RESUMO
RATIONALE: The gene deletion (5)(q22q35) is reported in 10-20% of myelodysplastic syndrome (MDS) cases and is associated with response to lenalidomide and favorable prognosis. The authors report here a clinical case of MDS transformation to B-cell acute lymphocytic leukemia (B-ALL) with an associated accrual of an additional mutation following treatment with lenalidomide. PATIENT CONCERNS: A 69-year-old man presented with progressive anemia, normal white blood cell count, and thrombocytopenia consistent with MDS. He was administered lenalidomide for 27 months, then developed acute B-cell lymphocytic leukemia and acquired a previously unreported mutation in the gene enhancer of zeste homolog 2 (EZH2). DIAGNOSES: After 27 months of therapy with lenalidomide, a surveillance bone marrow aspiration (BMA) revealed 90% cellularity with persistent multilineage dysplasia and a population of blasts comprising 54% of all bone marrow elements by morphology, consistent with B-ALL, even though the patient was asymptomatic. Conventional karyotype showed no signs of del(5)(q22q35) MDS, however bone marrow next-generation sequencing (NGS) demonstrated the accrual of a nonsense mutation (c.211del pL71*) in exon 3 of EZH2. A confirmatory BMA yielded 70% blasts and clinical features indicative of B-ALL. INTERVENTIONS: Mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5âg/mâ×â4 doses) was administered for 21 days. OUTCOMES: A follow-up BMA was performed 2 months after mini-hyper-CVD therapy, showing dysplastic features with 25% ring sideroblasts, but no evidence of B-ALL. The patient is currently receiving monthly-low dose decitabine, ofatumumab, and dexamethasone, and is transfusion independent and asymptomatic after 7 cycles. LESSONS: The present study shows an extremely rare progression of del(5)(q22q35) MDS to B-ALL with accompanying NGS data and a newly described acquisition of an EZH2 frameshift mutation. This case highlights the importance of NGS as a diagnostic and surveillance tool for MDS.
Assuntos
Linfócitos B/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Síndromes Mielodisplásicas/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Idoso , Anemia/complicações , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Medula Óssea/patologia , Deleção Cromossômica , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Progressão da Doença , Humanos , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Masculino , Mutação , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Trombocitopenia/complicações , Resultado do TratamentoRESUMO
BACKGROUND: Minimally invasive techniques for surfactant administration for infants with respiratory distress syndrome (RDS) of moderate severity have been proposed. The laryngeal mask airway (LMA) helps in securing the airway without the need of laryngoscopy, but still requires the use of positive pressure ventilation (PPV) to flush surfactant into the lungs. OBJECTIVE: This article compares the effectiveness of two techniques for LMA surfactant administration, instillation into the LMA lumen followed by PPV versus direct laryngeal instillation through a preinserted feeding tube inside the LMA during spontaneous respirations. STUDY DESIGN: This is a randomized controlled trial (RCT) of 18 rabbits with acquired respiratory distress after lung lavage. After surfactant was given, the rabbits remained on continuous positive airway pressure (CPAP). Gas exchange parameters were assessed at baseline and at 30 minutes and lung parenchyma pathology features were analyzed. RESULTS: Time required for surfactant administration, oxygenation improvement, and histopathologic findings did not differ between groups. The new technique decreased the need of PPV (p < 0.05). CONCLUSION: In this animal model, surfactant administration through a preinserted feeding tube within the LMA lumen is safe and effective while providing the benefits of a minimally invasive approach. This technique reduces the need of PPV and may prevent its potential risks.
Assuntos
Máscaras Laríngeas , Surfactantes Pulmonares , Síndrome do Desconforto Respiratório , Tensoativos , Animais , Feminino , Masculino , Coelhos , Pressão Positiva Contínua nas Vias Aéreas , Ventilação com Pressão Positiva Intermitente , Intubação Intratraqueal , Surfactantes Pulmonares/administração & dosagem , Distribuição Aleatória , Síndrome do Desconforto Respiratório/terapia , Tensoativos/administração & dosagemRESUMO
We report a 73-year-old female patient with Castleman's disease coexistent with large B cell type non-Hodgkin's lymphoma in a right axillary lymphadenopathy. An excisional biopsy was performed: microscopically, the lymph node revealed the presence of numerous plasma cells and small lymphoid cells characteristic of Castleman's disease. An analysis of another portion of the specimen revealed lymphoid cells with large abnormal nuclei gathered locally that were CDD 79+, CD 38+ and MUM-1+ as well as positive for Kaposi sarcoma-associated herpesvirus and negative for Epstein Barr virus encoded RNA-1 (EBER).
