RESUMO
A 70-year-old woman was admitted to the hospital with loss of appetite and melena. She was diagnosed with multiple myeloma 7 years ago and had been on carfilzomib, lenalidomide, and dexamethasone (KRd) therapy for a month because her disease had a relapsed/refractory. On admission, her laboratory tests revealed hemolytic anemia with schizocytes, thrombocytopenia, and acute renal dysfunction. TMA (thrombotic microangiography) caused by carfilzomib was suspected. The possibility of thrombotic thrombocytopenia was considered, and steroid pulse therapy was initiated. Her condition improved significantly after she stopped taking carfilzomib, plasma exchange, hemodiafiltration, steroid pulse therapy, and abstaining from food. The previously reported cases of carfilzomib-induced TMA included fever, gastrointestinal symptoms (nausea/vomiting, diarrhea), and acute renal disorders (lower extremity edema, decreasing urine output). As far as we know, this is the first case of carfilzomib-induced TMA with bleeding as the first symptom.
Assuntos
Mieloma Múltiplo , Microangiopatias Trombóticas , Humanos , Feminino , Idoso , Mieloma Múltiplo/tratamento farmacológico , Dexametasona/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Microangiopatias Trombóticas/diagnóstico , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/terapiaRESUMO
We found a HLA class II histocompatibility antigen gene, DQ alpha 1 chain (HLA-DQA1), that was expressed more than 9-fold higher in high-load hepatitis C virus (HCV) livers than low-load HCV livers using transcriptomics of chronic HCV-infected livers. To further investigate this finding, we examined which cells were positive for HLA-DQA1 and what liver immune responses were different between HCV-high and -low livers. HLA-DQA1-positive cells were significantly increased in the HCV-high group, and most positive cells were identified as non-parenchymal sinusoid cells and lymphocytic infiltrates in the portal area. Parenchymal hepatocytes were negative for HLA-DQA1. HLA-DQA1-positive cells in the liver sinusoid were positive for CD68 (macrophages or Kupffer cells); those in the lymphocytic infiltrates were positive for CD20 (B cells) or CD3 (T cells). mRNA levels of antigen-presenting cell (APC) markers such as CD68 and CD11c were significantly upregulated in the HCV-high group and were correlated with HLA-DQA mRNA levels. CD8B mRNA (CD8+ T cells) was upregulated in both HCV-positive livers compared with HCV-negative livers, whereas CD154 mRNA (CD4+ T helper cell) was upregulated in the HCV-high group compared with the HCV-low group. The immune regulatory molecules FOXP3 mRNA (regulatory T cell, T reg) and programmed cell death ligand-1 (PD-L1) mRNA were significantly increased in the HCV-high group. HCV-high livers had two molecular immune responses: increased APC numbers and adaptive immunity and the induction of immune tolerance. The local hepatic imbalance of contradictory immune responses might be responsible for high HCV loads.
Assuntos
Carcinoma Hepatocelular/genética , Cadeias alfa de HLA-DQ/genética , Hepatite C Crônica/genética , Neoplasias Hepáticas/genética , Carga Viral/genética , Imunidade Adaptativa , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos CD20/genética , Antígenos CD20/imunologia , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/imunologia , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Antígeno CD11c/genética , Antígeno CD11c/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Ligante de CD40/genética , Ligante de CD40/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/virologia , Células Dendríticas/imunologia , Células Dendríticas/virologia , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Regulação da Expressão Gênica , Cadeias alfa de HLA-DQ/imunologia , Hepacivirus/crescimento & desenvolvimento , Hepacivirus/imunologia , Hepacivirus/patogenicidade , Hepatite C Crônica/complicações , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Hepatócitos/imunologia , Hepatócitos/virologia , Humanos , Tolerância Imunológica , Células de Kupffer/imunologia , Células de Kupffer/virologia , Fígado/imunologia , Fígado/virologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/virologia , Transdução de Sinais , Transcriptoma/imunologia , Carga Viral/imunologiaRESUMO
An 80-year-old man presented to our hospital with a thoracic vertebrae compression fracture. He was diagnosed with IgG-λ myeloma (International Staging System stage II, Durie-Salmon stage IIIA). Since melphalan-prednisolone (MP) was not effective, we treated him with lenalidomide and low-dose dexamethasone (DEX) (Ld), achieving a partial response. As DEX provoked edema and psychiatric symptoms, the patient disagreed with its use, and pomalidomide (POM) monotherapy was initiated. Although the POM dosage was reduced to 1-2 mg/day due to somnolence, which was reported as an adverse event, stringent complete response (sCR) was achieved and sustained for 10 months following 11 cycles of low-dose POM monotherapy. It is assumed that sCR was achieved with low-dose POM monotherapy due to its early introduction as well as there being no high-risk chromosomal abnormalities. Even though adverse events develop with a standard dose, a continuation of low-dose POM is considered more important than discontinuation.
