RESUMO
The safety and efficacy of treatment with liposomal amphotericin B (L-AMB) in elderly patients has not been clarified, especially in Japanese patients. Therefore, we retrospectively analyzed 33 elderly patients with hematological diseases of at least 65 years old who received L-AMB between 2009 and 2012. Their clinical outcomes were compared to those of 21 patients who were younger than 65 years. L-AMB was administered for empirical therapy (n = 2) or target therapy for possible (n = 14) or probable/proven (n = 17) invasive fungal infection. There was no discontinuation of L-AMB due to adverse events. More than 2-fold increases from the baseline Cre, AST, and ALT values were observed in 21.2%, 39.4%, and 45.5% of the older group and 38.1%, 61.9%, and 52.4% of the younger group, respectively. The concurrent use of nephrotoxic antibiotics was the only risk factor for the development of a 2-fold increase in the serum Cre level. The duration of L-AMB was significantly longer in patients who developed grade III-IV hypokalemia. A partial or complete response was observed in 54.8% and 62.5% of the elderly and younger groups, respectively. In conclusion, L-AMB therapy appeared to be acceptably safe as empirical therapy or treatment for invasive fungal infection.
Assuntos
Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , Doenças Hematológicas/complicações , Hospedeiro Imunocomprometido , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Since the long-term safety profile of tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML) therapy has not been well characterized, we investigated renal impairment in 50 CML patients treated with TKI in our institute. During the median follow up period of 63 months, 29% of patients developed chronic kidney disease (CKD). Although the glomerular filtration rate (GFR) gradually declined, it dropped most markedly in the first 2 years after starting TKI. The CKD incidence was higher in patients older than 40 years or with decreased GFR, hypertension, or dyslipidemia at baseline. These findings highlight the necessity of careful monitoring of renal function in TKI-treated CML patients with these risk factors.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Insuficiência Renal Crônica/induzido quimicamente , Adulto , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Insuficiência Renal Crônica/fisiopatologiaRESUMO
We report a 37-year-old pregnant woman with paroxysmal nocturnal hemoglobinuria (PNH) treated with eculizumab. She had been diagnosed with PNH-aplastic anemia at age 19 years, and started to receive eculizumab at age 35 years. Thereafter, she had no hemolytic attacks. She became pregnant 2 years later, and treatment with eculizumab was continued. During her pregnancy, she showed no exacerbation of hemolysis. She delivered a girl by Caesarean section at 37 weeks and 3 days of gestation. Postpartum, anticoagulant therapy was started. Although mild hemolysis and a rise in FDP/Ddimer were seen, she had no symptoms of thrombosis. Ten days after delivery, she and her baby were discharged. Eculizumab was present in the first breast milk and cord blood but was below detectable levels. The cord blood showed blockage of hemolysis.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Hemoglobinúria Paroxística/tratamento farmacológico , Complicações Hematológicas na Gravidez/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/metabolismo , Feminino , Sangue Fetal/metabolismo , Humanos , Recém-Nascido , Troca Materno-Fetal , Leite Humano/metabolismo , Gravidez , Resultado da GravidezRESUMO
A 72-year-old man visited our hospital in July 2009 with a major complaint of lightheadedness. Based on bone marrow aspiration, myelodysplastic syndrome (MDS), refractory anemia with excessive blast-2 was diagnosed. Complete remission (CR) was achieved after low-dose cytarabine and aclarubicin therapy. After two courses of low-dose cytarabine therapy, at the first CR, cord blood transplantation (CBT) was performed after reduced-intensity conditioning in January 2010. However, recurrence was found in September 2011. Azacitidine (AZA) was administered subcutaneously daily for either 7 or 5 days and repeated every 4 weeks at doses of 100 mg/day. During nine cycles of AZA treatment, no graft-versus-host disease was observed and no transfusions of red cells/platelet concentrate were required. As of 1 year after the relapse was detected, the patient remains alive with stable disease. As there are few reports on AZA treatment for patients with MDS who experience relapse after CBT, the efficacy of this approach remains unclear. Further clinical trials including dose, duration, and number of cycles of AZA for MDS patients who relapse after transplantation are required.