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1.
Int J Hematol ; 111(3): 388-395, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31897888

RESUMEN

There is a controversy which short term high dose dexamethasone therapy (HDD) or standard dose prednisolone therapy as the initial treatment leads to long term efficacy in idiopathic thrombocytopenic purpura (ITP) patients. We conducted a multicenter, prospective trial to determine the efficacy and safety of short-term HDD in ITP patients aged 18-80 years with platelet counts of < 20 × 109/l, or < 50 × 109/l and bleeding symptoms. The primary endpoints are the proportion of complete response (CR) plus partial response (R) on day 180 after the completion of the 46-day HDD. Twenty-three patients were enrolled. Test for Helicobacter pylori (H. pylori) was positive for 6 patients and negative for 17 patients. In positive patients, 5 were received successful H. pylori eradication therapy. The proportion of CR + R was 60.9% (14/23) with 90% confidence interval of 41.7-77.8%. For patients with positive H. pylori and successful eradication, the proportion of CR + R was 80.0% (4/5). There was one grade 4 adverse event. Although we have enrolled relatively old, severe ITP patients with a median age of 63 years in this study, the efficacy was comparable to the reported clinical trials with HDD therapy.

2.
Acta Med Okayama ; 73(6): 547-552, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31871340

RESUMEN

Elderly multiple myeloma (MM) patients, who are generally ineligible for transplantation, have high risks of death and treatment discontinuation, and require a regimen incorporating novel agents that balance safety, tolerability, and efficacy. We evaluated alternating bortezomib-dexamethasone and lenalidomide-dexamethasone treatments administered over a 63-day cycle in transplant-ineligible elderly patients with newly diagnosed MM. Subcutaneous bortezomib 1.3 mg/m2 was administered weekly on Days 1, 8, 15, and 22; oral lenalidomide 15 mg daily on Days 36-56; and oral dexamethasone 20 mg on Days 1, 8, 15, 22, 36, 43, 50, and 57 for 6 cycles. The primary endpoint was the overall response rate.

3.
Clin Exp Med ; 2019 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-31620907

RESUMEN

Single-nucleotide polymorphisms (SNPs) of the programmed cell death protein-1 (PDCD1), programmed cell death protein-1 ligand-1 (PDCD1LG1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA4) genes are implicated in the pathogenesis of some cancers. We investigated the role of PDCD1, PDCD1LG1, and CTLA4 SNPs in MM pathogenesis and the susceptibility to and clinical features of multiple myeloma (MM). We obtained genomic DNA from 124 patients with MM and 211 healthy controls and detected PDCD1 (rs36084323, rs41386349, and rs2227982), PDCD1LG1 (rs2297136 and rs4143815), and CTLA4 (rs733618, rs11571316, rs231775, and rs3087243) genotypes using the polymerase chain reaction-restriction fragment length polymorphism method or the TaqMan allelic discrimination real-time PCR method. The patients with MM had a significantly higher frequency of the PDCD1 GCC/GCC haplotype (rs36084323/rs41386349/rs2227982) compared with the healthy controls. PDCD1 rs2227982 CC genotype was associated significantly with a higher frequency of bone lesions. Patients with PDCD1LG1 rs2297136 TT and TC types (high-expression types) showed lower albumin level than those with CC genotype. In addition, the PDCD1LG1 rs4143815 CC and CG types (high-expression types) were associated significantly with higher frequency of patients who were treated with thalidomide and/or bortezomib. However, there was no statistical significance between CTLA4 polymorphisms and clinical variables of patients with MM. There were no significant differences between all the polymorphisms and OS. Our study indicates that the PDCD1 haplotype is associated with a susceptibility to MM. The PDCD1 rs2227982 and PDCD1LG1 rs2297136 affect the clinical features of multiple myeloma patients.

