RESUMO
Recently, the use of targeted synthetic or biological disease-modifying anti-rheumatic drugs (ts/bDMARDs) in addition to conventional synthetic (cs)DMARDs including methotrexate (MTX) for rheumatoid arthritis (RA) has increased. However, whether ts/bDMARDs are associated with the development and clinicopathological features of MTX-associated lymphoproliferative disorder (MTX-LPD) in patients with RA remains unknown. Therefore, we evaluated the clinical outcomes of 121 patients with MTX-LPD. Results showed that prior use of ts/bDMARDs was not associated with the different histopathological subtypes of MTX-LPD. Patients with polymorphic-type LPD had a better event-free survival than those with diffuse large B-cell lymphoma (DLBCL), classical Hodgkin lymphoma and peripheral T-cell lymphoma. The pathological subtype of lymphoma could predict the clinical outcome of MTX-LPD. In patients with DLBCL, the use of tumour necrosis factor-alpha (TNF-α) inhibitors prior to MTX-LPD onset was associated with a higher non-relapse mortality. Further, patients with RA previously treated with Janus kinase (JAK) inhibitors more commonly required chemotherapy than those treated with csDMARDs alone, indicating disease aggressiveness. Hence, special caution should be observed when managing patients with MTX-LPD previously treated with JAK or TNF-α inhibitors for RA.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Transtornos Linfoproliferativos/tratamento farmacológico , Metotrexato/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Janus Quinases/antagonistas & inibidores , Estimativa de Kaplan-Meier , Linfoma não Hodgkin/mortalidade , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/mortalidade , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Rituximab/administração & dosagem , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Vimblastina/administração & dosagem , Vincristina/administração & dosagemRESUMO
To elucidate dynamic changes in native BCR-ABL and alternatively spliced tyrosine kinase inhibitor (TKI)-resistant but function-dead BCR-ABLIns35bp variant, following commencement or discontinuation of TKI therapy, each transcript was serially quantified in patients with chronic myeloid leukemia (CML) by deep sequencing. Because both transcripts were amplified together using conventional PCR system for measuring International Scale (IS), deep sequencing method was used for quantifying such BCR-ABL variants. At the initial diagnosis, 7 of 9 patients presented a small fraction of cells possessing BCR-ABLIns35bp , accounting for 0.8% of the total IS BCR-ABL, corresponding to actual BCR-ABLIns35bp value of 1.1539% IS. TKI rapidly decreased native BCR-ABL but not BCR-ABLIns35bp , leading to the initial increase in the proportion of BCR-ABLIns35bp . Thereafter, both native BCR-ABL and BCR-ABLIns35bp gradually decreased in the course of TKI treatment, whereas small populations positive for TKI-resistant BCR-ABLIns35bp continued fluctuating at low levels, possibly underestimating the molecular response (MR). Following TKI discontinuation, sequencing analysis of 54 patients revealed a rapid relapse, apparently derived from native BCR-ABL+ clones. However, IS fluctuating at low levels around MR4.0 marked a predominant persistence of cells expressing function-dead BCR-ABLIns35bp , suggesting that TKI resumption was unnecessary. We clarified the possible mechanism underlying mis-splicing BCR-ABLIns35bp , occurring at the particular pseudo-splice site within intron8, which can be augmented by TKI treatment through inhibition of RNA polymerase II phosphorylation. No mutations were found in spliceosomal genes. Therefore, monitoring IS functional BCR-ABL extracting BCR-ABLIns35bp would lead us to a correct evaluation of MR status, thus determining the adequate therapeutic intervention.
Assuntos
Processamento Alternativo , Proteínas de Fusão bcr-abl/genética , Mutação , Inibidores de Proteínas Quinases/farmacologia , RNA Polimerase II/metabolismo , Adulto , Idoso , Feminino , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Loci Gênicos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Íntrons , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , RNA Polimerase II/antagonistas & inibidores , Análise de Célula ÚnicaRESUMO
Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA)-related disease that manifests as a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) and is caused by uncontrolled activation of the complement system. We report the case of a 61-year-old woman with acute type A aortic dissection that subsequently developed into aHUS. The hematologic disorders underlying aHUS improved after treatment with the complement inhibitor eculizumab. It is important to consider aHUS when a patient clinically develops a triad of microangiopathic hemolytic anemia, thrombocytopenia, and an increasing creatinine level following cardiovascular surgery.