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Medula Óssea/patologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Humanos , Masculino , Síndromes Mielodisplásicas/diagnóstico , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: Preemptive therapy against cytomegalovirus (CMV) disease has succeeded in reducing the incidence of CMV disease, but the toxicity of ganciclovir remains problematic. METHODS: We prospectively evaluated the efficacy and toxicity of a preemptive protocol with ganciclovir at a reduced initial dose in 40 patients who achieved engraftment after allogeneic hematopoietic stem cell transplantation. RESULTS: Twenty-three (58%) patients had high-risk features, including transplant from an HLA-mismatched or unrelated donor, or associated acute graft-versus-host disease. CMV antigenemia assay was performed weekly, and ganciclovir was started in a risk-adapted manner, in which the initial dose of ganciclovir was fixed at 5 mg/kg/d and then adjusted based on the results of a weekly CMV antigenemia assay. In this protocol, 23 (58%) patients demonstrated positive antigenemia, and 19 (48%) received a preemptive administration of ganciclovir. Only one patient had CMV disease in the gastrointestinal system, which was successfully treated with a regular therapeutic dose of ganciclovir. Consequently, the total dose of ganciclovir was significantly less than that in a previous protocol using the conventional double dose (5 mg/kg twice daily) of ganciclovir (134 mg/kg vs. 190 mg/kg on average, P=0.046). There were no significant toxicities attributed to ganciclovir, except for neutropenia <0.5 x 109/L, which developed in three patients for 3, 4, and 14 days, respectively, with granulocyte colony-stimulating factor support. CONCLUSION: Preemptive therapy with a low initial dose of ganciclovir appeared to be effective even in high-risk patients. Further randomized controlled trial is warranted.
Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Adulto , Idoso , Antígenos Virais/sangue , Infecções por Citomegalovirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Transplante HomólogoRESUMO
BACKGROUND: Reactivation of chronic hepatitis B virus (HBV) infection is a major complication when HBV carriers receive immunosuppressive therapy. Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) carry the highest risk of fatal HBV disease (up to 12%). METHODS: In an attempt to identify a suitable procedure for the prevention and management of HBV reactivation, the administration of lamivudine over the course was tested in two patients. RESULTS: Generally, the patients transplant courses were successfully managed despite their difficult clinical situations: a high HBV load before transplant in one patient and intense steroid therapy for complicated acute graft-versus-host disease (GVHD) in the other patient. However, one patient showed a reactivation of HBV after discontinuing lamivudine and the other showed persistently high DNA polymerase activity despite prolonged administration of lamivudine. CONCLUSIONS: We concluded that lamivudine could have a place in the management of patients who suffer from chronic HBV infection and who are undergoing allogeneic HSCT. However, the efficacy of lamivudine seemed to be limited compared with other settings, including solid organ transplantation and autologous HSCT.
Assuntos
Antivirais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Adulto , Medula Óssea/efeitos dos fármacos , DNA Viral/sangue , Feminino , Humanos , Lamivudina/efeitos adversos , Transplante HomólogoRESUMO
We retrospectively analyzed data of 47 patients aged 60 years or older, hospitalized in our institution with the diagnosis of acute myelogenous leukemia (AML), and searched for prognostic factors. Induction with anthracyclines significantly correlated with better complete remission (CR) rate (P = 0.0016) and overall survival (OS) (P < 0.001). Another factor significantly affecting CR rate was higher age (> 70 years) (P = 0.042). Therapy-non-related factors predictive for shorter OS in univariate analyses were age older than 70 years (P = 0.003), percentage of blasts in bone marrow more than 80% (P = 0.048), serum lactate dehydrogenase level higher than 250 U l(-1) (P = 0.032). In stepwise cox proportional hazard regression model, all the four factors predictive for poor OS remained to be independently and significantly prognostic for shorter OS. Only two patients receiving anthracyclines died within 30 days and the frequency was not different from that in patients not receiving anthracyclines. The use of anthracyclines as induction therapy is recommended even in the elderly patients.
