Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.094
Filtrar
1.
Ann Hematol ; 99(1): 65-72, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31832751

RESUMO

The management of patients with myelofibrosis (MF) has dramatically changed since the introduction of ruxolitinib as a tailored treatment strategy. However, the perceptions about the use of this drug in clinical practice remain, at times, a matter of discussion. We conducted a survey about the diagnostic evaluation, prognostic assessment, and management of ruxolitinib in real-life clinical practice in 18 Italian hematology centers. At diagnosis, most hematologists do not use genetically or molecularly inspired score systems to assess prognosis, mainly due to scarce availability of next-generation sequencing (NGS) methodology, with NGS conversely reserved only for a subset of lower-risk MF patients with the aim of possibly improving the treatment strategy. Some common points in the management of ruxolitinib were 1) clinical triggers for ruxolitinib therapy, regardless of risk category; 2) evaluation of infectious risk before the starting of the drug; and 3) schedule of monitoring during the first 12 weeks with the need, in some instances, of supportive treatment. Further development of international recommendations and insights will allow the achievement of common criteria for the management of ruxolitinib in MF, before and after treatment, and for the definition of response and failure.


Assuntos
Tomada de Decisão Clínica , Mielofibrose Primária/tratamento farmacológico , Pirazóis/administração & dosagem , Feminino , Humanos , Masculino , Mielofibrose Primária/diagnóstico , Prognóstico
2.
Medicine (Baltimore) ; 98(50): e18266, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852097

RESUMO

INTRODUCTION: Common symptoms of hereditary spherocytosis (HS) include intermittent jaundice and splenomegaly. Here, we present an unusual clinical course wherein a patient with HS treated with splenectomy developed secondary myelofibrosis and acute monocytic leukemia (M5). PATIENT CONCERNS: After presenting with paleness, fatigue and jaundice, the patient was diagnosed with HS. After splenectomy, follow-up testing, including bone marrow biopsy, revealed myelofibrosis. Subsequently, the patient exhibited blood cell abnormalities consistent with M5. DIAGNOSIS: M5 comorbid with myelofibrosis and a history of HS. INTERVENTIONS: HS was treated with splenectomy. Myelofibrosis was treated with hydroxyurea. The patient refused chemotherapy for M5 and was discharged. He was maintained on hydroxyurea and received periodic blood product transfusions with regular routine blood test monitoring. OUTCOMES: Because of intracranial hemorrhage, the patient died on May 17, 2018, a little >10 months after being diagnosed with leukemia. CONCLUSION: The present patient developed M5 while undergoing treatment for myelofibrosis and after undergoing splenectomy for HS, raising the question of whether these conditions might be associated. Examination of this question will require the analysis of additional cases.


Assuntos
Leucemia Monocítica Aguda/complicações , Mielofibrose Primária/etiologia , Esferocitose Hereditária/complicações , Esplenectomia/efeitos adversos , Biópsia , Seguimentos , Humanos , Hidroxiureia/uso terapêutico , Leucemia Monocítica Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/tratamento farmacológico , Esferocitose Hereditária/diagnóstico , Esferocitose Hereditária/cirurgia , Fatores de Tempo , Resultado do Tratamento
3.
Hematol Oncol ; 37(4): 424-433, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31359447

RESUMO

Currently available prognostic scoring systems in primary myelofibrosis (PMF) do not integrate clinical, histological, and molecular data, or they also required information on "other" mutations that are available in the clinical practice only in a very limited number of laboratories. In the present multicenter study, including 401 PMF patients, an integrated International Prognostic Scoring System (I-IPSS) was developed by combining IPSS, grade of bone marrow fibrosis (GBMF), and driver mutations molecular status (MS) to define PMF prognosis at diagnosis. Four prognostic categories were identified: I-IPSS-low risk (113 patients), I-IPSS-intermediate-1 risk (56 patients), I-IPSS-intermediate-2 risk (154 patients), and I-IPSS-high risk (78 patients). Median overall survival was 26.7 years in I-IPSS-intermediate-1, 10.8 in I-IPSS-intermediate-2, and 6.4 in I-IPSS-high-risk patients (log-rank test <0.0001); instead, it was not reached in the I-IPSS-low-risk cohort because of the extremely low number of registered deaths. The addition of GBMF and MS to IPSS improved the efficacy for predicting the risk of death. Indeed, the sensitivity of I-IPSS was significantly higher (P < .05) than that of IPSS, considering both total deaths and 5- and 10-year mortality. This comprehensive approach allows clinicians to evaluate mutual interactions between IPSS, GBMF, and MS and identify high-risk patients with poor prognosis who may benefit from aggressive treatments. More importantly, this integrated score can be easily applicable worldwide as it only required information that represent the good clinical practice in the management of PMF patients.


