Assuntos
Mastocitose Sistêmica/genética , Mutação , Proteínas Proto-Oncogênicas c-cbl/genética , Proteínas Repressoras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Mastocitose Sistêmica/mortalidade , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-cbl/metabolismo , Proteínas Repressoras/metabolismo , Análise de SobrevidaRESUMO
Momelotinib (a JAK1 and JAK2 inhibitor) induces both anaemia and spleen responses in myelofibrosis (MF). Momelotinib treatment-emergent peripheral neuropathy (TE-PN) was documented in 44 (44%) of 100 MF patients treated at our institution; median time of TE-PN onset was 32 weeks and duration 11 months. Improvement after drug dose reduction or discontinuation was documented in only two patients. TE-PN was significantly associated with treatment response (P = 0·02) and longer survival (P = 0·048) but significance was lost during multivariate analysis that included treatment duration. TE-PN did not correlate with initial or maximum momelotinib dose or previous treatment with JAK inhibitor or thalidomide.
Assuntos
Benzamidas/efeitos adversos , Doenças do Sistema Nervoso Periférico/epidemiologia , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/epidemiologia , Pirimidinas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzamidas/administração & dosagem , Feminino , Humanos , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 2/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/enzimologia , Prevalência , Mielofibrose Primária/enzimologia , Pirimidinas/administração & dosagem , Fatores de RiscoRESUMO
Iron homeostasis is dysregulated in primary myelofibrosis (PMF), given the high prevalence of anemia, need for red blood cell (RBC) transfusions, and disease-associated inflammatory state. We measured plasma hepcidin levels in 203 consecutive PMF patients at the time of first referral; hepcidin levels were significantly higher as compared to healthy controls (P < 0.0001), and were correlated with hemoglobin of <10 g/dL, RBC transfusion requirement, serum ferritin of >500 µg/L, higher dynamic international prognostic scoring system (DIPSS)-plus risk category, the presence of circulating blasts, age of >65 years, and leukocyte count of <4 × 10(9) /L. Increased hepcidin levels predicted for inferior survival independent of six out of the eight DIPSS-plus prognostic parameters (hazard ratio [HR] = 1.8; P = 0.02), but not when RBC transfusion requirement, hemoglobin of <10 g/dL, or increased serum ferritin were included in the Cox model. Multivariable analysis that considered the four overlapping prognostic variables revealed that increased hepcidin (HR = 1.9; P = 0.03) and increased ferritin (HR = 2.3; P = 0.04), but not hemoglobin of <10 g/dL or RBC transfusion requirement, independently retained their significance for predicting survival. Accordingly, increased levels of both hepcidin and serum ferritin (seen in 29% of patients) predicted inferior survival independent of DIPSS-plus or increased inflammatory cytokine levels (HR = 2.4; P = 0.002), and could be considered in future prognostic models for PMF.
