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1.
Rinsho Ketsueki ; 65(6): 492-497, 2024.
Artículo en Japonés | MEDLINE | ID: mdl-38960646

RESUMEN

A 69-year-old man presented with lumbago and was diagnosed with multiple myeloma (IgD-λ type, R-ISS stage II) with bone-destructive lesions in the lumbar spine and sacrum. Chromosome analysis showed t (8;14)(q24;q32) and t (11;14)(q13;q32). Treatment with daratumumab, lenalidomide, and dexamethasone resulted in partial response, but the disease relapsed, with a copy number increase in t (11;14) and abnormal amplification of the 1q21 region. The patient was treated for CMV enteritis, and was admitted to the hospital due to sudden abdominal pain. Gastrointestinal perforation was diagnosed by CT scan showing free air and wall thickening in the small intestine. Emergency surgery was performed, and the tumors in the perforated area were positive for CCND1 but negative for MYC on immunostaining. The patient's general condition did not improve after the surgery and he died. Pathological autopsy revealed extramedullary infiltration of multiple organs in addition to the small intestine. Extramedullary infiltration is thought to be caused by clonal evolution, and further research is warranted to clarify its pathogenesis and establish effective therapeutic strategies in high-risk patients.


Asunto(s)
Mieloma Múltiple , Humanos , Masculino , Mieloma Múltiple/patología , Mieloma Múltiple/diagnóstico , Anciano , Resultado Fatal , Translocación Genética , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 11
2.
Rinsho Ketsueki ; 64(3): 198-202, 2023.
Artículo en Japonés | MEDLINE | ID: mdl-37019673

RESUMEN

The patient is a 45-year-old man who was diagnosed with severe hemophilia A during childhood and received FVIII replacement therapy, which became ineffective due to inhibitor production (5-225 BU/ml). After initiating emicizumab therapy, bleeding symptoms markedly improved, but he developed an intramuscular hematoma at the right thigh due to a fall. He was hospitalized and maintained on bed rest; however, the size of the hematoma increased, and anemia developed. Since the inhibitor level was markedly decreased at 0.6 BU/ml, a recombinant FVIII preparation was administered, and the size of the hematoma decreased along with an increase in FVIII activity. Levels of the inhibitor increased to 54.2 BU/ml, but tended to decrease during continued emicizumab treatment. Emicizumab therapy seems useful in hemophilia A patients with inhibitor production.


Asunto(s)
Factor VIII , Hemofilia A , Masculino , Humanos , Persona de Mediana Edad , Hemofilia A/diagnóstico , Hemorragia , Hematoma
3.
Rinsho Ketsueki ; 63(7): 733-739, 2022.
Artículo en Japonés | MEDLINE | ID: mdl-35922940

RESUMEN

Acquired factor V deficiency is a rare disease that presents with various bleeding symptoms because of the acquired production of factor V inhibitors and decrease in factor V activity. We have experienced five cases of acquired factor V deficiency diagnosed on the basis of abnormalities in coagulation tests in the last 10 years. All five patients were older men, of whom one had no bleeding symptoms, and three had a history of renal failure and malignant tumors. In the cross-mixing test, two of three cases demonstrated an inhibitor pattern, but one case showed a deficient pattern. In all cases, steroid treatment improved factor V activity as well as prothrombin time and activated partial thromboplastin time. However, patients with intracranial hemorrhage had a poor prognosis. Although this disease is rare, careful management is necessary, especially in the absence of bleeding symptoms and where cross-mixing test does not show an inhibitor pattern.


Asunto(s)
Deficiencia del Factor V , Anciano , Pruebas de Coagulación Sanguínea/efectos adversos , Factor V/genética , Deficiencia del Factor V/complicaciones , Deficiencia del Factor V/diagnóstico , Hemorragia/etiología , Humanos , Masculino , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina
4.
Br J Haematol ; 195(2): 217-229, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34318926