RESUMO
Use of novel agents, including proteasome inhibitors and immunomodulatory drugs, has markedly improved outcomes in multiple myeloma (MM) patients. However, most MM patients eventually relapse and require salvage treatments. We report herein the result of a phase I/II study, performed from 2014 to 2017 to assess the feasibility and efficacy of a maximum tolerated dose (MTD) of lenalidomide (Len) combined with a fixed dose of once weekly subcutaneous (sc) 1.3 mg/m2 of bortezomib plus 20 mg of dexamethasone (scVRd regimen) in relapsed/refractory MM patients in the Japanese population. In the phase I part, dose-limiting toxicities were observed in three of six patients treated with 20 mg of Len; the MTD was accordingly defined as 15 mg in our cohort. In the phase II part, the recommended dose of the scVRD regimen showed a 71.4% best overall response rate, with a median overall survival of 14.8 months and a median progression-free survival of 8 months. Severe adverse events (≥ grade 3) were observed in ~ 15% of the patients, indicating the tolerability and efficacy of the regimen. Less prior treatment was associated with higher probability of durable response. This scVRd regimen may thus be a better fit for MM patients in early-stage relapse.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Lenalidomida/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Humanos , Recidiva , Resultado do TratamentoRESUMO
Umbilical cord blood transplantation (UCBT) is a curative treatment for hematological malignancies. However, appropriate prophylaxis against graft-versus-host disease (GVHD), aimed at obtaining rapid and stable engraftment and avoiding toxicity, remains controversial in UCBT. We retrospectively compared outcomes in 409 patients who received calcineurin inhibitors (CIs) plus conventional-dose methotrexate (conv-MTX/CIs, n = 77; methotrexate, 10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6) with those who received CIs plus reduced-dose methotrexate (reduced-MTX/CIs, n = 209; methotrexate, 5 mg/m2 or 5 mg/body on days 1, 3, and 6) or CIs with mycophenolate mofetil (MMF/CIs, n = 123) for GVHD prophylaxis after UCBT. The cumulative incidence of neutrophil engraftment was significantly higher in the reduced-MTX/CI (82.3%) and MMF/CI (86.6%) groups than the conv-MTX/CI (71.4%) group (p = 0.014), although there were no differences in platelet recovery or infectious complications among the three groups. The incidence and severity of GVHD were comparable among the three groups, and there were no significant differences in transplantation-related mortality among the three groups. In conclusion, GVHD prophylaxis with reduced-dose methotrexate and MMF was closely associated with high incidence of neutrophil engraftment without an effect on the incidence and severity of GVHD, which was compared to GVHD prophylaxis with conventional-dose methotrexate.
