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1.
Int J Med Sci ; 20(2): 206-210, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36794163

RESUMO

Aggressive natural killer cell leukemia (ANKL) is a rare disease with an aggressive clinical course. We aimed to assess the clinicopathological characteristics of the difficult to diagnose ANKL. During ten years, nine patients with ANKL were diagnosed. All the patients exhibited aggressive clinical course and underwent the BM study to rule out lymphoma and hemophagocytic lymphohistiocytosis (HLH). BM examination showed varying degrees of infiltration of neoplastic cells, which were mainly positive for CD2, CD56, cytoplasmic CD3 and EBV in situ hybridization. Five BM aspirates showed histiocytic proliferation with active heomphagocytosis. Normal or increased NK cell activity test results were obtained from 3 patients who were available for testing. Four had multiple BM studies until diagnosis. An aggressive clinical course and positive EBV in situ hybridization, often with associated secondary HLH, should raise the suspicion of an ANKL. Conducting additional supplementary tests such as NK cell activity and NK cell proportion would be helpful for the diagnosis of ANKL.


Assuntos
Leucemia Linfocítica Granular Grande , Linfoma , Humanos , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/patologia , Células Matadoras Naturais/patologia , Progressão da Doença
2.
Br J Haematol ; 198(4): 703-712, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35612271

RESUMO

Clonal cytopenia of undetermined significance (CCUS) is characterized by persistent cytopenias with genetic aberrations, which do not meet the diagnostic criteria for myelodysplastic syndrome (MDS). We aimed to compare the clinical and genetic characteristics of CCUS with lower-risk MDS and identify patients with CCUS with a high risk of progression. We performed targeted sequencing of bone marrow (BM) samples from patients with idiopathic cytopenia of undetermined significance (ICUS) (n = 139) and MDS (n = 226). Overall survival (OS) of patients with CCUS (n = 78) was worse than non-clonal ICUS (n = 61) and superior to lower-risk MDS (n = 99). Patients with CCUS showed similar characteristics to those with lower-risk MDS, except for higher haemoglobin, lower BM cellularity, and less frequent SF3B1 mutations. Lower haemoglobin, DDX41 (biallelic germline and somatic), ETV6, and RUNX1 mutations were independent prognostic factors for worse OS. Lower haemoglobin and DDX41 mutations were also associated with lower progression-free survival. Patients with CCUS with high-risk features showed similar or worse OS than patients with lower-risk MDS. Our findings suggest that patients with CCUS having certain clinical or genetic features should be regarded and treated as lower-risk MDS despite lacking significant dysplasia or MDS-associated chromosomal abnormalities.


Assuntos
Hematopoiese Clonal , Síndromes Mielodisplásicas , Aberrações Cromossômicas , Hemoglobinas/genética , Humanos , Mutação , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética
3.
Ann Neurol ; 89(3): 444-458, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33219556

RESUMO

OBJECTIVE: It is unclear if stopping treatment with dabigatran, a new oral anticoagulant (NOAC), induces a paradoxical rebound prothrombotic state. We investigated if short-term (1-3 days) dabigatran cessation is associated with a higher thrombus volume than expected from a simple reversal of the anticoagulant effect. METHODS: Ten-week-old C57Bl/6 mice (n = 338) received one of the following oral treatments: phosphate-buffered saline (PBS), dabigatran for 7 days with or without 1 to 4 day cessation, and aspirin in either a single dose or daily for 7 days. Some of the animals that ceased dabigatran for 1 to 3 days received single-dose aspirin. Thereafter, we induced FeCl3 -mediated carotid thrombosis in 130 mice, after which we performed micro computed tomography thrombus imaging. The other 208 mice underwent coagulation assays or platelet function tests. As an explorative pilot study, we reviewed the medical records of 18 consecutive patients with NOAC cessation-related cerebral infarction in a large acute stroke cohort. RESULTS: We observed a ~ 40% higher volume of carotid thrombus after dabigatran cessation at 1 to 3 days than after vehicle treatment and showed that this effect could be prevented by single-dose aspirin pretreatment. Dabigatran cessation unduly increased platelet aggregability for 2 days after drug cessation, an effect mediated through thrombin or arachidonic acid, which effect was significantly attenuated by single-dose aspirin pretreatment. In patients, short-term (≤ 3 days) cessation of NOAC therapy, compared with longer-term (≥ 5 days) cessation, tended to be associated with relatively high stroke severity. INTERPRETATION: We provide the first preclinical evidence that a rebound prothrombotic state follows short-term cessation of dabigatran therapy. ANN NEUROL 2021;89:444-458.