Assuntos
Leucemia Mieloide Aguda/mortalidade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/uso terapêutico , Crise Blástica , Células da Medula Óssea/patologia , Feminino , Humanos , Japão/epidemiologia , L-Lactato Desidrogenase/sangue , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Indução de Remissão , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: TRALI is one of the most serious, life-threatening complications after blood transfusion. Antibodies against neutrophils or HLA molecules from the donor are thought to be the primary causative agents. Rarely, antibodies in the recipient may react with transfused neutrophils and initiate the same events, which raises the possibility that TRALI may also occur in an allogeneic PBPC transplantation setting. CASE REPORT: A 30-year-old Japanese man with acute lymphoblastic leukemia developed TRALI immediately after the infusion of marrow cells from an unrelated donor. The infusion was suspended, and he gradually improved after receiving steroids and oxygen support. The next day, the remaining cells, which were separated to MNCs, were infused with no reactions. He then recovered over 5 days without the use of mechanical ventilation. RESULTS: Laboratory evaluation disclosed the presence of antibodies to neutrophils in his sera sampled after transplantation, but not in the donor's marrow graft. Hence, antibodies to neutrophils in the recipient may have reacted with neutrophils in the graft and contributed to the development of TRALI. CONCLUSION: This is the first reported case of TRALI after allogeneic BMT. TRALI should be recognized as a rare but serious complication in allogeneic hematopoietic stem cell transplantation.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Hipóxia/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Edema Pulmonar/etiologia , Síndrome do Desconforto Respiratório/etiologia , Doença Aguda , Adulto , Anticorpos/sangue , Células da Medula Óssea/imunologia , Transplante de Medula Óssea/imunologia , Humanos , Masculino , Neutrófilos/imunologia , Edema Pulmonar/diagnóstico por imagem , Radiografia Torácica , Síndrome do Desconforto Respiratório/diagnóstico por imagemRESUMO
Little information is available on the clinical characteristics of infectious complications that occur in the early period after reduced-intensity stem cell transplantation (RIST). We retrospectively investigated the clinical features of neutropenic fever and infectious episodes within 30 days after RIST in 76 patients who had received fluoroquinolones as part of their antibacterial prophylaxis. Preparative regimens included cladribine 0.66 mg/kg or fludarabine 180 mg/m2 plus busulfan 8 mg/kg. All but 1 patient survived 30 days after transplantation, and 75 patients (99%) became neutropenic within a median duration of 9 days. Neutropenic fever was observed in 29 patients (38%), and bacterial infection was confirmed in 15 (20%) of these, including bacteremia (n = 13), bacteremia plus pneumonia (n = 1), and urinary tract infection (n = 1). The causative organisms were gram-positive (n = 9) and gram-negative organisms (n = 7), with a mortality rate of 6%. Neither viral nor fungal infection was documented. Multivariate analysis showed that the presence of neutropenia at the initiation of preparative regimens was an independent risk factor for subsequent documented bacterial infections (P =.026; 95% confidence interval, 1.25-35.1). We conclude that neutropenic fever and bacteremia remain common complications in RIST.
Assuntos
Infecções Bacterianas/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neutropenia/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Vidarabina/análogos & derivados , Adolescente , Adulto , Antibacterianos/uso terapêutico , Infecções Bacterianas/prevenção & controle , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Cladribina/administração & dosagem , Feminino , Febre/etiologia , Fluoroquinolonas/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Vidarabina/administração & dosagemRESUMO
We evaluated erythrocyte recovery in 121 allogeneic haematopoietic stem cell transplantation (HSCT) recipients. There were 35 major and minor ABO-incompatible transplants, respectively, including 10 bi-directionally ABO-incompatible transplants. The use of peripheral blood stem cells facilitated erythrocyte recovery, regardless of the presence or absence of major ABO-incompatibility, and was associated with a frequent detection of anti-host isohaemagglutin early after minor ABO-incompatible transplantation, which was not associated with clinically relevant haemolysis. The use of a reduced-intensity regimen combining a purine analogue and busulphan did not delay erythrocyte recovery after major ABO-incompatible transplantation, suggesting this regimen had a strong activity against host plasma cell.