RESUMEN
All-trans retinoic acid (ATRA) is used as standard induction therapy for acute promyelocytic leukemia (APL), but it is contraindicated for patients on hemodialysis. We present a case of a patient with APL on hemodialysis, intubated, and with marked disseminated intravascular coagulation (DIC) who was successfully treated with ATRA. A 49-year-old man was transferred to our hospital and admitted into the intensive care unit due to renal dysfunction, DIC, and pneumonia. Promyelocytes were noted in the peripheral blood, and he was diagnosed with APL after bone-marrow examination. Because of renal dysfunction, only Ara-C was used but with a reduced dose. The patient's condition improved, and he was extubated and withdrawn from dialysis on the 5th day of hospitalization. The patient suffered from APL syndrome during induction therapy, which necessitated ATRA withdrawal and steroid administration. Remission was achieved after induction therapy, and the patient is currently on maintenance therapy. There are few cases of patients with APL on hemodialysis who were treated with ATRA; hence, it is necessary to review the treatment plan for these patients.
Asunto(s)
Lesión Renal Aguda , Leucemia Promielocítica Aguda , Masculino , Humanos , Persona de Mediana Edad , Leucemia Promielocítica Aguda/tratamiento farmacológico , Inducción de Remisión , Tretinoina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Diálisis RenalRESUMEN
The patient, a 56-year-old lady, also exhibited numerous lymphadenopathy, hepatosplenomegaly, hyperleukocytosis (167,200/µl, aberrant lymphocytes 91.5%), and fever. A lymph node biopsy revealed follicular lymphoma (FL), grade 1. Peripheral blood tumor cells did not express CD10, which was a distinctive characteristic of the lymph node specimen. To prevent tumor lysis syndrome (TLI), CHOP was delivered without an anti-CD20 antibody, but afterward, residual lymphoma cells were found in peripheral blood (>80%). As a result, obinutuzumab (Obi) was given on day 8 following the second round of CHOP, and the tumor cells in the peripheral blood vanished without any major side effects like TLI. She underwent six chemotherapy sessions before receiving maintenance therapy with Obi and achieving a full metabolic response. According to reports, leukemic FL exhibits negative CD10 expression in peripheral blood lymphoma cells, while leukemic mantle cell lymphoma also shows this trait. Therefore, it is important not to confuse the two types in diagnosis. Leukemic FL with significant leukocytosis is reportedly uncommon and has a bad prognosis. Our case indicates that CHOP with Obi would be a good alternative for cases like yours, however, there have been a few cases recorded. Further case accumulation or investigation is warranted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Folicular , Femenino , Humanos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Prednisolona/uso terapéutico , Prednisona/uso terapéutico , Rituximab/uso terapéutico , Vincristina/uso terapéuticoRESUMEN
To elucidate the relevance of genetic alterations, we analysed 17 genes known to be involved in haematological neoplasms in patients with chronic leucocytosis and patients with persistent thrombocytosis. Mutations of the JAK2, SETBP1 and ASXL1 genes were found in 1/13, 1/13, and 2/13 patients with leucocytosis, respectively. Mutations of the JAK2, CALR, SETBP1 and ASXL1 genes were found in 1/5, 1/5, 1/5 and 2/5 patients with thrombocytosis, respectively. One leucocytosis patient with a JAK2 V617F mutation developed polycythaemia vera. Another leucocytosis patient developed Philadelphia chromosome-negative chronic myeloid leukaemia (Ph(-) CML) accompanied by t(9;12)(q34.1;p13.?3) (Mori et al. 2016). Another leucocytosis patient with mutations of the SETBP1 and ASXL1 genes progressed to blast crisis of Ph(-) CML accompanied by i(17)(q10). Chronic leucocytosis patients who had genetic alterations tended to develop haematological neoplasms, while thrombocytosis unexpectedly resolved in two persistent thrombocytosis patients with genetic alterations.
