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A patient undergoing cord blood transplantation for refractory angioimmunoblastic T-cell lymphoma was subsequently managed with long-term immunosuppressants for chronic graft-versus-host disease (GVHD). On day 591 post-transplant, she exhibited disorientation and cognitive dysfunction. Magnetic resonance imaging (MRI) of the brain revealed two hyperintense foci in the white matter, suggestive of progressive multifocal leukoencephalopathy (PML). However, we did not include PML in the differential diagnosis at that time. Unfortunately, she developed progressive cognitive impairment, and repeated brain MRIs showed a progression in lesion size. She was still taking immunosuppressants to control her GVHD, therefore we suspected PML. The diagnosis of PML was confirmed through the detection of a John Cunningham (JC) virus in the cerebrospinal fluid on day 640 post-transplant. This report highlights the critical need to consider PML in differential diagnoses for post-allogeneic transplant patients, especially those who exhibit progressive neurological symptoms while on prolonged immunosuppressant therapy.
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Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Imunossupressores , Leucoencefalopatia Multifocal Progressiva , Imageamento por Ressonância Magnética , Humanos , Leucoencefalopatia Multifocal Progressiva/etiologia , Leucoencefalopatia Multifocal Progressiva/diagnóstico , Leucoencefalopatia Multifocal Progressiva/líquido cefalorraquidiano , Feminino , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Linfoma de Células T/terapia , Vírus JC/isolamento & purificação , Diagnóstico Diferencial , Pessoa de Meia-Idade , Encéfalo/diagnóstico por imagem , Encéfalo/patologiaRESUMO
IKZF1 deletion is a recurrent genomic alteration in B-cell acute lymphoblastic leukemia (B-ALL) and is divided into dominant-negative (DN) and loss of function (LOF) deletions. The prognostic impact of each deletion has not been fully elucidated. We retrospectively analyzed 117 patients with adult B-ALL including 60 patients with BCR::ABL1-positive B-ALL and 57 patients with BCR::ABL1-negative B-ALL by the fluorescence in situ hybridization (FISH) method for IKZF1 deletion and multiplex PCR for the 4 most common IKZF1 deletions (∆4-7, ∆2-7, ∆2-8, and ∆4-8). Samples, in which IKZF1 deletion was detected by FISH but a specific type of deletion was not identified by the PCR, were categorized as "other." Patients were classified into a DN group that had at least 1 allele of ∆4-7 (n = 23), LOF and other group (n = 40), and wildtype group (n = 54). DN type IKZF1 deletions were found in 33.3% of BCR::ABL1-positive cases and 5.2% of BCR::ABL1-negative cases. LOF and other type IKZF1 deletions were found in 43.4% of BCR::ABL1-positive cases and 24.6% of BCR::ABL1-negative cases. Patients with the DN group showed significantly higher overall survival (OS) than that of the LOF and other and WT groups (P = 0.011). Multivariate analysis including age, WBC counts, complex karyotype, and DN type IKZF1 deletion showed that the DN type of IKZF1 deletion (HR = 0.22, P = 0.013) had a positive impact and age ≥ 65 (HR = 1.92, P = 0.029) had a negative impact on OS. The prognostic impact of IKZF1 deletion depends on the type of deletion and DN type of IKZF1 deletion showed better prognosis in adult B-ALL patients.Clinical trial registration This study was part of a prospective observational study (Hokkaido Leukemia Net, UMIN000048611). It was conducted in compliance with ethical principles based on the Helsinki Declaration and was approved by the institutional review board of Hokkaido University Hospital (#015-0344).
