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1.
Cureus ; 15(10): e47816, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38022225

RESUMEN

INTRODUCTION: Recently, laparoscopic surgery has been used in many fields of surgery. It has been reported that cuff pressure becomes high during laparoscopic surgery. Increased cuff pressure may cause postoperative sore throat and hoarseness. Considering previous reports, we hypothesized that maintenance of a fixed low cuff pressure during laparoscopic surgery might be associated with low grades of postoperative sore throat and hoarseness. METHODS: The participants were 100 patients between 20 and 80 years of age who were scheduled to undergo laparoscopic surgery lasting over 2 hours. Patients were randomly allocated to two groups with endotracheal tube cuff pressures fixed at 20 cmH2O (low-pressure group; LPG) and 30 cmH2O (high-pressure group; HPG). We evaluated mainly sore throat and hoarseness on postoperative day 1 using a visual analog scale (VAS; 0-10 cm). Statistical comparisons of values were performed using the unpaired t-test, Mann-Whitney U-test, and chi-square test with values of p < 0.05 considered statistically significant. RESULTS: There were no significant differences in background characteristics between the two groups. Median postoperative scores for the LPG and HPG were 1 (interquartile range, 0-3) and 0 (0-2; p = 0.560) for sore throat and 2 (0-4) and 1 (0-3; p = 0.311) for hoarseness, respectively, and the differences were not significant. CONCLUSION: The effects of maintenance of a fixed low cuff pressure and a fixed high cuff pressure on the degrees of postoperative sore throat and hoarseness after laparoscopic surgery were the same and the grades were low.

2.
Acta Haematol ; 143(3): 250-259, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31461700

RESUMEN

BACKGROUND: Danaparoid sodium and synthetic protease inhibitors (SPIs) have been approved for the treatment of disseminated intravascular coagulation (DIC) in Japan. OBJECTIVES: To compare the clinical results of the treatment of DIC with danaparoid or SPIs. METHODS: We retrospectively examined 188 patients with hematological malignancy-related DIC. RESULTS: DIC resolution rate in the danaparoid group was higher than that in the SPIs group (61.5 vs. 42.6%; p = 0.031) on day 7. Multivariate analysis identified the response to chemotherapy as independent predictive factor for DIC resolution on day 7 (odds ratio, OR, 2.28; 95% confidence interval, CI, 1.21-4.31; p = 0.011). While there was no significant difference in the DIC resolution rate on day 14 (75.0 vs. 62.4%; p = 0.117), in a subgroup analysis of patients who did not show an improvement in the underlying disease, the danaparoid group showed a significantly better DIC resolution rate (OR 3.89; 95% CI 1.15-13.2; p = 0.030). There was no difference in the rate of cumulative mortality from bleeding within 28 days between the 2 groups (6.6 vs. 3.3%; p = 0.278). CONCLUSIONS: Danaparoid may be associated with more frequent resolution of DIC in patients with refractory underlying disease.


Asunto(s)
Sulfatos de Condroitina/uso terapéutico , Dermatán Sulfato/uso terapéutico , Neoplasias Hematológicas/sangre , Heparitina Sulfato/uso terapéutico , Inhibidores de Proteasas/uso terapéutico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Transfusión de Componentes Sanguíneos , Sulfatos de Condroitina/efectos adversos , Dermatán Sulfato/efectos adversos , Coagulación Intravascular Diseminada/tratamiento farmacológico , Coagulación Intravascular Diseminada/terapia , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinógeno/análisis , Neoplasias Hematológicas/tratamiento farmacológico , Hemorragia/etiología , Hemorragia/mortalidad , Heparitina Sulfato/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Plasma , Inhibidores de Proteasas/efectos adversos , Tiempo de Protrombina , Estudios Retrospectivos , Resultado del Tratamiento
3.
Ann Hematol ; 99(1): 49-55, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31853702

RESUMEN

Immune thrombocytopenia (ITP) has been reported to be associated with thrombotic events. The incidence of thrombosis in 303 newly diagnosed ITP patients in our institute between 2000 and 2016 was retrospectively reviewed. During a median follow-up of 3.6 years, 16 thrombotic events (12 arterial and four venous) occurred. The median platelet count at thrombotic events was 102 × 109/l. At 10 years, the cumulative thrombosis incidence was 10%. A univariate analysis showed that smoking, hypertension, male gender, a history of thrombosis, and atrial fibrillation (Af) were significantly associated with the occurrence of thrombosis, and a multivariate analysis identified smoking and Af as independent risk factors. The thrombotic risk was not increased by lupus anticoagulant positivity or ITP treatment. At 5 years, the cumulative incidence of bleeding and overall survival probability was 5.6% and 92%, respectively. This study demonstrates that smoking and Af were associated with an increased risk of thrombosis. Previously identified risk factors were not confirmed in these Japanese ITP patients.