Assuntos
Antitrombinas/efeitos adversos , Trombose das Artérias Carótidas/diagnóstico por imagem , Dabigatrana/efeitos adversos , Desprescrições , Agregação Plaquetária/efeitos dos fármacos , Síndrome de Abstinência a Substâncias/sangue , Trombofilia/sangue , Idoso , Idoso de 80 Anos ou mais , Animais , Antitrombinas/farmacologia , Ácido Araquidônico/sangue , Aspirina/farmacologia , Trombose das Artérias Carótidas/induzido quimicamente , Trombose das Artérias Carótidas/prevenção & controle , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/etiologia , Infarto Cerebral/fisiopatologia , Infarto Cerebral/prevenção & controle , Cloretos/toxicidade , Angiografia por Tomografia Computadorizada , Dabigatrana/farmacologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Compostos Férricos/toxicidade , Humanos , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/etiologia , AVC Isquêmico/fisiopatologia , AVC Isquêmico/prevenção & controle , Angiografia por Ressonância Magnética , Masculino , Volume Plaquetário Médio , Camundongos , Noxas/toxicidade , Projetos Piloto , Inibidores da Agregação Plaquetária/farmacologia , Contagem de Plaquetas , Pirazóis/efeitos adversos , Piridonas/efeitos adversos , Rivaroxabana/efeitos adversos , Índice de Gravidade de Doença , Síndrome de Abstinência a Substâncias/etiologia , Síndrome de Abstinência a Substâncias/prevenção & controle , Trombina/metabolismo , Trombofilia/etiologia , Trombofilia/prevenção & controle , Microtomografia por Raio-X
4.
Haematologica ; 107(2): 510-518, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33626862

RESUMO

DDX41 mutations are associated with hematologic malignancies including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but the incidence in idiopathic cytopenia of undetermined significance (ICUS) is unknown. We investigated the incidence, genetic characteristics, and clinical features of DDX41 mutations in Korean patients with ICUS, MDS, or AML. We performed targeted deep sequencing of 61 genes including DDX41 in 457 patients with ICUS (n=75), MDS (n=210), or AML (n=172). Germline DDX41 mutations with causality were identified in 28 (6.1%) patients, of whom 27 (96.4%) had somatic mutations in the other position of DDX41. Germline origins of the DDX41 mutations were confirmed in all of the 11 patients in whom germline-based testing was performed. Of the germline DDX41 mutations, p.V152G (n=10) was most common, followed by p.Y259C (n=8), p.A500fs (n=6), and p.E7* (n=3). Compared with non-mutated patients, patients with a DDX41 mutation were more frequently male, older, had a normal karyotype, low leukocyte count, and hypocellular marrow at diagnosis. Three of the four ICUS patients with germline DDX41 mutations progressed to MDS. The incidence of DDX41 mutations in Korean patients was high and there was a distinct mutation pattern, in that p.V152G was a unique germline variant. ICUS harboring germline DDX41 mutations may be regarded as a hereditary myeloid neoplasm. Germline DDX41 mutations are not uncommon and should be explored when treating patients with myeloid malignancies.


