RESUMO
BACKGROUND: Peripheral blood stem cell (PBSC) transplantation is a key treatment option for hematological diseases and is widely performed in clinical practice. Platelet loss is one of the major complications of PBSC apheresis, and platelet-rich plasma (PRP) return is considered in case of platelet decrease following apheresis; however, little is known about the frequency and severity of platelet loss and the efficacy of PRP return postapheresis. METHODS: We assessed changes in platelet counts following PBSC-related apheresis in 270 allogeneic (allo)- and 105 autologous (auto)-PBSC settings. We also evaluated the efficacy of PRP transfusion on platelet recovery postapheresis. RESULTS: In both allo- and auto-PBSC settings, the preapheresis platelet count (range, 84-385 and 33-558 × 109 /L, respectively) decreased postapheresis (range, 57-292 and 20-429 × 109 /L, respectively), whereas severe platelet decrease (<50 × 109 /L) was only observed in auto-PBSC patients (n = 9). We confirmed that platelet count before apheresis was a risk factor for severe platelet decrease (<50 × 109 /L) following auto-PBSC apheresis (odds ratio 0.749, P < .049). PRP return postapheresis facilitated platelet recovery in more than 80% of cases in both allo and auto settings. CONCLUSION: Lower platelet count preapheresis is a useful predictor of severe platelet decrease following auto-PBSC apheresis and PRP return is an effective process to facilitate platelet recovery postapheresis.
Assuntos
Remoção de Componentes Sanguíneos/métodos , Transplante de Células-Tronco de Sangue Periférico , Plasma Rico em Plaquetas , Remoção de Componentes Sanguíneos/efeitos adversos , Humanos , Contagem de Plaquetas , Transfusão de PlaquetasRESUMO
Vaccination against vaccine-preventable diseases (VPDs) is highly recommended for hematopoietic stem cell transplantation (HSCT) recipients by several guidelines; however, the safety and seropositivity after live attenuated vaccines remain unclear in adult HSCT recipients. We analyzed titers of antibodies against measles, rubella, mumps, and varicella zoster virus (VZV) from Japanese adult patients who underwent allogeneic HSCT (allo-HSCT) (nâ¯=â¯74), autologous HSCT (auto-HSCT) (nâ¯=â¯39), or chemotherapy (nâ¯=â¯93). The seropositive rates for measles, rubella, mumps, and VZV in allo-HSCT recipients were 20.2%, 36.4%, 5.4%, and 55.4%, respectively. These rates were equivalent to those in auto-HSCT recipients but were significantly lower than those in patients receiving chemotherapy. Antibody titers tended to gradually decrease with time. Twenty-nine allo-HSCT recipients and 8 auto-HSCT recipients received live attenuated vaccines against VPDs for which they tested seronegative. The titers of antibodies against measles, rubella, and mumps significantly increased after 2 shots of vaccine, and the seropositive rate increased up to 19%, 30%, and 27%, respectively. Three patients (8.1%) experienced mild adverse events, which resolved promptly, indicating safe administration of the live attenuated vaccines. In multivariate analysis, history of chronic graft-versus-host disease was significantly associated with high seropositivity for measles as well as high seroconversion rate for measles after vaccination. Live attenuated vaccines against VPDs were safely administered in seronegative adult HSCT recipients. A further observational study is crucial to evaluate the efficacy of vaccination in seronegative HSCT patients.