Asunto(s)
Púrpura Trombocitopénica Idiopática , Trombosis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia , Trombosis/etiología , Trombosis/mortalidad
4.
Blood Adv ; 3(21): 3266-3277, 2019 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-31698458

RESUMEN

The cost of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) is a substantial economic burden. In Japan, imatinib, dasatinib, and nilotinib are now approved as first-line treatment of CML in chronic phase. Recent "stop TKI" trials have shown that TKIs can be safely discontinued in nearly one-half of patients with sustained deep molecular response (DMR). In this study, we analyzed the cost-effectiveness of a simulated 10 years of CML treatment including stop TKI in both the United States and Japan. We constructed Markov models to compare 4 strategies in which treatment was initiated with imatinib, dasatinib, nilotinib, or any of these TKIs at the physician's discretion. Treatment was switched to another TKI in the case of intolerance or resistance to the initial TKI, and TKIs were discontinued if DMR persisted for 2 years. "Imatinib first" offered 7.34 quality-adjusted life years (QALYs) at the cost of $1 022 148 in the United States (US dollars) and ¥32 526 785 in Japan (Japanese yen). In comparison with imatinib first, the incremental cost-effectiveness ratio per QALY of "dasatinib first" (7.68 QALY, $1 236 052, ¥51 506 254), "nilotinib first" (7.64 QALY, $1 245 667, ¥39 635 598), and "physician's choice" (7.55 QALY, $1 167 818, ¥41 187 740) was $641 324, $696 717, and $666 634 in the United States and ¥54 456 325, ¥23 154 465, and ¥39 635 615 in Japan, respectively. None of the 3 strategies met the willingness-to-pay threshold. The results were robust to univariate and multivariate sensitivity analyses. Imatinib first was shown to be the most cost-effective approach even with the incorporation of stop TKI.


Asunto(s)
Terapia Combinada/economía , Análisis Costo-Beneficio , Leucemia Mielógena Crónica BCR-ABL Positiva/epidemiología , Antineoplásicos/uso terapéutico , Toma de Decisiones Clínicas , Terapia Combinada/métodos , Árboles de Decisión , Manejo de la Enfermedad , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Cadenas de Markov , Terapia Molecular Dirigida/economía , Terapia Molecular Dirigida/métodos , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Años de Vida Ajustados por Calidad de Vida , Resultado del Tratamiento
5.
Acta Haematol ; 141(3): 158-163, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30799408

RESUMEN

TAFRO syndrome, a rare systemic inflammatory disease, can lead to multiorgan failure without appropriate treatment. Although thrombocytopenia is frequently seen in patients with TAFRO syndrome, little is known about its pathogenesis. Moreover, while recent studies have reported the presence of an anterior mediastinal mass in some patients, the pathological status of this remains unclear. Here, we report a case of fatal bleeding in a patient with TAFRO syndrome accompanied by an anterior mediastinal mass. A 55-year-old female was transferred to our hospital with a 2-week history of fever, epistaxis, and dyspnea. Laboratory tests revealed severe thrombocytopenia, computed tomography (CT) showed pleural effusions, and bone marrow biopsy revealed reticulin myelofibrosis. We suspected TAFRO syndrome, but the CT scan showed an anterior mediastinal mass that required a biopsy to exclude malignancy. She soon developed severe hemorrhagic diathesis and died of intracranial hemorrhage despite intensive treatment. She had multiple autoantibodies against platelets, which caused platelet destruction. An autopsy of the mediastinal mass revealed fibrous thymus tissues with infiltration by plasma cells. Our case suggests that thrombocytopenia could be attributed to antibody-mediated destruction and could be lethal. Hence, immediate treatment is imperative in cases of severe thrombocytopenia, even when accompanied by an anterior mediastinal mass.


