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BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is known as a transfusion-related complication with typically favorable prognosis and no report fatalities. Pathological evaluation of PRES is also scarce. CASE REPORT: An 88-year-old female with myelodysplastic syndromes (MDS) attended our hospital because of a compression fracture and chronic heart failure with chronic anemia. While her hemoglobin levels improved from 4.6 to 8.0 g/dL and the pleural effusions substantially decreased following six units of red blood cell transfusion and diuretic therapy, a gradual decline in cognitive function and speech reduction was noted. PRES was diagnosed by magnetic resonance imaging of the head. Despite treatment of intensive supportive care, the patient fell into a coma by the 20th day and passed away on the 22nd day. Although the pathophysiological link between blood-transfusion-related PRES and its impact on survival is not fully understood, autopsy findings confirmed the diagnosis of PRES and revealed multiple cerebral hemorrhages that were not detected in earlier imaging studies. CONCLUSION: This case highlights the importance of vigilant monitoring and management of PRES, especially in high-risk populations such as elderly patients with multiple comorbidities or those with thrombocytopenia. Further studies are needed to elucidate the mechanisms of PRES in patients with hematologic diseases.
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A 27-year-old woman was diagnosed with idiopathic thrombocytopenic purpura in the neonatal period, and was admitted to our hospital after presenting with impaired consciousness, purpura, nausea and vomiting, with a platelet count of 10×109/l. Congenital thrombotic thrombocytopenic purpura (cTTP) was suspected on the basis of recurrent thrombocytopenia and impaired consciousness, so tests for ADAMTS13 activity and inhibitor were performed. ADAMTS13 activity was severely decreased, ADAMTS13 inhibitor was negative, and platelet count increased after transfusion of fresh frozen plasma. These findings and the results of genetic testing done on all family members led to a diagnosis of cTTP. cTTP requires differential diagnosis even in adults. If a patient diagnosed with ITP in childhood has a history or findings that suggest cTTP during follow-up observation, it is necessary to actively consider ADAMTS13 testing.
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Púrpura Trombocitopênica Idiopática , Púrpura Trombocitopênica Trombótica , Adulto , Recém-Nascido , Feminino , Humanos , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Contagem de Plaquetas , Plasma , Transfusão de Sangue , Proteína ADAMTS13/genéticaRESUMO
OBJECTIVE: We sought to assess the safety and feasibility of outpatient management in Japanese patients with relapsed/refractory lymphoma who had received pegfilgrastim after salvage therapy. METHOD: This was a single-center, open-label, non-randomized, prospective interventional analysis. Patients were completely hospitalized for cycle 1 of chemotherapy. Those who met the outpatient management criteria (outpatient group) were subsequently admitted to the hospital for chemotherapy cycles but were discharged after each cycle was completed. The inpatient group was discharged when white blood cell and platelet counts improved. Pegfilgrastim was given as a single 3.6 mg dose by subcutaneous injection 2 days after the completion of each chemotherapy cycle. RESULTS: The percentage of outpatient management days (primary endpoint) ranged from 68.2%-75.0% in the outpatient group and 28.6%-50.0% in the inpatient group. According to the secondary endpoints, there were no hospitalizations due to febrile neutropenia during the outpatient period. There were no major safety concerns raised. CONCLUSIONS: For patients with relapsed/refractory lymphoma, pegfilgrastim administration after salvage therapy in an outpatient setting was feasible and safe for those who satisfied the outpatient management criteria.
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Fator Estimulador de Colônias de Granulócitos , Linfoma , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos de Viabilidade , Linfoma/tratamento farmacológico , Pacientes Ambulatoriais , Estudos Prospectivos , Terapia de SalvaçãoRESUMO
A 27-year-old woman with pancytopenia was admitted to our hospital. Bone marrow aspiration revealed 52.2% myeloperoxidase-positive myeloblasts, leading to a diagnosis of acute myeloid leukemia. While a screening test for chimeric genes related to leukemia initially yielded negative results, including for the CBFB::MYH11 fusion gene, G-banded karyotyping uncovered the presence of inv (16)(p13.1q22). Further investigation by fluorescence in situ hybridization (FISH) confirmed the split signals for CBFB. A second screening test for leukemia-related chimeric genes with different PCR primers revealed the elusive CBFB::MYH11 fusion gene. Subsequently, the type I CBFB::MYH11 fusion gene was identified through exhaustive exploration using RNA sequencing for fusion gene discovery. This exceptional case highlights the existence of a distinctive subtype of CBFB::MYH11 that may yield false-negative results in conventional chimeric fusion screening, thus emphasizing the indispensable utility of PCR primer modification, FISH, and RNA sequencing in the investigative process.