RESUMEN

This nationwide multicentre retrospective study was performed to analyze clinical features that predict the prognosis of central nervous system invasion in multiple myeloma (CNS-MM, approximately 1% of MM). Overall, of the 77 adult patients with CNS-MM identified between 2005 and 2016, those diagnosed at MM diagnosis (n = 3) had longer overall survival (OS) than those diagnosed at relapse (n = 74; median: 48·5 vs 2·7 months). Therefore, we compared the relapsed MM with CNS-MM in patients with any treatment (n = 60). Multivariate analyses revealed that lenalidomide treatment [hazard ratio (HR) 0·27, P = 0·003], intrathecal chemotherapy (IT; HR 0·54, P = 0·05), and radiation therapy (RTx; HR 0·33, P < 0·001) for CNS-MM had a positive effect on longer OS. These factors were used to develop a scoring system combining the number of treatments with lenalidomide, IT, and RTx (0, 1, 2, 3). The OS of CNS-MM patients was stratified based on these factors, with a median OS of 1·1, 4·5, and 7·5 months for patients with zero, one, two to three favourable features, respectively (0 vs 1, P = 0·0002; 1 vs 2-3, P = 0·08). Multimodal treatment including lenalidomide in addition to conventional IT and RTx can improve OS.


Asunto(s)
Sistema Nervioso Central/patología , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Invasividad Neoplásica/patología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Casos y Controles , Terapia Combinada , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/uso terapéutico , Inyecciones Espinales , Japón/epidemiología , Lenalidomida/administración & dosificación , Lenalidomida/uso terapéutico , Masculino , Persona de Mediana Edad , Mieloma Múltiple/epidemiología , Pronóstico , Radioterapia/métodos , Proyectos de Investigación , Estudios Retrospectivos , Encuestas y Cuestionarios , Análisis de Supervivencia
5.
Ann Hematol ; 99(5): 1063-1072, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32248251

RESUMEN

These are the results of phase II study of bortezomib-melphalan-prednisolone (VMP) induction therapy followed by lenalidomide-dexamethasone (Rd) consolidation and lenalidomide maintenance in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), overall response rates (ORRs), and safety. Eighty-three eligible patients were enrolled between October 2012 and August 2014. The median PFS was 28.0 months (95% CI 19.6-36.7) and the median OS was 55.3 months (95% CI 51.6-NA). Among the patients who received lenalidomide maintenance therapy, median PFS was significantly improved in patients who had achieved a very good partial response (VGPR) or better (41.8 vs 20.7 months, p = 0.0070). As the best response, the rates of partial response or better were 85.5% comprising stringent complete response (sCR, 21.7%), complete response (CR, 10.8%), VGPR (18.1%), and partial response (PR, 34.9%). The most frequently observed grade 3 or higher adverse events during the VMP therapy were anemia (28.9%), neutropenia (15.6%), thrombocytopenia (6.0%), and peripheral neuropathy (2.4%). The most frequently observed grade 3 or higher adverse events during the Rd therapy were anemia (3.5%), neutropenia (1.8%), and skin rush (5.3%). The most frequently observed grade 3 or higher adverse events during lenalidomide maintenance therapy were anemia (7.4%) and neutropenia (24.1%). Thus, VMP induction therapy followed by Rd consolidation and lenalidomide maintenance is considered a well-tolerated and effective regimen in transplant-ineligible NDMM. This trial is registered with UMIN-CTR with the identification number UMIN000009042.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mieloma Múltiple , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bortezomib/administración & dosificación , Bortezomib/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Lenalidomida/administración & dosificación , Lenalidomida/efectos adversos , Masculino , Melfalán/administración & dosificación , Melfalán/efectos adversos , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Prednisolona/administración & dosificación , Prednisolona/efectos adversos , Tasa de Supervivencia
6.
Cancer Sci ; 110(9): 2924-2932, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31336012

RESUMEN

This multicenter, open-label phase 1/2 study evaluated single-agent carfilzomib in 50 heavily pretreated Japanese patients with relapsed/refractory multiple myeloma (median of five prior treatments). In phase 1, patients were dosed at three levels: 15, 20, or 20/27 mg/m2 . Maximum tolerated dosage was not reached at the tolerability evaluation. Patients in phase 2 were treated with 20/27 mg/m2 carfilzomib. Median duration of exposure to carfilzomib in the 20/27 mg/m2 group at this final analysis was 4.7 months (range: 0.3-39.4). Overall response rate in the 20/27 mg/m2 group, primary endpoint of the study, was 22.5% (n = 9) (95% confidence interval, 12.3-37.5) with 2.5% (n = 1) stringent complete response. Median progression-free survival and overall survival in the 20/27 mg/m2 group were 5.1 months (95% CI, 2.8-13.6) and 22.9 months (95% CI, 14.1-not estimable), respectively. Frequently occurring grade ≥3 adverse events in the 20/27 mg/m2 group included lymphopenia (72.5%), neutropenia (40.0%), and leukopenia (32.5%). Giving long-term carfilzomib monotherapy led to long-term overall survival for heavily pretreated multiple myeloma patients with a favorable safety profile. Carfilzomib monotherapy can be a good option for heavily pretreated multiple myeloma patients.