Assuntos
Mielofibrose Primária/diagnóstico , Índice de Gravidade de Doença , Adulto , Idoso , Biomarcadores , Medula Óssea/patologia , Calreticulina/genética , Feminino , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/genética , Mielofibrose Primária/genética , Mielofibrose Primária/mortalidade , Mielofibrose Primária/patologia , Prognóstico , Receptores de Trombopoetina/genética , Reticulina/ultraestrutura , Estudos Retrospectivos , Fatores de Risco
4.
BMJ Case Rep ; 12(6)2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31164383

RESUMO

Primary idiopathic myelofibrosis is a clonal disorder arising from the neoplastic transformation of early haematopoietic stem cells leading to abnormal fibrous tissue within bone marrow. We present a 51-year-old man complaining of sudden loss of vision in the right eye along with multiple superficial retinal haemorrhages and perivascular infiltration. Fundus fluorescein angiography and optical coherence tomography confirmed the diagnosis of inflammatory central retinal vein occlusion with macular oedema which mimicked frosted branch angiitis. Laboratory tests and bone marrow biopsy confirmed underlying systemic disease to be Janus kinase 2 mutation positive primary idiopathic myelofibrosis. He received one intravitreal injection of antivascular endothelial growth factor along with dexamethasone for his ocular condition. In view of his systemic disease, he was started on systemic chemotherapy and oral corticosteroid which helped in stabilising the eye condition.


Assuntos
Edema Macular/diagnóstico , Mielofibrose Primária/diagnóstico , Oclusão da Veia Retiniana/diagnóstico , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Diagnóstico Diferencial , Quimioterapia Combinada , Angiofluoresceinografia , Humanos , Edema Macular/complicações , Edema Macular/diagnóstico por imagem , Edema Macular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/complicações , Mielofibrose Primária/diagnóstico por imagem , Mielofibrose Primária/tratamento farmacológico , Oclusão da Veia Retiniana/complicações , Oclusão da Veia Retiniana/diagnóstico por imagem , Oclusão da Veia Retiniana/tratamento farmacológico , Tomografia de Coerência Óptica , Vasculite/diagnóstico , Baixa Visão/etiologia
5.
Clin Adv Hematol Oncol ; 17(5): 299-307, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31188809

RESUMO

Myelofibrosis (MF) is the most aggressive of the classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). In some patients with essential thrombocytopenia or polycythemia vera, which are relatively benign MPNs, MF develops as a natural evolution of their disease, resulting in post-essential thrombocythemia myelofibrosis (PET-MF) or post-polycythemia vera myelofibrosis (PPV-MF). Presenting with the same clinical features, including debilitating symptoms and signs of bone marrow failure, PET/PPV-MF has traditionally been considered akin to primary myelofibrosis (PMF). However, recent observations that PET/PPV-MF may be a distinct clinical entity from PMF have triggered efforts to improve prognostication in these diseases. Novel predictive models that incorporate rapidly emerging clinical and molecular data are being developed to improve outcomes in patients with PMF or PET/PPV-MF. This review focuses on the major clinical features and prognostic classification systems used in PMF and PET/PPV-MF.