Asunto(s)
Autoanticuerpos , Enfermedad de Castleman , Enfermedades del Mediastino , Púrpura Trombocitopénica Idiopática , Tomografía Computarizada por Rayos X , Autopsia , Enfermedad de Castleman/sangre , Enfermedad de Castleman/diagnóstico por imagen , Enfermedad de Castleman/patología , Enfermedad de Castleman/terapia , Resultado Fatal , Femenino , Humanos , Hemorragias Intracraneales/sangre , Hemorragias Intracraneales/diagnóstico por imagen , Hemorragias Intracraneales/patología , Hemorragias Intracraneales/terapia , Enfermedades del Mediastino/sangre , Enfermedades del Mediastino/diagnóstico por imagen , Enfermedades del Mediastino/patología , Enfermedades del Mediastino/terapia , Persona de Mediana Edad , Derrame Pleural/sangre , Derrame Pleural/diagnóstico , Derrame Pleural/patología , Derrame Pleural/terapia , Mielofibrosis Primaria/sangre , Mielofibrosis Primaria/diagnóstico por imagen , Mielofibrosis Primaria/patología , Mielofibrosis Primaria/terapia , Púrpura Trombocitopénica Idiopática/sangre , Púrpura Trombocitopénica Idiopática/diagnóstico por imagen , Púrpura Trombocitopénica Idiopática/patología , Púrpura Trombocitopénica Idiopática/terapia
6.
Ann Hematol ; 98(5): 1127-1133, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30474718

RESUMEN

It is controversial whether blast percentage based on all nucleated cells (ANC) or non-erythroid cells (NEC) more accurately reflects the prognosis of patients with myelodysplastic syndromes (MDS). We considered that the impact of blast percentage on survival should be similar in MDS with erythroid hyperplasia (MDS-E) and MDS with no erythroid hyperplasia (MDS-NE), and from this perspective, we retrospectively analyzed 322 patients, including 44 with MDS-E and 278 with MDS-NE. Overall survival was similar between the MDS-E and MDS-NE groups (P = 0.94). In a subgroup of patients with bone marrow (BM) blasts of < 5%, no difference in survival was found between MDS-E and MDS-NE by either calculation method. However, in patients with a blast percentage between 5 and 10%, a significant difference in survival was observed only when the blast percentage in MDS-E was calculated from ANC (P < 0.001 by ANC and P = 0.66 by NEC). A similar result was observed when we analyzed the remaining patients with higher blasts together with those with blasts between 5 and 10%. These results suggest that the calculation of the BM blast percentage based on NEC in MDS-E provides a blast percentage value with a clinical impact consistent with that in MDS-NE.


Asunto(s)
Crisis Blástica , Células de la Médula Ósea , Leucocitos Mononucleares , Síndromes Mielodisplásicos , Adulto , Anciano , Anciano de 80 o más Años , Crisis Blástica/clasificación , Crisis Blástica/metabolismo , Crisis Blástica/mortalidad , Crisis Blástica/patología , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Hiperplasia , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/clasificación , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/patología , Estudios Retrospectivos , Tasa de Supervivencia
7.
Leuk Lymphoma ; 60(3): 703-710, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30188227

RESUMEN

Wilms tumor gene 1 (WT1) is highly expressed in myelodysplastic syndrome (MDS) cells and is known to reflect the tumor burden in MDS. We evaluated the usefulness of WT1 mRNA levels for predicting the prognosis of MDS. At diagnosis, WT1 levels were strongly correlated with the percentage of blasts calculated based on non-erythroid cells, but not with that based on all nucleated cells (r = 0.57, p < .05 vs r = 0.42, p = .13). Among the allogeneic transplant recipients, the presence of two consecutive WT1 levels ≥100 copies/µg RNA with a median interval of one month was associated with a 77.8% relapse rate at nine months from the first detection of a high WT1 level, and the median time to relapse was only 114 [36-257] days. WT1 levels at diagnosis were correlated with known prognostic factors. In addition, the presence of two consecutive high WT1 levels after allogeneic transplantation may predict early relapse of MDS.