Assuntos
Inibidores de Calcineurina/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores de Calcineurina/administração & dosagem , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Incidência , Infecções/epidemiologia , Infecções/etiologia , Japão/epidemiologia , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Neutrófilos , Contagem de Plaquetas , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Outcomes for patients with multiple myeloma (MM) have improved through use of novel treatments, especially lenalidomide combined with autologous stem cell transplantation. However, because of their increased life expectancy, an increased risk of secondary primary malignancies (SPMs) has been observed in MM patients, particularly after lenalidomide maintenance in both transplant-eligible (TE) and transplant-ineligible (TI) patients. To evaluate the incidence and risk factors of developing SPMs, we identified 17 TE-MM and 12 TI-MM patients with SPMs among 211 TE-MM and 280 TI-MM patients, including seven TE-MM and four TI-MM patients with hematological malignancies and ten TE-MM and eight TI-MM patients with non-hematological cancers, respectively. The median follow-up time from diagnosis was > 4 years. Multivariate analysis identified a history of high-dose cyclophosphamide use for peripheral blood stem cell harvest in TE-MM patients and > 65 years of age at diagnosis, or a history of adriamycin, lenalidomide, or thalidomide use in TI-MM patients as independent risk factors for SPMs (P < 0.001). Patients with a history of lenalidomide use had a lower risk of death among both TE-MM (P = 0.0326) and TI-MM (P < 0.001) patients. The survival benefit of receiving lenalidomide outweighed the increased risk of SPMs in both TE-and TI-MM patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/secundário , Segunda Neoplasia Primária , Incidência , Lenalidomida/uso terapêutico , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Segunda Neoplasia Primária/induzido quimicamente , Segunda Neoplasia Primária/etiologia , Fatores de Risco , Análise de Sobrevida , Transplante Autólogo/métodosRESUMO
We experienced a breakthrough fungal infection caused by Geotrichum capitatum during empirical therapy with caspofungin. A 68-year-old male patient with refractory acute lymphoblastic leukemia had received umbilical cord blood transplantation after two courses of induction therapy. Empirical therapy with caspofungin was initiated 5 days before transplantation. Tacrolimus was continuously infused to prevent graft-versus-host disease. A minidose of methotrexate was intravenously administered on days 1 and 3 post-transplantation, which was changed to prednisolone from day 7 due to severe mucositis. During a recurrence of fever on day 11, blood cultures were found to be positive for a yeast-like organism, which was later confirmed by mass spectrometry to be G. capitatum. The serum levels of beta-D-glucan were elevated to 747 pg/mL. Caspofungin was switched to liposomal amphotericin B; however, radiological findings revealed pulmonary, splenic, and central nervous system involvement. Progressive renal and hepatic dysfunction subsequently developed. The patient died on day 25 post-transplantation secondary to the development of hemophagocytic syndrome and respiratory failure. We emphasize that recurrent febrile episodes, prolonged neutropenia, and underlying gastrointestinal mucosal damage require extreme caution due to the possibility of breakthrough infection caused by new fungal pathogens during empirical therapy with caspofungin.
Assuntos
Antifúngicos/uso terapêutico , Caspofungina/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Geotrichum , Micoses/tratamento farmacológico , Micoses/etiologia , Idoso , Hemocultura , Evolução Fatal , Violeta Genciana , Geotrichum/efeitos dos fármacos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Microscopia , Micoses/diagnóstico , Fenazinas , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMO
Autologous stem cell transplantation (ASCT) has been employed for patients with relapsed multiple myeloma (MM) after up-front ASCT. The present retrospective study aimed to examine the survival benefit from salvage ASCT. Among 446 patients with relapsed MM after up-front single ASCT, 70 patients received salvage ASCT, the employment of which reduced the risk of mortality after relapse (p = 0.041). Using the parameters before initial ASCT, the advantage of salvage ASCT compared to standard therapy was confirmed in the subgroup with an international staging system stage of I or II (p = 0.040), good performance status (PS; p = 0.043), or no/mild renal comorbidity (p = 0.029). The advantage of salvage ASCT was also confirmed in the subgroup excluding those with early relapse within 7 months after initial ASCT (p = 0.026). Among patients who received salvage ASCT, a favorable prognosis is apparent for those with a time to relapse after initial ASCT of longer than 24 months. The overall survival after salvage ASCT was favorable excluding patients with the following factors: early relapse, poor PS, moderate/severe renal comorbidity, and progressive disease (p < 0.001). In conclusion, our results reinforced the evidence for encouraging salvage ASCT for eligible patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Adulto , Idoso , Biomarcadores Tumorais , Progressão da Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Estadiamento de Neoplasias , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Terapia de Salvação , Transplante Autólogo , Adulto JovemRESUMO