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A 25-year-old male with a medical history of stress polycythemia was admitted to a previous hospital for leukocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed left-shifted myeloid hyperplasia without increased blasts and normal male karyotype. No mutations of JAK2, V617F, and colony-stimulating factor 3 receptor gene (CSF3R) were detected. Fluorescence in-situ hybridization for BCR-ABL1 and FIP1L1-PDGFRA were negative. Based on these findings, a diagnosis of an unclassifiable myeloproliferative neoplasm was made, and he was started on hydroxyurea treatment. He was referred to our hospital in April 2016 for transfusion dependence. Bone marrow examination performed at our hospital revealed granulocytic dysplasia and CSF3R T618I was detected. After induction therapy, CSF3R T618I became undetectable, and he went on to undergo allogeneic stem cell transplantation in October 2016. He has been in remission for >4 years posttransplantation. CSF3R T618I is one of the genes responsible for chronic neutrophilic leukemia and atypical chronic myeloid leukemia, suggesting its involvement in the pathogenesis of this case.
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Leucemia Mieloide Crônica Atípica BCR-ABL Negativa , Receptores de Fator Estimulador de Colônias , Adulto , Fatores Estimuladores de Colônias , Seguimentos , Humanos , Masculino , Mutação , Receptores de Fator Estimulador de Colônias/genéticaRESUMO
BACKGROUND: Pegfilgrastim has equivalent efficacy to daily granulocyte colony-stimulating factor (G-CSF) in enhancing neutrophil recovery after chemotherapy, but data on its use for peripheral blood stem cell (PBSC) mobilization are limited. We evaluated the safety and efficacy of CD34+ PBSC mobilization by low-dose (3.6 mg) pegfilgrastim after chemotherapy in patients with malignant lymphoma. STUDY DESIGN AND METHODS: Twenty patients with malignant lymphoma were enrolled in this study. Cytotoxic chemotherapy was started on day 1, and 3.6 mg of pegfilgrastim was subcutaneously administered on day 7. CD34+ cells were counted in the peripheral blood daily from days 11 to 14 using a flow cytometric analysis. RESULTS: In 19 of the 20 patients (95%), the CD34+ cell counts in the peripheral blood exceeded 10 × 106/L, with a mean value of 20.3 on day 11, 38.0 on day 12, 40.3 on day 13, and 40.1 on day 14. Older age was associated with lower maximum CD34+ cell mobilization. The most frequent adverse events associated with pegfilgrastim were back pain, nausea, appetite loss, and lactate dehydrogenase elevation. CONCLUSION: Our data indicated that a single dose of 3.6 mg pegfilgrastim on day 7 after chemotherapy safely and effectively mobilized CD34+ cells.
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Filgrastim/farmacologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Linfoma/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Polietilenoglicóis/farmacologia , Adulto , Idoso , Estudos de Viabilidade , Feminino , Filgrastim/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Estudos ProspectivosRESUMO
Percolative composites consisting of potassium carbonate dispersed in polyvinylidene fluoride (PVDF) polymeric matrix have shown high dielectric constant and electrical conductivity due to the formation of chemically activated carbon interfaces in the composite. In this paper, a series of PVDF/K2CO3 films with different component contents were prepared and investigated by Raman and X-ray photoelectron spectroscopies to clarify chemical composition, structure and formation mechanism of activated carbon. The results revealed the presence of a reaction loop to consume both constituent phases and the formation of sp2 carbon rings in the yielded activated carbon due to cross-linking dehydrofluorination of PVDF during thermal treatment. The sp2 content showed a non-linear dependence on K2CO3 content with the presence of an optimal value corresponding to the highest dielectric constant and electrical conductivity. This study thus can give a direction for future fabrication of PVDF/K2CO3 electrode materials for supercapacitors.
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Benign precursors of B lymphocytes, termed hematogones, are observed in the regenerative state of hematopoiesis following chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). Previous studies have demonstrated that expansion of hematogones correlates with better clinical outcomes after allo-HSCT. We retrospectively analyzed the association between hematogones and clinical outcomes in 309 consecutive patients who underwent allo-HSCT, which is the largest population-based cohort reported so far. The incidence of hematogones was significantly higher in complete remission (CR) patients at the time of transplantation than in non-CR patients, after myeloablative conditioning than after reduced-intensity conditioning, with tacrolimus-based graft-versus-host disease (GVHD) prophylaxis than with cyclosporine-based prophylaxis, and with disease other than malignant lymphoma (all P < .05). Patients with hematogones developed less acute GVHD and infections than did those without them (P < .05). Emergence of hematogones was associated with superior GVHD-free relapse-free survival and lower nonrelapse mortality, and was an independent prognostic factor for overall survival, irrespective of donor sources.
