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1.
Cureus ; 15(10): e47816, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38022225

RESUMO

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.
Ann Hematol ; 99(1): 49-55, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31853702

RESUMO

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.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombose , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Trombose/etiologia , Trombose/mortalidade
3.
Acta Haematol ; 143(3): 250-259, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31461700

RESUMO

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.


Assuntos
Sulfatos de Condroitina/uso terapêutico , Dermatan Sulfato/uso terapêutico , Neoplasias Hematológicas/sangue , Heparitina Sulfato/uso terapêutico , Inibidores de Proteases/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transfusão de Componentes Sanguíneos , Sulfatos de Condroitina/efeitos adversos , Dermatan Sulfato/efeitos adversos , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/terapia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Neoplasias Hematológicas/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/mortalidade , Heparitina Sulfato/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Plasma , Inibidores de Proteases/efeitos adversos , Tempo de Protrombina , Estudos Retrospectivos , Resultado do Tratamento
4.
Blood Adv ; 3(21): 3266-3277, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31698458

RESUMO

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.


Assuntos
Terapia Combinada/economia , Análise Custo-Benefício , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Antineoplásicos/uso terapêutico , Tomada de Decisão Clínica , Terapia Combinada/métodos , Árvores de Decisões , Gerenciamento Clínico , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Cadeias de Markov , Terapia de Alvo Molecular/economia , Terapia de Alvo Molecular/métodos , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , Resultado do Tratamento
5.
Acta Haematol ; 141(3): 158-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30799408

RESUMO

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.


Assuntos
Autoanticorpos , Hiperplasia do Linfonodo Gigante , Doenças do Mediastino , Púrpura Trombocitopênica Idiopática , Tomografia Computadorizada por Raios X , Autopsia , Hiperplasia do Linfonodo Gigante/sangue , Hiperplasia do Linfonodo Gigante/diagnóstico por imagem , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/terapia , Evolução Fatal , Feminino , Humanos , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/patologia , Hemorragias Intracranianas/terapia , Doenças do Mediastino/sangue , Doenças do Mediastino/diagnóstico por imagem , Doenças do Mediastino/patologia , Doenças do Mediastino/terapia , Pessoa de Meia-Idade , Derrame Pleural/sangue , Derrame Pleural/diagnóstico , Derrame Pleural/patologia , Derrame Pleural/terapia , Mielofibrose Primária/sangue , Mielofibrose Primária/diagnóstico por imagem , Mielofibrose Primária/patologia , Mielofibrose Primária/terapia , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico por imagem , Púrpura Trombocitopênica Idiopática/patologia , Púrpura Trombocitopênica Idiopática/terapia
6.
Int J Hematol ; 109(2): 141-146, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30536180

RESUMO

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.


Assuntos
Coagulação Intravascular Disseminada/tratamento farmacológico , Gabexato/uso terapêutico , Guanidinas/uso terapêutico , Neoplasias Hematológicas/complicações , Adulto , Anticoagulantes/uso terapêutico , Benzamidinas , Coagulação Intravascular Disseminada/etiologia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inibidores de Serina Proteinase/uso terapêutico , Resultado do Tratamento
7.
Ann Hematol ; 98(5): 1127-1133, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30474718

RESUMO

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.


Assuntos
Crise Blástica , Células da Medula Óssea , Leucócitos Mononucleares , Síndromes Mielodisplásicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Crise Blástica/classificação , Crise Blástica/metabolismo , Crise Blástica/mortalidade , Crise Blástica/patologia , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Intervalo Livre de Doença , Feminino , Humanos , Hiperplasia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/classificação , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Estudos Retrospectivos , Taxa de Sobrevida
8.
Leuk Lymphoma ; 60(3): 703-710, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30188227

RESUMO

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.


Assuntos
Biomarcadores Tumorais , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Medula Óssea/patologia , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Proteínas WT1/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Transfusão de Sangue , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/terapia , Prognóstico , RNA Mensageiro/genética , Curva ROC , Estudos Retrospectivos , Transplante Homólogo , Proteínas WT1/sangue
9.
Clin Lymphoma Myeloma Leuk ; 18(12): e521-e527, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30181104

RESUMO

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.