Asunto(s)
Trombocitosis , Humanos , Mutación , Trombocitosis/genéticaRESUMEN
To evaluate the long-term efficacy of high-dose dexamethasone (HD-DXM) treatment for immune thrombocytopenia (ITP), we retrospectively analysed 36 newly diagnosed ITP patients treated with HD-DXM as a first-line treatment. An initial response was obtained in 23 (63.9%) patients, including 11 with a complete response (CR) and 12 with a partial response (PR). Six months after HD-DXM treatment, 26 of 33 (78.8%) evaluable patients achieved objective responses, including 18 CR and 8 PR. Among 13 patients without initial response, very early increased platelet count within a week (VEIP) was observed in 7 patients, 5 (71.4%) of whom achieved a response at 6 months. In 29 patients who had available platelet count within a week, patients showing VEIP revealed longer survival than those who did not (p = 0.026). HD-DXM was an effective treatment for newly diagnosed ITP patients. VEIP after HD-DXM treatment initiation was associated with a long-term objective response in newly diagnosed ITP patients.
Asunto(s)
Púrpura Trombocitopénica Idiopática , Dexametasona/uso terapéutico , Humanos , Recuento de Plaquetas , Púrpura Trombocitopénica Idiopática/diagnóstico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We investigated the clinical implications of preferentially expressed antigen in melanoma (PRAME) expression in bone marrow cells of 116 patients with myelodysplastic syndromes (MDS). Quantitative RT-PCR was carried out to examine the PRAME expression level. High PRAME expression was observed in MDS patients classified into higher revised International Prognostic Scoring System (IPSS-R) risk categories (Very high and High) with a high bone marrow blast percentage (5% or higher). Kaplan-Meier analysis demonstrated that high PRAME expression is significantly associated with a poorer overall survival (OS) in MDS patients with a low bone marrow blast percentage (less than 5%) (log-rank test p = .0014) and those classified into lower IPSS-R risk categories (Very Low, Low, and Intermediate) (log-rank test, p = .0035). In contrast, there was no significant association between PRAME expression and OS in MDS patients with a high bone marrow blast percentage or those classified into higher IPSS-R risk categories. In addition, high PRAME expression was associated with early disease progression in MDS patients with a low bone marrow blast percentage. This study suggested PRAME expression to be a prognostic factor in MDS.
Asunto(s)
Médula Ósea , Síndromes Mielodisplásicos , Antígenos de Neoplasias/genética , Progresión de la Enfermedad , Humanos , Estimación de Kaplan-Meier , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , PronósticoRESUMEN
We herein report two cases of thrombotic thrombocytopenic purpura (TTP) complicated by other autoimmune disorders, autoimmune hepatitis and immune thrombocytopenia, respectively. In both cases, corticosteroids were continuously administered for the treatment of preceding autoimmune disorders. However, a sufficient objective response for TTP was not obtained by plasma exchange and corticosteroid treatment. Once a week rituximab (375 mg/m2) treatment for 4 times was initiated within 2 weeks from the diagnosis. Both patients achieved a sufficient response, and have never had any recurrence as of the last follow-up dates. The early introduction of rituximab could be an effective treatment option in TTP patients complicated with other autoimmune disorders.
Asunto(s)
Púrpura Trombocitopénica Idiopática , Púrpura Trombocitopénica Trombótica , Humanos , Intercambio Plasmático , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Trombótica/complicaciones , Púrpura Trombocitopénica Trombótica/diagnóstico , Púrpura Trombocitopénica Trombótica/tratamiento farmacológico , Recurrencia , Rituximab/uso terapéuticoRESUMEN
In the published online paper, the data "p = 0.144" was not deleted from the line "Median and mean number of prior treatments (range)" in Table 4.