Assuntos
Policitemia Vera/complicações , Mielofibrose Primária/mortalidade , Trombocitemia Essencial/complicações , Cariótipo Anormal , Fatores Etários , Idoso , Tomada de Decisão Clínica , Progressão da Doença , Humanos , Modelos Biológicos , Mutação , Policitemia Vera/genética , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/etiologia , Mielofibrose Primária/genética , Prognóstico , Risco , Trombocitemia Essencial/genética
6.
Medicine (Baltimore) ; 98(25): e15882, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31232923

RESUMO

RATIONALE: Primary immune thrombocytopenia (ITP) is an immune-mediated disease that is defined as increased platelet destruction and impaired platelet production. Treatment is recommended for highly selected patients, the standard regimen includes glucocorticoid, intravenous immunoglobulin (IVIG). The recombinant thrombopoietin (TPO) receptor agonists, romiplostim, stimulate platelet production and have approved for glucocorticoid or IVIG, splenectomy-refractory chronic ITP patients. PATIENT CONCERNS: A patient has been diagnosed with ITP, reftractory to steroid, IVIG, splenectomy, danazol, and cyclosporine. The patient received romiplostim to normalize his platelet count, however, over the course of the following year, his platelet counts progressively decreased despite increasing the romiplostim dosing. DIAGNOSES: A peripheral blood smear showed a severe leukoerythroblastic reaction and bone marrow biopsy demonstrated myelofibrosis due to romiplostim. OUTCOMES: Since this diagnosis, romiplostim was discontinued for a while, after 3 months, romiplostim was re-administered to improve thrombocytopenia. His platelet count recovered to 70,000/mm after the administration of romiplostim at 2 µg/kg, and he did not experience complications for 6 months. LESSONS: This report represents the first evidence of romiplostim-induced myelofibrosis, which was associated with increased levels of bone marrow reticulin and Masson trichrome staining.


Assuntos
Mielofibrose Primária/diagnóstico , Receptores de Trombopoetina , Proteínas Recombinantes de Fusão/efeitos adversos , Trombocitopenia/tratamento farmacológico , Trombopoetina/efeitos adversos , Medula Óssea , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/induzido quimicamente , Receptores Fc
7.
Ann Biol Clin (Paris) ; 77(3): 327-330, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31219422

RESUMO

Hematologic involvement is a common manifestation during systemic lupus erythematosus (SLE). Pancytopenia represents an infrequent mode of revelation, most often of peripheral origin, exceptionally secondary to a bone marrow disorder and particularly to an autoimmune myelofibrosis (AIMF). This entity, distinct from a primary myelofibrosis (MFP), is characterized by reticulin fibrosis of the bone marrow lack of atypical bone marrow cells, the presence of auto-antibodies and absence of classical signs of myeloproliferation. Generally the AIMF associated to the SLE had a favorable evolution and appears to often respond to corticosteroids and/or immunosuppressive treatments. This case illustrates the original association of an SLE revealed by a pancytopenic MFAI in a male patient with a dramatic improvement under corticosteroids.


Assuntos
Doenças Autoimunes/complicações , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Pancitopenia/etiologia , Mielofibrose Primária/complicações , Adulto , Doenças Autoimunes/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Pancitopenia/diagnóstico , Mielofibrose Primária/diagnóstico
8.
Hematol Oncol ; 37(3): 291-295, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31050810

RESUMO

There have been some reports on a possible role of azacytidine (AZA) in the treatment of accelerated/blastic phase evolved from Philadelphia-negative myeloproliferative neoplasms (MPN-AP/BP), but results are conflicting. In this study, we analyzed a cohort of 39 patients with MPN-AP/BP treated frontline with AZA at the standard dosage (75 mg/m2 ). Median time from diagnosis to AP/BP evolution was 92.3 months (IR 29.9-180.1). All patients were evaluable for hematologic response: two patients (5.2%) died early after AZA initiation, 13 patients (33.3%) had a progressive or stable disease, nine (23.1%) had a hematologic improvement (HI), seven (17.9%) achieved a partial response (PR), and eight (20.5%) a complete response (CR). Overall, 24 patients achieved a clinical hematologic response (HI + PR + CR), with an overall response rate of 61.5%. Median overall survival (OS) from AZA start of the whole cohort was 13.5 months (95% CI, 8.2-18.7). There was no difference in median OS among patients with HI, PR, or CR (P = .908). These three subgroups as "responders" having been considered, a significantly better OS was observed in responder compared with nonresponder patients, with a median OS of 17.6 months (95% CI, 10.1-25.0) versus 4.1 months (95% CI, 0.4-10.0) (P = .001) Only female gender was significant for both achievement of response (.010) and OS duration (P = .002). In conclusion, AZA is useful for the management of MPN-AP/BP, with an overall response rate (HI + PR + CR) of 61.5% and a longer OS in responders.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Crise Blástica/tratamento farmacológico , Transtornos Mieloproliferativos/tratamento farmacológico , Idoso , Crise Blástica/diagnóstico , Feminino , Humanos , Hidroxiureia/uso terapêutico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/diagnóstico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/tratamento farmacológico , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mutação , Transtornos Mieloproliferativos/diagnóstico , Pipobromano/uso terapêutico , Policitemia Vera/diagnóstico , Policitemia Vera/tratamento farmacológico , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/tratamento farmacológico , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/tratamento farmacológico , Resultado do Tratamento
9.
BMC Res Notes ; 12(1): 286, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31126326