Assuntos
Anticorpos Antivirais/sangue , Transplante de Células-Tronco Hematopoéticas , Segurança , Vacinas Virais/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Autoenxertos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Virais/efeitos adversosRESUMO
Human herpes virus-6 (HHV6)-associated myelitis and calcineurin inhibitor-induced pain syndrome (CIPS) are serious complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because these 2 complications cause similar sensory nerve-related symptoms, such as paresthesia, pruritus, and severe pain occurring around the engraftment, it can be difficult to differentially diagnose the 2 conditions. We retrospectively analyzed 435 recipients to distinguish clinical symptoms of these 2 complications. Twenty-four patients (5.5%) developed HHV6-associated encephalitis/myelitis; of these, 11 (2.5%) presented only with myelitis-related symptoms (HHV6-associated myelitis), which was confirmed by the detection of HHV6 DNA, and 8 (1.8%) had CIPS, with undetected HHV6 DNA. All patients with HHV6-associated myelitis or CIPS exhibited similar sensory nerve-related symptoms. Diagnostic images did not provide definite evidence specific for each disease. Symptoms of all patients with CIPS improved after switching to another immunosuppressant. Overall survival rate at 2 years for patients with HHV6-associated encephalitis/myelitis was significantly lower than that of CIPS (13.1% versus 29.2%; Pâ¯=â¯.049) or that of patients without HHV6-associated encephalitis/myelitis or CIPS (42.4%; Pâ¯=â¯.036), whereas there was no significant difference among the latter 2 groups (Pâ¯=â¯.889). The development of HHV6-associated encephalitis/myelitis but not CIPS was significantly associated with poor prognosis. Thus, transplant physicians should be aware that sensory nerve-related symptoms indicate early manifestations that might be correlated with reactivation of HHV6 or CIPS. Therefore, identification of HHV6 DNA is crucial for making a differential diagnosis and immediately starting appropriate treatments for each complication.
Assuntos
Inibidores de Calcineurina/efeitos adversos , Encefalite Viral/etiologia , Herpesvirus Humano 6/patogenicidade , Dor/induzido quimicamente , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/patologia , Adulto JovemRESUMO
Bloodstream infection (BSI) is a well-known cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Here, we conducted a retrospective study to assess the morbidity, etiology, risk factors, and outcomes of BSI in the postengraftment period (PE-BSI) after allo-HSCT. Forty-three of 316 patients (13.6%) developed 57 PE-BSI episodes, in which 62 pathogens were isolated: Gram-positive bacteria, gram-negative bacteria, and fungi, respectively, accounted for 54.8%, 35.5%, and 9.7% of the isolates. Multivariate analysis revealed methylprednisolone use for graft-versus-host disease (GVHD) prophylaxis (odds ratio [OR], 6.49; 95% confidence interval [CI], 1.49 to 28.2; P = .013) and acute gastrointestinal GVHD (GI-GVHD) (OR, 8.82; 95% CI, 3.99 to 19.5; P < .0001) as risk factors for developing PE-BSI. This finding suggested that GI-GVHD increases the risk of bacterial translocation and subsequent septicemia. Moreover, among patients with GI-GVHD, insufficient response to corticosteroids, presumably related to an intestinal dysbiosis, significantly correlated with this complication. Patients with PE-BSI presented worse outcome compared with those without (3-year overall survival, 47.0% versus 18.6%; P < .001). Close microbiologic monitoring for BSIs and minimizing intestinal dysbiosis may be crucial to break the vicious cycle between GI-GVHD and bacteremia and to improve transplant outcomes especially in patients who require additional immunosuppressants.
Assuntos
Bacteriemia/etiologia , Trato Gastrointestinal/patologia , Doença Enxerto-Hospedeiro/complicações , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adolescente , Adulto , Idoso , Bacteriemia/patologia , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
In the present study, the antiemetic effect of palonosetron, not combined with dexamethasone and aprepitant, on chemotherapy-induced nausea and vomiting was evaluated in patients with malignant lymphoma receiving first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy, and was compared to that of granisetron. A total of 74 patients with non-Hodgkin lymphoma were included in this study (April 2007 to December 2015). Palonosetron (0.75 mg) or granisetron (3 mg) was intravenously administered before R-CHOP therapy. The proportions of patients with complete response (CR) during the overall (0-120 h after the start of R-CHOP therapy), acute (0-24 h) and delayed (24-120 h) phases were evaluated. CR was defined as no vomiting and no use of antiemetic rescue medication. A total of 32 and 42 patients were treated with palonosetron and granisetron, respectively. The CR rate in the palonosetron group was significantly higher than that in the granisetron group during the delayed phase (90.6 and 61.9%, respectively; p=0.007). Logistic regression analysis showed that use of palonosetron improved the CR rate during the delayed phase, compared to use of granisetron. Female sex, age less than 60 years, no habitual alcohol intake, and Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 1 were significant risk factors associated with non-CR. The findings of this study suggested the superiority of palonosetron to granisetron, without accompanying dexamethasone and aprepitant, for chemotherapy-induced nausea and vomiting in patients with malignant lymphoma.