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Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Aloenxertos , Ciclosporina/administração & dosagem , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Tacrolimo/administração & dosagemRESUMO
We identified a novel heterozygous ITGB3 p.T720del mutation in a pedigree with macrothrombocytopenia exhibiting aggregation dysfunction. Platelet aggregation induced by ADP and collagen was significantly reduced, while ristocetin aggregation was normal. Integrin αIIbß3 was partially activated in a resting status, but platelet expression of αIIbß3 was downregulated. Functional analysis using a cell line showed spontaneous phosphorylation of FAK in αIIb/ß3 (p.T720del)-transfected 293T cells in suspension conditions. Abnormal cytoplasmic protrusions, membrane ruffling, and cytoplasmic localization of αIIbß3 were observed in αIIb/ß3 (p.T720del)-transfected CHO cells. Such morphological changes were reversed by treatment with an FAK inhibitor. These findings imply spontaneous, but partial, activation of αIIbß3 followed by phosphorylation of FAK as the initial mechanism of abnormal thrombopoiesis. Internalization and decreased surface expression of αIIbß3 would contribute to aggregation dysfunction. We reviewed the literature of congenital macrothrombocytopenia associated with heterozygous ITGA2B or ITGB3 mutations. Reported mutations were highly clustered at the membrane proximal region of αIIbß3, which affected the critical interaction between αIIb R995 and ß3 D723, resulting in a constitutionally active form of the αIIbß3 complex. Macrothrombocytopenia caused by a heterozygous activating mutation of ITGA2B or ITGB3 at the membrane proximal region forms a distinct entity of rare congenital thrombocytopenia.
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Deleção de Genes , Genes Dominantes , Heterozigoto , Integrina beta3/genética , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/agonistas , Trombocitopenia/genética , Adulto , Animais , Células CHO , Cricetulus , Saúde da Família , Feminino , Células HEK293 , Humanos , Integrina beta3/metabolismo , Japão , Masculino , Pessoa de Meia-Idade , Mutagênese Sítio-Dirigida , Linhagem , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Proteínas Recombinantes/metabolismo , Trombocitopenia/sangue , Trombocitopenia/metabolismo , Trombocitopenia/fisiopatologia , Adulto JovemRESUMO
Intestinal microbiota plays an important role in the regulation of allogeneic immune reaction after allogeneic hematopoietic stem cell transplantation (allo-SCT). Intestinal graft-vs-host disease (GVHD) is one of the major causes of mortality after allo-SCT and often complicated with intestinal dysbiosis. Recent studies suggest that antibiotic-induced dysbiosis is a risk factor for intestinal GVHD. We retrospectively evaluated the impacts of antibiotic use on the incidence of intestinal GVHD occurring before day 100 after allo-SCT. Among 213 patients who underwent allo-SCT, 200 patients achieving engraftment were analyzed. Antibiotics were classified into carbapenem, quinolone, penicillin, cephem, and glycopeptide. Among 128 patients who developed acute GVHD, intestinal GVHD developed in 36 patients. Patients with intestinal GVHD received significantly longer administration of carbapenem and glycopeptide compared to those without it in periengraftment period. In multivariate analysis, use of carbapenem for greater than 7 days was associated with an increased risk of intestinal GVHD. However, use of antibiotics for greater than 7 days was not associated with poor overall survival and high nonrelapse mortality. Long use of carbapenem in periengraftment period may be a risk for intestinal GVHD. Prospective studies are required to validate our findings.