Assuntos
Biomarcadores Tumorais , Expressão Gênica , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Proteínas WT1/genética , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Detecção Precoce de Câncer , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Prognóstico , RNA Mensageiro/genética , Recidiva , Adulto Jovem
10.
J Infect Chemother ; 24(10): 812-814, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30006248

RESUMO

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.


Assuntos
Antibacterianos/administração & dosagem , Osteomielite/tratamento farmacológico , Penicilina G/administração & dosagem , Infecções Pneumocócicas/tratamento farmacológico , Streptococcus pneumoniae/efeitos dos fármacos , beta-Glucanas/sangue , Antibacterianos/farmacologia , Reações Falso-Positivas , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite/sangue , Osteomielite/etiologia , Penicilina G/farmacologia , Infecções Pneumocócicas/sangue , Infecções Pneumocócicas/complicações
11.
Hematology ; 23(8): 470-477, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29486661

RESUMO

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.


Assuntos
Rearranjo Gênico , Neoplasias Hematológicas , Transtornos Mieloproliferativos , Proteínas de Neoplasias/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Adulto , Feminino , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/metabolismo , Transtornos Mieloproliferativos/mortalidade , Transtornos 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/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo
12.
Cancer Genet ; 220: 44-48, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29310838

RESUMO

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.


Assuntos
Cadeias Pesadas de Imunoglobulinas/genética , Linfoma Folicular/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Translocação Genética , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 18 , Cromossomos Humanos Par 8 , Análise Citogenética/métodos , Citometria de Fluxo , Genes myc , Humanos , Linfoma Folicular/metabolismo , Masculino , Pessoa de Meia-Idade
13.
Int J Hematol ; 107(6): 712-715, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29185155

RESUMO

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.


Assuntos
Compostos de Anilina/administração & dosagem , Dasatinibe/administração & dosagem , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Mesilato de Imatinib/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Linfoma Folicular/complicações , Linfoma Folicular/tratamento farmacológico , Nitrilas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Quinolinas/administração & dosagem , Compostos de Anilina/efeitos adversos , Dasatinibe/efeitos adversos , Substituição de Medicamentos , Humanos , Mesilato de Imatinib/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
14.
Int J Hematol ; 106(3): 411-417, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28508228

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/tratamento farmacológico , Contagem de Leucócitos , Aclarubicina/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Adulto Jovem
15.
Hematology ; 22(9): 521-526, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28413914

RESUMO

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.


Assuntos
Linfoma Folicular/sangue , Linfoma Folicular/mortalidade , Receptores de Interleucina-2/sangue , Adulto , Idoso , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores , Ciclofosfamida , Doxorrubicina , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prednisona , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Rituximab , Resultado do Tratamento , Vincristina
16.
Ann Hematol ; 96(5): 719-724, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28144729

RESUMO

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.


Assuntos
Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/etiologia , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/etiologia , Idoso , Biomarcadores , Medula Óssea/patologia , Evolução Fatal , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Incidência , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Masculino , Estadiamento de Neoplasias , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/mortalidade , Indução de Remissão , Análise de Sobrevida , Resultado do Tratamento
17.
Acta Haematol ; 137(2): 93-99, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28118621

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/mortalidade , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Linfoma/mortalidade , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
18.
Leuk Lymphoma ; 58(2): 316-323, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27267694

RESUMO

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.


Assuntos
Biomarcadores Tumorais , Transformação Celular Neoplásica , Linfoma Folicular/sangue , Linfoma Folicular/diagnóstico , Receptores de Interleucina-2/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Linfoma Folicular/mortalidade , Linfoma Folicular/terapia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco
19.
Hematol Oncol ; 35(3): 357-364, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26639319

RESUMO

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.


Assuntos
Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Células Mieloides/patologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Área Sob a Curva , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Curva ROC , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
20.
Ann Hematol ; 95(9): 1513-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27365141

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Neutropenia Febril/induzido quimicamente , Feminino , Humanos , Linfoma/classificação , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Compostos de Nitrosoureia/administração & dosagem , Compostos de Nitrosoureia/efeitos adversos , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
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