Asunto(s)
Antineoplásicos/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Oligopéptidos/administración & dosificación , Anciano , Antineoplásicos/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Resistencia a Antineoplásicos , Femenino , Estudios de Seguimiento , Humanos , Japón/epidemiología , Leucopenia/inducido químicamente , Leucopenia/epidemiología , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Oligopéptidos/efectos adversos , Supervivencia sin Progresión , Análisis de Supervivencia
7.
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 , Pueblo Asiatico , 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
8.
Int J Clin Oncol ; 24(12): 1620-1628, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31172332

RESUMEN

BACKGROUND: Differentiation between primary ocular adnexal mucosa-associated lymphoid tissue (POA-MALT) lymphoma and reactive lymphoid hyperplasias sometimes may be difficult. We have examined the treatment-associated mortality of POA-MALT lymphoma after confirmed diagnosis and evaluated their proper treatments. PATIENTS AND METHODS: From 1991 through 2016, cases of POA-MALT lymphoma were retrospectively analyzed based on their pathological and molecular/immunological diagnoses. RESULTS: A total of 78 cases with POA-MALT lymphoma with a median age of 66 years were analyzed over median/mean observations of 6.4/7.1 years. Forty-four patients (56%) were diagnosed with IgH gene clonality and 10 patients (13%) were diagnosed with flow cytometric analysis in addition to the pathological decision. The rest (24 patients, 31%) were diagnosed employing pathological decisions of hemato-pathologists and clinical decisions. All patients, except cases of watchful waiting, achieved complete remission. After initial treatment, 68 patients (87%) presented disease-free during the observation period. As treatment, a radiotherapy-based strategy was followed with 15 patients (19%, group A). Immuno-chemotherapy was administered to 24 patients (31%, B). Surgical extraction only was selected for 36 patients (46%, C). Watchful waiting was selected with three patients (4%). Recurrence after the initial treatment was found in one patient (7%) out of A, in three patients (13%) out of B, and in six patients (17%) out of C, respectively. Progression-free survivals at 5 and 10 years were 100 and 100% in A, 95 and 75% in B, and 88 and 81% in C, respectively. The recurrence rates between the patients who were diagnosed with only pathological decision (n = 24) and the patients who were diagnosed with molecular and immunological procedures (n = 54) did not show any statistical differences. CONCLUSION: Our results indicate that radiotherapy-based treatment strategies for patients with POA-MALT lymphoma show a low rate of recurrence and may improve their prognosis even after the accurate diagnosis. However, contamination of the cases with reactive (polyclonal) lymphoid hyperplasia into those with MALT lymphoma should be carefully removed to avoid unnecessary treatment for malignancies that do not exist.


Asunto(s)
Neoplasias del Ojo/diagnóstico , Neoplasias del Ojo/terapia , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma de Células B de la Zona Marginal/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Neoplasias del Ojo/mortalidad , Femenino , Humanos , Inmunoterapia , Linfoma de Células B de la Zona Marginal/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Resultado del Tratamiento
9.
Hematol Oncol ; 36(5): 792-800, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30176173