RESUMO

OBJECTIVE: The incidence of the combined myeloproliferative neoplasms (MPNs) was determined for a major Canadian city. Retrospective cases of MPN diagnoses (essential thrombocythemia, polycythemia vera, and primary myelofibrosis) between 2011 to 2015 were retrieved from the Southern Alberta Cancer Cytogenetics Laboratory's database at Alberta Public Laboratories. RESULTS: An incidence rate of 2.05 cases per 100,000 person-years (95% CI 1.73-2.41) was determined, giving an age-standardized Canadian incidence of 2.71 cases per 100,000 person years (95% CI 2.63-2.78). MPN diagnoses occurred at a wide age range of 8-93 (median 66) and an age-dependent increase in incidence. Incidence rates for the MPNs are first reported here for a Canadian population.


Assuntos
Policitemia Vera/epidemiologia , Mielofibrose Primária/epidemiologia , Trombocitemia Essencial/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alberta/epidemiologia , Criança , Citogenética , Bases de Dados Factuais , Feminino , Humanos , Incidência , Laboratórios , Masculino , Pessoa de Meia-Idade , Policitemia Vera/diagnóstico , Policitemia Vera/genética , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/genética , Estudos Retrospectivos , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética
10.
Hematol Oncol ; 37(4): 418-423, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30985017

RESUMO

The 2016 WHO criteria identified early primary myelofibrosis (PMF) as an individual entity with milder clinical features and better outcome compared with overt PMF. Here, we compared early and overt PMF patients treated with ruxolitinib in terms of baseline clinical/laboratory characteristics, response, and toxicity to treatment. We observed that early-PMF patients achieve better and more stable spleen and symptoms responses, with significantly lower rates of hematological toxicities. No differences in overall and leukemia-free survival were detected between the two cohorts. The application of 2016 WHO criteria is crucial to identify those PMF patients who deserve a stricter monitoring during treatment.


Assuntos
Antineoplásicos/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas de Laboratório Clínico/normas , Diagnóstico Diferencial , Diagnóstico Precoce , Feminino , Humanos , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Tamanho do Órgão , Mielofibrose Primária/diagnóstico , Estudos Retrospectivos , Baço/patologia , Trombocitemia Essencial/diagnóstico , Resultado do Tratamento , Organização Mundial da Saúde
11.
Eur J Haematol ; 102(6): 516-520, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30977935

RESUMO

OBJECTIVE: Prefibrotic/early primary myelofibrosis (pre-PMF) and essential thrombocythemia (ET) exhibited different features of bone marrow; however, this is not always easy to judge objectively, making pathologists' distinction often suboptimal. In the WHO 2008 criteria, pre-PMF was not defined as a subgroup of PMF; therefore, affected patients were at a higher risk of misdiagnosis with ET. In this study, we examined the prevalence of pre-PMF patients among those previously diagnosed with ET in Japan. METHOD: We reviewed bone marrow specimens and clinical and molecular parameters of patients who were previously diagnosed with ET by the WHO 2008 criteria. RESULTS: Among 107 ET patients, 13 patients were redefined as having pre-PMF. Pre-PMF patients exhibited a higher frequency of MPL mutation and increased platelet counts compared to true ET patients. Molecular analysis revealed the frequencies of high-risk molecular mutations, such as ASXL1, EZH2, and SRSF2, were significantly increased in pre-PMF patients than those in true ET patients. CONCLUSION: These results demonstrated the value of reexamining clinical records for patients diagnosed with ET by the WHO 2008 criteria and emphasized that adequate examinations of patients' bone marrow are crucial for an accurate diagnosis of pre-PMF and ET.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Fenótipo , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/genética , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/genética , Adolescente , Adulto , Idoso , Biomarcadores , Biópsia , Medula Óssea/patologia , Diagnóstico Diferencial , Feminino , Humanos , Janus Quinase 2/genética , Japão , Masculino , Pessoa de Meia-Idade , Mutação , Adulto Jovem
12.
Medicine (Baltimore) ; 98(12): e14594, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30896614