Assuntos
Hiperplasia do Linfonodo Gigante/complicações , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/complicações , Idoso , Hiperplasia do Linfonodo Gigante/patologia , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologiaRESUMO
Blastic plasmacytoid dendritic cell neoplasm is a rare hematological malignancy derived from immature plasmacytoid dendritic cells. The tumor cells have an immature blastic appearance, and diagnosis is based on the expression of CD4, CD56 y CD123 in the absence of other lymphoid, natural killer, or myeloid antigens. The majority of affected individuals are older people with a mean age of 66 years. Male to female ratio is approximately 3:1. Common presentation includes cutaneous lesions followed by tumor dissemination. Treatment with conventional chemotherapy is ineffective and allogeneic hematopoietic stem cell transplantation is required to achieve remission. We report three male patients, aged 23, 27 and 51 years with the disease. All had multiple, infiltrated pink plaques and nodules on the skin of their face, neck and thorax, measuring 1 to 12 cm in diameter. All tumors were histologically characterized by a monotonous proliferation of medium size cells with blastic features. Tumor cells were positive for CD123, CD56, CD4 and CD7 in all cases. After a mean of follow-up of 14.6 months, one patient died of the disease, one patient is alive and the disease relapsed after 17 months of remission and one patient is alive with no evidence of the disease.
Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Células Dendríticas/patologia , Neoplasias Hematológicas/patologia , Pele/patologia , Biópsia , Medula Óssea/patologia , Imuno-Histoquímica , Evolução FatalRESUMO
The hypomethylating agents azacytidine and decitabine are unaffordable for many patients with MDS. The combination of the DNA methyltransferase inhibitor hydralazine and the histone deacetylase inhibitor valproate has shown preliminary efficacy in MDS. The aim of this study is to evaluate the clinical efficacy and safety of hydralazine/valproate in a case series of MDS patients treated in a compassionate manner. Hydralazine was dosed according to the acetylation genotype of patients (slow acetylators 83 mg daily; fast acetylators 182 mg daily), and valproate was dosed at 30 mg/kg/day. Both drugs were given daily until disease progression. Response and toxicity were evaluated with the International Working Group criteria and CTCAE, version 4, respectively. Survival parameters were estimated with the Kaplan-Meier method. From 2009 to 2012, 14 patients were treated. The median age ± SD was 55.2 ± 19.52 (range 23-87) years. According to the IPSS, cases were graded as intermediate-1 (n = 8/14; 57.2%) or intermediate-2 (n = 6/14; 42.8%). Responses were as follows: five (35.7%) complete response, one (7.1%) partial response, and two (14.28%) became transfusion independent. The mean duration of response ± SD was 60 ± 35.28 months (range 5-94). Three patients progressed to AML. At a median follow-up of 57 months (range 1-106), the median OS was 27 months. At that point, five patients remained on the treatment, one with partial response and four with complete response. The median OS was not reached in the eight patients who saw a clinical benefit from the treatment, in comparison to an OS of 7 months in the six patients who had no treatment. The combination of hydralazine and valproate is safe and effective in MDS, and its further testing is highly desirable.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ensaios de Uso Compassivo/métodos , Epigênese Genética/efeitos dos fármacos , Hidralazina/administração & dosagem , Síndromes Mielodisplásicas/tratamento farmacológico , Ácido Valproico/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios de Uso Compassivo/mortalidade , Epigênese Genética/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Adulto JovemRESUMO
We report a 73-year-old female patient with Castleman's disease coexistent with large B cell type non-Hodgkin's lymphoma in a right axillary lymphadenopathy. An excisional biopsy was performed: microscopically, the lymph node revealed the presence of numerous plasma cells and small lymphoid cells characteristic of Castleman's disease. An analysis of another portion of the specimen revealed lymphoid cells with large abnormal nuclei gathered locally that were CDD 79+, CD 38+ and MUM-1+ as well as positive for Kaposi sarcoma-associated herpesvirus and negative for Epstein Barr virus encoded RNA-1 (EBER).
Assuntos
Humanos , Feminino , Idoso , Linfoma Difuso de Grandes Células B/complicações , Hiperplasia do Linfonodo Gigante/complicações , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/patologia , Hiperplasia do Linfonodo Gigante/patologiaRESUMO
Blastic plasmacytoid dendritic cell neoplasm is a rare hematological malignancy derived from immature plasmacytoid dendritic cells. The tumor cells have an immature blastic appearance, and diagnosis is based on the expression of CD4, CD56 y CD123 in the absence of other lymphoid, natural killer, or myeloid antigens. The majority of affected individuals are older people with a mean age of 66 years. Male to female ratio is approximately 3:1. Common presentation includes cutaneous lesions followed by tumor dissemination. Treatment with conventional chemotherapy is ineffective and allogeneic hematopoietic stem cell transplantation is required to achieve remission. We report three male patients, aged 23, 27 and 51 years with the disease. All had multiple, infiltrated pink plaques and nodules on the skin of their face, neck and thorax, measuring 1 to 12 cm in diameter. All tumors were histologically characterized by a monotonous proliferation of medium size cells with blastic features. Tumor cells were positive for CD123, CD56, CD4 and CD7 in all cases. After a mean of follow-up of 14.6 months, one patient died of the disease, one patient is alive and the disease relapsed after 17 months of remission and one patient is alive with no evidence of the disease.