RESUMO
Impaired platelet production is a mechanism of immune thrombocytopenia (ITP). Morphological abnormalities of megakaryocytes (MKs) are sometimes observed in this disease. Two studies have suggested an association between MK abnormalities and response to corticosteroids in primary ITP, but none have investigated this association for thrombopoietin-receptor agonists (TPO-RAs). This was the aim of this study. The source of population was the French CARMEN registry with prospective follow-up of adult patients with incident ITP. We included patients with primary ITP, treated by TPO-RA and with a bone marrow smear before initiating TPO-RA. MK abnormalities were categorized by the presence of dysplasia and by the stage of maturation. Among 451 patients screened, 38 were included in the analysis. There was no difference in the median percentage of dysplastic MKs between responders to TPO-RA (4.0%, 95% confidence interval - CI: 2.3-6.4) and non-responders (4.5%, 95% CI: 0.7-7.1). There was a slightly higher proportion of granular MKs (4.5%, 95% CI: 3-6) and basophilic MKs (30.1%, 95% CI: 21.9-39.1) in non-responders compared to responders (granular: 2.0%, 95% CI: 0-4.1; basophilic: 21.3%, 95% CI: 11.4-40.7). In conclusion, MK abnormalities were not associated with response achievement in ITP patients treated with TPO-RA in this series of 38 patients.
Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Adulto , Medula Óssea , Humanos , Megacariócitos/fisiologia , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores de Trombopoetina/agonistas , Trombocitopenia/tratamento farmacológico , Trombopoetina/farmacologia , Trombopoetina/uso terapêuticoRESUMO
OBJECTIVES: Complete responses have been observed in NPM1-mutated AML patients with dactinomycin, a nucleolar stress-inducing drug. Here, we report a single-center experience of compassionate use of dactinomycin in untreated or relapsed/ refractory NPM1-mutated AML. METHODS: From September 2015 to February 2019, 26 adult patients with NPM1-mutated AML received dactinomycin in different situations: front-line treatment in 4 unfit patients (16%); morphologic (n = 16, 62%), molecular relapses (n = 4, 16%), refractory disease (n = 1, 13%), or postremission therapy in second complete response (n = 1, 13%). RESULTS: Median age was 62.5 years. Median number of dactinomycin cycle was 1 (1-8), and 7 patients (27%) received more than 3 cycles. Three out of 17 patients (18%) in morphologic relapse or refractory to chemotherapy achieved complete remission after the first cycle of dactinomycin. None of the 4 patients unfit for intensive chemotherapy responded to dactinomycin as front-line therapy. Grade 3-4 adverse events were thrombocytopenia (n = 11, 42%), neutropenia (n = 11, 42%), GI toxicity (n = 6, 23%), mucositis (n = 5, 19%), lung infection (n = 5, 19%), and skin rash (n = 2, 7.6%). CONCLUSIONS: Dactinomycin is an inexpensive and easily available drug that may induce significant responses in few AML patients with NPM1 mutations with an acceptable safety profile.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Dactinomicina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Mutação , Proteínas Nucleares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/farmacologia , Biomarcadores Tumorais , Dactinomicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Prognóstico , Recidiva , Indução de Remissão , Retratamento , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemAssuntos
Doenças Autoimunes , Células da Medula Óssea , Macrófagos , Neutropenia , Neutrófilos , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Células da Medula Óssea/imunologia , Células da Medula Óssea/patologia , Humanos , Lactente , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Neutropenia/imunologia , Neutropenia/patologia , Neutrófilos/imunologia , Neutrófilos/patologiaAssuntos
Medula Óssea/patologia , Mastócitos/ultraestrutura , Policitemia/patologia , Adulto , Forma Celular , Diagnóstico Diferencial , Éxons/genética , Mutação em Linhagem Germinativa , Humanos , Masculino , Mastocitose Sistêmica/diagnóstico , Mutação , Policitemia/genética , Receptores da Eritropoetina/genéticaAssuntos
Anemia Sideroblástica/diagnóstico , Medula Óssea/patologia , Células Precursoras Eritroides/ultraestrutura , Células Precursoras de Granulócitos/ultraestrutura , Inflamação/etiologia , Síndrome de Sweet/etiologia , Enzimas Ativadoras de Ubiquitina/genética , Vacúolos/ultraestrutura , Idoso , Anemia Sideroblástica/complicações , Anemia Sideroblástica/genética , Anemia Sideroblástica/patologia , Humanos , Inflamação/genética , Inflamação/patologia , Masculino , Mutação de Sentido Incorreto , Mutação Puntual , SíndromeAssuntos