4.
Ann Hematol ; 98(7): 1703-1711, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31049648

RESUMEN

In spite of recent development in the treatment armamentarium for multiple myeloma, overall survival (OS) still depends on risk status and sensitivity to treatment of each patient. We have evaluated the clinical relevance of the Revised International Staging System (R-ISS) by comparing it with the original ISS in 718 Japanese patients. The distribution of patients according to response was similar between the ISS and R-ISS stages. Treatment response was greatly influenced by initial treatment modalities and deeper response was observed more frequently in transplanted patients. The R-ISS discriminated the difference in OS between the stages more distinctly than the ISS (p = 9.0 × 10-15 and p = 4.0 × 10-10, respectively). Differences in OS were clarified by both R-ISS and ISS in non-transplanted patients (p = 2.4 × 10-12 and p = 1.4 × 10-8, respectively), but the ISS failed to distinguish the difference between the stages in transplanted patients (p = 0.13). In contrast, the R-ISS could at least discriminate the excellent prognosis of stage I patients whereas the distinction between stage II and III was not that clear (p = 0.033). The R-ISS stage II encompassed a large number of patients, and the prognosis was heterogeneous depending on the fulfillment of prognostic factors such as LDH and adverse cytogenetics. These results suggest that treatment factors and prognostic factors greatly affect the therapeutic response and outcome, and the R-ISS is superior to ISS in prognostication of both transplant-eligible and -ineligible patients in our current clinical practice.


Asunto(s)
Mieloma Múltiple , Adulto , Anciano , Anciano de 80 o más Años , Grupo de Ascendencia Continental Asiática , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia
5.
BMC Infect Dis ; 19(1): 11, 2019 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-30611204

RESUMEN

BACKGROUND: Circulating interferon-γ (IFN-γ) concentration may be sustained at a high level regardless of the initiation of antiretroviral therapy (ART) in some patients with HIV-1 infection. In the present study, we examined the clinical characteristics of HIV-1-infected patients with high levels of plasma IFN-γ. METHODS: The study subjects were patients infected with HIV-1 who were either naïve to ART with CD4+ cell count > 200 cells/µL (n = 12), or had achieved viral suppression after ART for over a year (n = 188). The levels of plasma IFN-γ and interleukin-6 (IL-6) were measured by the enzyme-linked immunosorbent assay. Patients were divided into high IFN-γ and low IFN-γ groups based on a cutoff level of 5 pg/mL. RESULTS: The high IFN-γ group included 41 patients (21%). Compared to the patients on ART with low IFN-γ levels, those on ART in the high IFN-γ group were more likely to be younger than 50 years of age (P = 0.0051) and less likely to have dyslipidemia (P = 0.0476) or to be on a protease inhibitor (P = 0.0449). There was no significant difference between groups in the median increase of CD4+ cell counts from the initiation of ART for up to 3 years. However, after 4 years, the increase in CD4+ cell counts was significantly lower in the high IFN-γ group compared with that in the low IFN-γ group. There were no such significant differences between patients with low and high (> 2 pg/mL) levels of plasma IL-6. CONCLUSION: We concluded that HIV-1-infected patients with high levels of circulating IFN-γ did not have a higher rate of comorbidities related to immune activation. However, they exhibited lower CD4+ cell count recovery after 4 years of being on ART. This deficit could be a consequence of persistent immune activation.


Asunto(s)
Antirretrovirales/uso terapéutico , Farmacorresistencia Viral/genética , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Interferón gamma/sangre , Adulto , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/patología , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Seropositividad para VIH/sangre , Seropositividad para VIH/tratamiento farmacológico , Seropositividad para VIH/epidemiología , VIH-1/clasificación , VIH-1/aislamiento & purificación , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , ARN Viral/análisis , ARN Viral/genética
6.
Int J Hematol ; 108(2): 161-166, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29605873

RESUMEN

Clinical information regarding non-Hodgkin lymphoma (NHL) in adolescents and young adults (AYA) is lacking. We retrospectively analyzed 1426 consecutively registered patients with newly diagnosed NHL. Of 798 DLBCL patients, 42 (5.3%) were identified as AYA (16-39 years). The characteristics of AYA DLBCL patients showed no significant differences compared to older adult DLBCL patients (age ≥ 40 years). Progression-free survival (PFS) and overall survival (OS) in AYA were similar to those in patients aged 40-60 years. However, in older adult groups, PFS and OS were significantly different according to the age group (40-60, 61-79, and ≥ 80 years). In univariate analysis in AYA, performance status, clinical stage, International Prognostic Index (IPI), and age-adjusted IPI significantly affected both PFS and OS. In multivariate analysis, only clinical stage was identified as an independent predictor among AYA. In conclusion, disease characteristics and outcomes of DLBCL in AYA were nearly the same as those in older adults.