Assuntos
RNA Helicases DEAD-box , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Transtornos Mieloproliferativos , RNA Helicases DEAD-box/genética , Etnicidade/genética , Doenças Hematológicas/genética , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Mutação , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Transtornos Mieloproliferativos/genética
5.
Clin Lab ; 68(4)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35443589

RESUMO

BACKGROUND: Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/ MPN-RS-T) was newly introduced as a full entity in the 2016 revision of the WHO classification. In this study, we investigated the morphologic, laboratory, and clinical features of MDS/MPN-RS-T. METHODS: We reviewed the bone marrow and genetic studies of patients whose diagnoses were coded as "refractory anemia with ring sideroblasts (RARS)" or "MDS/MPN, unclassifiable" between January 2008 and April 2018. RESULTS: A total of 8 cases fulfilled the criteria for a diagnosis of MDS/MPN-RS-T. All of them had no specific symptoms. Half of the cases had less than 450 × 109/L platelet counts by an automated hematology analyzer; however, all platelet counts exceeded 450 × 109/L when performed manually. JAK2 mutation tests were performed in 7 cases, and a heterozygous mutation was detected in 1 case. SF3B1 mutations were present in 3 of the 4 cases tested. CONCLUSIONS: When RARS is suspected in patients without thrombocytopenia, manual platelet counts should be performed. For patients with suspected essential thrombocythemia, RS evaluation through careful observation of an iron-stained slide is crucial. Since the independent evaluation of RS was reflected in the revised classification, the ambiguous disease classification becomes clearer and more consistent.


Assuntos
Anemia Refratária , Anemia Sideroblástica , Doenças Mieloproliferativas-Mielodisplásicas , Neoplasias , Trombocitose , Anemia Refratária/diagnóstico , Anemia Refratária/genética , Anemia Sideroblástica/diagnóstico , Anemia Sideroblástica/genética , Humanos , Mutação , Doenças Mieloproliferativas-Mielodisplásicas/diagnóstico , Doenças Mieloproliferativas-Mielodisplásicas/genética , Trombocitose/diagnóstico , Trombocitose/genética
6.
Clin Lab ; 68(6)2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35704735

RESUMO

BACKGROUND: Thromboelastography (TEG) provides assessment of global coagulation. The TEG6s (Haemonetics Corporation) is a newly developed cartridge-based system, fully automated and the first true point-of-care TEG. In this study, we evaluated the precision and established the reference intervals (RIs) for TEG6s. METHODS: TEG assays were performed on the blood of healthy donors to determine RIs and on the QC materials for precision testing. The study design was developed in accordance with Clinical and Laboratory Standards Institute Guidelines. RESULTS: TEG6s precision testing yielded low variability except R, due to a low value for the mean. The newly established RIs of R, MA, and LY30 were similar to the manufacturer's RIs. Some were different, showing short K and increased α. CONCLUSIONS: This study has shown that TEG6s has high precision and each institution should verify the manufacturer's RIs before adopting TEG6s and establish RIs if necessary.


Assuntos
Laboratórios Clínicos , Tromboelastografia , Coagulação Sanguínea , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Valores de Referência
7.
J Bus Res ; 139: 529-542, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36536893

RESUMO

Peer-to-peer (P2P) accommodation markets have been disrupted by the COVID-19 pandemic. However, little attention is paid to how to remedy the disruption in terms of P2P accommodation performance. This study empirically investigates the spatially heterogeneous COVID-19 disruptions in the Airbnb business and offers place-based remedying strategies through local resources, including tourism clusters and community resilience. Using real data on Airbnb operating performance and local resources in Florida, we employ spatial econometric models and visualization techniques to estimate the pandemic-disrupted Airbnb performance model. The results show that leisure and hospitality clusters and three resilience resources-social, community capital, and environmental-had spatially heterogeneous effects on Airbnb revenue and booking performance across Floridian counties during the pandemic. Furthermore, community resilience moderated the effect of tourism clusters on Airbnb performance across individual and subclustered counties. These findings enable P2P accommodation hosts and policymakers to adopt destination-specific remedying strategies to cope with the pandemic.