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Antibacterianos/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Doença Enxerto-Hospedeiro/epidemiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Enteropatias/tratamento farmacológico , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Humanos , Enteropatias/microbiologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Disseminated fusariosis (DF) is a rare life threatening fungal infection in immunocompromised hosts. We herein report a case of a fatal DF mimicking varicella zoster virus (VZV) infection that was emerged from a localized genital infection during cord blood transplantation (CBT) in a patient with severe aplastic anemia (SAA). The patient developed an ulcer following small painful vesicles mimics herpes simplex virus infection (HSV) on the glans penis before CBT, but a Fusarium species was identified. Despite administration of voriconazole, liposomal amphotericin B and granulocyte transfusion, the lesion was extended to extensive skin looked like VZV infection and the patients died after CBT. Massive fusarium infiltration was detected in multiple organs at autopsy. A genetic analysis of the mold identified Fusarium solani after his death. It should be noted that in patients with fusarium infection, localized and disseminated lesions of fusarium infection sometimes mimic HSV and VZV infections, which hampers an early diagnosis.
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Anemia Aplástica/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Fusariose/imunologia , Hospedeiro Imunocomprometido , Adulto , Antifúngicos/uso terapêutico , Antivirais , Diagnóstico Diferencial , Evolução Fatal , Sangue Fetal/transplante , Fusariose/diagnóstico , Fusariose/tratamento farmacológico , Fusariose/microbiologia , Fusarium/isolamento & purificação , Herpesvirus Humano 3/isolamento & purificação , Humanos , Masculino , Pênis/microbiologia , Fatores de Tempo , Transplante Homólogo/efeitos adversos , Infecção pelo Vírus da Varicela-Zoster/diagnóstico , Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológicoRESUMO
An 84-year-old man, who had received artificial pneumothorax for pulmonary tuberculosis 67 years previously, complained of severe chest pain. Chest CT revealed chronic pyothorax with multiple heterogeneously enhanced cavity lesions in the wall of the right intrathoracic space. 18FDG-PET revealed that the lesions showed an abnormal uptake. CT-guided biopsy was performed and he was diagnosed with pyothorax-associated lymphoma (PAL); the histological diagnosis was diffuse large B cell lymphoma (DLBCL). Furthermore, immunohistochemical staining revealed that the tumor cells were positive for EBNA-2 and LMP-1, suggesting that the latent gene products of Epstein-Barr virus were associated with the development of PAL. The patient was treated with chemotherapy, including rituximab; however, the treatment was discontinued due to the development of severe delirium after chemotherapy. We should keep in mind that elderly patients with a long history of chronic pyothorax are at risk of developing malignant lymphoma. We report the present case with a brief review of the literature.
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Empiema Pleural/etiologia , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/genética , Linfoma Difuso de Grandes Células B/etiologia , Idoso de 80 Anos ou mais , Regulação Viral da Expressão Gênica , Humanos , MasculinoAssuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Albuminas , Creatinina , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/diagnóstico , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Estudos Retrospectivos , Transplante Homólogo/efeitos adversosRESUMO
We herein report a patient who had disseminated toxoplasmosis after hematopoietic stem cell transplantation showing atypical clinical presentation and neuroimaging. Parkinsonism symptoms such as muscle rigidity, bradykinesia, tremor, and postural instability were initial manifestations. Magnetic resonance imaging showed diffuse symmetrical lesions of bilateral basal ganglia lacking ringed enhancement. Post-mortem analysis revealed multiple tachyzoites of Toxoplasma gondii in the basal ganglia, mid brain, cerebellum, and cardiac muscle.