Asunto(s)
Biomarcadores de Tumor , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Médula Ósea/patología , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , Proteínas WT1/genética , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Transfusión Sanguínea , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/terapia , Pronóstico , ARN Mensajero/genética , Curva ROC , Estudios Retrospectivos , Trasplante Homólogo , Proteínas WT1/sangre
8.
Int J Hematol ; 109(2): 141-146, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30536180

RESUMEN

We evaluated clinical outcomes of disseminated intravascular coagulation (DIC) in patients with hematological malignancies treated with synthetic protease inhibitors (SPIs) and compared the effects of gabexate mesilate (FOY) and nafamostat mesilate (FUT). We retrospectively examined 127 patients [acute myeloid leukemia (n = 48), acute lymphoblastic leukemia (n = 25), and non-Hodgkin lymphoma (n = 54)] with DIC, who were diagnosed according to Japanese Ministry of Health, Labour and Welfare criteria and treated with SPIs [FOY (n = 55) and FUT (n = 72)] at our hospital from 2006 to 2015. The DIC resolution rates on days 7 and 14 were 42.6% and 62.4%, respectively. No significant differences were observed in DIC resolution rates between the FUT and FOY groups [40.3% vs. 45.5% (day 7), P = 0.586; 56.3% vs. 69.8% (day 14), P = 0.179, respectively]. Multivariate analysis revealed that response to chemotherapy was the only independent predictor of DIC resolution on days 7 and 14 (ORR 2.81, 95% CI 1.32-5.98, P = 0.007; ORR 2.51, 95% CI 1.12-5.65, P = 0.026). Resolution of DIC was correlated with improvement of background hematological malignancies, and no significant differences were observed between the two SPIs.


Asunto(s)
Coagulación Intravascular Diseminada/tratamiento farmacológico , Gabexato/uso terapéutico , Guanidinas/uso terapéutico , Neoplasias Hematológicas/complicaciones , Adulto , Anticoagulantes/uso terapéutico , Benzamidinas , Coagulación Intravascular Diseminada/etiología , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Inhibidores de Serina Proteinasa/uso terapéutico , Resultado del Tratamiento
9.
Clin Lymphoma Myeloma Leuk ; 18(12): e521-e527, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30181104

RESUMEN

BACKGROUND: Wilms' tumor 1 (WT1) mRNA expression is a universal marker of minimal residual disease in patients with acute myeloid leukemia (AML). The aim of this retrospective study was to evaluate the ability of serial measurement of peripheral blood WT1 mRNA levels to predict relapse in patients with AML in remission. PATIENTS AND METHODS: From April 2012 to May 2015, 131 patients with AML were admitted to our hospital. Among them, 55 were examined for WT1 mRNA at least 3 times during complete remission to assess minimal residual disease, and thus were included in the following analyses. RESULTS: With a median follow-up duration of 921 days, 34 remained in remission, but their WT1 values frequently increased to 100 copies/µg RNA. Therefore, we focused on the 40 posttreatment observation periods of 37 patients who experienced high WT1 values (defined as those above 100 copies/µg RNA) at least once after they achieved remission. The cumulative incidence of hematologic relapse was 75.8% at 6 months in 26 patients with 2 consecutive high WT1 values, whereas just 1 of the 14 patients with only 1 high WT1 value relapsed (P < .01). Similar results were obtained in subgroup analyses of allogeneic stem cell transplant recipients. CONCLUSION: Sequential monitoring of the WT1 mRNA is of value for the early detection of hematologic relapse in patients with AML in remission after chemotherapy or stem cell transplantation.


Asunto(s)
Biomarcadores de Tumor , Expresión Génica , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Proteínas WT1/genética , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Detección Precoz del Cáncer , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Proteínas de Fusión Oncogénica/genética , Pronóstico , ARN Mensajero/genética , Recurrencia , Adulto Joven
10.
J Infect Chemother ; 24(10): 812-814, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30006248

RESUMEN

The 1,3-beta-D-Glucan (BDG) assay is widely used for the diagnosis of fungal infections, especially in patients with hematologic malignancies. Some antimicrobials have been reported to cause false-positive results for BDG, but there has been no report on the effect of penicillin G (PCG) on BDG levels. We experienced a patient who developed false-positive BDG elevation during the administration of PCG for osteomyelitis due to Streptococcus pneumoniae infection. The serum BDG level increased up to 81.0 pg/ml during the continuous administration of PCG at 24 million units per day. However, chest and paranasal CT scan showed no evidence of fungal infection. The BDG level decreased to 38.0 pg/ml at 14 hours after the discontinuation of PCG. The amount of BDG in one vial of PCG inferred from these serum BDG levels is very similar to the actual BDG concentration in a vial of PCG. Therefore, during the administration of PCG, elevated BDG levels should be interpreted with caution, as they may be false-positive results.


