RESUMO
Casitas B-cell lineage (CBL) syndrome is a rare RASopathy known to predispose to CBL-mutated juvenile myelomonocytic leukemia (JMML) in childhood. Adulthood acute myeloid leukemia arising out of a genetic aberrancies consistent with prior CBL-mutated JMML has been twice previously described, but chronic myeloproliferative neoplasia has not. We present a case of progressive myeloproliferative neoplasm in adulthood in the context of CBL syndrome alongside a novel CSF3R variant. We also review pathogenic splice-site mutations in CBL-mutated JMML.
RESUMO
The prognosis of AML in elderly patients is poor and research into novel therapeutic approaches is urgently needed. This study examined the use of low-dose chemotherapy with cytarabine and thioguanine administered in repetitive cycles in 62 elderly patients with newly diagnosed or relapsed/refractory AML. The overall response rate was 58% in the total cohort. Response rates (CR/CRi) were significantly higher in patients with newly diagnosed AML (74%) compared to patients with relapsed/refractory disease (25%, p = .0004). Kaplan-Meier estimate of overall survival was 289 days (95% CI; 183-395 days) with a relapse rate of 65.7%. The induction mortality rate was 16.1% with treatment successfully undertaken in the outpatient setting. Similar clinical outcomes were observed in a retrospective analysis of a second cohort of 25 AML patients treated at a different site. These results support the use of a sustained low intensity chemotherapy approach as a therapeutic option for elderly patients with AML.
Assuntos
Citarabina , Leucemia Mieloide Aguda , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/uso terapêutico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Indução de Remissão , Estudos Retrospectivos , Tioguanina/uso terapêutico , Resultado do TratamentoAssuntos
Linfoma Difuso de Grandes Células B/genética , Macroglobulinemia de Waldenstrom/genética , Idoso , Idoso de 80 Anos ou mais , Evolução Clonal , Genes de Cadeia Pesada de Imunoglobulina/genética , Humanos , Região Variável de Imunoglobulina/genética , Linfoma Difuso de Grandes Células B/complicações , Masculino , Pessoa de Meia-Idade , Fator 88 de Diferenciação Mieloide/genética , Macroglobulinemia de Waldenstrom/complicaçõesRESUMO
Immune dysfunction attributed to hypogammaglobulinaemia is common in chronic lymphocytic leukaemia (CLL) and infection is a major contributor to morbidity and mortality. A higher incidence of multiple immunoglobulin and immunoglobulin G (IgG) subclass deficiency was associated with more advanced disease (P < 0·001 and P < 0·001, respectively) in a cohort of 147 CLL patients. Multiple immunoglobulin and IgG subclass deficiency were significantly associated with shorter treatment-free survival (TFS) (P < 0·001 and P = 0·006, respectively). The association between disease stage and immune dysfunction demonstrated by these data suggest aspects of immune deficiency correlate with disease severity and may be associated with shorter TFS in CLL.
Assuntos
Deficiência de IgG , Imunidade Humoral , Leucemia Linfocítica Crônica de Células B , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Deficiência de IgG/sangue , Deficiência de IgG/imunologia , Deficiência de IgG/mortalidade , Deficiência de IgG/terapia , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/terapia , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
Hypogammaglobulinemia is a common complication of chronic lymphocytic leukemia (CLL), but the significance of immunoglobulin G (IgG) subclass deficiency is unknown. We analyzed the prevalence of immunoglobulins G, A and M, IgG subclass deficiency and infection in 150 patients with CLL. Low IgG, IgA and IgM levels were observed in 27.3%, 30.7% and 56.7% of patients, respectively. IgG subclass deficiency was frequent, with reduced IgG1, IgG2, IgG3 and IgG4 in 28%, 19.3%, 52% and 22.7% of patients, respectively. IgG subclass deficiency (total 64.6%) and hypogammaglobulinemia (27.3%) were more prevalent than clinically significant infection (16%). Recurrent or significant infections were seen in 24 patients (16%), of whom 50% had hypogammaglobulinemia but 100% had at least one IgG subclass deficiency, indicating that half the patients with infection had IgG subclass deficiency but normal total IgG level. Deficiencies of IgG3 and IgG4 were statistically associated with infection risk. Normal immunoglobulin and IgG subclass levels were seen in 26 patients (17%) and none had infections. IgG subclass deficiency is commonly observed in patients with CLL with both normal and reduced total IgG levels, and is associated with infection. Screening patients with CLL for IgG subclass deficiency may be a useful adjunct in stratifying their infection risk.