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Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide/cirurgia , Transtornos Parkinsonianos/diagnóstico por imagem , Toxoplasma/isolamento & purificação , Toxoplasmose Cerebral/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/parasitologia , Encéfalo/patologia , Evolução Fatal , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/etiologia , Toxoplasmose Cerebral/complicações , Toxoplasmose Cerebral/parasitologia , Toxoplasmose Cerebral/patologiaRESUMO
Advanced-stage mycosis fungoides and Sezary syndrome (MF/SS) have a poor prognosis. Allogeneic hematopoietic stem cell transplantation (HSCT), particularly using a reduced-intensity conditioning (RIC) regimen, is a promising treatment for advanced-stage MF/SS. We performed RIC-HSCT in nine patients with advanced MF/SS. With a median follow-up period of 954 days after HSCT, the estimated 3-year overall survival was 85.7% (95% confidence interval, 33.4-97.9%) with no non-relapse mortality. Five patients relapsed after RIC-HSCT; however, in four patients whose relapse was detected only from the skin, persistent complete response was achieved in one patient, and the disease was manageable in other three patients by the tapering of immunosuppressants and donor lymphocyte infusion, suggesting that graft-versus-lymphoma effect and 'down-staging' effect from advanced stage to early stage by HSCT improve the prognosis of advanced-stage MF/SS. These results suggest that RIC-HSCT is an effective treatment for advanced MF/SS.
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Micose Fungoide/terapia , Síndrome de Sézary/terapia , Neoplasias Cutâneas/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro , Efeito Enxerto vs Tumor , Humanos , Imunossupressores/uso terapêutico , Transfusão de Linfócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Effects of the addition of water on solvation layers of imidazolium-type room temperature ionic liquids (RT-ILs) have been studied through force curve measurements of atomic force microscopy (AFM). Two kinds of RT-ILs were employed in this study; one is a hydrophilic RT-IL (1-butyl-3-methylimidazolium tetrafluoroborate, BmimBF4), and the other is a hydrophobic one (1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, EmimTFSI). These RT-ILs form solvation layers on hydrophilic solid substances (i.e., silica and mica) in the absence of added water. The addition of water into BmimBF4 resulted in the disruption of the solvation layers and then the formation of an interfacial water phase on silica. In contrast, the formation of the interfacial water phase was not evidenced on mica because of the absence of hydrogen-bonding sites on the mica surface. Interestingly, the addition of water into EmimTFSI induced the formation of the interfacial water phase on the two solid surfaces. In the EmimTFSI system, importantly, significantly greater adhesion forces were observed on silica than on mica. This reflects the different formation mechanisms of the interfacial water phase on the two solid surfaces. We conclude that the hydrogen bonding is a key factor in determining whether water molecules can be adsorbed on the solid surfaces, but it is also necessary to take into account the hydrophilic/hydrophobic nature of the RT-ILs.
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To examine risk factors for Stenotrophomonas maltophilia (S. maltophilia) infection during allogeneic hematopoietic stem cell transplantation (allo-HSCT), we retrospectively analyzed 259 patients who underwent allo-HSCT. Not only S. maltophilia infection but also S. maltophilia colonization was associated with mortality during allo-HSCT. Among 52 episodes in 39 patients in whom S. maltophilia was detected, documented infection developed in 33 episodes (25 patients). The onset of S. maltophilia infection in the period from the conditioning regimen to engraftment was associated with a high mortality rate. Breakthrough S. maltophilia infection developed in 24% of the patients during prophylactic administration of fluoroquinolones, to which S. maltophilia is sensitive. Reinsertion of a central venous catheter (CVC) immediately after removal was suggested to be a risk for persistent S. maltophilia infection in the period of neutropenia. Our results indicated that (i) onset of S. maltophilia infection in the period from the conditioning therapy to engraftment and (ii) removal and immediate reinsertion of a CVC as treatment after the onset of S. maltophilia infection are possible risk factors for S. maltophilia-related mortality during allo-HSCT.