The characteristics of adult patients with chronic active Epstein-Barr virus infection are poorly recognized, hindering early diagnosis and an improved prognosis. We studied 54 patients with adult-onset chronic active Epstein-Barr virus infection diagnosed between 2005 and 2015. Adult onset was defined as an estimated age of onset of 15 years or older. To characterize the clinical features of these adults, we compared them to those of 75 pediatric cases (estimated age of onset <15 years). We compared the prognosis of adult-onset chronic active Epstein-Barr virus infection with that of patients with nasal-type (n=37) and non-nasal-type (n=45) extranodal NK/T-cell lymphoma. The median estimated age of onset of these lymphomas was 39 years (range, 16-86 years). Compared to patients with pediatric-onset disease, those in whom the chronic active Epstein-Barr virus infection developed in adulthood had a significantly decreased incidence of fever (P=0.005), but greater frequency of skin lesions (P<0.001). Moreover, hypersensitivity to mosquito bites and the occurrence of hydroa vacciniforme were less frequent in patients with adult-onset disease (P<0.001 and P=0.0238, respectively). Thrombocytopenia, high Epstein-Barr virus nuclear antigen antibody titer, and the presence of hemophagocytic syndrome were associated with a poor prognosis (P=0.0087, P=0.0236, and P=0.0149, respectively). Allogeneic hematopoietic stem cell transplantation may improve survival (P=0.0289). Compared to pediatric-onset chronic active Epstein-Barr virus infection and extranodal NK/T-cell lymphoma, adult-onset chronic active Epstein-Barr virus infection had a poorer prognosis (P<0.001 and P=0.0484, respectively). Chronic active Epstein-Barr virus infection can develop in a wide age range, with clinical differences between adult-onset and pediatric-onset disease. Adult-onset chronic active Epstein-Barr virus infection is a disease with a poor prognosis. Further research will be needed.
Assuntos
Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/fisiologia , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/etiologia , Células T Matadoras Naturais/metabolismo , Células T Matadoras Naturais/virologia , Adolescente , Adulto , Fatores Etários , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Biópsia , Feminino , Humanos , Transtornos Linfoproliferativos/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Avaliação de Sintomas , Carga Viral , Adulto JovemRESUMO
A 64-year-old woman presented with generalized lymphadenopathy and systemic manifestations. The examination of a biopsy specimen revealed peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) expressing cytotoxic molecules. Umbilical cord blood transplantation was successful during a partial remission state after the administration of salvage chemotherapy. The donor-derived large granular lymphocytes started to increase as a result of cytomegalovirus reactivation. The fraction of natural killer (NK) cells expressing the NKG2C molecule accounted for one-third of the total lymphocytes for almost two years. We implicitly indicate the association between the persistence of donor-derived NKG2C+ NK cell-expansion and maintaining a complete remission in similar cases of aggressive PTCL-NOS.
Assuntos
Sangue Fetal/transplante , Células Matadoras Naturais/imunologia , Linfoma de Células T Periférico/imunologia , Linfoma de Células T Periférico/terapia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/genética , Transplante de Células-Tronco de Sangue Periférico/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
We present the case of a 56-year-old man with an upper respiratory infection followed by fatigue, hypotension, and hyponatremia. Bilateral adrenal hemorrhage was confirmed, based on T2-weighted magnetic resonance imaging. The patient had previously undergone allogeneic hematopoietic stem cell transplantation and had been diagnosed with antiphospholipid syndrome (APS) during the development of chronic graft-versus-host disease. A prompt diagnosis and steroid replacement, in addition to anticoagulant therapy, resulted in a favorable outcome. Once the diagnosis of APS has been confirmed, which might be the sign of bilateral adrenal hemorrhage, the initial manifestations of adrenal insufficiency should never be overlooked.