RESUMO

RATIONALE: Pulmonary hypertension (PH) is a complicated disease which has complex causes and poor outcome. Many factors are involved in the increase of pulmonary artery pressure. It is often difficult to identify the specific cause of a particular patient. However, identifying the etiology is of great importance for specifying treatment strategies and improving the prognosis of patients. PATIENT CONCERNS: A 58-year-old male was admitted because of fatigue, breath shortness for 6 months, which got worse in the last 3 months. The ultrasound cardiogram (UCG) indicated a remarkably elevated pulmonary artery systolic pressure (PASP = 82 mm Hg). He had hypertension for 15 years. Besides, his spleen was found to be enlarged since 15 years ago. Bone marrow biopsy of the patient revealed myeloproliferative neoplasm (MPN) with severe myelofibrosis (MF). DIAGNOSIS: Myeloproliferative neoplasm (MPN) with severe myelofibrosis (MF) which in turn caused PH and portal vein hypertension (PVH). INTERVENTIONS: We treated the patient with diuretics and fosinopril, and also steroids and thalidomide for his MPN/MF. OUTCOMES: Two weeks later, the pulmonary artery pressure (PAP) was remarkably decreased (PASP = 53.1 mm Hg by UCG, mean PAP = 21 mm Hg by right cardiac catheterization). Within 2 years' follow-up, his circulatory state and hematological state remained stable. LESSONS: It is often difficult to define the cause of PH, but it is important for making the appropriate treatment at the same time.


Assuntos
Hipertensão Portal/etiologia , Hipertensão Pulmonar/etiologia , Transtornos Mieloproliferativos/complicações , Mielofibrose Primária/complicações , Esplenomegalia/etiologia , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/genética
13.
Blood ; 133(20): 2233-2242, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-30760453

RESUMO

Allogeneic hematopoietic stem cell transplantation is curative in myelofibrosis, and current prognostic scoring systems aim to select patients for transplantation. Here, we aimed to develop a prognostic score to determine prognosis after transplantation itself, using clinical, molecular, and transplant-specific information from a total of 361 patients with myelofibrosis. Of these, 205 patients were used as a training cohort to create a clinical-molecular myelofibrosis transplant scoring system (MTSS), which was then externally validated in a cohort of 156 patients. Multivariable analysis on survival identified age at least 57 years, Karnofsky performance status lower than 90%, platelet count lower than 150 × 109/L, leukocyte count higher than 25 × 109/L before transplantation, HLA-mismatched unrelated donor, ASXL1 mutation, and non-CALR/MPL driver mutation genotype being independent predictors of outcome. The uncorrected concordance index for the final survival model was 0.723, and bias-corrected indices were similar. Risk factors were incorporated into a 4-level MTSS: low (score, 0-2), intermediate (score, 3-4), high (score, 5), and very high (score, >5). The 5-year survival according to risk groups in the validation cohort was 83% (95% confidence interval [CI], 71%-95%), 64% (95% CI, 53%-75%), 37% (95% CI, 17%-57%), and 22% (95% CI, 4%-39%), respectively (P < .001). Increasing score was predictive of nonrelapse mortality (P < .001) and remained applicable to primary (0.718) and post-essential thrombocythemia (ET)/polycythemia vera (PV) myelofibrosis (0.701) improving prognostic ability in comparison with all currently available disease-specific systems. In conclusion, this MTSS predicts outcome of patients with primary and post-ET/PV myelofibrosis undergoing allogeneic stem cell transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária/terapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/diagnóstico , Prognóstico , Fatores de Risco , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
14.
Am J Case Rep ; 20: 146-150, 2019 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-30712053