Assuntos
Antieméticos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Granisetron/uso terapêutico , Isoquinolinas/uso terapêutico , Náusea/induzido quimicamente , Náusea/prevenção & controle , Quinuclidinas/uso terapêutico , Vômito/induzido quimicamente , Vômito/prevenção & controle , Adulto , Idoso , Envelhecimento , Anticorpos Monoclonais Murinos/efeitos adversos , Antieméticos/efeitos adversos , Povo Asiático , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Feminino , Granisetron/efeitos adversos , Humanos , Isoquinolinas/efeitos adversos , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Palonossetrom , Prednisona/efeitos adversos , Quinuclidinas/efeitos adversos , Fatores de Risco , Rituximab , Caracteres Sexuais , Resultado do Tratamento , Vincristina/efeitos adversos , Adulto JovemRESUMO
Mogamulizumab (MOG), a humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, has recently played an important role in the treatment of adult T cell leukemia/lymphoma (ATLL). Because CCR4 is expressed on normal regulatory T cells as well as on ATLL cells, MOG may accelerate graft-versus-host disease (GVHD) by eradicating regulatory T cells in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is limited information about its safety and efficacy in patients treated with MOG before allo-HSCT. In the present study, 25 patients with ATLL were treated with MOG before allo-HSCT, after which 18 patients (72%) achieved remission. The overall survival and progression-free survival at 1 year post-transplantation were 20.2% (95% CI, 6.0% to 40.3%) and 15.0% (95% CI, 4.3% to 32.0%), respectively. The cumulative incidence of acute GVHD was 64.0% (95% CI, 40.7% to 80.1%) for grade II-IV and 34.7% (95% CI, 15.8% to 54.4%) for grade III-IV. The cumulative incidence of transplantation-related mortality (TRM) was 49.0% (95% CI, 27.0% to 67.8%). Six of 7 patients with acute GVHD grade III-IV died from GVHD, which was the leading cause of death. In particular, a shorter interval from the last administration of MOG to allo-HSCT was associated with more severe GVHD. MOG use before allo-HSCT may decrease the ATLL burden; however, it is associated with an increase in TRM due to severe GVHD. Because MOG is a potent anti-ATLL agent, new treatment protocols should be developed to integrate MOG at suitable doses and timing of administration to minimize unwanted GVHD development.
Assuntos
Anticorpos Monoclonais Humanizados/toxicidade , Doença Enxerto-Hospedeiro/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia-Linfoma de Células T do Adulto/complicações , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Doença Aguda , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/terapia , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodos , Estudos Retrospectivos , Análise de Sobrevida , Transplante HomólogoRESUMO
UNLABELLED: Transient marrow expansion of normal B-cell precursors, termed hematogones, is occasionally observed after hematopoietic stem cell transplantation (HSCT). To understand the clinical significance of this phenomenon, we enumerated hematogones in 108 consecutive patients who received allogeneic HSCT for the treatment of hematologic malignancies, including acute myelogenous leukemia, advanced myelodysplastic syndromes, acute lymphoblastic leukemia, and non-Hodgkin lymphoma. Hematogone quantitation was performed at the time of complete donor engraftment (median day 25 and 32 in patients who received bone marrow and cord blood cell transplants, respectively). Hematogones were polyclonal B cells, and their frequencies correlated positively with blood B-cell numbers, and inversely with donors' but not recipients' age, suggesting that hematogones reflect cell-intrinsic B-cell potential of donor cells. Interestingly, patients developing hematogones that comprised > 5% of bone marrow mononuclear cells constituted a group with significantly prolonged overall survival and relapse-free survival, irrespective of their primary disease or donor cell source. In addition, patients with > 5% hematogones developed severe acute graft-versus-host diseases less frequently, which may contribute toward their improved survival. We therefore conclude that the amount of hematogones at the time of engraftment may be a useful tool in predicting the prognosis of patients treated with allogeneic HSCT. KEY POINTS: Quantitation of hematogones at engraftment is useful to predict prognosis of patients treated with allogeneic stem cell transplantation.
