 x 103/microliter [<100 x 109/L]) (1) 0 points: Low risk; 32 months median survival 1 point: Intermediate risk; 18.5 months median survival 2 to 4 points: High risk; 10 months median survival References 1.Patnaik MM, Padron E, LaBorde RR, et. al. Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: ASXL1 and spliceosome component mutations and outcomes. Leukemia. 2013 Jul;27(7):1504-10.