Assuntos
Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona/uso terapêutico , Humanos , Lenalidomida/uso terapêutico , Masculino , Talidomida/uso terapêuticoRESUMO
TAFRO syndrome is an inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly. Despite great advancements in research on the TAFRO syndrome in the last decade, its diagnosis and treatment are still challenging for most clinicians because of its rarity and severity. Since the initial proposal of the TAFRO syndrome as a distinct disease entity in 2010, two independent diagnostic criteria have been developed. Although these are different in the concept of whether TAFRO syndrome is a subtype of idiopathic multicentric Castleman disease or not, they are similar except for the magnitude of lymph node histopathology. Because there have been no specific biomarkers, numerous diseases must be ruled out before the diagnosis of TAFRO syndrome is made. The standard of care has not been fully established, but interleukin-6 blockade therapy with siltuximab or tocilizumab and anti-inflammatory therapy with high-dose corticosteroids are the most commonly applied for the treatment of TAFRO syndrome. The other immune suppressive agents or combination cytotoxic chemotherapies are considered for patients who do not respond to the initial treatment. Whereas glowing awareness of this disease improves the clinical outcomes of patients with TAFRO syndrome, further worldwide collaborations are warranted.
RESUMO
We investigated the incidence, risk factors, and clinical outcomes of cytomegalovirus (CMV) disease in patients with B-cell lymphoma treated with a bendamustine-containing regimen. The incidence of CMV disease was analyzed after starting treatment with 139 regimens in 126 patients. Clinically significant CMV disease was observed in seven patients. The median duration between bendamustine initiation and the diagnosis of CMV disease was 69 d (range, 40-233), and the median of cycles completed at onset was 2 (range, 1-6). Furthermore, the incidence of CMV disease was significantly higher in the elderly patients than that in the younger patients. The target organs of CMV disease were the liver, gastrointestinal tract, lungs, and retinas. Antiviral therapy was administered to all patients. However, the recurrence of CMV disease was observed in two patients. This study provides information that could contribute to clinicians' decision-making on lymphoma therapy using bendamustine.