Assuntos
Sobrevivência de Enxerto , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Células Precursoras de Linfócitos B , Doadores não Relacionados , Doença Aguda , Adolescente , Adulto , Idoso , Transplante de Medula Óssea , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Transplante HomólogoRESUMO
A 65-year-old man with multiple lymphadenopathies was diagnosed with IgG4-related disease (IgG4-RD) based on findings of a cervical lymph node biopsy and an elevated serum IgG4 level. Treatment was initiated after the onset of autoimmune pancreatitis, and he achieved remission. He developed diffuse large B-cell lymphoma one year later. Pericardial involvement of lymphoma resulted in cardiac tamponade, and he died before histopathological confirmation of lymphoma was made due to a lethal arrhythmia caused by massive involvement of lymphoma into the myocardium. Because patients with IgG4-RD might have an increased risk of malignant diseases, including lymphoma, histopathological examinations should be considered at any time during the course of IgG4-RD.
Assuntos
Pancreatite Autoimune , Tamponamento Cardíaco , Doença Relacionada a Imunoglobulina G4 , Linfadenopatia , Linfoma Difuso de Grandes Células B , Masculino , Humanos , Idoso , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/diagnóstico , Tamponamento Cardíaco/etiologia , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológicoRESUMO
Hematopoiesis is the process whereby BM HSCs renew to maintain their number or to differentiate into committed progenitors to generate all blood cells. One approach to gain mechanistic insight into this complex process is the investigation of quantitative genetic variation in hematopoietic function among inbred mouse strains. We previously showed that TGF-ß2 is a genetically determined positive regulator of hematopoiesis. In the presence of unknown nonprotein serum factors TGF-ß2, but not TGF-ß1 or -ß3, enhances progenitor proliferation in vitro, an effect that is subject to mouse strain-dependent variation mapping to a locus on chr.4, Tb2r1. TGF-ß2-deficient mice show hematopoietic defects, demonstrating the physiologic role of this cytokine. Here, we show that TGF-ß2 specifically and predominantly cell autonomously enhances signaling by FLT3 in vitro and in vivo. A coding polymorphism in Prdm16 (PR-domain-containing 16) underlies Tb2r1 and differentially regulates transcriptional activity of peroxisome proliferator-activated receptor-γ (PPARγ), identifying lipid PPAR ligands as the serum factors required for regulation of FLT3 signaling by TGF-ß2. We furthermore show that PPARγ agonists play a FLT3-dependent role in stress responses of progenitor cells. These observations identify a novel regulatory axis that includes PPARs, Prdm16, and TGF-ß2 in hematopoiesis.