Asunto(s)
Linfoma de Células B Grandes Difuso , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
7.
Acta Med Okayama ; 72(2): 197-201, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29674771

RESUMEN

Standard therapy for idiopathic thrombocytopenic purpura (ITP) has not been established. We are conducting a multicenter, prospective trial to determine the efficacy and safety of short-term, high-dose dexamethasone therapy in ITP patients aged 18-80 years with platelet counts of <20, 000 /µL, or with <50, 000/ µL and bleeding symptoms. The primary endpoints of this trial are the proportion of responses (complete plus partial response) on day 180 (day 46+180) after the completion of the 46-day high-dose dexamethasone therapy. The results of this investigation of the effectiveness and safety of this regimen will be essential for the establishment of standard therapy for ITP.


Asunto(s)
Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Adulto , Anciano , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Dexametasona/administración & dosificación , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Glucocorticoides/administración & dosificación , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/aislamiento & purificación , Hepatitis B/complicaciones , Hepatitis B/tratamiento farmacológico , Antagonistas de los Receptores Histamínicos H2/uso terapéutico , Humanos , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/uso terapéutico , Adulto Joven
8.
J Clin Exp Hematop ; 58(1): 10-16, 2018 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-29415976

RESUMEN

Recent studies have revealed the clinical and biological features of stage I follicular lymphoma (FL), but information about patients with stage I FL who underwent total resection after tissue biopsy is limited. Among 305 FL patients diagnosed between 2001 and 2013, clinical stage I disease was observed in 36 patients. Of these, 18 patients underwent total resection after diagnostic tissue biopsy. We used 18F-fluorodeoxyglucose positron emission CT for staging assessment in 13 of 18 patients (72.2%). The median age was 56.5 years. Six patients (33.3%) were male. The soluble interleukin-2 receptor alpha concentration was significantly lower than in patients with residual disease. Among these 18 patients, 7 patients (38.9%) were treated with a "watch-and-wait" (WW) policy, 7 (38.9%) were treated with involved-field irradiation, and 4 (22.2%) received systemic chemotherapy. Patients with resected disease were treated with significantly different strategies from those with residual disease (p = 0.0026). Five patients experienced relapse during follow-up (median follow-up: 48.2 months). All relapses were distant from the primary site, irrespective of treatment strategy. Among all stage I patients, disease resection was not a significant factor for survival (p = 0.9294). Collectively, the choice of treatment strategy was significantly influenced by patient status. Resection status was not significantly associated with survival after several treatment strategies.


Asunto(s)
Glucosa-6-Fosfato/análogos & derivados , Linfoma Folicular , Tomografía de Emisión de Positrones , Anciano , Supervivencia sin Enfermedad , Femenino , Glucosa-6-Fosfato/administración & dosificación , Humanos , Linfoma Folicular/diagnóstico por imagen , Linfoma Folicular/mortalidad , Linfoma Folicular/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasia Residual , Tasa de Supervivencia
10.
Hematol Oncol ; 36(1): 196-201, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28786198

RESUMEN

Single nucleotide polymorphisms (SNPs) in interleukin 17 (IL17A) and IL-23 receptor (IL23R) are involved in the pathogenesis of many cancers and autoimmune diseases. We investigated the influence of IL17A and IL23R SNPs on the risk of developing multiple myeloma (MM) and its clinical features. We obtained genomic DNA from 120 patients with MM and 201 healthy controls and detected IL17A -197 G/A (rs2275913) and IL23R H3Q (rs1884444) genotypes using the polymerase chain reaction-restriction fragment length polymorphism method. There were no significant differences in the genotype and allele frequencies of IL17A -197 G/A and IL23R H3Q between the controls and patients with MM. Compared with the GG and GA genotypes, the IL17A AA genotype was significantly associated with lower hemoglobin levels. The IL23R HH genotype was significantly associated with higher frequency of bone lesions and plasmacytoma than the HQ and QQ genotypes. We observed significant differences in overall survival (OS) between patients treated with thalidomide and/or bortezomib and those treated conventionally. Therefore, we also examined the effect of IL17A and IL23R polymorphisms on the clinical variables and OS in patients treated with thalidomide and/or bortezomib. We observed that the IL23R HH genotype was significantly associated with poor survival compared with the QH and HH genotypes in these patients. Our findings indicate that IL17A -197 G/A and IL23R H3Q are not associated with susceptibility to MM. However, IL-17 and IL-23R polymorphisms may affect severity, bone lesions, and extra-medullary disease in patients with MM. Moreover, IL23R polymorphisms may contribute to poor prognosis in patients with MM treated with thalidomide and/or bortezomib.