Assuntos
Infecções por Citomegalovirus , Linfoma , Humanos , Idoso , Cloridrato de Bendamustina/efeitos adversos , Citomegalovirus , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Linfoma/complicações , Linfoma/diagnóstico , Linfoma/tratamento farmacológico , Fatores de Risco , Antivirais/efeitos adversos , Estudos RetrospectivosRESUMO
Pulmonary veno-occlusive disease (PVOD) is an extremely rare condition in oncology practice. Although PVOD is clinically similar to pulmonary arterial hypertension, the conditions differ in terms of pathophysiology, management, and prognosis. This report discusses the case of a 47-year-old woman who developed dyspnea and fatigue after high-dose cyclophosphamide chemotherapy and autologous hematopoietic stem cell transplantation for relapsed lymphoma. The patient exhibited tachycardia, tachypnea, and hypotension, but other findings in the physical examination were unremarkable. The imaging studies showed no evidence of pulmonary embolism, but multiple ground-glass opacities and bilateral pleural effusions were observed on chest high-resolution computed tomography scans. In the right heart catheterization study, the mean pulmonary artery pressure and pulmonary vascular resistance were 35 mm Hg and 5.93 Wood units, respectively, with a normal pulmonary capillary wedge pressure of 10 mm Hg. Pulmonary function tests revealed a remarkable reduction in the percentage predicted value of diffusing capacity of the lungs for carbon monoxide to 31%. Lymphoma progression, collagen diseases, infectious diseases such as human immunodeficiency virus or parasitic infections, portal hypertension, and congenital heart disease were carefully excluded as these are also capable of causing pulmonary arterial hypertension. Thereafter, we reached a final diagnosis of PVOD. The patient was treated with supplemental oxygen and a diuretic during 1 month of hospitalization, which relieved her right heart overload symptoms. Herein, we present the patient's clinical course and diagnostic workup because misdiagnosis or inappropriate treatment can lead to unfavorable outcomes in patients with PVOD.
RESUMO
Background/Aim: Here, we investigated whether bortezomib as a maintenance therapy affected outcomes in transplant-ineligible patients with multiple myeloma (MM). Patients and Methods: Following induction therapy with bortezomib, maintenance therapy with bortezomib (1.3 mg/m 2 ) and dexamethasone (20 mg) was administered once or twice every 4 weeks until disease progression. The endpoints of this study were time to next treatment and overall survival. Results: Seventy-six newly diagnosed, transplant-ineligible patients were treated with a bortezomib-based regimen; 28 discontinued induction therapy, 27 did not receive maintenance therapy after induction therapy (the non-maintenance group), and 21 did (the maintenance group). In the three groups, the median times to the next required treatment were 3, 14, and 37 months, respectively. The 3-year overall survival rates were 55%, 69%, and 85%, respectively. There were no significant differences in patient characteristics between the non-maintenance and maintenance groups, except for poorer estimated glomerular filtration rates in the maintenance group. Conclusion: Bortezomib maintenance therapy may be a useful option for transplant-ineligible patients with MM.
RESUMO
The mitochondrial DNA (mtDNA) displacement loop (D-loop) is often altered in various cancer types, including with regard to simple sequence repeat number variation (SSRNV), which includes the C-tract and CA-tract. However, because of mitochondrial heteroplasmy and slippage errors by the Taq DNA polymerase used in polymerase chain reaction (PCR) analysis, it is difficult to precisely evaluate mtDNA D-loop SSRNV experimentally. In this study, to precisely determine cancer-specific variants in mtDNA SSRNV, various microscopic portions of cancerous tissues and normal control tissues were obtained from a patient with breast cancer, followed by laser-capture microdissection of formalin-fixed paraffin-embedded specimens. Regions containing (CA)7 repeats (positions 514-523) and (C)8 repeats (positions 303-315) of the mitochondria DNA D-loop were amplified and sequenced. Variant signals of mtDNA SSRs of (CA)7 and (C)8 were observed in normal and cancerous tissues, with the content of minor alleles (CA)6 and (C)7/(C)9 differing among samples. These results were confirmed by PCR using various primers and proofreading DNA polymerases. PCR of genomic SSRs of (CA)7 in the NAALD2 gene and (C)8 in the BMP6 gene showed a simple repeat in all samples that was different from the observed mtDNA SSRNV. The present study suggests a reliable procedure for determining cancer-specific variants in mtDNA SSRNV: Using a proofreading DNA polymerase for PCR, the background of slippage by PCR is determined by PCR of the same genomic sequence as the target. Due to the varied heteroplasmy level of mtDNA SSRNV among normal tissues, the second background of polymorphic variations should be determined by several normal tissue DNA as PCR templates. Finally, the cancer-specific variant, including its variation frequency, is determined by subtracting the two background signals from the variant signals in cancer. However, care must be taken, as normal heteroplasmy drifts observed in mtDNA SSRNV may complicate such estimations.