Assuntos
Proteínas de Ligação a DNA/genética , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/fisiologia , PPAR gama/genética , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta2/genética , Tirosina Quinase 3 Semelhante a fms/genética , Animais , Células COS , Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Chlorocebus aethiops , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica/fisiologia , Hematopoese/genética , Células-Tronco Hematopoéticas/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , PPAR gama/agonistas , PPAR gama/metabolismo , Polimorfismo Genético/fisiologia , Locos de Características Quantitativas/fisiologia , Estresse Fisiológico/fisiologia , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta2/metabolismo , Tirosina Quinase 3 Semelhante a fms/metabolismoRESUMO
The safety, efficacy, and pharmacokinetics of copanlisib were evaluated in this phase Ib/II study in Japanese patients with relapsed/refractory indolent non-Hodgkin lymphoma (NHL). The primary endpoint was safety at the recommended dose; efficacy endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival. In phase Ib, patients received copanlisib 45 mg intravenously on days 1, 8, and 15 of a 28-day cycle, and when tolerated, consecutive patients received copanlisib 60 mg. As no dose-limiting toxicities occurred at the 45 mg (n = 3) or 60 mg (n = 7) dose in phase Ib, the recommended dose for Japanese patients was determined to be 60 mg, and this dose was used in phase II (n = 15). Although all patients experienced at least one treatment-emergent adverse event (TEAE), with hyperglycemia being the most common AE, no AE-related deaths were reported. The ORR was 68.0% (17/25 patients), median PFS was 302 (95% CI 231-484) days, and the duration of response was 330 (range 65-659) days. The pharmacokinetic properties of copanlisib were similar between Japanese and non-Japanese patients. Overall, copanlisib 60 mg had an acceptable safety profile and showed promising antitumor activity in Japanese patients with relapsed/refractory indolent NHL.
Assuntos
Linfoma não Hodgkin , Recidiva Local de Neoplasia , Quinazolinas , Humanos , Antineoplásicos/efeitos adversos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Quinazolinas/efeitos adversosRESUMO
Virus-associated hemorrhagic cystitis (HC) is a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT). Although numerous studies have attempted to identify factors that predispose patients to viral HC, its causes remain controversial. We analyzed retrospectively the results of 266 allogeneic HSCTs to identify factors associated with HC. Of this group, 42 patients (15.8%) were diagnosed with viral HC, because of either adenovirus (ADV; n = 26; 9.8%) or BK virus (BKV; n = 16; 6.0%). ADV-HC was frequently associated with T cell purging, and was less common in patients with acute graft-versus-host-disease (GVHD). Conversely, BKV-HC was more frequently observed in patients with excessive immune reactions such as GVHD, preengraftment immune reaction, and hemophagocytic syndrome. These observations indicate that ADV- and BKV-HC may differ significantly in their risk factors and pathogenesis. Profound immune deficiency is more likely to be associated with ADV-HC, whereas immune hyperactivity might play a key role in BKV-HC.
Assuntos
Cistite/etiologia , Infecções por Citomegalovirus/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Infecções por Polyomavirus/etiologia , Infecções Tumorais por Vírus/etiologia , Adenoviridae/isolamento & purificação , Adolescente , Adulto , Idoso , Vírus BK/isolamento & purificação , Cistite/virologia , Infecções por Citomegalovirus/patologia , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Hemorragia/virologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/patologia , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo , Infecções Tumorais por Vírus/patologia , Adulto JovemRESUMO
A 66-year-old man presented with a six-month history of periodic fever. A CT scan of the chest and abdomen performed at another hospital one month before admission disclosed no evidence of inflammation or tumor, and at admission he had no symptoms other than the periodic fever. FDG-PET/CT demonstrated increased FDG uptake in multiple vertebrae, ribs, scapulae, pelvis, and femurs. A core needle biopsy of the vertebra showing increased FDG uptake was performed, and he was diagnosed with primary osseous Hodgkin lymphoma. ABVD therapy was begun and the fever resolved immediately. After 6 cycles of ABVD, he achieved complete remission and has maintained remission for five years since diagnosis. Primary osseous Hodgkin lymphoma is rare and its lack of distinguishing clinical and radiological features makes it difficult to achieve an early differential diagnosis. FDG-PET/CT is a useful tool for detecting tumors when periodic fever suggests the possibility of malignant disease but when specific symptoms are absent.