Asunto(s)
Antibacterianos/administración & dosificación , Osteomielitis/tratamiento farmacológico , Penicilina G/administración & dosificación , Infecciones Neumocócicas/tratamiento farmacológico , Streptococcus pneumoniae/efectos de los fármacos , beta-Glucanos/sangre , Antibacterianos/farmacología , Reacciones Falso Positivas , Humanos , Masculino , Persona de Mediana Edad , Osteomielitis/sangre , Osteomielitis/etiología , Penicilina G/farmacología , Infecciones Neumocócicas/sangre , Infecciones Neumocócicas/complicaciones
11.
Hematology ; 23(8): 470-477, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29486661

RESUMEN

OBJECTIVE: Myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement are hematopoietic stem cell disorders with a poor prognosis, but no established standard therapy. METHODS: We experienced a patient with T-lymphoblastic lymphoma (LBL) associated with FGFR1 rearrangement who underwent cord blood transplantation, but died of pulmonary complication. We collected the clinical data of patients with FGFR1 rearrangement from the medical literature and analyzed 45 patients, including our patient. RESULTS: The primary diagnoses were myeloproliferative neoplasm (MPN) or myelodysplastic syndromes (MDS) in 14 and acute leukemia or LBL in 31. In MPN and MDS patients, the cumulative incidence of transformation to blast phase (BP) at 12 months was 46.2%. The 1-year overall survival (OS) from diagnosis in all cases was 43.1%. With regard to the impact of treatment response on survival, the achievement of complete response with a landmark at 2 months after diagnosis of BP was associated with a superior OS (40.0% vs. 26.0% P = 0.011 for 1-year OS from BP). Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 13 patients, and the 1-year OS from allogeneic HSCT was 61.5%. The hazard ratio for mortality was 0.34 (95% CI, 0.08-1.51, P = 0.15) for allogeneic HSCT treated as a time-dependent covariate, which suggests that allogeneic HSCT may confer a clinical benefit. CONCLUSION: The further accumulation of clinical data is needed to determine the optimal therapeutic approach for these neoplasms.


Asunto(s)
Reordenamiento Génico , Neoplasias Hematológicas , Trastornos Mieloproliferativos , Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Adulto , Femenino , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/mortalidad , Neoplasias Hematológicas/terapia , Humanos , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/metabolismo , Trastornos Mieloproliferativos/mortalidad , Trastornos Mieloproliferativos/terapia , Proteínas de Neoplasias/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo
12.
Cancer Genet ; 220: 44-48, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29310838

RESUMEN

Double-hit lymphoma (DHL) is defined as lymphoma with concurrent BCL2 and MYC translocations. While the most common histological subtype of DHL is diffuse large B-cell lymphoma, the present patient had leukemic follicular lymphoma (FL). A 52-year-old man was admitted to our hospital due to general fatigue and cervical and inguinal lymph node swelling. The patient was leukemic and the pathological diagnosis of the inguinal lymph node was FL grade 1. Chromosomal analysis revealed a complex karyotype including a rare three-way translocation t(8;14;18)(q24;q32;q21) involving the BCL2, MYC, and IGH genes. Based on a combination of fluorescence in situ hybridization (FISH), using BCL2, MYC and IGH, and spectral karyotyping (SKY), the karyotype was interpreted as being the result of a multistep mechanism in which the precursor B-cell gained t(14;18) in the bone marrow and acquired a translocation between der(14)t(14;18) and chromosome 8 in the germinal center, resulting in t(8;14;18). The pathological diagnosis was consistently FL, not only at presentation but even after a second relapse. The patient responded well to standard chemotherapies but relapsed after a short remission. This patient is a unique case of leukemic DH-FL with t(8;14;18) that remained in FL even at a second relapse.