RESUMEN

The international staging system (ISS) is the most commonly used risk-stratification system for patients with multiple myeloma (MM) and is determined by serum albumin and ß2-microglobulin levels. In the two determinants, ß2-microglobulin levels are frequently observed to be elevated in patients with myeloma, particularly in those with renal impairment. In comparison with patients with intact immunoglobulin myeloma, patients with LC myeloma do not necessarily show decreased levels of serum albumin. The clinical impact of ISS in patients with LCMM, in particular the distinction between ISS I and II, may be complicated due to non-decreased levels of serum albumin in both stages. Accordingly, we have attempted to assess clinical relevance of the ISS in patients with LC myeloma. The clinical data of 1899 patients with MM diagnosed between January 2001 and December 2012 were collected from 38 affiliated hospitals of the Japanese Society of Myeloma. Significant difference was not found between stage I (n = 72) and stage II (n = 92) in LC myeloma patients (n = 307). The mean serum albumin concentration of patients with LC myeloma was within the reference range but higher than that of patients with IgG + IgA myeloma (n = 1501), which complicates the distinction between ISS stage I and II myeloma. Patients with LC myeloma had low frequencies of t(4; 14) and high frequency of elevated lactate dehydrogenase, and despite a relevant amount of missing data in our registry (R-ISS stage I; n = 11, stage II; n = 32, and stage III: n = 18), the information included in the R-ISS scoring system seems to be more accurate than ISS to obtain a reliable risk stratification approach in non-ISS stage III LC myeloma patients.


Asunto(s)
Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Cadenas Ligeras de Inmunoglobulina/sangre , Mieloma Múltiple/sangre , Mieloma Múltiple/patología , Albúmina Sérica Humana/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias
10.
Rinsho Ketsueki ; 59(10): 2178-2188, 2018.
Artículo en Japonés | MEDLINE | ID: mdl-30305524

RESUMEN

The development of novel agents for treating multiple myeloma (MM) has markedly improved the treatment outcome and has caused a major paradigm shift in treatment strategies. In Japan, bortezomib and lenalidomide have been approved for the initial treatment; additionally, seven novel drugs, including next-generation proteasome inhibitors, immunomodulatory drugs, histone deacetylase inhibitors, and monoclonal antibodies, have been approved for relapsed and/or refractory MM treatment. Of these novel agents, daratumumab-containing regimens have been reported to induce a deep response, such as minimal residual disease-negative status, even in relapsed patients. Thus, compared with the initial therapy, many efficacious choices are available for treatment at the time of MM relapse; and salvage therapy is currently considered to be the most important treatment strategy for MM. In clinical practice, it is desirable to consider patient, disease, and therapeutic factors to make an optimal treatment decision for each patient.


Asunto(s)
Antineoplásicos/uso terapéutico , Mieloma Múltiple/terapia , Anticuerpos Monoclonales/uso terapéutico , Bortezomib/uso terapéutico , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Inmunomodulación , Japón , Lenalidomida/uso terapéutico , Recurrencia Local de Neoplasia , Guías de Práctica Clínica como Asunto , Inhibidores de Proteasoma/uso terapéutico , Terapia Recuperativa
11.
Cancer Sci ; 108(3): 461-468, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28092421

RESUMEN

This is the first study in which the carfilzomib, lenalidomide and dexamethasone (KRd) regimen was evaluated in heavily pretreated multiple myeloma. This study is a multicenter, open-label phase 1 study of KRd in Japanese patients with relapsed or refractory multiple myeloma (RRMM) patients. The objectives were to evaluate the safety, tolerability, efficacy and pharmacokinetics of the regimen. Carfilzomib was administrated intravenously over 10 min on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. In cycle 1, the dosage for days 1 and 2 was 20 mg/m2 , followed by 27 mg/m2 . Lenalidomide and dexamethasone were administered at 25 mg (days 1-21) and 40 mg (days 1, 8, 15 and 22), respectively. Twenty-six patients were enrolled. Patients had received a median of four prior regimens and 88.5% and 61.5% received previous bortezomib and lenalidomide, respectively. High-risk cytogenetics were seen in 53.8% of patients. The overall response rate was 88.5%. A higher rate of hyperglycemia was observed than in a previous carfilzomib monotherapy study, but this was attributed to dexamethasone. Carfilzomib pharmacokinetics were not affected by lenalidomide and dexamethasone. The KRd regimen was well tolerated and showed efficacy in Japanese RRMM patients.