Assuntos
Neoplasias Ósseas/diagnóstico , Fluordesoxiglucose F18 , Doença de Hodgkin/diagnóstico , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Doença de Hodgkin/diagnóstico por imagem , Humanos , Masculino , Tomografia Computadorizada por Raios X/métodosRESUMO
Prednisolone, used as a standard initial treatment for immune thrombocytopenia (ITP), is an important risk factor for osteoporosis. To investigate the prevention of glucocorticoid-induced osteoporosis (GIO) in elderly ITP patients receiving prolonged steroid therapy, associations between GIO prevention and the real-world data of score changes of a dual-energy X-ray absorptiometry (DXA) scan, FRAX® and the Garvan tool during the initial loading of prednisolone were examined. In our institute, 22 ITP patients aged ≥ 70 years received 0.5−1.0 mg/kg prednisolone for 2−3 weeks as the initial ITP treatment between 2014 and 2021. The femoral neck bone mineral density (BMD) measured by DXA scan was entered into FRAX® to define the risk-adapted approach to bisphosphonate during the initial loading of prednisolone. Bisphosphonate was administered according to <−1.0 femoral neck BMD T-score measured by DXA scan. Worse scores of FRAX® and the Garvan tool were associated with bisphosphonate use for short-term fracture prevention in primary GIO; however, there were no incidents of fracture or significant differences in probabilities determined by FRAX® and the Garvan tool. During the initial loading of prednisolone, prescribing bisphosphonate might prevent the reduction in BMD in elderly patients with ITP receiving prolonged steroid therapy.
RESUMO
Post-transplant cytomegalovirus (CMV) disease can be almost completely avoided by current infection control procedures. However, CMV reactivation occurs in more than half of patients, and some patients can develop clinically resistant CMV infections. Whether resistance is due to the host's immune status or a viral resistance mutation is challenging to confirm. Therefore, a prospective observational analysis of refractory CMV infection was conducted in 199 consecutive patients who received allogeneic hematopoietic stem cell transplantation at a single institution. Among them, 143 (72%) patients received anti-CMV drugs due to CMV reactivation, and only 17 (8.5%) exhibited refractory CMV infection. These patients had clinically refractory infection. However, viral genome analysis revealed that only one patient exhibited a mutation associated with the anti-CMV drug resistance. Clinical resistance was mainly correlated with host immune factors, and the incidence of resistance caused by gene mutations was low at the early stage after a transplantation.
Assuntos
Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Transplante Homólogo/efeitos adversos , Adolescente , Adulto , Idoso , Citomegalovirus/genética , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/virologia , Farmacorresistência Viral/genética , Feminino , Humanos , Hospedeiro Imunocomprometido , Incidência , Controle de Infecções , Masculino , Pessoa de Meia-Idade , Mutação , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Adulto JovemRESUMO
Invasive aspergillosis (IA) is an important cause of infectious morbidity and mortality in patients who undergo haematopoietic stem cell transplantation (HSCT). History of IA before allogeneic HSCT is still challenging because of the high risk of recurrence after HSCT. Recent advances in early-stage diagnosis and new, more effective classes of antifungal agents have improved the management of IA in the HSCT recipients. We report two cases with acute myelogenous leukaemia after primary failure of induction chemotherapy with the patients developing pulmonary IA. They responded well to a combination of voriconazole (VCZ) and micafungin, resulting in a remarkable reduction of pulmonary IA lesions at short intervals. Thereafter, antifungal therapy was switched to liposomal amphotericin B (L-AmB), followed by conditioning regimen for allogeneic HSCT, because of the possibility of VCZ altering the metabolism of chemotherapeutic agents and calcineurin inhibitors. Successful engraftment was achieved without severe adverse side-effects or aggravation of IA after HSCT. Combining VCZ with micafungin followed by L-AmB throughout HSCT could be advantageous in stabilising IA in HSCT patients.