8.
Mikrochim Acta ; 188(12): 431, 2021 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-34822013

RESUMO

Affordable point-of-care (POC) CD4 + T lymphocyte counting techniques have been developed as alternatives to flow cytometry-based instruments caring for patients with human immunodeficiency virus (HIV)-1. However, POC CD4 enumeration technologies can be inaccurate. Here, we developed a microparticle-based visual detector of CD4 + T lymphocytes (ImmunoSpin) using microparticles conjugated with anti-CD4 antibodies, independent of microfluidic or fluorescence detection systems. Visual enumeration of CD4 + T cells under conventional light microscope was accurate compared to flow cytometry. Microparticle-tagged CD4 + T cells were well-recognized under a light microscope. ImmunoSpin showed very good precision (coefficients of variation of ImmunoSpin were ≤ 10%) and high correlation with clinical-grade flow cytometry for the enumeration of CD4 + T cells (y = 0.4232 + 0.9485 × for the %CD4 + T cell count, R2 = 0.99). At thresholds of 200 and 350 cells/µL, there was no misclassification of the ImmunoSpin system compared to the reference flow cytometry. ImmunoSpin showed clear differential classification of CD4 + T lymphocytes from granulocytes and monocytes. Because non-fluorescence microparticle-tags and cytospin slides are used in ImmunoSpin, they can be applied to an automatic digital image analyzer. Slide preparation allows long-term storage, no analysis time limitations, and image transfer in remote areas.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Micropartículas Derivadas de Células/metabolismo , Sistemas Automatizados de Assistência Junto ao Leito/normas , Diferenciação Celular , Humanos
9.
Cancer Immunol Immunother ; 69(11): 2223-2232, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32474769

RESUMO

Malignant cells can increase in number using immune escape mechanisms such as immune checkpoints. In this study, we evaluated the expression of an immune checkpoint programmed death 1 (PD-1) on T-cell subsets in chronic myeloid leukemia (CML). We obtained bone marrow aspirate samples from CML patients and from individuals without evidence of hematologic malignancies (controls). PD-1 expression on T-cell subsets was measured using flow cytometric analysis. PD-1 expression levels on CD8+ T-cells were significantly lower in complete hematologic response (CHR) than in controls, chronic phase, and blast phase (BP). In CML patients receiving imatinib and dasatinib, PD-1 expression levels on CD8+ T-cells were lower than that at diagnosis. PD-1 expression levels on CD8+ T-cells were positively correlated with quantitative levels of the BCR/ABL fusion gene. PD-1 expression levels on CD4+ T-cells were higher in BP than in CHR. PD-1 expression levels on CD4+ T-cells did not differ significantly according to different medications or quantitative BCR/ABL1 fusion gene levels. Low PD-1 expression on CD8+ T-cells might play a role in maintaining CHR in CML patients. Immune monitoring of PD-1 expression on CD8+ T-cells may predict the disease course. In cases of refractory disease or resistance to imatinib or dasatinib, the use of PD-1 inhibitors would be helpful.


Assuntos
Antineoplásicos/uso terapêutico , Linfócitos T CD8-Positivos/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Receptor de Morte Celular Programada 1/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Dasatinibe/uso terapêutico , Feminino , Humanos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
J Thromb Thrombolysis ; 49(2): 245-250, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31506888

RESUMO

Laboratory monitoring of rivaroxaban (RIV) is required under certain conditions. Mass spectrometry and anti-factor Xa assays are the recommended methods, which may not be readily available. Prothrombin time (PT) is the most widely used and simple coagulation assay. To set the cutoff PT and international normalized ratio (INR) to estimate RIV overdose status. RIV-spiked pooled normal plasma was used. PT test was performed using a CA-7000 coagulometer and Thromborel S reagent. The precise measurement of RIV concentration at the cut-off PT was evaluated according to the Clinical and Laboratory Standard Institute (CLSI) EP12-A2 guideline. The RIV concentration at 275 ng/mL was analyzed using 40 replicates. Receiver operating characteristic (ROC) analysis was performed to determine the cutoff value for the determination of RIV potential overdose status. An imprecision estimation of PT was conducted with 220.00 ng/mL, 247.50 ng/mL, 261.25 ng/mL, 288.75 ng/mL, 302.50 ng/mL and 330.00 ng/mL concentrations of RIV in 60 replicates. According to the ROC analysis, the cutoff clotting times and INR values to determine the overdose status of RIV were 13.45 s and 1.39. With these values, there was a 92.6% probability that plasma samples with RIV concentration ≤ 247.50 ng/mL yielded consistently negative (on-therapy dose) results, and those with ≥ 302.50 ng/mL yield consistent positive (potential overdose) results using our PT assay. PT with a reliable cutoff clotting time and INR can be used to determine the potential overdose status of RIV to facilitate the diagnosis and treatment by controlling the dose.