Asunto(s)
Interleucina-17/genética , Mieloma Múltiple/genética , Receptores de Interleucina/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Polimorfismo de Nucleótido Simple , Pronóstico , Análisis de Supervivencia
11.
Leuk Lymphoma ; 58(12): 2845-2851, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28509595

RESUMEN

Rituximab has markedly improved the outcomes of B cell lymphoma, and its maintenance has been shown to be beneficial in low grade B cell lymphoma (LGBCL). We conducted a multicenter, phase II trial of intensive rituximab induction and maintenance therapy for LGBCL to optimize the rituximab monotherapy. Patients with newly diagnosed or rituximab naïve relapsed LGBCL received 8 weekly rituximab as induction, then continued maintenance therapy with rituximab for 4 weeks at 6-month intervals. The primary endpoint was the overall response rate (ORR). Forty-five patients were enrolled from 2005 to 2009 and 36 were eligible. The ORR was 83.3% (30/36) with a complete response rate of 72.2% (26/36). The 3-year progression-free survival (PFS) was 76.7% with a median follow-up of 43.0 months. Five grade three toxicities were observed (no grade 4). Our findings suggest that this regimen demonstrates high activity with durable PFS and minimal toxicity in LGBCL patients.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/patología , Rituximab/uso terapéutico , Adulto , Anciano , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Esquema de Medicación , Femenino , Humanos , Quimioterapia de Inducción , Linfoma de Células B/mortalidad , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Rituximab/administración & dosificación , Rituximab/efectos adversos , Resultado del Tratamiento
12.
Hematol Oncol ; 35(4): 711-718, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27405747

RESUMEN

Interleukin-10 (IL-10) and IL-10 receptor (IL-10R) single nucleotide polymorphisms have been implicated in the pathogenesis of many cancers. We investigated the influence of IL-10 -592C/A, IL-10RA I224V, and IL-10RB K47E on the risk of developing multiple myeloma (MM) and the clinical features of MM. We extracted the genomic DNA from 128 MM patients and 202 healthy controls and used polymerase chain reaction-restriction fragment length polymorphism method to detect IL-10 promoter -592C/A (rs1800872), IL-10RA (rs2228055), and IL-10RB K47E (rs2834167) genotypes. Overall survival (OS) was defined as the interval from the date of diagnosis to the date of death or last clinical appointment. No statistically significant difference was observed in the genotype and allele frequencies of IL-10 -592C/A, IL-10RA I224V, and IL-10RB K47E between MM patients and healthy controls. IL-10RA II genotype was significantly associated with a hemoglobin level lower than that of IV and VV genotypes (mean ± standard deviation, 9.21 ± 2.46 vs 10.3 ± 2.33 g/dL; P = .021). IL-10 -592 AA genotype was significantly associated with OS better than that of CA and CC genotypes (median OS, 74.5 vs 46.3 months; P = .047). We observed significant differences in survival between patients treated with thalidomide and/or bortezomib and those treated with conventional treatments (median OS, 74.5 vs 38.2 months; P = .021). Therefore, we also examined the effect of IL-10 and IL-10R polymorphisms on the clinical variables and OS of patients treated with thalidomide and/or bortezomib. In addition, IL-10RB EE genotype was significantly associated with poorer survival than KK and KE genotypes (median OS, 46.3 vs 78.8 months; P = .015). Our findings indicate that IL-10 and IL-10R gene polymorphisms may not contribute to the susceptibility to MM but may be associated with the severity and prognosis of MM. In particular, IL-10RB K47E polymorphism may contribute to the poor prognosis of MM patients treated with thalidomide and/or bortezomib.