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Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Stenotrophomonas maltophilia/isolamento & purificação , Adulto , Idoso , Feminino , Seguimentos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante HomólogoRESUMO
Intermittent low dose dasatinib therapy brought about a beneficial effect in elderly patients with chronic-phase chronic myeloid leukemia (CML-CP) without inducing severe adverse events (AEs). An 85-year-old male patient, who received twice-weekly, thrice-weekly, or four-times-weekly administration of 20 mg/day dasatinib after once-weekly administration, achieved a major molecular response two years after the start of dasatinib treatment and later sometimes achieved a deep molecular response, maintaining the efficacy for 11 years. The mean daily dose ranged from 5.7 mg to 11.4 mg. Furthermore, a 79-year-old male patient, who received thrice-weekly or every other day administration of 20 mg/day dasatinib after once-weekly administration, achieved a deep molecular response at four and half years after the start of dasatinib treatment. The mean daily dose is 8.6 mg. Intermittent low dose dasatinib therapy appears to be feasible in elderly patients with CML-CP. The goal of treatment in elderly patients with CML-CP appears to be different from that in younger patients, since they often suffer from serious AEs in the case of standard dose tyrosine kinase inhibitor therapy, followed by the dose reduction or cessation of treatment.
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Objective The prognosis of the patients who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poor, and therapeutic options are limited. In the present study, we investigated the efficacy and factors associated with the survival in patients with acute leukemia or myelodysplastic syndrome (MDS) who relapsed following allo-HSCT and were treated with donor lymphocyte infusion (DLI) in real-world practice. Patients Twenty-nine patients with acute myeloid leukemia21, acute lymphoid leukemia4 or MDS4 were enrolled. Eleven patients were diagnosed with hematological relapse, and 18 were diagnosed with molecular or cytogenetic relapse. Results The median injection number and median total number of infused CD3+ T cells were 2 and 5.0×107/kg, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) of grade ≥II at 4 months after the initiation of DLI was 31.0%. Extensive chronic graft-versus-host disease (cGVHD) occurred in 3 (10.3%) patients. The overall response rate was 51.7%, including 3 cases of hematological complete remission (CR) and 12 cases of molecular/cytogenetic CR. Cumulative relapse rates at 24 and 60 months following DLI in patients who achieved CR were 21.4% and 30.0%, respectively. The overall survival rates at 1, 2 and 3 years after DLI were 41.4%, 37.9% and 30.3%, respectively. Molecular/cytogenetic relapse, a longer interval from HSCT to relapse, and concomitant chemotherapy with 5-azacytidine (Aza) were significantly associated with a relatively long survival following DLI. Conclusion These results indicated that DLI was beneficial for patients with acute leukemia or MDS who relapsed after allo-HSCT and suggested that DLI in combination with Aza for molecular or cytogenetic relapse might result in favorable outcomes.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Estudos Retrospectivos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicações , Síndromes Mielodisplásicas/terapia , Síndromes Mielodisplásicas/complicações , Doença Aguda , Doença Crônica , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Recidiva , Resposta Patológica Completa , LinfócitosRESUMO
BACKGROUND: Recurrent esophageal cancer (EC) has a poor prognosis. However, the recurrence patterns and therapeutic outcomes after definitive chemoradiotherapy (CRT) are not fully understood. We analyzed survival and prognostic factors associated with post-definitive CRT recurrent EC. METHODS: We retrospectively reviewed 71 consecutive patients with post-definitive CRT EC recurrence between 2008 and 2021 at our institution. Recurrence was locoregional, distant, and combined in 42 (59%), 18 (25%), and 11 (16%) patients, respectively. The median time from definitive CRT to recurrence was 8.3 months. Treatment modalities included local therapy, systemic therapy, and palliative care. Overall survival (OS) after recurrence was analyzed using the Kaplan-Meier and Cox proportional hazards models. RESULTS: The median follow-up time from recurrence was 7.1 months, and the median survival time (MST) was 12.5 months. In the univariate analysis, longer time to recurrence, earlier stage at initial treatment, surgical tolerance at initial diagnosis, treatment modalities, and oligo-recurrence were associated with a better prognosis. The MST of the local therapy, systemic therapy, and palliative care groups were not reached, 11.8 months and 4.1 months, respectively (P < 0.001). In the multivariate analysis, treatment modalities and oligo-recurrence emerged as independent prognostic factors (P < 0.001 and P = 0.009). CONCLUSIONS: Aggressive local therapy should be considered to improve the prognosis for patients with oligo-recurrence and/or indication of local therapy to treat recurrent EC.