Assuntos
Doenças das Glândulas Suprarrenais/diagnóstico por imagem , Síndrome Antifosfolipídica/diagnóstico , Doença Enxerto-Hospedeiro/diagnóstico , Hemorragia/diagnóstico por imagem , Doenças das Glândulas Suprarrenais/tratamento farmacológico , Insuficiência Adrenal/diagnóstico , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Fadiga/diagnóstico , Hemorragia/tratamento farmacológico , Humanos , Hiponatremia/diagnóstico , Hipotensão/diagnóstico , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/diagnósticoAssuntos
Hepatite B/epidemiologia , Mieloma Múltiplo/virologia , Ativação Viral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Vírus da Hepatite B/fisiologia , Humanos , Incidência , Japão , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Fatores de Risco , Transplante AutólogoRESUMO
Pulmonary hypertension (PH) is a rare, but life-threatening, adverse event in patients treated with tyrosine kinase inhibitors (TKIs), such as dasatinib, but has not been fully evaluated in patients treated with imatinib or nilotinib. We used echocardiography to noninvasively assess the incidence of PH in 105 patients with chronic myeloid leukaemia (CML) treated with imatinib (n = 37), nilotinib (n = 30) or dasatinib (n = 38). The mean triscupid regurgitation peak gradient (TRPG), which reflects pulmonary arterial pressure, was 22·7 mmHg in the imatinib group, 23·1 mmHg in the nilotinib group and 23·4 mmHg for dasatinib group. These values were not significantly different, but higher than those (19·0 mmHg) in newly diagnosed CML patients. A TRPG > 31 mmHg, marking possible PH onset, was detected in 9 of 105 patients: one (2·7%) treated with imatinib, three (10·0%) with nilotinib and five (13·2%) with dasatinib. Only three patients complained of dyspnoea, whereas the other six were asymptomatic. In addition, there was a tendency toward correlation of TRPG value and age or TKI treatment duration. These results suggested that treatment with not only dasatinib, but also imatinib and nilotinib, can be associated with subclinical PH. Noninvasive echocardiography is useful for screening, especially in older patients with long-term TKI treatment.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Dasatinibe/uso terapêutico , Ecocardiografia , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico por imagem , Mesilato de Imatinib/uso terapêutico , Leucemia Mieloide de Fase Crônica/complicações , Masculino , Pessoa de Meia-Idade , Pirimidinas/uso terapêutico , Resultado do Tratamento , Insuficiência da Valva Tricúspide/etiologia , Adulto JovemRESUMO
OBJECTIVES: T-cell prolymphocytic leukemia (T-PLL) is a very rare, aggressive T-cell neoplasm. Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is also a highly aggressive lymphoma. These two diseases can often be confused with each other; therefore, we aimed to determine the clinical and pathological differences between T-PLL and PTCL-NOS. METHODS: We analyzed 15 T-PLL and 91 PTCL-NOS patients and also compared clinical features between T-PLL and PTCL-NOS with leukemic presentation. Peripheral blood images and biopsy specimens were analyzed, and treatment responses were determined via imaging modalities. The clinicopathological characteristics were statistically compared. RESULTS: T-PLL cells were smaller in size than those of PTCL-NOS with leukemic presentation (P=.0068); moreover, PTCL-NOS cells with leukemic presentation were smaller than those of PTCL-NOS without leukemic presentation (P=.0017). Immunophenotypic patterns in T-PLL and PTCL-NOS were similar. Five-year overall survival rates of T-PLL and all PTCL-NOS patients were 57.5% and 36.8%, respectively. No significant differences were found in clinical manifestations or prognoses; T-PLL and PTCL-NOS with leukemic presentation had essentially equivalent characteristics. CONCLUSION: T-PLL and PTCL-NOS may share common biological and clinical characteristics in Japanese patients.
Assuntos
Leucemia Prolinfocítica de Células T/diagnóstico , Linfoma de Células T Periférico/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Biópsia , Criança , Diagnóstico Diferencial , Feminino , Rearranjo Gênico , Humanos , Imunofenotipagem , Leucemia Prolinfocítica de Células T/genética , Leucemia Prolinfocítica de Células T/mortalidade , Leucemia Prolinfocítica de Células T/terapia , Contagem de Leucócitos , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/terapia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Receptores de Antígenos de Linfócitos T/genética , Resultado do Tratamento , Adulto JovemRESUMO
We describe two hemodialysis patients with high-risk myelodysplastic syndrome (MDS) treated with azacitidine. A 65-year-old woman (case 1) received azacitidine at 75 mg/m(2) for 7 days, and a 52-year-old man (case 2) with liver cirrhosis received a 70% dose of azacitidine. Both cases developed grade 4 cytopenia, but they achieved transfusion independence after 3 and 2 courses, and the durations of remission were 10 and 11 months, respectively. Case 1 had the complication of febrile neutropenia (FN) twice during the 1(st) and 2(nd) courses, but continued to receive azacitidine treatment thereafter. Case 2 developed infectious peritonitis during the sixth course, and azacitidine treatment was thus discontinued. After a 4-month treatment interruption, he became transfusion-dependent, and re-induction of azacitidine was successful. Of note, the course of case 1 was complicated by erythema nodosum on admission, which then disappeared after one course of azacitidine treatment. The mean durations of hospitalization were 17.5 and 23 days per course of azacitidine treatment, respectively. Though there are few reports of azacitidine treatment for hemodialysis patients with high-risk MDS, we advocate administering azacitidine to such patients, while paying close attention to the dose intensity of azacitidine and taking prompt action to manage infectious complications.
Assuntos
Azacitidina/efeitos adversos , Azacitidina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Transfusão de Sangue , Neutropenia Febril/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Diálise Renal , Fatores de RiscoRESUMO
A 74-year-old woman with refractory adult T-cell leukemia/lymphoma (ATLL) received three courses of mogamulizumab. Despite obtaining complete remission, she thereafter presented with progressive ascites. An analysis of the ascites and laboratory tests revealed no evidence of ATLL invasion, infectious disease, or liver cirrhosis. The mogamulizumab concentrations were maintained in the ascites at approximately 10-15% of that in the plasma. Mogamulizumab was considered to be a plausible pathogenesis of her ascites. To the best of our knowledge, this is the first report suggesting mogamulizumab-induced ascites.
Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Ascite/induzido quimicamente , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/patologiaRESUMO
Mogamulizumab (MOG), a humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, has recently played an important role in the treatment of adult T cell leukemia/lymphoma (ATLL). Because CCR4 is expressed on normal regulatory T cells as well as on ATLL cells, MOG may accelerate graft-versus-host disease (GVHD) by eradicating regulatory T cells in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is limited information about its safety and efficacy in patients treated with MOG before allo-HSCT. In the present study, 25 patients with ATLL were treated with MOG before allo-HSCT, after which 18 patients (72%) achieved remission. The overall survival and progression-free survival at 1 year post-transplantation were 20.2% (95% CI, 6.0% to 40.3%) and 15.0% (95% CI, 4.3% to 32.0%), respectively. The cumulative incidence of acute GVHD was 64.0% (95% CI, 40.7% to 80.1%) for grade II-IV and 34.7% (95% CI, 15.8% to 54.4%) for grade III-IV. The cumulative incidence of transplantation-related mortality (TRM) was 49.0% (95% CI, 27.0% to 67.8%). Six of 7 patients with acute GVHD grade III-IV died from GVHD, which was the leading cause of death. In particular, a shorter interval from the last administration of MOG to allo-HSCT was associated with more severe GVHD. MOG use before allo-HSCT may decrease the ATLL burden; however, it is associated with an increase in TRM due to severe GVHD. Because MOG is a potent anti-ATLL agent, new treatment protocols should be developed to integrate MOG at suitable doses and timing of administration to minimize unwanted GVHD development.
Assuntos
Anticorpos Monoclonais Humanizados/toxicidade , Doença Enxerto-Hospedeiro/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia-Linfoma de Células T do Adulto/complicações , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Doença Aguda , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/terapia , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Estudos Retrospectivos , Análise de Sobrevida , Transplante HomólogoRESUMO
A 70-year-old woman was admitted to our hospital because of fatigue and renal dysfunction and was diagnosed with light chain deposition disease (LCDD) with multiple organ involvement (kidney, thyroid gland, heart and eyes). After chemotherapy with bortezomib, cyclophosphamide and dexamethasone, hepatobiliary enzyme levels increased abruptly. A liver biopsy showed light chain deposition in Disse spaces. After two years of treatment with bortezomib, melphalan and prednisone (VMP) administered at shorter intervals relative to regular cycles, the patient showed a hematological and organ response. This case indicates that a relatively low dose intensity VMP regimen is preferable for elderly patients with LCDD with multiple organ involvement.