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Leucemia Mieloide Aguda , Feminino , Humanos , Adulto , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Cariotipagem , Proteínas de Fusão Oncogênica/genética , Subunidade beta de Fator de Ligação ao Core/genética , Cadeias Pesadas de Miosina/genéticaRESUMO
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.
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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
Classic hairy cell leukemia (classic HCL) is a rare disease associated with indolent mature B-cell lymphoma. A 50-year-old man presented with pancytopenia for 3 years and was diagnosed with classic HCL because his lymphoid cells showed a hairy morphology with oval nuclei and indistinct nucleoli both in the peripheral blood and bone marrow (BM) smears. Flow cytometric analysis revealed that these cells expressed CD11c, CD25, and CD103, and the Sanger sequence method detected BRAF V600E mutation. Cladribine (0.09 mg/kg/day) was initiated for 7 days via continuous intravenous injection. On day 13, the patient died from bloodstream infection caused by methicillin-resistant Staphylococcus epidermidis. Autopsy findings revealed BM necrosis without residual leukemia cells caused by classic HCL, severe infection, and agents, such as cladribine and granulocyte-colony stimulating factor; however, its cause remained undetermined. Both early diagnosis and immediate clinical intervention are required to improve the clinical outcomes in classic HCL. The cause of hematopoiesis disturbance should also be identified using BM biopsy or magnetic resonance imaging before initiating treatment in classic HCL with severe pancytopenia.
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Medula Óssea/patologia , Cladribina/administração & dosagem , Leucemia de Células Pilosas/diagnóstico , Infecções Estafilocócicas , Antineoplásicos/administração & dosagem , Evolução Fatal , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina , Pessoa de Meia-IdadeRESUMO
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.
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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 JovemAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/efeitos adversos , Linfoma Folicular/tratamento farmacológico , Linfopenia/induzido quimicamente , Rituximab/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Bendamustina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Rituximab/uso terapêuticoRESUMO
Infection is a major contributor to non-relapse mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Detecting infectious diseases in febrile patients during pretransplant conditioning is crucial for subsequent transplant success. Procalcitonin (PCT) is an auxiliary diagnostic marker of severe bacterial infections and has been proposed as a useful predictor of infection in patients undergoing allo-HSCT. Pre-transplant use of anti-thymocyte globulin (ATG) can cause side effects, such as fever and hypotension, which must be distinguished from infectious diseases. Although ATG administration may increase PCT levels, data on PCT levels in febrile patients after ATG administration are limited. Furthermore, no studies have compared PCT levels during allo-HSCT conditioning using ATG or non-ATG regimens. To investigate whether ATG increases PCT levels during febrile episodes in pre-transplant conditioning and whether PCT could be used to discriminate infections during this period, we analyzed 17 ATG and 59 non-ATG patients with fever and who underwent PCT level measurements during pre-transplant conditioning. Our findings revealed that ATG administration was the only significant factor that increased PCT positivity during fever (p = 0.01). In contrast, infectious diseases did not affect PCT positivity in the ATG group (p = 0.24). Furthermore, bloodstream infection was a significant risk factor for PCT positivity in patients who received non-ATG regimens (p < 0.01). Incorporating PCT levels into the diagnostic workup for infectious diseases requires careful consideration, particularly for patients receiving ATG regimens.
