RESUMO
Haemophagocytic lymphohistiocytosis (HLH) is a rare, aggressive, excess immune activation syndrome. Diagnosis can be challenging due to its several clinical mimics including sepsis. There are multiple aetiologies of HLH; in adults, it is most commonly triggered by infection, malignancy, drugs and autoimmune processes. Failure to rapidly diagnose and treat this condition can be fatal. The management of HLH includes identifying and removing the trigger, supportive management and immunosuppression. Identifying the trigger is essential to inform the most appropriate type of immunosuppression. Here, we report a case of likely drug-induced HLH in a patient recently treated for hairy cell leukaemia. The culprit drug was thought to be co-trimoxazole and this case report highlights a very rare complication of this commonly used drug. We discuss our management approach with steroid monotherapy and withdrawal of co-trimoxazole.
Assuntos
Leucemia de Células Pilosas , Linfo-Histiocitose Hemofagocítica , Neoplasias , Sepse , Humanos , Leucemia de Células Pilosas/complicações , Leucemia de Células Pilosas/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/induzido quimicamente , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Neoplasias/complicações , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Masculino , Pessoa de Meia-IdadeRESUMO
The use of the CD38 monoclonal antibody daratumumab in combination with standard myeloma chemotherapy regimens has been studied extensively in recent years. We undertook an updated meta-analysis of phase III randomized controlled trials (RCT) to determine the efficacy of daratumumab combination regimens. The relative risk for progression was significantly lower in daratumumab-treated cohorts (HR 0.46, 95% CI 0.38-0.55) and this was consistent across newly diagnosed and relapsed cases. No statistically significant improvement was identified in newly diagnosed patients with high-risk cytogenetics and this group remains a therapeutic challenge.
RESUMO
The heritability of classical Hodgkin lymphoma (cHL) has yet to be fully deciphered. We report a family with five members diagnosed with nodular sclerosis cHL. Genetic analysis of the family provided evidence of linkage at chromosomes 2q35-37, 3p14-22 and 21q22, with logarithm of odds score >2. We excluded the possibility of common genetic variation influencing cHL risk at regions of linkage, by analysing GWAS data from 2,201 cHL cases and 12,460 controls. Whole exome sequencing of affected family members identified the shared missense mutations p.(Arg76Gln) in FAM107A and p.(Thr220Ala) in SLC26A6 at 3p21 as being predicted to impact on protein function. FAM107A expression was shown to be low or absent in lymphoblastoid cell lines and SLC26A6 expression lower in lymphoblastoid cell lines derived from p.(Thr220Ala) mutation carriers. Expression of FAM107A and SLC26A6 was low or absent in Hodgkin Reed-Sternberg (HRS) cell lines and in HRS cells in Hodgkin lymphoma tissue. No sequence variants were detected in KLHDC8B, a gene previously suggested as a cause of familial cHL linked to 3p21. Our findings provide evidence for candidate gene susceptibility to familial cHL.
RESUMO
The addition of plerixafor to G-CSF decreases the risk of failed stem cell collection, but at considerable extra cost. Using a logistic regression model based on 354 autologous mobilizations, we have identified a local minimum peripheral blood CD34 count at which the probability of a successful collection is 50%. This seems an appropriate CD34 count at which to add immediate salvage plerixafor.
Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/uso terapêutico , Linfoma/terapia , Mieloma Múltiplo/terapia , Transplante de Células-Tronco/métodos , Transplante Autólogo/métodos , Antígenos CD34/metabolismo , Benzilaminas , Remoção de Componentes Sanguíneos , Peso Corporal , Análise Custo-Benefício , Ciclamos , Fator Estimulador de Colônias de Granulócitos/economia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/economia , Compostos Heterocíclicos/economia , Humanos , Leucemia Mieloide Aguda/terapia , Linfoma não Hodgkin/terapia , Análise de Regressão , Estudos Retrospectivos , Transplante de Células-Tronco/economia , Transplante Autólogo/economia , Resultado do TratamentoRESUMO
The 3q21q26 inversion is associated with both myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), often in association with monosomy 7. In this report, we present a young woman and her mother, both diagnosed with AML, exhibiting similar morphological and identical cytogenetic features. AML with abnormalities of chromosome 3q is often characterized by abnormal megakaryopoeisis and diabetes insipidus, and both were seen in these cases. To our knowledge, this is the first report of familial aggregation of AML displaying an inversion of chromosome 3q and monosomy 7. We discuss possible mechanisms for the development of familial AML with identical karyotypic abnormalities and the link between 3q aberrations and monosomy 7.