Assuntos
Overdose de Drogas/sangue , Inibidores do Fator Xa/sangue , Tempo de Protrombina/métodos , Rivaroxabana/sangue , Adulto , Overdose de Drogas/diagnóstico , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Coeficiente Internacional Normatizado/métodos , Coeficiente Internacional Normatizado/normas , Masculino , Pessoa de Meia-Idade , Tempo de Protrombina/normas , Rivaroxabana/efeitos adversos
11.
Biol Blood Marrow Transplant ; 25(5): 965-974, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30639824

RESUMO

Haploidentical family donors have been used as an alternative source in hematopoietic cell transplantation for patients with severe aplastic anemia. We evaluated and compared the outcomes of transplantation in pediatric acquired severe aplastic anemia based on donor type. Sixty-seven patients who underwent transplantation between 1998 and 2017 were included. Fourteen patients received grafts from matched sibling donors, 21 from suitable unrelated donors, and 32 from haploidentical family donors. Ex vivo CD3+ or αß+ T cell-depleted grafts were used for haploidentical transplantation. Sixty-five patients (97.0%) achieved neutrophil engraftment at a median of 11 days. Haploidentical transplantation resulted in significantly faster neutrophil engraftment at a median of 10 days, compared with 14 days in cases of matched sibling donors and 12 days in cases of unrelated donor recipients. Nine patients experienced graft failure, and 5 of 7 who underwent a second transplantation are alive. There was no difference in the incidence of acute or chronic graft-versus-host disease based on donor type. The 5-year overall survival and failure-free survival rates were 93.8% ± 3.0% and 83.3% ± 4.6%, respectively, and there was no significant survival difference based on donor type. The survival outcomes of haploidentical transplantation in patients were comparable with those of matched sibling or unrelated donor transplantation. Optimized haploidentical transplantation using selective T cell depletion and conditioning regimens including low-dose total body irradiation for enhancing engraftment may be a realistic therapeutic option for pediatric patients with severe aplastic anemia.


Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Doadores de Tecidos , Transplante Haploidêntico/métodos , Anemia Aplástica/mortalidade , Criança , Intervalo Livre de Doença , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Depleção Linfocítica/métodos , Pediatria , Irmãos , Taxa de Sobrevida , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Doadores não Relacionados , Irradiação Corporal Total/métodos
12.
Pediatr Hematol Oncol ; 36(4): 222-235, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31313940

RESUMO

We investigated bone marrow (BM) recovery of hematopoietic stem cells (HSC) and hematopoietic microenvironment after chemotherapy in childhood acute lymphoblastic leukemia (ALL). Twenty-nine de novo childhood ALL patients were enrolled and BM biopsy sections at diagnosis (BM0), after induction (BM1), consolidation (BM3), interim maintenance (BM5) and delayed intensification (BM7) chemotherapy were obtained. Expressions of CD133, CD34, CD117, osteopontin, osteonectin, CXCL12, and CXCR4 were evaluated by semiquantitative immunohistochemical stains. All markers recovered significantly following chemotherapy while highest values at BM3 (for CD133/CD117/CXCL12/CXCR4), BM5 (for CXCL12/CD34/osteonectin), and BM7 (for osteopontin). Patients with cytogenetic good risk expressed significantly more CD133+/CD34+ cells than those with standard and poor risk in BM5. Patients without aberrant immunophenotype expressed significantly more CD133+ cells in BM1, and more CD117+ cells in BM5 than those with aberrant immunophenotype. Patients treated with standard risk-average chemotherapeutic protocol expressed significantly more CXCR4+ cells than those treated with other protocols in BM7. Patients who showed lowest ANC ≥ 200/µL during induction chemotherapy expressed significantly more CXCR4+ cells at from BM1 to BM5, and more CD133+ cells in BM3 than those who did not. Early and full recovery of BM HSC is most vigorous at BM3 and BM5, respectively. Reconstruction of BM niche and stromal cell recovery is mostly active at BM5, and hematopoietic activity of BM niche recovers mostly at BM7. Patients with cytogenetic good risk, nonaberrant immunophenotype, standard risk-average chemotherapeutic protocol and less BM suppression during induction chemotherapy show prompt recovery of some BM HSC and microenvironment markers compared to others.