Asunto(s)
Predisposición Genética a la Enfermedad , Subunidad beta del Receptor de Interleucina-10/genética , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib/administración & dosificación , Bortezomib/uso terapéutico , Estudios de Casos y Controles , Terapia Combinada , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Interleucina-10/genética , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Talidomida/administración & dosificación , Talidomida/uso terapéutico
13.
Int J Hematol ; 105(4): 478-484, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27873176

RESUMEN

Chemotherapy-induced nausea and vomiting (CINV) is a significant side effect in multiple myeloma (MM) patients receiving high-dose melphalan treatment followed by autologous stem cell transplantation (ASCT). We evaluated the efficacy and safety of a triple antiemetic combination of palonosetron, aprepitant, and low-dose dexamethasone in 24 MM patients who received melphalan conditioning (100 mg/m2 on days 1-2) before ASCT (on day 4). Intravenous palonosetron (0.75 mg on day 1), oral aprepitant (125 mg on day 1; 80 mg on days 2-4), and intravenous dexamethasone (6.6 mg on days 1-4) were administered for prevention of CINV. Complete response (no emesis and no rescue antiemetic) and complete control (no emesis, no rescue antiemetic, and no more than mild nausea) rates were 75 and 68% during the overall phase (0-120 h), while they were 88 and 86% in the acute phase (0-48 h), 75 and 68% in the delayed phase (48-120 h), and 67 and 59% in the extended phase (120-168 h), respectively. There were no serious adverse events related to the antiemetic therapy. In conclusion, the three-antiemetic regimen consisting of palonosetron, aprepitant, and dexamethasone was safe and effective for controlling CINV due to high-dose melphalan treatment, especially during the delayed phase.


Asunto(s)
Antieméticos/uso terapéutico , Quimioterapia Combinada/métodos , Melfalán/administración & dosificación , Mieloma Múltiple/terapia , Náusea y Vómito Posoperatorios/prevención & control , Trasplante Autólogo/métodos , Adulto , Anciano , Aprepitant , Dexametasona/administración & dosificación , Humanos , Isoquinolinas/administración & dosificación , Persona de Mediana Edad , Morfolinas/administración & dosificación , Agonistas Mieloablativos/uso terapéutico , Palonosetrón , Náusea y Vómito Posoperatorios/tratamiento farmacológico , Quinuclidinas/administración & dosificación , Resultado del Tratamiento
14.
Rinsho Ketsueki ; 57(6): 771-3, 2016 06.
Artículo en Japonés | MEDLINE | ID: mdl-27384859

RESUMEN

We describe a patient who developed repeated rituximab-induced serum sickness (RISS) followed by anaphylaxis soon after the third administration of rituximab at relapse. A 65-year-old woman with Sjögren's syndrome and relapsed mucosal associated lymphoma tissue (MALT) lymphoma of the lung underwent rituximab monotherapy (375 mg/m(2)/week). Several days after the second exposure to rituximab, she developed a rash, fever, and arthralgia. These symptoms showed relief, but a severe anaphylactic reaction occurred when she was treated with rituximab for the third time. Although a rare complication in patients with lymphoma, clinicians should be aware of RISS symptoms and avoid repeatedly administering rituximab to such patients.


Asunto(s)
Anafilaxia/inducido químicamente , Antineoplásicos/efectos adversos , Rituximab/efectos adversos , Enfermedad del Suero/inducido químicamente , Anciano , Antineoplásicos/uso terapéutico , Femenino , Humanos , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Rituximab/uso terapéutico
15.
Ann Hematol ; 95(6): 921-9, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27044390

RESUMEN

Bortezomib is one of the most widely used novel drugs for the treatment of multiple myeloma (MM). However, twice-weekly intravenous administration is associated with innegligible adverse events and treatment discontinuation. We therefore evaluated the long-term efficacy and feasibility of reduced frequency treatment with intravenous bortezomib in elderly patients with relapsed and/or refractory MM. A total of 47 bortezomib-naïve patients (median age 75 years) received bortezomib (1.3 mg/m(2), intravenously) and dexamethasone (20 mg) on days 1, 8, and 15 of every 4-week cycle. Twenty-six patients completed the planned 8 cycles. Best responses were stringent complete response (sCR) in 5 patients, very good partial response (VGPR) in 3, PR in 15, stable disease (SD) in 18, and disease progression (PD) in 6, respectively. Median progression-free and overall survivals were 9.6 and 35.1 months, respectively. After progression, 11 patients were retreated with bortezomib-based regimens and another 24 patients with immunomodulatory drugs. Multivariate analysis revealed that ISS 3, t(4;14), and <4 therapy cycles were significantly poor prognostic factors and that subsequent therapy with bortezomib-based regimens was a favorable factor for extended OS. The common adverse events were diarrhea, constipation, and peripheral neuropathy with no grade 4 toxicity. In conclusion, reduced frequency treatment with intravenous bortezomib + dexamethasone is an effective option for elderly patients with MM.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bortezomib/administración & dosificación , Dexametasona/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/epidemiología , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/epidemiología , Estudios Prospectivos , Resultado del Tratamiento
16.
Int J Hematol ; 103(1): 79-85, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26588925