Asunto(s)
Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Dexametasona/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Oligopéptidos/uso terapéutico , Talidomida/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Hiperglucemia/inducido químicamente , Japón , Lenalidomida , Masculino , Persona de Mediana Edad , Talidomida/uso terapéutico
14.
Rinsho Ketsueki ; 58(8): 1014-1023, 2017.
Artículo en Japonés | MEDLINE | ID: mdl-28883264

RESUMEN

Recent progress in the development of novel therapeutic agents has remarkably improved the treatment outcome for multiple myeloma (MM). Proteasome inhibitors such as bortezomib, carfilzomib, and ixazomib; immunomodulatory drugs (IMiDs) such as thalidomide, lenalidomide, and pomalidomide; the histone deacetylase (HDAC) inhibitor panobinostat; and the monoclonal antibody, elotuzumab, have all been approved in Japan, although only bortezomib and lenalidomide have been approved for initial therapy. Accordingly, the Japanese Society of Hematology has released updated treatment guidelines for MM. Initial treatments with bortezomib-based 2-3 drug regimens and lenalidomide+dexamethasone are recommended for patients eligible for autologous stem cell transplantation (ASCT), while bortezomib+melphalan+prednisolone and lenalidomide+dexamethasone are recommended for patients who are not eligible for ASCT. These novel agents provide us with wider therapeutic options for relapsed or refractory patients. Consequently, treatment paradigms for MM continue to rapidly evolve, and it is important to select the optimal treatment strategy for each patient.


Asunto(s)
Mieloma Múltiple/terapia , Algoritmos , Antineoplásicos/uso terapéutico , Humanos , Mieloma Múltiple/epidemiología , Trasplante de Células Madre , Trasplante Autólogo
15.
Rinsho Ketsueki ; 58(12): 2369-2374, 2017.
Artículo en Japonés | MEDLINE | ID: mdl-29332868

RESUMEN

Azacitidine (AZA) is useful for the treatment of myelodysplastic syndrome; however, there are a few case reports involving patients receiving hemodialysis and no case reports involving patients receiving peritoneal dialysis. We describe a patient with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) receiving peritoneal dialysis who was treated with AZA. Peritoneal dialysis was initiated for an 85-year-old man with chronic renal failure in April 2014. In February 2015, peripheral blood analysis showed pancytopenia and bone marrow examination revealed excess of myeloblasts and dysplasia of trilineage cells. He was diagnosed with AML-MRC and treated with AZA because of being elderly and suffering from chronic renal failure. He achieved transfusion independence after 1 course and hematological remission after 3 courses of AZA treatment, without severe side effects. This case suggests that AZA is an effective therapeutic option for patients with AML-MRC receiving peritoneal dialysis.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Azacitidina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/complicaciones , Diálisis Peritoneal , Anciano de 80 o más Años , Humanos , Leucemia Mieloide Aguda/etiología , Masculino , Inducción de Remisión
16.
Rinsho Ketsueki ; 58(4): 303-308, 2017.
Artículo en Japonés | MEDLINE | ID: mdl-28484157

RESUMEN

Aeromonas species are known to be a cause of diarrhea and acute enterocolitis. However, only a few cases have been reported and the pathophysiology of Aeromonas infection has not as yet been clarified. We experienced 2 cases developing severe enterocolitis during the course of hematological malignancies, specifically multiple myeloma and diffuse large B-cell lymphoma. Both patients presented with watery diarrhea that persisted for more than a week, followed by bloody diarrhea. Total colon endoscopy showed multiple ulcers on the mucosa from the sigmoid colon to the rectum, and biopsies from the ulcer revealed infiltration of neutrophils and eosinophils in the mucosa and submucosa. Aeromonas hydrophila and Aeromonas sobria were isolated from stool cultures, respectively. Treatment with oral ciprofloxacin was effective in both patients and clinical symptoms showed significant improvement. These cases raise the possibility of Aeromonas infection as a cause of severe enterocolitis and the importance of making a correct differential diagnosis and appropriate antibiotic treatment in immunocompromised patients including those with hematological malignancies.