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Hematologic diseases frequently affect people >60 years old, and allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for these patients. Although several multicenter studies proposed the risk assessment of allo-SCT for the elderly, they receive different treatments and management at each facility. Therefore, accumulating data from institutions that exhibit relatively the same treatment policy and patient care is important. This retrospective study aimed to clarify the prognostic factors of allo-SCT for the elderly in our institution. Of the 104 patients, 51.0% were 60-64 years old, and 49.0% were ≥65 years old. The 3-year overall survival (OS) was 40.9% and 35.7% for patients 60-64 and ≥65 years old, respectively, which is not significant. While the disease status prior to allo-SCT demonstrated strong effects on the 3-year OS for patients that are 60-64 years old (in remission, 76.9%; non-remission, 15.7%, p<0.001), this effect was smaller for patients ≥65 years old (in remission, 43.1%; non-remission, 30.1%, p=0.048). Multivariate analysis revealed that the performance status (PS), not the disease status prior to allo-SCT, was the prognostic risk factor of OS for patients aged ≥65 years. Our data suggest that PS is a useful predictor of better OS following allo-SCT, especially for patients ≥65 years old.
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PURPOSE: Comprehensive geriatric assessment (CGA) has been used to help identify elderly patients with diffuse large B-cell lymphoma (DLBCL) who were suitable for rituximab combined with CHOP therapy (cyclophosphamide, Adriamycin, vincristine, and prednisolone), but there are few reports of CGA for elderly patients with DLBCL who received R-mini-CHOP. METHODS: We retrospectively analyzed the risk factors for outcomes among 142 patients aged 80 years and older (≤ 85 years, n = 102; > 85 years, n = 40) with DLBCL who received R-mini-CHOP at 4-week intervals at our institute between 2008 and 2019. We performed a comparison between CGA and treatment outcomes. RESULTS: There were significant differences in progression-free survival between patients with international prognostic index (IPI) scores of > 3 and ≤ 3 at diagnosis and in overall survival between patients with instrumental activities of daily living (IADL) scores of ≥ 5 and IADL < 5 before the initial treatment and patients aged ≤ 85 years and > 85 years. CONCLUSION: Strategies that carefully select elderly patients aged 80 years and older with DLBCL using CGA may help to identify individuals suitable for novel therapies.
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Avaliação Geriátrica , Linfoma Difuso de Grandes Células B , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Estudos Retrospectivos , Rituximab/uso terapêuticoRESUMO
BACKGROUND AND AIMS: We have started a new population-based endoscopic gastric cancer screening program in Kurashiki city with consideration of Helicobacter pylori infection status based on endoscopic features. We aimed to verify the feasibility of this attempt in a prospective case-registration study (UMIN000028629). METHODS: Data were collected from 1784 subjects without past eradication of H. pylori and who underwent endoscopic gastric cancer screening in Kurashiki Central Hospital Preventive Healthcare Plaza from September 2017 to June 2018. Endoscopic judgment of H. pylori infection status was made according to the Kyoto classification of gastritis. For comparison, a combination serum test of anti-H. pylori antibody and pepsinogen I and II, the ABC method, was used. RESULTS: The endoscopic diagnoses were nongastritis, 1215 (68.1%); active or inactive gastritis, 469 (26.3%); and undefined, 23 (1.3%). With the ABC method as a reference standard, the false-negative rate of the endoscopic judgment for H. pylori infection was 16.3% (95% confidence interval: 13.1%-20.0%). Most false-negative cases were of Group B in the ABC method, which is considered gastritis with mild mucosal atrophy. Antibody titers in this population were mostly in the weak-positive range but clinically significant elevation of the antibody suggesting current infection was observed in some cases. CONCLUSIONS: Endoscopic diagnosis of H. pylori infection status in a population-based gastric cancer screening program is mostly reliable, but false-negative results may occur, especially in patients with mild gastric atrophy. To avoid this limitation, we recommend adding H. pylori antibody test to the program.