RESUMO

BACKGROUND Tumor lysis syndrome (TLS) is an oncologic emergency resulting from the massive destruction of tumor cells after cytotoxic chemotherapy for chemosensitive malignancies with a high tumor burden. Its clinical manifestations include severe electrolyte disturbances, metabolic acidosis, acute renal failure secondary to urate deposition in the kidney, heart, and skeletal muscle, and nervous system dysfunction. We report an extremely rare case of spontaneous TLS (STLS) in idiopathic primary myelofibrosis (PMF). CASE REPORT A 51-year-old Korean man was admitted to our hospital with general weakness and left-side abdominal pain. The patient was diagnosed with acute urate nephropathy with hyperphosphatemia, hyperkalemia, hypocalcemia, and metabolic acidosis. Splenomegaly was accompanied by leukocytosis and a peripheral blood smear revealed immature granulocytes without blast cells. Bone marrow biopsy showed PMF. Initially, we presumed it was a spontaneous tumor lysis syndrome of PMF. We immediately performed emergency hemodialysis. We concluded that the patient, who had chronic hyperuricemia due to undiagnosed PMF, was recently admitted to the emergency room with STLS due to overwork and dehydration. CONCLUSIONS We present an extremely rare case of STLS in idiopathic PMF. The mechanism of chronic hyperuricemia in our case might be rapid cell turnover due to ineffective erythropoiesis of PMF.


Assuntos
Mielofibrose Primária/diagnóstico , Síndrome de Lise Tumoral/diagnóstico , Humanos , Hiperuricemia/complicações , Masculino , Pessoa de Meia-Idade
15.
Blood Adv ; 3(1): 83-95, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30622146

RESUMO

Although allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment for myelofibrosis (MF), data are limited on how molecular markers predict transplantation outcomes. We retrospectively evaluated transplantation outcomes of 110 consecutive MF patients who underwent allo-HCT with a fludarabine/melphalan (Flu/Mel) conditioning regimen at our center and assessed the impact of molecular markers on outcomes based on a 72-gene next-generation sequencing panel and Mutation-Enhanced International Prognostic Scoring System 70+ v2.0 (MIPSS70+ v2.0). With a median follow-up of 63.7 months, the 5-year overall survival (OS) rate was 65% and the nonrelapse mortality (NRM) rate was 17%. In mutational analysis, JAK2 V617F and ASXL1 mutations were the most common. By univariable analysis, higher Dynamic International Prognostic Scoring System scores, unrelated donor type, and very-high-risk cytogenetics were significantly associated with lower OS. Only CBL mutations were significantly associated with lower OS (hazard ratio [HR], 2.64; P = .032) and increased NRM (HR, 3.68; P = .004) after allo-HCT, but CALR, ASXL1, and IDH mutations did not have an impact on transplantation outcomes. Patient classification per MIPSS70 showed worse OS for high-risk (HR, 0.49; P = .039) compared with intermediate-risk patients. Classification per MIPSS70+ v2.0 demonstrated better OS when intermediate-risk patients were compared with high-risk patients (HR, 0.291) and much lower OS when very-high-risk patients were compared with high-risk patients (HR, 5.05; P ≤ .001). In summary, we present one of the largest single-center experiences of Flu/Mel-based allo-HCT, demonstrating that revised cytogenetic changes and MIPSS70+ v2.0 score predict transplantation outcomes, and thus can better inform physicians and patients in making decisions about allo-HCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária/mortalidade , Mielofibrose Primária/terapia , Condicionamento Pré-Transplante , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mutação , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/etiologia , Prognóstico , Transplante Homólogo , Resultado do Tratamento , Doadores não Relacionados , Fosfato de Vidarabina/administração & dosagem , Fosfato de Vidarabina/análogos & derivados
16.
Blood Cells Mol Dis ; 75: 35-40, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30612065