Asunto(s)
Aeromonas/aislamiento & purificación , Enterocolitis/microbiología , Infecciones por Bacterias Gramnegativas/complicaciones , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/complicaciones , Mieloma Múltiple/complicaciones , Anciano , Antibacterianos/uso terapéutico , Antineoplásicos/uso terapéutico , Ciprofloxacina/uso terapéutico , Diarrea/etiología , Femenino , Humanos , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico
17.
Rinsho Ketsueki ; 58(11): 2197-2204, 2017.
Artículo en Japonés | MEDLINE | ID: mdl-29212969

RESUMEN

Cardiac AL amyloidosis (CA) is generally known as a severe disease with very poor prognosis. Here we retrospectively examined seven patients with CA in our cohort who achieved long-term survival. All six patients who underwent high-dose melphalan and autologous stem cell transplantation (ASCT) survived for >3 years, whereas four patients survived for >5 years. Patients who underwent ASCT had prompt hematological responses, and five patients showed organ responses. ASCT helps to achieve a quick and deep hematological response required for long-term survival in patients with CA. New agents have been implemented for the treatment of CA. However, the risks and benefits of each treatment modality should be considered according to patient condition, thus making the best use of ASCT in combination with new agents for the treatment of CA.


Asunto(s)
Cardiopatías/diagnóstico , Cardiopatías/tratamiento farmacológico , Adulto , Anciano , Amiloidosis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sobrevivientes , Factores de Tiempo , Resultado del Tratamiento
18.
Br J Haematol ; 172(5): 745-56, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26732066

RESUMEN

We conducted a phase 1/2 study of single-agent carfilzomib in Japanese patients with relapsed/refractory multiple myeloma. Safety, pharmacokinetics and pharmacodynamics of carfilzomib were examined in phase 1. The primary endpoint in phase 2 was the overall response rate (ORR). Carfilzomib was administered in a twice-weekly, consecutive-day dosing schedule. In Phase 1, doses of 15 or 20 mg/m(2) were administered on this schedule or 20 mg/m(2) on Days 1 and 2 of Cycle 1 and then 27 mg/m(2) in the 20/27 mg/m(2) cohort. Patients had a median of five prior therapies, including bortezomib and an immunomodulatory agent. The dose level did not reach the maximum tolerated dose. The most common adverse events were haematological. Notably, carfilzomib either induced new hypertension (n = 4) or aggravated previously existing hypertension (n = 6) in 10 of 50 patients. Four of the eight patients who previously experienced peripheral neuropathy (PN) experienced a recurrence with carfilzomib use, but no new cases of PN occurred. The ORR of the 20/27 mg/m(2) 40 patient cohort was similar to that in the pivotal US study. The dose was efficacious and tolerable in heavily pre-treated Japanese patients; however, meticulous control of hypertension may be necessary for further carfilzomib use.


Asunto(s)
Antineoplásicos/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Oligopéptidos/uso terapéutico , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/sangre , Enfermedades Cardiovasculares/inducido químicamente , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/patología , Estadificación de Neoplasias , Oligopéptidos/administración & dosificación , Oligopéptidos/efectos adversos , Oligopéptidos/sangre , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Recurrencia
19.
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
20.
Acta Haematol ; 135(2): 113-21, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26505781

RESUMEN

We investigated the treatment and outcome of Japanese patients with primary plasma cell leukemia (pPCL) in the era of novel agents and analyzed the risk factors affecting survival. Among 3,318 patients with symptomatic multiple myeloma (MM), 38 patients were diagnosed with pPCL. The median overall survival (OS) of the pPCL patients was 2.85 years, which was significantly extended compared with that in previous reports. The proportion of patients treated with novel agents was 61%. The OS of the patients treated with novel agents was significantly extended compared with that of patients treated without novel agents according to the generalized Wilcoxon test (2.85 vs. 1.16 years, p = 0.049). This statistical finding suggests that treatment with novel agents could have prevented early death in the patients with pPCL. Age was the only statistically significant prognostic factor associated with an inferior OS (hazard ratio 4.57). Five patients received maintenance therapy with novel agents, and their OS tended to be longer than that of the other patients without maintenance (4.45 vs. 2.85 years). Unlike MM, OS for pPCL has not been improved significantly over the last decade, especially in elderly patients. Therefore, it is important to establish the treatment strategy, particularly after induction treatment.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia de Células Plasmáticas/terapia , Trasplante de Células Madre , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Japón , Leucemia de Células Plasmáticas/tratamiento farmacológico , Leucemia de Células Plasmáticas/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Sociedades Médicas , Células Madre/citología , Tasa de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento
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