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Quimiorradioterapia , Neoplasias Esofágicas , Recidiva Local de Neoplasia , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Masculino , Feminino , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/mortalidade , Quimiorradioterapia/métodos , Quimiorradioterapia/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Idoso , Adulto , Idoso de 80 Anos ou mais , Seguimentos , Taxa de SobrevidaRESUMO
Monitoring of hepatitis B virus (HBV)-DNA and HBV-DNA-guided preemptive therapy using nucleos(t)ide analogs (NAs) are recommended to prevent the development of hepatitis due to HBV reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in recipients with resolved HBV infection. However, little is known about the appropriate duration of NA treatment and the effect of NA cessation on the recurrence of HBV reactivation. This study aimed to clarify the consequences of NA cessation in allo-HSCT recipients with resolved HBV infection who experienced HBV reactivation following transplantation. We retrospectively reviewed the clinical records of recipients with resolved HBV infection (hepatitis B surface antigen [HBsAg]-negative, anti-HBc-positive) before allo-HSCT who had been diagnosed with HBV reactivation (HBsAg-positive and/or HBV-DNA detectable) after allo-HSCT between January 2010 and December 2020. A total of 72 patients from 16 institutions were registered (median age, 60 years; age range, 27 to 73 years; 42 males and 30 females). The day of initial HBV reactivation ranged from day 10 to day 3034 after allo-HSCT (median, 513 days). Anti-HBs were lost in >80% of the patients at the time of HBV reactivation. All 72 patients received preemptive NAs, and no fatal HBV reactivation-related hepatitis was observed. HBV-DNA without hepatitis was continuously detected in 5 patients during the follow-up period. Administration of NAs was discontinued in 24 of 72 patients (33%) by physician decision. Second HBV reactivation occurred in 11 of the 24 patients (46%) in whom administration of NAs was discontinued. The duration of NA treatment did not differ significantly between patients with or without second HBV reactivation. The frequency of further HBV reactivation tended to be lower in patients with an anti-HBs titer of >10 mIU/mL at the time of NA cessation. Multiple reactivations of HBV after NA cessation was common in patients with HBV reactivation who underwent allo-HSCT despite the long duration of NAs. Careful monitoring of HBV-DNA is important even after the discontinuation of NAs in the case with HBV reactivation after allo-HSCT, because multiple reactivations could occur. Active immunization by HB vaccine might be effective for suppressing further HBV reactivation after cessation of NAs.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatite A , Hepatite B , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Adulto , Idoso , Vírus da Hepatite B/genética , Estudos Retrospectivos , Antígenos de Superfície da Hepatite B/uso terapêutico , DNA Viral/uso terapêutico , Hepatite B/prevenção & controle , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Anticorpos Anti-Hepatite B/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
Hepatic sinusoidal obstruction syndrome (SOS) is a severe and life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a multi-center retrospective study to evaluate the utility of our ultrasonographic scoring system for the diagnosis of SOS (HokUS-10) in predicting SOS-related mortality (SOS-RM). We analyzed a total of 42 patients who developed SOS after HSCT. The cumulative incidences of SOS-RM, non-relapse mortality (NRM), and overall survival at day 180 after the diagnosis of SOS were 26.4%, 28.8% and 54.5%, respectively. The area under the receiver operating characteristic curve analysis showed that the optimal cut-off value of HokUS-10 total score to predict SOS-RM was 8 points after the treatment of SOS. In the individual HokUS-10 score, ascites and portal vein flow-related scores (PV mean velocity and PV flow direction) after the treatment of SOS were shown as significant risk factors for SOS-RM. Our study suggested that US findings after the treatment can predict the treatment outcomes for SOS.