Assuntos
Medula Óssea/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras , Recuperação de Função Fisiológica , Adolescente , Medula Óssea/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Células-Tronco Hematopoéticas/patologia , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Células Estromais/metabolismo , Células Estromais/patologia
13.
Clin Transplant ; 32(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29090489

RESUMO

To investigate reconstitution of T and NK cells after αß T lymphocyte-depleted haploidentical hematopoietic cell transplantation (HHCT) and the clinical implications of γδ T cells, we analyzed 50 pediatric patients who received 55 HHCTs using αß T cell-depleted grafts. The number of CD3+ T cells and CD8+ T cells recovered rapidly and reached donor levels at days 180 and 60, respectively. Recovery of NK cells was rapid, and the median of NK cells at day 14 was comparable to the donor level. At day 14, median percentage of γδ T lymphocytes was 70.5%. After day 14, the percentage of γδ T cells gradually decreased, while the percentage of αß T cells gradually increased. Patients with a low percentage (≤21%) of γδ T cells at day 30 had significantly higher incidence of cytomegalovirus (CMV) reactivation compared to patients with a high percentage (>70%) of γδ T cells (P < .01). In patients with acute leukemia, patients with high percentage of γδ T cells at day 30 showed significantly higher relapse-free survival compared to those with low percentage of γδ T cells (P = .02). Data suggest that early recovery of γδ T cells decreases the risk of CMV reactivation and leukemia relapse.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Células Matadoras Naturais/imunologia , Depleção Linfocítica/métodos , Linfócitos T/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/imunologia , Neoplasias Hematológicas/imunologia , Humanos , Lactente , Masculino , Prognóstico , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos T/metabolismo , Doadores de Tecidos , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto Jovem
14.
Acta Haematol ; 139(3): 185-192, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29635247

RESUMO

BACKGROUND: Immunoglobulin D multiple myeloma (IgD MM) is characterized by a poor prognosis. Data are lacking on the survival benefits associated with the use of novel agents followed by autologous stem cell transplantation (ASCT) in IgD MM patients. We evaluated the clinical outcomes of induction treatment with novel agents followed by ASCT. METHODS: This was a single-center, retrospective study of 22 IgD MM patients who underwent ASCT between 1995 and 2016. Of these, 10 (45.4%) received novel agents and 12 (54.6%) received nonnovel agents. Clinical features and survival outcomes were examined. RESULTS: Median overall survival (OS) was 37.7 months in the 22 patients. Those in the novel-agents group received bortezomib or thalidomide-based regimens, whereas 91.7% of the nonnovel-agents group received a vincristine-based regimen. The median progression-free survival and OS in the novel-agent/nonnovel-agent groups were 8.3/7.4 and 38.6/12.5 months, respectively. The median OS of patients receiving maintenance therapy was not reached. CONCLUSION: This study showed improved survival outcomes compared to our previous study (37.7 vs. 12 months), suggesting that the use of a novel agent as induction and maintenance therapy may be beneficial in patients with IgD MM who undergo ASCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Imunoglobulina D , Terapia de Alvo Molecular , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Terapia Combinada , Feminino , Humanos , Imunoglobulina D/sangue , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento
15.
Acta Haematol ; 139(4): 220-227, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29860259