Assuntos
Antifúngicos/administração & dosagem , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco , Anfotericina B/administração & dosagem , Equinocandinas/administração & dosagem , Feminino , Humanos , Lipopeptídeos/administração & dosagem , Micafungina , Pessoa de Meia-Idade , Pirimidinas/administração & dosagem , Transplante Homólogo , Resultado do Tratamento , Triazóis/administração & dosagem , VoriconazolRESUMO
Human herpes virus (HHV)6-associated limbic encephalitis and/or myelitis is one of the life-threatening central nervous system complications following allogeneic hematopoietic stem cell transplantation (HSCT). Recent reports have shown significant correlations of these complications with unrelated cord blood transplantation (UCBT). We retrospectively analyzed 228 allogeneic HSCT recipients in our single institution; 13 patients (5.7%) were diagnosed with HHV6-associated encephalitis/myelitis. This complication was documented in 8 of 51 UCBT recipients (15.7%) and 5 of 177 recipients (2.8%) transplanted with bone marrow or peripheral blood stem cells, indicating a higher incidence of this complication occurring in UCBT recipients (P = .0005). In addition, HHV6-associated encephalitis/myelitis occurred more frequently in recipients who underwent 2 or more HSCTs (7 of 59 recipients [11.9%]), compared to those who received only 1 HSCT (6 of 169 recipients [3.6%], P = .018). Of note, the incidence of this complication increased to 28.6% (6 of 21 recipients), when the analysis was restricted to a second or more UCBT recipients. All 13 patients presented preengraftment immune response prior to the onset of encephalitis. Two patients manifested typical symptoms at the onset of HHV6-associated encephalitis/myelitis, such as memory dysfunction, disorientation, and consciousness disturbance. However, 4 patients presented only with dysesthesia and pruritus, described as typical manifestations of patients with calcineurin-inhibitor-induced pain syndrome (CIPS), and the remaining 7 showed both symptoms, indicating that CIPS-like symptoms might be manifestations of HHV6-associated myelitis. Thus, physicians should be alert to this rare but often fatal complication, particularly for those who receive 2 or more HSCTs using UCB.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Encefalite Viral/epidemiologia , Herpesvirus Humano 6/isolamento & purificação , Mielite/epidemiologia , Infecções por Roseolovirus/complicações , Adolescente , Adulto , Idoso , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , DNA Viral/sangue , DNA Viral/líquido cefalorraquidiano , Encefalite Viral/diagnóstico , Encefalite Viral/tratamento farmacológico , Encefalite Viral/etiologia , Encefalite Viral/patologia , Feminino , Histocompatibilidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mielite/diagnóstico , Mielite/tratamento farmacológico , Mielite/etiologia , Mielite/patologia , Estudos Retrospectivos , Fatores de Risco , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/epidemiologia , Análise de Sobrevida , Fatores de Tempo , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
Invasive aspergillosis (IA) remains one of the most significant causes of morbidity and mortality in patients with hematological malignancies undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT), mainly due to the difficulty in its early diagnosis. Monitoring of galactomannan (GM) antigen, an exoantigen of Aspergillus, in the blood by sandwich ELISA is a useful and noninvasive method for early diagnosis of IA. The GM test has a sensitivity of 67-100% with a specificity of 81-99% in neutropenic patients and allogeneic transplant recipients [1-3]. Although it has been widely used as a diagnostic criterion for IA [4,5], one of the major limitations of this assay is false-positivity, particularly in pediatric patients [1], patients with graft-versus-host disease (GVHD) [6,7], and those taking dietary GM [8,9] or fungus-derived antibiotics, such as piperacillin-tazobactam (PIPC/TAZ) [10-12].