RESUMEN
Although treatment outcomes for diffuse large B cell lymphoma (DLBCL) have improved with the introduction of rituximab, approximately half of patients experience relapsed/refractory (r/r) disease. Furthermore, no standard salvage therapy has yet been established to date, while limitations in treatment options exist due to toxicity and restricted tolerability among elderly patients and/or those with comorbidities. The ICE (ifosfamide, cyclophosphamide, and etoposide) regimen is often used as salvage therapy for r/r DLBCL. Several modified ICE regimens not requiring continuous ifosfamide infusion are available, which can be used in outpatient clinics. This study analyzed the efficacy and toxicity of fractionated ICE with rituximab (f-R-ICE) as a salvage regimen among 47 patients with relapsed/refractory DLBCL (median age upon f-R-ICE initiation, 71 years). The whole cohort had an overall (ORR) and complete response rate of 53.1% (n = 25) and 25.5% (n = 12), respectively, and an estimated 1-year overall survival after f-R-ICE initiation of 57%. Comorbidities were evaluated using the Charlson Comorbidity Index (CCI) upon f-R-ICE initiation. Patients with low CCI scores (68%) had a higher ORR than those with high CCI scores (36.4%) upon f-R-ICE initiation (P = 0.042). In contrast, no significant differences in overall survival (OS) were observed between the low and high CCI groups (1-year OS 56.6% vs. 52.2%; median OS 24 vs. 22.8 months) after initiating f-R-ICE. Our results suggest that f-R-ICE is a safe and effective salvage therapy for r/r DLBCL and can be used for older patients and/or those with high CCI scores in outpatient clinics.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Comorbilidad , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Masculino , Persona de Mediana Edad , Rituximab/administración & dosificación , Tasa de SupervivenciaRESUMEN
The PLCG1 gene, which encodes the phospholipase C γ1 isoform, is located within the commonly deleted region of the long arm of chromosome 20 (del(20q)) observed in myelodysplastic syndromes (MDS). Phospholipase C is involved in diverse physiological and pathological cellular processes through inositide signaling. We hypothesized that reduced PLCG1 expression because of haploinsufficiency by del(20q) plays a role in the molecular pathogenesis of MDS. Therefore, we analyzed PLCG1 expression in bone marrow mononuclear cells at diagnosis in 116 MDS patients with or without del(20q) by quantitative RT-PCR to evaluate its clinical significance. The expression level of PLCG1 was significantly lower not only in MDS patients with del(20q) but also in those without del(20q) compared to that of the controls, which suggests that reduced PLCG1 expression is a common molecular event in MDS. Patients in the lowest quartile (Q4) group for PLCG1 expression had lower overall survival (OS) compared to that of other patients (Q1-Q3) (log-rank test, P = .0004) with estimated median OS times of 22 in the Q4 group and 106 months in the Q1-3 group. Univariate and multivariate analysis indicated reduced PLCG1 expression (Q4) was associated with lower OS (hazard ratio 2.58, 95% CI 1.35-4.84, P = .0049), which suggests that reduced PLCG1 expression is an independent prognostic factor for OS. In addition, patients were well-stratified for OS by combining PLCG1 expression level (Q4 vs Q1-3) and bone marrow blast percentage (5% or more vs less than 5%). Thus, the level of PLCG1 expression at time of diagnosis is a prognostic biomarker for MDS.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Médula Ósea/patología , Síndromes Mielodisplásicos/mortalidad , Fosfolipasa C gamma/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/metabolismo , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/patología , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
Deletion of the long arm of chromosome 20 (del(20q)) is observed in 5-10% of patients with myelodysplastic syndromes (MDS). We examined the expression of 28 genes within the common deleted region (CDR) of del(20q), which we previously determined by a CGH array using clinical samples, in 48 MDS patients with (nâ¯=â¯28) or without (nâ¯=â¯20) chromosome 20 abnormalities and control subjects (nâ¯=â¯10). The expression level of 8 of 28 genes was significantly reduced in MDS patients with chromosome 20 abnormalities compared to that of control subjects. In addition, the expression of BCAS4, ADA, and YWHAB genes was significantly reduced in MDS patients without chromosome 20 abnormalities, which suggests that these three genes were commonly involved in the molecular pathogenesis of MDS. To evaluate the clinical significance, we analyzed the impact of the expression level of each gene on overall survival (OS). According to the Cox proportional hazard model, multivariate analysis indicated that reduced BCAS4 expression was associated with inferior OS, but the difference was not significant (HR, 3.77; 95% CI, 0.995-17.17; Pâ¯=â¯0.0509). Functional analyses are needed to understand the biological significance of reduced expression of these genes in the pathogenesis of MDS.