RESUMO

Classical Philadelphia-negative myeloproliferative neoplasms include Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). They are characterized by the presence of driver mutations of JAK2, CALR or MPL genes. Overexpression of WT1 is used as a marker of minimal residual disease in acute myeloid leukemia, especially after allogeneic stem cell transplantation (SCT). We investigated WT1 expression at diagnosis in 152 MPN patients and showed that the WT1 transcript was overexpressed in PMFs and PVs compared to controls. In particular, WT1 transcript levels were higher in PMF than in ET and PV. WT1 transcript levels were significantly increased during myelofibrotic transformation of ET or PV. Using multivariate linear regression, high WT1 transcript levels in PMF were associated with age over 65, splenomegaly and thrombocytopenia. The ROC curve analysis showed that a level of WT1 transcript >10 WT1 copies/104ABL1 enabled the diagnosis of PMF with a specificity of 95.8% (PMF vs ET; ROC AUC = 0.91). In myelofibrosis, studying follow-ups of WT1 transcript showed that this marker is of interest after allogeneic SCT. These results demonstrate that WT1 overexpression is a simple marker of myelofibrosis in MPN and could be used during patient follow-up.


Assuntos
Transtornos Mieloproliferativos/diagnóstico , Mielofibrose Primária/diagnóstico , Proteínas WT1/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Policitemia Vera , RNA Mensageiro/sangue , Curva ROC , Trombocitemia Essencial
17.
Int J Rheum Dis ; 22(3): 516-520, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25643819

RESUMO

Chylous polyserositis and autoimmune myelofibrosis occurring concomitantly inn a case of SLE are a rare phenomenon. We here report a case of a 38-year-old woman who was admitted with a history of cough and shortness of breath for 1½ months along with fever and abdominal distension for 1 month. She also had arthralgias, weight loss and pancytopenia. She was diagnosed as a case of SLE with Chylous polyserositis and autoimmune myelofibrosis. She was started on steroids and immunosuppressive therapy, to which she responded. To summarize, this is the first case report where chylous polyserositis and pancytopenia due to autoimmune myelofibrosis occurred which was responsive to steroids and immunosuppressive therapy.


Assuntos
Doenças Autoimunes/imunologia , Ascite Quilosa/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Mielofibrose Primária/imunologia , Adulto , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/tratamento farmacológico , Biópsia , Exame de Medula Óssea , Ascite Quilosa/diagnóstico , Ascite Quilosa/tratamento farmacológico , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/tratamento farmacológico , Indução de Remissão , Serosite/diagnóstico , Serosite/tratamento farmacológico , Serosite/imunologia , Esteroides/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
18.
Am J Hematol ; 94(3): 299-305, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30516848

RESUMO

JAK2 mutations in myeloproliferative neoplasms (MPNs) are associated with the germline GGCC (46/1) haplotype. In 2010, we reported an association between shortened survival in primary myelofibrosis (PMF) and nullizygosity for the JAK2 46/1 haplotype. In the current study, we have increased the number of informative cases from 130 to 414 (median age 63 years; 63% males), in order to revisit with the phenotypic and prognostic relevance of the JAK2 46/1 haplotype in PMF. JAK2 46/1 haplotype was documented in 69% of the study patients, including 25% in homozygous and 44% in heterozygous state. Driver mutation frequency in patients homozygous/heterozygous/nullizygous for the 46/1 haplotype was 78%/60%/56% JAK2, 10%/20%/18% type 1-like CALR, 3%/2%/5% type 2-like CALR, 4%/8%/7% MPL, and 6%/10%/14% triple-negative (P = .02). In univariate analysis, nullizygosity for the JAK2 46/1 haplotype was associated with inferior overall survival (HR 1.5, 95% CI 1.1-1.9), most pronounced in JAK2 (P <.001), as opposed to CALR/MPL mutated (P = .48) or triple-negative cases (P = .27). Multivariable analysis that included karyotype, driver mutational status and high-molecular risk mutations confirmed the independent prognostic contribution of nullizygosity for the 46/1 haplotype (P = .02; HR 1.4, 95% CI 1.1-1.8). Nullizygosity for 46/1 also remained significant in the context of the genetically-inspired GIPSS risk model (P = .04), but not in the context of the integrated genetics-clinical MIPSS70+ version 2.0 model (P = .4). Leukemia-free survival was not affected by the 46/1 haplotype (P = .6). The current study confirms the association of nullizygosity for the JAK2 GGCC (46/1) haplotype with inferior survival in JAK2-mutated PMF.