Asunto(s)
Cadenas Pesadas de Inmunoglobulina/genética , Linfoma Folicular/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-myc/genética , Translocación Genética , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 18 , Cromosomas Humanos Par 8 , Análisis Citogenético/métodos , Citometría de Flujo , Genes myc , Humanos , Linfoma Folicular/metabolismo , Masculino , Persona de Mediana Edad
13.
Int J Hematol ; 107(6): 712-715, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29185155

RESUMEN

Tyrosine kinase inhibitors (TKIs) are standard therapy for chronic myeloid leukemia (CML). However, the effects of these agents on mature B cell lymphoma are not well known. We describe a 50-year-old man who was diagnosed with CML in the chronic phase and treated with imatinib. After 3 years of imatinib therapy that achieved a complete cytogenetic response of CML, he developed Philadelphia-negative follicular lymphoma (FL). Rituximab monotherapy induced a partial response of FL, and he subsequently achieved a major molecular response (MMR) of CML. Three years later, however, the MMR was lost, followed by the progression of FL. Imatinib was switched to nilotinib for the treatment of CML, while we chose watchful waiting for FL. He achieved MMR again under treatment with nilotinib for 8 months including one month of substitutional use of dasatinib due to adverse events, but thereafter nilotinib was switched to bosutinib due to hyperbilirubinemia. With the administration of second-generation TKIs (2G-TKIs) for a total of 18 months, he achieved a complete response to FL without antilymphoma treatment. This is the first report to suggest that 2G-TKIs may have direct or indirect effects on FL.


Asunto(s)
Compuestos de Anilina/administración & dosificación , Dasatinib/administración & dosificación , Proteínas de Fusión bcr-abl/antagonistas & inhibidores , Mesilato de Imatinib/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Linfoma Folicular/complicaciones , Linfoma Folicular/tratamiento farmacológico , Nitrilos/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Quinolinas/administración & dosificación , Compuestos de Anilina/efectos adversos , Dasatinib/efectos adversos , Sustitución de Medicamentos , Humanos , Mesilato de Imatinib/efectos adversos , Masculino , Persona de Mediana Edad , Nitrilos/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Quinolinas/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
14.
Int J Hematol ; 106(3): 411-417, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28508228

RESUMEN

We retrospectively analyzed the relationship between white blood cell (WBC) count elevation after priming and clinical response in 115 patients with AML (61 untreated and 54 relapsed or refractory) treated with low-dose cytarabine, aclarubicin, and G-CSF priming. Receiver operating characteristic curve analysis showed that the ratio of maximum WBC count to pretreatment WBC count (WBCratio) was most strongly associated with complete remission (CR) in previously untreated patients among several parameters we analyzed in this study; however, the prediction accuracy was not clinically significant considering the area under the curve of 0.694. Based on the cutoff value of the WBCratio, CR rate and event-free survival in the high WBCratio group were significantly better than those in the low WBCratio group in untreated patients. Regarding the WBC differential counts, a high ratio of the maximum to pretreatment value of neutrophils rather than that of peripheral blasts was associated with a superior CR rate. In addition, an increase in blasts after G-CSF priming had a significant negative impact on CR rate in untreated patients. In conclusion, an increase in blast counts after G-CSF priming was not predictive of achieving CR.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Leucemia Mieloide Aguda/sangre , Leucemia Mieloide Aguda/tratamiento farmacológico , Recuento de Leucocitos , Aclarubicina/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Adulto Joven
15.
Hematology ; 22(9): 521-526, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28413914

RESUMEN

OBJECTIVES: Follicular lymphoma (FL) is a clinically and biologically heterogeneous disease. Therefore, it is important to identify factors that can predict its clinical outcome. METHODS: We retrospectively evaluated the usefulness of soluble interleukin-2 receptor (sIL-2R) levels after R-CHOP (posttreatment sIL-2R) in 72 patients with newly diagnosed FL who had either a complete response (CR) or partial response. With the use of a recursive partitioning analysis, we determined the cut-off values of post- and pretreatment sIL-2R levels that were associated with disease progression, which corresponded to 486.5 and 5405 U/mL, respectively. RESULTS: The high posttreatment sIL-2R group showed a significantly inferior progression-free survival (PFS) compared to the low posttreatment sIL-2R group in all patients (3-year PFS 52.6% vs. 77.4%, P = 0.003), and in patients with CR (3-year PFS 57.1% vs. 82.1%, P = 0.034). Although a multivariate analysis showed that pretreatment sIL-2R, but not posttreatment sIL-2R, was an independently significant predictive factor for disease progression, among patients with low pretreatment sIL-2R levels, those with high posttreatment sIL-2R levels tended to have inferior PFS. There was a significant trend in PFS among the high pretreatment sIL-2R group, the low pre- and high posttreatment sIL-2R group, and the low pre- and low posttreatment sIL-2R group (P < 0.001). CONCLUSION: Among patients with a low pretreatment sIL-2R level who exhibited a positive response to R-CHOP, the posttreatment sIL-2R level may help to identify those with a poor prognosis.