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BACKGROUND AND AIM: Duodenal ulcer bleeding has a higher risk of mortality than bleeding from other portions of the gastrointestinal tract. AIMS65 is an effective risk-scoring system to predict prognosis of upper gastrointestinal bleeding and can be easily calculated without endoscopic findings. In this study, we investigate the usefulness of AIMS65 to predict prognosis of patients with duodenal ulcer bleeding. METHODS: Two hundred and fifty-five patients with endoscopically diagnosed duodenal ulcer bleeding at Kurashiki Central hospital from July 2007 to June 2017 were studied. We compared AIMS65, Glasgow Blatchford score (GBS), admission Rockall, and full Rockall scoring systems for predicting in-hospital mortality by calculating area under the receiver operating characteristic curve (AUROC). RESULTS: In-hospital mortality due to duodenal ulcer bleeding occurred in 17 (6.7%). Scores of all scoring systems were significantly higher in patients with in-hospital mortality than in patients without it. AUROC values for predicting in-hospital mortality was 0.83 in AIMS65, 0.74 in GBS, 0.76 in admission Rockall score, and 0.82 in full Rockall score, a statistically insignificant difference among the systems. In AIMS65, score more than or equal to 2 was an optimal value to predict in-hospital mortality, with sensitivities of 88.2% and specificities of 59.7%, respectively. CONCLUSIONS: AIMS65 predicted in-hospital mortality of patients with duodenal ulcer bleeding as accurately as did other scoring systems. Given its simplicity of calculation, AIMS65 may be a more clinically practical system in the management of bleeding duodenal ulcer patients.
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Úlcera Duodenal , Úlcera Duodenal/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Humanos , Prognóstico , Curva ROC , Medição de Risco , Índice de Gravidade de DoençaRESUMO
We stratified patients with newly diagnosed acute promyelocytic leukemia (APL) according to a white blood cell (WBC) count of ≥ 3 × 109/L (high risk) or < 3 × 109/L (low risk) before administering risk-adapted chemotherapy in combination with all-trans retinoic acid (ATRA). In total, 27 low-risk and 23 high-risk patients were assigned to receive induction and three courses of consolidation with ATRA and anthracycline, followed by 2-year maintenance regimen. High-risk group additionally received cytarabine during 1st consolidation and another one-shot idarubicin treatment during 3rd consolidation. We prospectively monitored measurable residual disease (MRD) after induction and each consolidation. In the low-risk and high-risk groups, 5-year disease-free survival (DFS) rates were 86.5% and 81.2% (p = 0.862), and 5-year overall survival rates were 100% and 84.8% (p = 0.062), respectively. In the MRD-negative and MRD-positive groups, 5-year DFS rates were 91.7% and 78.4% (p = 0.402) and 84.7% and 60.0% (p = 0.102) after induction and 1st consolidation, respectively. Relapse rates were 8.3% and 13.3% (p = 0.570) and 9.0% and 40.0% (p = 0.076) after induction and 1st consolidation, respectively. Achieving MRD-negativity after 1st consolidation, rather than after induction, was a potential predictor of relapse and DFS in patients with APL treated with ATRA + chemotherapy.
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Quimioterapia de Consolidação , Leucemia Promielocítica Aguda/tratamento farmacológico , Neoplasia Residual/mortalidade , Tretinoína/uso terapêutico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/administração & dosagem , Feminino , Previsões , Humanos , Idarubicina/administração & dosagem , Leucemia Promielocítica Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/diagnóstico , Prognóstico , Estudos Prospectivos , Recidiva , Taxa de Sobrevida , Resultado do Tratamento , Tretinoína/administração & dosagem , Adulto JovemRESUMO
In the original publication of the article, the "CNS involvement" in the last row under the column "Total N=50" has been published incorrectly. The correct Table 1 is given in this correction.
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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.
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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/diagnósticoRESUMO
Langerhans cell histiocytosis (LCH) is a rare disease in adults. The treatment strategy for this condition remains controversial. Intensified systemic chemotherapy is required in pediatric patients with the multiple system form of LCH (MS-LCH) for aggressive forms of the disease. Recent clinical trials have shown that intensified chemotherapy for pediatric patients diagnosed with MS-LCH results in improved outcomes. However, whether the feasibility and efficacy of an intensified systemic chemotherapy regimen are also beneficial for adult patients with MS-LCH remains unclear. Here, we report two cases of adult MS-LCH that were successfully treated with an intensified treatment protocol as used in pediatric patients. One patient fully completed the protocol, and has since maintained a complete response (CR) for 2 years following completion of the treatment. The other patient also achieved CR after induction therapy, and is now undergoing maintenance therapy in an outpatient clinic. The cases presented in this study suggest that intensified systemic chemotherapy as used for pediatric patients with MS-LCH is well tolerated and effective for adult patients as well.