Assuntos
Calreticulina/genética , Mutação em Linhagem Germinativa , Janus Quinase 2/genética , Modelos Genéticos , Mielofibrose Primária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Estudos de Coortes , Feminino , Expressão Gênica , Haplótipos , Heterozigoto , Homozigoto , Humanos , Cariótipo , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/mortalidade , Mielofibrose Primária/patologia , Prognóstico , Receptores de Trombopoetina/genética , Análise de Sobrevida
19.
Am J Hematol ; 94(3): 286-290, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30516867

RESUMO

In the last decade, several prognostic models for primary myelofibrosis (PMF) have been introduced and shown to be effective in predicting overall survival. The main objective for this study was to identify clinical and genetic markers of very long (20+ years) survival in PMF. A total of 1282 patients with PMF were considered (median age 65 years, range 19-92; 63% males); 26 (2%) patients (median age 51 years, range 28-71; 38% males) survived their disease for at least 20 years (long-lived patients) and 626 (49%) patients (median age 68 years, range 27-92; 66% males) died within 5 years of their diagnosis (short-lived patients). Multivariable logistic regression analysis identified 7 variables that were associated with survival beyond 20 years: age ≤ 70 years (P = .002); female sex (P = .03); hemoglobin level ≥ 10 g/dL for women and ≥ 11 g/dL for men (P = .03), leukocyte count ≤25 × 109 /L (P = .009), platelet count ≥100 × 109 /L (P = .002), circulating blasts <2% (P = .03) and absence of constitutional symptoms (P = .04). Five-year mortality was independently predicted by high-molecular risk mutations (P < .001); unfavorable or very high risk karyotype (P < .001); absence of type 1/like CALR mutation (P < .001); age > 70 years (P < .001); constitutional symptoms (P < .001); hemoglobin level < 10 g/dL for women and < 11 g/dL for men (P < .001); leukocyte count >25 × 109 /L (P = .004); and circulating blasts ≥2% (P = .001). This study suggests that genetic risk factors in PMF are associated with early mortality while survival beyond 20 years could be predicted by easily accessible clinical variables, including age, sex, blood counts, and symptoms.


Assuntos
Calreticulina/genética , Mielofibrose Primária/diagnóstico , Sobreviventes , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/metabolismo , Medula Óssea/patologia , Calreticulina/metabolismo , Feminino , Hemoglobinas/metabolismo , Humanos , Contagem de Leucócitos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Contagem de Plaquetas , Mielofibrose Primária/genética , Mielofibrose Primária/mortalidade , Mielofibrose Primária/patologia , Prognóstico , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Risco , Fatores de Processamento de Serina-Arginina/genética , Fatores de Processamento de Serina-Arginina/metabolismo , Fatores Sexuais , Fator de Processamento U2AF/genética , Fator de Processamento U2AF/metabolismo , Análise de Sobrevida
20.
Ann Hematol ; 98(2): 241-253, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30343328

RESUMO

Myelofibrosis (MF) is a Philadelphia chromosome-negative myeloproliferative neoplasm associated with bone marrow fibrosis, splenomegaly, a high symptom burden, and poor prognosis. Treatment is based on a risk-adapted approach, with treatment guidelines generally recommending allogeneic stem cell transplant or drug-based therapy for patients with higher-risk or more advanced disease and recommending observation or the "watch-and-wait" strategy for those with lower-risk or early-stage MF. With the advent of targeted therapies, such as the Janus kinase inhibitors, many patients have experienced substantial clinical benefits, including reduction in splenomegaly and symptoms and, in some instances, improvement or stabilization of bone marrow fibrosis and reduction of JAK2 V617F allele burden. These observations raise the possibility of patients in earlier phases of the disease also benefiting from treatment with targeted therapies. In this review, we discuss the current treatment options for patients with early-stage MF and the available evidence supporting the treatment of patients with less-advanced disease. Overall, therapies used to treat patients with early-stage MF will have to be assessed in randomized studies, with the potential benefits balanced against adverse events associated with treatment.


Assuntos
Neoplasias Hematológicas/terapia , Mielofibrose Primária/terapia , Substituição de Aminoácidos , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/enzimologia , Neoplasias Hematológicas/genética , Humanos , Janus Quinase 2/antagonistas & inibidores , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Mutação de Sentido Incorreto , Cromossomo Filadélfia , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/enzimologia , Mielofibrose Primária/genética , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Esplenectomia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA