RESUMO
Immune checkpoint inhibitor-related thrombocytopenia (irTCP) is a relatively rare immune-related adverse event (irAE); however, overall survival may worsen when it occurs. Prolonged use of high-dose steroids can diminish the effectiveness of immune checkpoint inhibitor (ICI) therapy on the primary disease because of T lymphocyte suppression, thus early tapering is necessary. We experienced a rare case of a 79-year-old male who concurrently developed irTCP and multiple myeloma (MM) during treatment with ICIs for lung adenocarcinoma. The patient exhibited severe thrombocytopenia and elevated serum IgA levels. Based on various tests, we diagnosed MM and irTCP. Despite administering the standard bortezomib plus dexamethasone (Bd therapy) treatment for MM, there was no response and the irTCP was steroid-resistant. Consequently, we administered a regimen including daratumumab (DPd therapy) for steroid-resistant irTCP and refractory MM, which resulted in a response. As a result, we were able to avoid prolonged use of high-dose steroids and the patient is stable without exacerbation of lung adenocarcinoma for 1 year and 5 months after the onset of MM. To our knowledge, there are no cases of MM developing during ICI treatment and this is the first case report in which daratumumab was effective for the treatment of irTCP.
RESUMO
BACKGROUND: CD36 is a glycoprotein expressed on platelets and monocytes of the blood. There are two types of CD36 deficiency, type I and type II. Individuals with type I-deficiency do not express CD36 in any cell type and can produce the CD36 antibody, which causes pathological conditions, such as fetal/neonatal alloimmune thrombocytopenia (FNAIT) and platelet transfusion refractory (PTR), through antigenic exposure via transfusion or pregnancy. CASE PRESENTATION: We experienced a case of Philadelphia-positive acute lymphoblastic leukaemia with PTR. In addition to the CD36 antibody, multiple-specificity HLA antibodies were present in the patient's plasma, requiring transfusion of HLA-compatible and CD36-negative platelets (PC-HLA). Since the number of donors was limited, it was necessary to set-up a blood transfusion schedule so that hyper-fractionated cyclophosphamide, vincristine and doxorubicin therapy (hyper-CVAD) and ponatinib combination chemotherapy could be safely administered to achieve molecular remission. Rituximab administration resulted in reduced levels of both CD36 antibody and HLA antibody. Given the expression of CD36 on haematopoietic stem cells and the limited availability of CD36-negative PC-HLA, haematopoietic stem cell transplantation (HSCT) was not considered to be an option. CONCLUSION: If CD36-negative, allogeneic haematopoietic stem cell donors are unable to be found, the indications for HSCT in patients with type I CD36-deficiency should be carefully weighed. In the present case, molecular remission has been able to be maintained to the present day after completion of a two-year maintenance regimen.
Assuntos
Transtornos Plaquetários , Leucemia-Linfoma Linfoblástico de Células Precursoras , Trombocitopenia Neonatal Aloimune , Feminino , Doenças Genéticas Inatas , Humanos , Cromossomo Filadélfia , GravidezRESUMO
A 35-year-old man who previously underwent splenectomy for hereditary spherocytosis at age 29 visited our hospital complaining of fatigue that had started 7 days ago and right upper abdominal pain. Laboratory data showed increased white blood cell and eosinophil count accompanied by severe transaminitis and clotting abnormalities. Computed tomography scan showed multiple embolisms in the portal vein, superior mesenteric vein, right pulmonary artery, and inferior vena cava. Severe liver damage presumably caused by portal vein thrombosis was also observed. Anticoagulant therapies consisting of continuous arterial infusion of urokinase from the superior mesenteric artery and an intravenous infusion of recombinant human thrombomodulin and heparin dissolved the systemic thrombosis. Concurrently administered prednisone decreased the eosinophil count. With regard to eosinophilia, we were unable to find any connective tissue diseases, antibodies to parasites, or genetic anomalies including PDGFRA, PDGFRB, and FGFR1. Hence we diagnosed the patient with idiopathic hypereosinophilic syndrome (HES). Although thromboembolisms in patients with HES have been reported, the literature on portal vein thrombosis associated with HES is scarce. In the present case, the previous splenectomy may have contributed to the portal vein thrombosis.
Assuntos
Síndrome Hipereosinofílica/complicações , Veia Porta , Trombose Venosa/etiologia , Adulto , Humanos , Hepatopatias/etiologia , Masculino , EsplenectomiaRESUMO
A novel induction therapy, including intensive L-asparaginase, was designed in 2007 for patients aged <45 years with Philadelphia-negative acute lymphoblastic leukemia (ALL). We analyzed seven de novo cases and one case of recurrence who received this treatment. The median age was 21 years (range: 16-35 years). Four patients had T-ALL and the others had B-ALL. All the patients achieved complete remission and proceeded to cord blood transplantation. In the median 72-month follow-up, there were no cases of observed mortality or recurrence. Our results indicate scope for further development of both induction therapy and postremission therapy.
Assuntos
Antineoplásicos/uso terapêutico , Asparaginase/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
PURPOSE: To clarify the impact of serum free light chain (sFLC) ratio normalization in patients with multiple myeloma (MM) treated with novel agents. PATIENTS AND METHODS: Treatment response in 126 consecutive patients over 7 years was assessed by IMWG criteria and sFLC assay. RESULTS: Thirty-four patients (27%) showed complete response (CR), 37 (29%) very good partial response (VGPR), 39 (31%) partial response (PR), and 16 (13%) stable disease (SD) or less at a median follow-up of 28 months. Fifty-two patients (41%) with sFLC ratio normalization showed superior progression-free survival (PFS) and overall survival (OS) compared to those who did not (3-yr OS, 94% vs. 48%; P < 0.001). This favorable effect of sFLC ratio normalization occurred irrespective of high (>1000 mg/dL) or low (<100 mg/dL) baseline sFLC. Rates of normal sFLC ratio were as follows: CR, 69%; VGPR, 64%; PR, 16%; and SD or less, 0%. OS was significantly superior in patients with than without normal sFCL ratio in respective response groups. Although various factors (advanced age >70, high LDH, ISS stage 3) showed negative prognostic impacts on PFS and OS on univariate analysis, normal sFLC ratio and achievement of CR emerged as the strongest prognostic predictors for longer OS in MM patients on multivariate analysis. CONCLUSIONS: This study demonstrated the significance of obtaining normal sFLC ratio independent of other clinical variables. Analysis of sFLC ratio could identify the favorable group of patients as well as immunofixation test and support the inclusion of sFLC ratio as part of the response criteria for MM.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cadeias kappa de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/sangue , Mieloma Múltiplo/sangue , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácidos Borônicos/administração & dosagem , Bortezomib , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Pirazinas/administração & dosagem , Taxa de Sobrevida , Talidomida/administração & dosagem , Talidomida/análogos & derivadosAssuntos
Síndrome de Fanconi/complicações , Gamopatia Monoclonal de Significância Indeterminada/complicações , Insuficiência Renal Crônica/etiologia , Idoso , Antineoplásicos/uso terapêutico , Ácidos Borônicos/uso terapêutico , Bortezomib , Dexametasona/uso terapêutico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pirazinas/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Resultado do TratamentoRESUMO
Influenza related to complications such as pneumonia and encephalitis have sporadically been reported. However, influenza A (H1N1)-virus-associated hemophagocytic syndrome (VAHS) has rarely been reported. A 39-year old woman complained of high fever and was referred to us. Chest infiltrations in both lungs and a positive polymerase chain reaction (PCR) for novel swine origin influenza A (H1N1) in bronchial alveolar lavage fluid (BALF) specimen was confirmed and she was diagnosed with influenza A (H1N1) pneumonia. Pancytopenia was found, and hemophagocytic syndrome (HPS) was diagnosed by bone marrow aspiration. Following intravenous administration of antiflu drug and combination therapy of steroid pulse and erythromycin IV, the patient's respiratory dysfunction and lab data gradually improved and she was discharged on day 21. Whereas secondary HPS related to viral infections such as EpsteinBarr virus, cytomegalovirus, and human herpesvirus type 6 are commonly seen, H1N1 pneumonia complicated with secondary VAHS is rare.
Assuntos
Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Influenza Humana/virologia , Linfo-Histiocitose Hemofagocítica/virologia , Adulto , Feminino , Humanos , Influenza Humana/diagnóstico , Pulmão/patologia , Pulmão/virologiaRESUMO
BACKGROUND: Intravascular large B-cell lymphoma (IVL) is characterized by lymphoma cell proliferation in the lumina of small vessels in various organs. A high incidence of neurologic symptoms associated with the central nervous system has been reported, but peripheral nerve involvement (neurolymphomatosis [NL]) rarely has been described. METHODS: The medical records from patients who were diagnosed with IVL over the past 4 years were reviewed. A diagnosis of NL was made based on the combination of neurologic symptoms and their correspondence with imaging studies, such as magnetic resonance imaging (MRI), (18) F-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computed tomography (PET/CT), and/or the histologic confirmation of lymphoma cells within the peripheral nerves, nerve root/plexuses, or cranial nerves. RESULTS: Four patients with NL were identified among 11 patients who had IVL. All cases of NL occurred as relapsed disease during or shortly after the completion of chemotherapy. Although MRI studies of the brains and whole spines revealed nerve infiltration by gadolinium enhancement in 2 patients, the technology was not sensitive enough to detect such infiltration in the remaining 2 patients. In contrast, FDG-PET/CT studies successfully revealed cranial or peripheral nerve lesions in all 4 patients and was useful for evaluating therapeutic response. Patients received treatment with high-dose methotrexate with or without other systemic chemotherapy, which achieved varied success. Further studies will be needed to determine the optimal treatment. CONCLUSIONS: Considering the rarity of IVL and NL, the current observations suggested that IVL may have a predilection not only for the vessels but also for both the central and peripheral nervous systems.
Assuntos
Linfoma Difuso de Grandes Células B/complicações , Doença de Marek/etiologia , Nervos Periféricos/patologia , Neoplasias Vasculares/complicações , Idoso , Idoso de 80 Anos ou mais , Animais , Nervos Cranianos/patologia , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Imageamento por Ressonância Magnética , Masculino , Doença de Marek/tratamento farmacológico , Doença de Marek/patologia , Prontuários Médicos , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prognóstico , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Neoplasias Vasculares/tratamento farmacológico , Neoplasias Vasculares/patologiaRESUMO
Intravascular lymphoma (IVL) is a rare type of extranodal lymphoma in which the lymphoma cells proliferate exclusively in the lumina of small vessels. The diagnosis of IVL requires histological confirmation. Although random skin biopsy from healthy-appearing skin in patients with suspected IVL appeared to be useful, the sensitivity of this method for the diagnosis of IVL remains unknown. We performed a random skin biopsy from 12 consecutive cases of IVL diagnosed at our institution over the past 4 years and evaluate its relevance of clinical and laboratory characteristics, presence or absence of skin lesions, and bone marrow involvement. All 12 patients were diagnosed antemortem by either random skin biopsy or bone marrow biopsy and treated with rituximab-containing chemotherapy. Random skin biopsy was performed in all 12 patients, and the results were positive in ten patients (83.3%). Erythematous skin lesions were seen in 3 of 12 patients, but biopsy was positive for lymphoma lesion in two patients. Bone marrow invasion was seen in 11 of the 12 patients (91.6%) by bone marrow smear and/or flow cytometric analysis, but was detected in only half of the patients by trephine biopsy. We concluded that random skin biopsy from normal-appearing skin is highly sensitive in the diagnosis of IVL comparable to bone marrow trephine biopsy. It should be performed irrespective of the presence or absence of skin lesions in patients who were suspicious of IVL.
Assuntos
Biópsia/métodos , Medula Óssea/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Pele/patologia , Neoplasias Vasculares/diagnóstico , Neoplasias Vasculares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab , Neoplasias Vasculares/tratamento farmacológicoRESUMO
BACKGROUND: Reactivation of hepatitis B virus (HBV) after rituximab-containing chemotherapy in patients with B-cell lymphoma has been recognized as a potentially serious complication in HBV immune patients. METHODS: To determine the HBV reactivation in patients treated with rituximab, a retrospective study of HBV-related markers was performed before and after rituximab-containing treatment in 261 consecutive patients with CD20-positive B-cell lymphoma. RESULTS: Of the 261 patients, 230 patients were tested for both hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc) before treatment. Fifty-six (24.3%) of 230 patients were anti-HBc positive, and the remaining 174 (75.6%) patients were anti-HBc negative. Among the 56 anti-HBc-positive patients, 5 (8.9%) became HBsAg positive (HBV reactivation), whereas none of the 174 anti-HBc-negative patients became HBsAg positive with a median follow-up of 24 months (P = .001). Among the 5 patients with HBV reactivation, 4 were negative for antibody to HBsAg (anti-HBs), and 1 patient was positive for anti-HBs. All 5 of these patients were treated successfully with entecavir on detection of HBsAg, although 4 of the 5 patients exhibited mild to moderate elevation of alanine aminotransferase. Among 56 anti-HBc-positive patients, those negative for anti-HBs had a higher probability of developing HBV reactivation compared with those positive for anti-HBs (4 of 19; 21.1% vs 1 of 37; 2.7%, P = .014). CONCLUSIONS: Patients with isolated anti-HBc are at high risk of HBV reactivation and should be monitored closely for HBsAg, anti-HBs, HBV-DNA, and transaminase levels during and after rituximab-containing treatment. Although preemptive use of entecavir enabled successful management of HBV reactivation, mild to moderate hepatic flare was still observed. These approaches should be further evaluated in a prospective study with regard to clinical usefulness, safety, and cost-effectiveness.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Antígenos CD20/metabolismo , Vírus da Hepatite B/isolamento & purificação , Hepatite B/complicações , Linfoma de Células B/virologia , Ativação Viral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , DNA Viral/análise , Feminino , Anticorpos Anti-Hepatite B/análise , Humanos , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , RituximabAssuntos
Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/terapia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia por Agulha , Terapia Combinada , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Cistoscopia , Diagnóstico Diferencial , Progressão da Doença , Evolução Fatal , Hematúria/diagnóstico , Hematúria/etiologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Piúria/diagnóstico , Piúria/etiologia , Medição de Risco , Índice de Gravidade de Doença , Urinálise , Irradiação Corporal Total/métodosRESUMO
Acute renal failure in patients with multiple myeloma (MM) requiring dialysis is a serious complication and is associated with extremely poor survival. In addition, its treatment included high-dose dexamethasone and/or thalidomide-containing regimens on the reversibility of renal function, which has not been adequately evaluated previously. We studied the impact on the reversibility of high-dose dexamethasone and/or thalidomide-containing regimen in 12 newly diagnosed MM patients (median 74 years, range; 63-85 years) who required dialysis at Kameda General Hospital from 2001 to 2008. There were seven light chain only myelomas, three IgD myelomas, and two IgG myelomas. Ten patients initially received high-dose dexamethasone-based treatment and two received thalidomide-based treatment, with modifications. Complete (CR) and partial responses (PR) were obtained in three and five patients, respectively. Dialysis independency was achieved in all eight patients (67%) who achieved better than PR, with a median duration of 2.0 months. Six of the ten patients who received high-dose dexamethasone-containing regimen and all of the two patients received thalidomide-containing regimen became dialysis-independent. A high concentration of serum-free light chain was detected in all patients examined, before the start of anti-myeloma treatment, and this was associated with the presence of advanced renal failure. Improved renal function was preceded by a significant decrease in serum-free light chain in patients who achieved dialysis independence. These results suggest that dialysis-dependent renal failure is reversible by dexamethasone- or thalidomide-based treatments in most patients with MM, even if the patient is in advanced age, and that serum-free light chain monitoring might be useful for predicting improvements in renal function.
Assuntos
Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Diálise Renal , Insuficiência Renal/tratamento farmacológico , Insuficiência Renal/etiologia , Idoso , Idoso de 80 Anos ou mais , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Humanos , Imunoglobulina D , Imunoglobulina G , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Indução de Remissão , Insuficiência Renal/terapia , Estudos Retrospectivos , Talidomida/farmacologia , Talidomida/uso terapêutico , Resultado do TratamentoAssuntos
Antineoplásicos/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Cromossomo Filadélfia , Piperazinas/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Pirimidinas/administração & dosagem , alfa 2-Antiplasmina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Benzamidas , Testes de Coagulação Sanguínea , Estudos Transversais , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/fisiopatologia , Masculino , Pessoa de Meia-Idade , Piperazinas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Pirimidinas/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombocitopenia/prevenção & controle , Resultado do Tratamento , Suspensão de Tratamento , alfa 2-Antiplasmina/genéticaRESUMO
We investigated the serological changes in hepatitis B virus (HBV)-related markers in 55 and 26 hepatitis B surface antigen (HBsAg)-negative patients undergoing allogeneic and autologous stem cell transplantation, respectively, over the past 4 yr. Five of the 17 allogeneic and one of the five autologous patients with pretransplant anti-hepatitis B core antigen antibodies (anti-HBc) were HBsAg-positive after transplantation, whereas none of the patients negative for anti-HBc were HBsAg-positive in both groups. All patients who became HBsAg-positive received steroid-containing immunosuppressive therapy for chronic graft versus host disease (GVHD) or myeloma. Four of the six patients developed flare of HBV hepatitis, and two patients did not. One patient developed fulminant hepatitis treated with lamivudine and plasma exchange. Other five patients received entecavir from the detection of HBsAg. Although HBV-DNA levels became below the limit of detection in all patients, HBsAg positivity remained in three patients after 6 months of treatment. We concluded that anti-HBc positivity is a risk factor for reactivation of HBV after both autologous and allogeneic transplantation, and HBV-related markers should be monitored regularly in these patients. We also stress the efficacy of pre-emptive use of antiviral agents in controlling HBV replication and limiting hepatic injury due to reactivation of HBV in these patients.