Asunto(s)
Linfoma Folicular/sangre , Linfoma Folicular/mortalidad , Receptores de Interleucina-2/sangre , Adulto , Anciano , Anticuerpos Monoclonales de Origen Murino , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores , Ciclofosfamida , Doxorrubicina , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Prednisona , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Rituximab , Resultado del Tratamiento , Vincristina
16.
Ann Hematol ; 96(5): 719-724, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28144729

RESUMEN

The development of acute myeloid leukemia (AML) in patients with untreated chronic lymphocytic leukemia (CLL) is rare. We experienced a 65-year-old man who developed AML with aberrant CD7 expression and monoallelic CEBPA mutation during watchful waiting for CLL. He failed to achieve complete response (CR) by standard induction therapy for AML. We retrospectively reviewed 27 patients who developed AML with untreated CLL published between 1973 and 2016. The median age at diagnosis of AML was 68 years, and the median duration between the diagnoses of AML and CLL was 4.2 years. Diagnosis of AML and CLL was made simultaneously in 16 patients. The CR rate of AML was 42.9%, and the median survival was only 1.5 months after the diagnosis of AML. Patients who achieved CR tended to survive longer than those who did not. Our results demonstrated that the development of AML in patients with untreated CLL was associated with a poor response to chemotherapy and an extremely poor prognosis.


Asunto(s)
Leucemia Linfocítica Crónica de Células B/patología , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/etiología , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/etiología , Anciano , Biomarcadores , Médula Ósea/patología , Resultado Fatal , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Incidencia , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Masculino , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/tratamiento farmacológico , Neoplasias Primarias Secundarias/mortalidad , Inducción de Remisión , Análisis de Supervivencia , Resultado del Tratamiento
17.
Acta Haematol ; 137(2): 93-99, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28118621

RESUMEN

The prognosis of patients with systemic lymphoma with central nervous system (CNS) involvement is very poor and there is no established standard therapy. We retrospectively analyzed 18 patients (4 untreated and 14 relapsed) with systemic lymphoma with CNS involvement who received methotrexate and cytarabine-based multiagent chemotherapy (modified Bonn protocol). Complete and partial responses were achieved in 56 and 22% of the patients, respectively. The 1-year overall survival (OS) and progression-free survival (PFS) was 81.0 and 39.2%, respectively. Patients with parenchymal involvement showed a better 1-year PFS than those with either leptomeningeal involvement or both. In a multivariate analysis, poor performance status (PS) was the only independent prognostic factor for the 1-year OS and PFS (HR 10.8, 95% CI 1.09-108, p = 0.042; HR 20.8, 95% CI 2.39-181, p = 0.006, respectively). Grade 4 neutropenia and thrombocytopenia occurred in 17 patients each (94%), but there were no grade 4 nonhematopoietic adverse events. The modified Bonn protocol resulted in relatively favorable response and survival, and provided clinical benefits to patients with good PS, in particular. This study demonstrated that the modified Bonn protocol could be a feasible and encouraging treatment approach for lymphoma with CNS and systemic involvement.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Adolescente , Adulto , Anciano , Neoplasias del Sistema Nervioso Central/mortalidad , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma/mortalidad , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia
18.
Leuk Lymphoma ; 58(2): 316-323, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27267694

RESUMEN

We evaluated 121 patients with follicular lymphoma (FL) and analyzed the association between the soluble interleukin-2 receptor (sIL-2R) level at diagnosis and the cumulative incidence of transformation. By a receiver-operating characteristic analysis, we determined a cutoff value of sIL-2R for transformation at 4360 U/mL to classify patients into two groups. Patients in the high sIL-2R group showed a shorter progression-free survival (PFS) and shorter disease-specific survival (DSS) (p < 0.001 and p = 0.018). Furthermore, the cumulative incidence of transformation in the high sIL-2R group was higher than that in the low sIL-2R group (40.9% vs. 7.3% at 5 years, p < 0.001). In a multivariate analysis, high sIL-2R was an independent predictive risk factor for transformation (HR 7.42, 95% CI: 2.75-20.0, p < 0.001). This study showed that the sIL-2R level at diagnosis may be a prognostic factor for transformation, PFS, and DSS in patients with FL.