Asunto(s)
Biomarcadores , Deleción Cromosómica , Cromosomas Humanos Par 20 , Regulación de la Expresión Génica , Síndromes Mielodisplásicos/genética , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Bandeo Cromosómico , Femenino , Perfilación de la Expresión Génica , Humanos , Cariotipo , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/terapiaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Herpes Zóster/mortalidad , Anciano , Autoinjertos , Carmustina/administración & dosificación , Citarabina/administración & dosificación , Femenino , Estudios de Seguimiento , Herpes Zóster/etiología , Herpes Zóster/prevención & control , Humanos , Melfalán/administración & dosificación , Persona de Mediana Edad , Podofilotoxina/administración & dosificaciónAsunto(s)
Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico por imagen , Macroglobulinemia de Waldenström/complicaciones , Macroglobulinemia de Waldenström/diagnóstico por imagen , Antibióticos Antineoplásicos/uso terapéutico , Diagnóstico Diferencial , Femenino , Humanos , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Macroglobulinemia de Waldenström/tratamiento farmacológicoRESUMEN
OBJECTIVES: We previously reported loss of heterozygosity on 1p in chronic myelogenous leukemia (CML). We analyzed promoter methylation and mutation of tumor suppressor genes on 1p36 in CML. METHODS: We performed methylation-specific PCR (MS-PCR) analysis of the PRDM2, RUNX3, and TP73 genes in 61 patients with CML (43 chronic phase, CP; two accelerated phase; and 16 blast crisis, BC). Oxidative MS-PCR, PCR-single-strand conformation polymorphism, and real-time reverse transcriptase PCR were also analyzed. K-562 cells were grown in the presence of 5-Aza-dC and trichostatin A. RESULTS: Methylation of the PRDM2, RUNX3, and TP73 genes was detected in 24/60 (40%), 21/61 (34%), and 28/60 (47%) patients, respectively. Methylation of all three genes was detected in 19/59 (32%) patients. Methylation was more frequent in BC than in CP. Oxidative MS-PCR analysis detected 5-mC in the PRDM2, RUNX3, and TP73 genes in 10/22 (45%), 15/21 (71%), and 16/26 (62%) samples with methylation detected by MS-PCR, respectively. Decreased expression was observed in several samples with methylation, while no mutations were found in the genes. Treatment of K-562 cells induced growth suppression, demethylation, and reexpression of the PRDM2 and RUNX3 genes. CONCLUSION: Multiple tumor suppressor genes on 1p were inactivated in CML by methylation.
Asunto(s)
Cromosomas Humanos Par 1 , Metilación de ADN , Genes Supresores de Tumor , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Adulto , Anciano , Línea Celular Tumoral , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Proteínas de Unión al ADN/genética , Femenino , Predisposición Genética a la Enfermedad , N-Metiltransferasa de Histona-Lisina/genética , Humanos , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Proteínas Nucleares/genética , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas , Análisis de Secuencia de ADN , Factores de Transcripción/genética , Proteína Tumoral p73/genéticaRESUMEN
A 56-year-old man was diagnosed with aplastic anemia and paroxysmal nocturnal hemoglobinuria at 43 years of age and treatment with cyclosporin A was started. Liver cirrhosis, ascites, and thrombus in the hepatic veins were found at 56 years of age and Budd-Chiari syndrome (BCS) was diagnosed according to angiography findings. He was treated with diuretics and paracentesis was performed several times, but with limited efficacy. A Denver® peritoneovenous shunt (PVS) was inserted into the right jugular vein; his ascites and renal function improved immediately and his general condition has remained good for 12 months since starting the above treatment regimen. A PVS is a treatment option for ascites due to BCS.