RESUMO

The prognosis of adult acute lymphoblastic leukemia is much worse than that of pediatric acute lymphoblastic leukemia, even when patients achieve complete remission. Early response to treatment can be an important alternative indicator of treatment outcomes. The purpose of our current study was to identify the prognostic value of the blast percentage of the induction interim bone marrow, which might predict relapse-free survival and overall survival in patients with adult acute lymphoblastic leukemia. A retrospective analysis was performed on 80 adult patients diagnosed with Philadelphia chromosome-negative acute lymphoblastic leukemia from 1994 to 2011. Complete remission was observed in 75 (93.8%) patients after induction chemotherapy. On multivariate analysis, a reduction of blasts to a level of 5% or less in the induction interim bone marrow and CD20 positivity were significant prognostic predictors of relapse-free survival (hazard ratio, HR = 2.88, p = 0.006, and HR = 2.67, p = 0.010) and overall survival (HR = 2.10, p = 0.033, and HR = 2.39, p = 0.013). The blast percentage of the induction interim bone marrow may be a useful prognostic factor to predict outcome.


Assuntos
Medula Óssea/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Biópsia , Exame de Medula Óssea , Terapia Combinada , Análise Citogenética , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunofenotipagem , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento
16.
J Clin Apher ; 33(4): 521-528, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29971847

RESUMO

A consistent and reproducible depletion technique is crucial for the successful transplantation of an ex vivo depleted graft. Our aim was to evaluate the efficacy of an ex vivo technique for depletion of αß+ T cells using a biotinylated anti-TCRαß monoclonal antibody, which was performed by one clinical nurse specialist. Between 2012 and 2017, 119 depletion procedures from 216 apheresis using the anti-TCRαß monoclonal antibody were performed on 105 pediatric patients. The median log depletion of αß+ T cells was 4.0 (range, 2.5-5.0). The median recovery rates of CD34+ , NK, and γδ+ T cells were 90.4%, 74.9%, and 75.9%, respectively. The efficacy of depletion of αß+ T cells significantly improved over time and the duration of the depletion procedure significantly decreased over time. Our study demonstrated that this procedure for depletion of αß+ T cells by skilled staff is highly effective at depleting target cells and obtaining CD34+ progenitor cells.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Procedimentos de Redução de Leucócitos/métodos , Receptores de Antígenos de Linfócitos T alfa-beta/isolamento & purificação , Linfócitos T/imunologia , Transplante Haploidêntico/métodos , Adolescente , Antígenos CD34/análise , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia
17.
Blood ; 126(6): 746-56, 2015 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-26065651

RESUMO

We investigated the effects of nilotinib plus multiagent chemotherapy, followed by consolidation/maintenance or allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with newly diagnosed Philadelphia-positive (Ph-pos) acute lymphoblastic leukemia (ALL). Study subjects received induction treatment that comprised concurrent vincristine, daunorubicin, prednisolone, and nilotinib. After achieving complete hematologic remission (HCR), subjects received either 5 courses of consolidation, followed by 2-year maintenance with nilotinib, or allo-HCT. Minimal residual disease (MRD) was assessed at HCR, and every 3 months thereafter. The molecular responses (MRs) were defined as MR3 for BCR-ABL1/G6PDH ratios ≤10(-3) and MR5 for ratios <10(-5). Ninety evaluable subjects, ages 17 to 71 years, were enrolled in 17 centers. The HCR rate was 91%; 57 subjects received allo-HCT. The cumulative MR5 rate was 94%; the 2-year hematologic relapse-free survival (HRFS) rate was 72% for 82 subjects that achieved HCR, and the 2-year overall survival rate was 72%. Subjects that failed to achieve MR3 or MR5 were 9.1 times (P = .004) or 6.3 times (P = .001) more prone to hematologic relapse, respectively, than those that achieved MR3 or MR5. MRD statuses just before allo-HCT and at 3 months after allo-HCT were predictive of 2-year HRFS. Adverse events occurred mainly during induction, and most were reversible with dose reduction or transient interruption of nilotinib. The combination of nilotinib with high-dose cytotoxic drugs was feasible, and it effectively achieved high cumulative complete molecular remission and HRFS rates. The MRD status at early postremission time was predictive of the HRFS. This trial was registered at www.clinicaltrials.gov as #NCT00844298.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Pirimidinas/administração & dosagem , Adolescente , Adulto , Idoso , Daunorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prednisolona/administração & dosagem , Estudos Prospectivos , Recidiva , Indução de Remissão , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Vincristina/administração & dosagem
18.
Pediatr Transplant ; 21(7)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28762602