Assuntos
Antígenos de Fungos/sangue , Aspergilose/diagnóstico , Aspergillus/química , Doenças Hematológicas/sangue , Mananas/sangue , Mieloma Múltiplo/sangue , Amoxicilina/farmacologia , Amoxicilina/uso terapêutico , Antibioticoprofilaxia , Artefatos , Aspergilose/sangue , Aspergillus/imunologia , Aspergillus/isolamento & purificação , Reações Falso-Positivas , Galactose/análogos & derivados , Neoplasias Hematológicas/sangue , Humanos , Imunoglobulina G/sangue , Mieloma Múltiplo/tratamento farmacológico , Proteínas do Mieloma/análise , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/farmacologia , Ácido Penicilânico/uso terapêutico , Piperacilina/farmacologia , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Left ventricular (LV) dysfunction due to anthracycline-induced cardiotoxicity (AIC) has been believed to be irreversible. However, this has not been confirmed and standard medical treatment for heart failure (HF) including renin-angiotensin inhibitors and ß-blockers may lead to its recovery. METHODS AND RESULTS: We thus retrospectively studied 350 cancer patients receiving anthracycline-based chemotherapy from 2001 to 2015 in our institution. Fifty-two patients (14.9%) developed AIC with a decrease in LV ejection fraction (LVEF) of 24.1% at a median time of 6 months [interquartile range (IQR) 4-22 months] after anthracycline therapy. By multivariate analysis, AIC was independently associated with cardiac comorbidities including ischemic heart disease, valvular heart disease, arrhythmia, and cardiomyopathy [odds ratio (OR) 6.00; 95% confidence interval (CI) 2.27-15.84, P = 0.00044), lower baseline LVEF (OR per 1% 1.09; 95% CI 1.04-1.14, P = 0.00034). During the median follow-up of 3.2 years, LV systolic dysfunction recovered among 33 patients (67.3%) with a median time of 4 months (IQR 2-6 months), which was independently associated with the introduction of standard medical treatment for HF (OR 9.39; 95% CI 2.27-52.9, P = 0.0014) by multivariate analysis. CONCLUSION: Early initiation of standard medical treatment for HF may lead to LV functional recovery in AIC.
Assuntos
Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Fármacos Cardiovasculares/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Neoplasias/tratamento farmacológico , Disfunção Ventricular Esquerda/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Adulto , Idoso , Cardiotoxicidade , Feminino , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND: Antiemetic effects and safety of granisetron or palonosetron alone and in combination with a corticosteroid against chemotherapy-induced nausea and vomiting (CINV) were retrospectively evaluated in patients with Hodgkin lymphoma receiving adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) therapy. METHODS: A total of 39 patients were eligible for this study. Before ABVD therapy, granisetron or palonosetron was intravenously administered with or without a corticosteroid (dexamethasone or hydrocortisone) and aprepitant. The proportions of patients with complete control (CC) during the overall (0-120 h after the start of ABVD therapy), acute (0-24 h) and delayed (24-120 h) phases were evaluated. CC was defined as no vomiting and no use of antiemetic rescue medication with only grade 0-1 nausea. RESULTS: Granisetron and palonosetron were administered in 21 and 18 patients, respectively. The CC rate during the acute, delayed and overall phases was not statistically different between the two groups. The CINV was completely controlled during overall phase in 58.3% of patients receiving granisetron or palonosetron in combination with a corticosteroid, whereas in 11.1% of those without co-treatment of a corticosteroid (P < 0.05). There were significantly higher frequencies of anorexia, leucopenia and neutropenia in the palonosetron group. There is a statistically significant difference in the frequency of febrile neutropenia between presence and absence of a corticosteroid (p = 0.024). CONCLUSION: These findings suggested that a combination use of a corticosteroid with a 5-HT3 receptor antagonist was preferable for CINV control in patients with Hodgkin lymphoma receiving ABVD therapy, although the careful management of febrile neutropenia is required. TRIAL REGISTRATION: The study approval numbers in the institution; 24-12 and 24-359. Registered April 17, 2012 and June 21, 2012.
RESUMO
Primary cardiac lymphoma (PCL) is defined as lymphoma involving only the heart and/or pericardium, or with an intrapericardial location of the main tumor mass. It is an extremely rare type of lymphoma and has a poor prognosis because of diagnostic delay and the disease site. PCL is histologically characterized by a mostly diffuse large B-cell lymphoma. The median survival time has been reported to be 7 months. We present the case of a 55-year-old woman who presented with chest oppression and dyspnea on effort. Following a close examination, PCL with a high International Prognostic Index was diagnosed. She received 6 courses of R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) and achieved complete remission. The patient then underwent a consolidation therapy consisting of high-dose chemotherapy including rituximab, followed by autologous peripheral blood stem cell transplantation. There were no complications, such as pulmonary embolism, fatal arrhythmia, or acute heart failure, throughout chemotherapy. Our experience indicates that this therapy is safe and effective and can improve the outcome of high-risk PCL.