Asunto(s)
Biomarcadores de Tumor , Transformación Celular Neoplásica , Linfoma Folicular/sangre , Linfoma Folicular/diagnóstico , Receptores de Interleucina-2/sangre , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Humanos , Linfoma Folicular/mortalidad , Linfoma Folicular/terapia , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Curva ROC , Estudios Retrospectivos , Factores de Riesgo
19.
Hematol Oncol ; 35(3): 357-364, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26639319

RESUMEN

The early clearance of blast cells in peripheral blood (PB) during induction chemotherapy can predict the clinical outcome in acute leukemia. We retrospectively analyzed the kinetics of white blood cell (WBC) count, blast cell percentage (BCP), and blast cell count (BCC) in PB in 78 patients with de novo acute myeloid leukemia who underwent a uniform induction chemotherapy between December 2001 and December 2015 at Jichi Medical University. By a repeated-measures analysis of variance, the interaction of the decline in BCP with the achievement of complete remission (CR) was stronger than those of the decline in WBC or BCC. A receiver operating characteristic curve analysis for the achievement of CR showed that the areas under the curve for the decline in WBC, BCP, and BCC were 0.592, 0.703, and 0.634, respectively, and a decline in BCP of 9.25%/day within 4 or 5 days from induction chemotherapy was the optimal cutoff value. A multivariate analysis showed that a rapid decline in BCP (≥9.25%/day) was a significant predictive factor for CR, independent of the cytogenetic risk (p = 0.0096). A rapid decline in BCP during the first 5 days of induction chemotherapy may be a good predictor of CR. Copyright © 2015 John Wiley & Sons, Ltd.


Asunto(s)
Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Células Mieloides/patología , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Área Bajo la Curva , Terapia Combinada , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Pronóstico , Curva ROC , Inducción de Remisión , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
20.
Ann Hematol ; 95(9): 1513-9, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27365141

RESUMEN

The BEAM regimen consisting of carmustine (BCNU), etoposide, cytarabine, and melphalan (MEL) is widely used before autologous hematopoietic stem cell transplantation (auto-HSCT) for lymphoma. However, intravenous BCNU is not available in Japan, and therefore, ranimustine (MCNU) has been used instead of BCNU (the MEAM regimen). We retrospectively analyzed the outcome of 79 adult patients who underwent auto-HSCT for lymphoma using this regimen in two centers, with 1- and 2-day dosing of MEL, respectively. Three-year overall survival (OS) and progression-free survival (PFS) probabilities were 77.3 and 56.5 % in the entire population and 71.7 and 58.0 % in patients with diffuse large B cell lymphoma. These outcomes were at least equivalent to those with the BEAM regimen. There was no regimen-related pulmonary toxicity. In a multivariate analysis, older age was the only factor that was significantly associated with for OS. In a comparison of the two MEL dosing schedules, while there was no significant differences in either OS or PFS, diarrhea was observed more frequently with 1-day dosing of MEL. In conclusion, the MEAM regimen appeared to be a promising conditioning regimen in auto-HSCT for lymphoma. A large prospective study is warranted to confirm the current findings.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Citarabina/administración & dosificación , Citarabina/efectos adversos , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Etopósido/administración & dosificación , Etopósido/efectos adversos , Neutropenia Febril/inducido químicamente , Femenino , Humanos , Linfoma/clasificación , Masculino , Melfalán/administración & dosificación , Melfalán/efectos adversos , Persona de Mediana Edad , Náusea/inducido químicamente , Compuestos de Nitrosourea/administración & dosificación , Compuestos de Nitrosourea/efectos adversos , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Autólogo , Resultado del Tratamiento , Adulto Joven
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