Asunto(s)
Anemia Aplásica/complicaciones , Ascitis/cirugía , Síndrome de Budd-Chiari/cirugía , Hemoglobinuria Paroxística/cirugía , Trombosis de la Vena/cirugía , Ascitis/complicaciones , Síndrome de Budd-Chiari/complicaciones , Hemoglobinuria Paroxística/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Derivación Peritoneovenosa , Resultado del Tratamiento , Trombosis de la Vena/complicacionesAsunto(s)
Cromosomas Humanos Par 12/genética , Cromosomas Humanos Par 9/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Proteínas de Fusión Oncogénica/genética , Translocación Genética , Anciano , Humanos , Masculino , Cromosoma FiladelfiaRESUMEN
We conducted a cross-sectional study to elucidate factors contributing to vasovagal reaction (VVR), the most frequent side effect following whole blood and apheresis donations. Complications recorded at the collection sites after voluntary donations by the Japanese Red Cross Tokyo Blood Center (JRC), in the 2006 and 2007 fiscal years, were analyzed by both univariate analysis and the multivariate conditional logistic regression model. Of 1,119,716 blood donations over the full two years, complications were recorded for 13,320 donations (1.18%), among which 67% were VVR. There were 4,303 VVR cases which had sufficient information and could be used for this study. For each VVR case, two sex- and age-matched controls (n = 8,606) were randomly selected from the donors without complications. Age, sex, body mass index (BMI), predonation blood pressure, pulse and blood test results, including total protein, albumin, and hemoglobin, were compared between the VVR group and the control group. In univariate analysis, the VVR group was significantly younger, with a lower BMI, higher blood pressure and higher blood protein and hemoglobin levels than the control group (p<0.001). Furthermore, blood protein and hemoglobin levels showed dose-dependent relationships with VVR incidences by the Cochran-Armitage trend test (p<0.01). For both sexes, after adjusting for confounders with the multivariate conditional logistic regression model, the higher than median groups for total protein (male: OR 1.97; 95%CI 1.76,-2.21; female: OR 2.29; 95%CI 2.05-2.56), albumin (male: 1.75; 1.55-1.96; female: 1.76; 1.57-1.97) and hemoglobin (male: 1.98; 1.76-2.22; female: 1.62; 1.45-1.81) had statistically significant higher risk of VVR compared to the lower than median groups. These elevated serum protein and hemoglobin levels might offer new indicators to help understand VVR occurrence.
Asunto(s)
Donantes de Sangre , Proteínas Sanguíneas , Hemoglobinas , Síncope Vasovagal/sangre , Síncope Vasovagal/etiología , Adulto , Presión Sanguínea , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Oportunidad Relativa , Factores Sexuales , Adulto JovenRESUMEN
Chromosome translocations involving the immunoglobulin heavy chain (IGH) gene locus at chromosome region 14q32 are often observed in B-cell lymphoid neoplasms. Of these, t(14;18)(q32;q21) results in juxtaposition of the IGH gene on chromosome 14 and the BCL2 gene on chromosome 18, leading to the overexpression of BCL2 anti-apoptotic protein, which plays a critical role in the development of follicular lymphoma (FL). However, BCL2 overexpression is not observed in approximately 10 % of FL, and the molecular pathogenesis of BCL2-negative FL has not been elucidated. Here, we identify the SRY-related high-morbidity-group (HMG) box 5 (SOX5) gene on chromosome 12p12 as a novel IGH-involved translocation partner in the case of BCL2-negative follicular lymphoma (FL) with a complex karyotype including t(12;14)(p12.2;q32) by long-distance inverse PCR. As a result of this translocation, the SOX5 gene is juxtaposed to the enhancer of the IGH gene; SOX5 overexpression in neoplastic cells was demonstrated by immunohistochemistry. The results of the present study suggest a role for SOX5 in the molecular pathogenesis of FL.
Asunto(s)
Cromosomas Humanos Par 12/genética , Cromosomas Humanos Par 14/genética , Linfoma Folicular , Proteínas Proto-Oncogénicas c-bcl-2 , Factores de Transcripción SOXD , Translocación Genética , Anciano , Femenino , Humanos , Linfoma Folicular/genética , Linfoma Folicular/metabolismo , Linfoma Folicular/patología , Factores de Transcripción SOXD/biosíntesis , Factores de Transcripción SOXD/genéticaRESUMEN
Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency in adults and children. We herein report a case of CVID, who was misdiagnosed with asthma due to wheezing episodes and relatively late onset. A 51-year-old woman had suffered from recurrent upper and lower airway infection for recent 2 years. She repeated wheezing attacks and was treated as asthma exacerbation triggered by infection. She was referred to our hospital for investigation and treatment. Lung function tests showed no reversibility of FEV1 by ß-adrenergic agonist, but the increase of V50/V25. Chest CT showed slight to moderate bronchial wall thickening and bronchiectasis. After that, she suffered from pneumonia with wheezing attacks twice a month, and immunodeficiency was strongly suspected. Her blood tests showed marked decreases of all classes of immunoglobulin and nearly lack of memory B cells, NKT cells and plasmacytoid dendritic cells. She was diagnosed with CVID, and was treated with replacement of gammaglobulin. Thereafter, her wheezing episodes with infection were remarkably improved. Because the delay of diagnosis with CVID likely causes poor mortality and morbidity, a possibility of CVID should be considered in patients with frequent asthma-like symptoms due to recurrent airway infection.