RESUMO

Intensified chemotherapy, HSCT, and supportive care improve the survival of pediatric patients with AML. However, no consensus has been reached regarding the role of HSCT in patients without favorable cytogenetics. We evaluated OS and EFS according to prognostic factors that affect clinical outcomes, including cytogenetics risk group, conditioning regimen, donor type, disease status at the time of HSCT, and number of chemotherapy cycles prior to HSCT in 65 pediatric patients with AML without favorable cytogenetics who underwent HSCT. Fifteen of the 65 patients died: three of TRM and 12 of disease-related mortality. The 5-year OS and EFS were 78.0% and 72.0%, respectively, and the 5-year cumulative relapse and TRM rates were 26.9% and 5.1%, respectively. Survival rates were not influenced by cytogenetic group (intermediated vs. poor), donor type (related vs. unrelated), transplant type (myeloablative vs. reduced-intensity conditioning), or number of pretransplant chemotherapy cycles (≤3 vs. >3 cycles). The low TRM rate and encouraging outcomes suggest that HSCT may be a feasible treatment for pediatric patients with AML without favorable cytogenetics.


Assuntos
Cariótipo Anormal , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Adolescente , Criança , Pré-Escolar , Análise Citogenética , Feminino , Seguimentos , Humanos , Lactente , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
20.
J Med Internet Res ; 18(10): e282, 2016 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-27784649

RESUMO

BACKGROUND: To evaluate patients with fever of unknown origin or those with suspected bacteremia, the precision of blood culture tests is critical. An inappropriate step in the test process or error in a parameter could lead to a false-positive result, which could then affect the direction of treatment in critical conditions. Mobile health apps can be used to resolve problems with blood culture tests, and such apps can hence ensure that point-of-care guidelines are followed and processes are monitored for blood culture tests. OBJECTIVE: In this pilot project, we aimed to investigate the feasibility of using a mobile blood culture app to manage blood culture test quality. We implemented the app at a university hospital in South Korea to assess the potential for its utilization in a clinical environment by reviewing the usage data among a small group of users and by assessing their feedback and the data related to blood culture sampling. METHODS: We used an iOS-based blood culture app that uses an embedded camera to scan the patient identification and sample number bar codes. A total of 4 medical interns working at 2 medical intensive care units (MICUs) participated in this project, which spanned 3 weeks. App usage and blood culture sampling parameters (including sampler, sampling site, sampling time, and sample volume) were analyzed. The compliance of sampling parameter entry was also measured. In addition, the participants' opinions regarding patient safety, timeliness, efficiency, and usability were recorded. RESULTS: In total, 356/644 (55.3%) of all blood culture samples obtained at the MICUs were examined using the app, including 254/356 (71.3%) with blood collection volumes of 5-7 mL and 256/356 (71.9%) with blood collection from the peripheral veins. The sampling volume differed among the participants. Sampling parameters were completely entered in 354/356 cases (99.4%). All the participants agreed that the app ensured good patient safety, disagreed on its timeliness, and did not believe that it was efficient. Although the bar code scanning speed was acceptable, the Wi-Fi environment required improvement. Moreover, the participants requested feedback regarding their sampling quality. CONCLUSIONS: Although this app could be used in the clinical setting, improvements in the app functions, environment network, and internal policy of blood culture testing are needed to ensure hospital-wide use.


Assuntos
Hemocultura/métodos , Telefone Celular , Aplicativos Móveis , Telemedicina/métodos , Hemocultura/normas , Estudos de Viabilidade , Febre de Causa Desconhecida/sangue , Humanos , Projetos Piloto , Interface Usuário-Computador
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