RESUMEN

UNLABELLED: We performed a phase 1 study to evaluate the safety and feasibility of bortezomib (BOR) with melphalan and dexamethasone (BMD) in patients with light chain amyloidosis (AL) without severe cardiac failure. Patients received BOR on a twice-weekly schedule (days 1, 4, 8, and 11 of 28-day treatment cycles) at planned doses of 1.0 (dose level 1) and 1.3 (dose level 2) mg/m(2) in combination with melphalan 8 mg/m(2) on days 1-4 and dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12. Dose-limiting toxicity (DLT) was evaluated at the end of cycle one, and treatment was continued for four cycles. Six patients were enrolled at dose level 1, and one showed DLT (grade 3: herpes zoster). Further 3 patients were enrolled at dose level 2, and none experienced DLT. Thus, the maximum tolerated dose was defined as BOR doses of 1.3 mg/m(2) for the twice-weekly schedule. A total of 32 cycles of BMD therapy were given, and the most common hematologic toxicity was thrombocytopenia (47%). Peripheral neuropathy was the most common non-hematologic toxicity (16%). We demonstrated that BMD is safe and tolerable for Japanese AL patients without severe cardiac damage. CLINICAL TRIAL REGISTRATION: UMIN000006604.


Asunto(s)
Amiloidosis/tratamiento farmacológico , Bortezomib/administración & dosificación , Dexametasona/efectos adversos , Melfalán/efectos adversos , Adulto , Anciano , Esquema de Medicación , Quimioterapia Combinada , Estudios de Factibilidad , Femenino , Humanos , Infusiones Intravenosas , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Recurrencia , Resultado del Tratamiento
17.
Int J Hematol ; 103(2): 219-26, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26588928

RESUMEN

The incidence of chronic lymphocytic leukemia (CLL) is low in Japan. The clinical course ranges from very indolent to rapidly progressive. Recently, several reports have indicated that mutation of the splicing factor 3b, subunit 1 (SF3B1) gene in CLL is predictive of a poor prognosis. Here, we investigated the SF3B1 mutational status of Japanese CLL patients and clarified the association between SF3B1 mutational status and prognostic factors. One hundred and two patients that were referred to our institutions between 1999 and 2013 were enrolled. Mutation analysis of SF3B1 (n = 87) and of the immunoglobulin heavy chain gene (IGHV) (n = 102) was performed at diagnosis. FISH analysis of del(11)(q22) was performed for 17 patients. Seven patients have SF3B1 mutation (8.0 %: K700E, 5/7; G742D, 1/7 and Y623C, 1/7). The median survival times for patients with mutated and non-mutated SF3B1 were 53 and 130 months, respectively. Overall survival of the mutated SF3B1 group was significantly lower than that of the non-mutated group (p = 0.0187). No relationship was observed between IGHV mutational status and SF3B1 mutation. There was no patient with SF3B1 mutation in the IGHV1-69 population (0/2). In conclusion, mutation of SF3B1 at diagnosis in Japanese CLL patients is predictive of a poor prognosis.


Asunto(s)
Cadenas Pesadas de Inmunoglobulina/genética , Leucemia Linfocítica Crónica de Células B/genética , Mutación , Fosfoproteínas/genética , Factores de Empalme de ARN/genética , Adulto , Anciano , Anciano de 80 o más Años , Grupo de Ascendencia Continental Asiática , Progresión de la Enfermedad , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico
18.
Int J Hematol ; 102(3): 271-7, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26177588