Leucemia Neutrofílica Crônica/patologia , Leucocitose/patologia , Neutrófilos/patologia , Idoso , Proteínas de Transporte/genética , Humanos , Leucemia Neutrofílica Crônica/complicações , Leucemia Neutrofílica Crônica/diagnóstico , Leucemia Neutrofílica Crônica/genética , Leucocitose/complicações , Leucocitose/diagnóstico , Leucocitose/genética , Masculino , Proteínas Nucleares/genética , Mutação Puntual , Receptores de Fator Estimulador de Colônias/genética , Proteínas Repressoras/genéticaAssuntos
Benzotiazóis/administração & dosagem , Leucemia Mieloide Aguda , Linfócitos , Linfocitose , Compostos de Fenilureia/administração & dosagem , Idoso , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Linfócitos/metabolismo , Linfócitos/patologia , Linfocitose/sangue , Linfocitose/induzido quimicamente , Linfocitose/genética , Linfocitose/patologia , Masculino , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismoRESUMO
BACKGROUND: Acute myeloid leukemia (AML) with myelodysplasia-related characteristics is a heterogeneous subset of AML that has been challenged throughout the history of myeloid malignancies classifications, considered to have similar outcomes as intermediate- or adverse-risk AML depending on the subgroup. However, little is known about the fate of these patients in refractory or relapsed situation (R/R) after first line therapy. METHODS: A large series of R/R AML patients, recorded in the French DATAML registry, have received either intensive chemotherapy (ICT), azacitidine (AZA) as single agent, or best supportive care (BSC). A cohort of 183 patients (median age 63-year-old) with what was called at the time AML-MRC has been explored, and data are reported here. RESULTS: Patient status was refractory for 93, while 90 had relapsed. Respectively, 88, 34, and 61 were included in the three treatment arms. The median OS of the whole cohort was 4.2 months (95%CI: 3.1-5.6) with a mean 1-year overall survival of 24% ± 3.2%. There was no significant survival difference between refractory and relapsed patients. The BSC group had overall a significantly worse outcome (p = 0.0001), and this remained true in both refractory (p = 0.01) and relapsed (p = 0.002) patients. Similar survivals were observed in both groups comparing ICT and AZA. CONCLUSIONS: These data, reporting about an ill-explored population, indicate the poor prognosis of this condition where both ICT and AZA can be proposed. The latter, which was demonstrated here to be a feasible option, should be added to new targeted therapies.
Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Azacitidina/uso terapêutico , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/tratamento farmacológico , RecidivaRESUMO
Acute myeloid leukemia (AML) with t(9;22) (q34.1; q11.2)/BCR::ABL1, a distinct entity within the group of AML with defining genetic abnormalities, belong to the adverse-risk group of the 2022 ELN classification. However, there is little data on outcome since the era of tyrosine kinase inhibitors. Among 5819 AML cases included in the DATAML registry, 20 patients with de novo BCR::ABL1+AML (0.3%) were identified. Eighteen patients treated with standard induction chemotherapy were analyzed in this study. Imatinib was added to chemotherapy in 16 patients. The female-to-male ratio was 1.25 and median age was 54 years. The t(9;22) translocation was the sole chromosomal abnormality in 12 patients. Main gene mutations detected by NGS were ASXL1, RUNX1 and NPM1. Compared with patients with myeloid blast phase of chronic myeloid leukemia (CML-BP), de novo BCR::ABL1+AML had higher WBC, fewer additional chromosomal abnormalities, lower CD36 or CD7 expression and no ABL1 mutations. Seventeen patients (94.4%) achieved complete remission (CR) or CR with incomplete hematologic recovery. Twelve patients were allografted in first remission. With a median follow-up of 6.3 years, the median OS was not reached and 2-year OS was 77% (95% CI: 50-91). Four out of five patients who were not transplanted did not relapse. Comparison of BCR::ABL1+AML, CML-BP, 2017 ELN intermediate (n = 643) and adverse-risk patients (n = 863) showed that patients with BCR::ABL1+AML had a significant better outcome than intermediate and adverse-risk patients. BCR::ABL1+AML patients treated with imatinib and intensive chemotherapy should not be included in the adverse-risk group of current AML classifications.