RESUMEN

Lenalidomide treatment in combination with dexamethasone and/or chemotherapy is associated with a significant risk of venous thromboembolism (VTE) in patients with multiple myeloma (MM). However, the incidence of asymptomatic VTE in lenalidomide-treated MM patients remains unclear. A total of 80 relapsed and refractory MM patients treated with lenalidomide-containing regimens in a single institution between July 2010 and July 2014 were retrospectively analyzed. Of these, eight patients had asymptomatic VTE before starting lenalidomide. The remaining 72 patients received thromboprophylaxis with low-dose aspirin (100 mg daily) and monitoring of plasma D-dimer levels on each visit. During the median follow-up time of 7.3 months (range 1.0-43.5 months), 29 patients (40.3 %) showed an elevation of D-dimer (≥2.5 µg/mL), and 13 (18.1 %) showed asymptomatic VTE in a lower extremity. Median time to asymptomatic VTE events from initiation of lenalidomide treatment was 3.0 months (range 1.0-13.1 months). All patients having an asymptomatic VTE continued lenalidomide treatment on warfarinization (target international normalized ratio 1.5-2.5), and none of them developed symptomatic VTE. In conclusion, an asymptomatic VTE event occurred in 18 % of Japanese MM patients receiving lenalidomide-containing therapy despite aspirin prophylaxis. Serial monitoring of plasma D-dimer levels and early intervention may help to prevent symptomatic or lethal VTE events.


Asunto(s)
Mieloma Múltiple/tratamiento farmacológico , Talidomida/análogos & derivados , Tromboembolia Venosa/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Lenalidomida , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/complicaciones , Estudios Retrospectivos , Talidomida/administración & dosificación , Tromboembolia Venosa/sangre , Tromboembolia Venosa/etiología
19.
Eur J Haematol ; 94(2): 145-51, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24981274

RESUMEN

Various prognostic markers for multiple myeloma (MM) have been identified, and stratification using these markers is considered important to optimize treatment strategies. The international staging system (ISS) is now a widely accepted prognostic staging system for MM patients; however, its validity is controversial in the era of new therapeutic regimens, since ISS had been established before introduction of new agents. We retrospectively reviewed prognostic factors in order to seek out an alternative staging system more suitably applied to MM patients treated with novel agents. We analyzed 178 newly diagnosed MM patients who received either conventional chemotherapy without novel agents (CT; n = 79) or chemotherapy with novel agents (NT; n = 99). Although median overall survival (OS) of patients treated with CT is significantly different depending on stages of ISS, ISS had no effect on OS among patients treated with NT. Meanwhile, we identified hemoglobin (Hb) and plasmacytoma as independent risk factors for OS in patients who received NT. Using these two parameters, we stratified NT patients into three stages; stage 1 (Hb≥10 g/dL and absence of plasmacytoma), stage 2 (not stage 1 or 3), and stage 3 (Hb <10 g/dL and presence of plasmacytoma). We found that there were significant differences in median OS among the three stages (8.13, 5.95, and 2.45 yr for stages 1, 2, and 3, respectively). This preliminary study suggests that this alternative staging system based on Hb and plasmacytoma is a simple and useful way to predict prognosis of MM patients in the novel agent era.


Asunto(s)
Mieloma Múltiple/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Estadificación de Neoplasias , Pronóstico , Resultado del Tratamiento
20.
Cancer Sci ; 105(11): 1496-502, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25220100

RESUMEN

L-type amino-acid transporter 1 (LAT1) plays a key role in cell growth and survival. To determine the prognostic significance of LAT1 in multiple myeloma (MM), we investigated the expression of LAT1 and its functional subunit, 4Fc heavy chain (CD98), on myeloma cells by immunohistochemistry in 100 newly diagnosed MM patients. High expression (moderate or strong staining intensity) of LAT1 and CD98 was detected in 56% and 45% of patients, respectively. The LAT1 expression score was positively correlated with Ki-67 index (r = 0.631, P < 0.001), and there was a statistically significant difference in Durie-Salmon stage between patients with high and low LAT1 expression (P = 0.03). In 43 patients treated with melphalan and prednisolone, the overall response rate was significantly higher in the high LAT1 expression group (60.0%) than in the low LAT1 expression group (17.6%) (P = 0.03). Multivariate analysis confirmed that high expression of LAT1 was a significant prognostic factor for predicting poor overall survival independently from the International Staging System (both P = 0.01). Here, we show that the overexpression of LAT1 is significantly associated with high proliferation and poor prognosis in newly diagnosed MM patients. Thus, LAT1 may be a promising pathological marker for identifying high-risk MM.


Asunto(s)
Transportador de Aminoácidos Neutros Grandes 1/genética , Mieloma Múltiple/genética , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Aberraciones Cromosómicas , Femenino , Proteína-1 Reguladora de Fusión/metabolismo , Expresión Génica , Humanos , Inmunohistoquímica , Transportador de Aminoácidos Neutros Grandes 1/metabolismo , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Estadificación de Neoplasias , Pronóstico , Resultado del Tratamiento
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