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1.
Lancet Haematol ; 7(2): e134-e145, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31704264

RESUMO

BACKGROUND: Benefits of cord blood transplantation include low rates of relapse and chronic graft-versus-host disease (GVHD). However, the use of cord blood is rapidly declining because of the high incidence of infections, severe acute GVHD, and transplant-related mortality. UM171, a haematopoietic stem cell self-renewal agonist, has been shown to expand cord blood stem cells and enhance multilineage blood cell reconstitution in mice. We aimed to investigate the safety and feasibility of single UM171-expanded cord blood transplantation in patients with haematological malignancies who do not have a suitable HLA-matched donor. METHODS: This single-arm, open-label, phase 1-2 safety and feasibility study was done at two hospitals in Canada. The study had two parts. In part 1, patients received two cord blood units (one expanded with UM171 and one unmanipulated cord blood) until UM171-expanded cord blood demonstrated engraftment. Once engraftment was documented we initiated part 2, reported here, in which patients received a single UM171-expanded cord blood unit with a dose de-escalation design to determine the minimal cord blood unit cell dose that achieved prompt engraftment. Eligible patients were aged 3-64 years, weighed 12 kg or more, had a haematological malignancy with an indication for allogeneic hematopoietic stem cell transplant and did not have a suitable HLA-matched donor, and a had a Karnofsky performance status score of 70% or more. Five clinical sites were planned to participate in the study; however, only two study sites opened, both of which only treated adult patients, thus no paediatric patients (aged <18 years) were recruited. Patients aged younger than 50 years without comorbidities received a myeloablative conditioning regimen (cyclophosphamide 120 mg/kg, fludarabine 75 mg/m2, and 12 Gy total body irradiation) and patients aged older than 50 years and those with comorbidities received a less myeloablative conditioning regimen (cyclophosphamide 50 mg/kg, thiotepa 10 mg/kg, fludarabine 150 mg/m2, and 4 Gy total body irradiation). Patients were infused with the 7-day UM171-expanded CD34-positive cells and the lymphocyte-containing CD34-negative fraction. The primary endpoints were feasibility of UM171 expansion, safety of the transplant, kinetics of hematopoietic reconstitution (time to neutrophil and platelet engraftment) of UM171-expanded cord blood, and minimal pre-expansion cord blood unit cell dose that achieved prompt engraftment. We analysed feasibility in all enrolled patients and all other primary outcomes were analysed per protocol, in all patients who received single UM171-expanded cord blood transplantation. This trial has been completed and was registered with ClinicalTrials.gov, NCT02668315. FINDINGS: Between Feb 17, 2016, and Nov 11, 2018, we enrolled 27 patients, four of whom received two cord blood units for safety purposes in part 1 of the study. 23 patients were subsequently enrolled in part 2 to receive a single UM171-expanded cord blood transplant and 22 patients received a single UM171-expanded cord blood transplantation. At data cutoff (Dec 31, 2018), median follow-up was 18 months (IQR 12-22). The minimal cord blood unit cell dose at thaw that achieved prompt engraftment as a single cord transplant after UM171 expansion was 0·52 × 105 CD34-positive cells. We successfully expanded 26 (96%) of 27 cord blood units with UM171. Among the 22 patients who received single UM171-expanded cord blood transplantation, median time to engraftment of 100 neutrophils per µL was 9·5 days (IQR 8-12), median time to engraftment of 500 neutrophils per µL was 18 days (12·5-20·0), and no graft failure occurred. Median time to platelet recovery was 42 days (IQR 35-47). The most common non-haematological adverse events were grade 3 febrile neutropenia (16 [73%] of 22 patients) and bacteraemia (nine [41%]). No unexpected adverse events were observed. One (5%) of 22 patients died due to treatment-related diffuse alveolar haemorrhage. INTERPRETATION: Our preliminary findings suggest that UM171 cord blood stem cell expansion is feasible, safe, and allows for the use of small single cords without compromising engraftment. UM171-expanded cord blood might have the potential to overcome the disadvantages of other cord blood transplants while maintaining the benefits of low risk of chronic GVHD and relapse, and warrants further investigation in randomised trials. FUNDING: Canadian Institutes of Health Research, Canadian Cancer Society and Stem Cell Network.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Indóis/farmacologia , Pirimidinas/farmacologia , Adolescente , Adulto , Autorrenovação Celular/efeitos dos fármacos , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/transplante , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Intervalo Livre de Doença , Estudos de Viabilidade , Neutropenia Febril/etiologia , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Células-Tronco Hematopoéticas/citologia , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Resultado do Tratamento , Adulto Jovem
2.
Ann Hematol ; 98(11): 2579-2591, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31628517

RESUMO

Umbilical cord blood transplantation (UCBT) is a curative treatment for hematological malignancies. However, appropriate prophylaxis against graft-versus-host disease (GVHD), aimed at obtaining rapid and stable engraftment and avoiding toxicity, remains controversial in UCBT. We retrospectively compared outcomes in 409 patients who received calcineurin inhibitors (CIs) plus conventional-dose methotrexate (conv-MTX/CIs, n = 77; methotrexate, 10 mg/m2 on day 1, 7 mg/m2 on days 3 and 6) with those who received CIs plus reduced-dose methotrexate (reduced-MTX/CIs, n = 209; methotrexate, 5 mg/m2 or 5 mg/body on days 1, 3, and 6) or CIs with mycophenolate mofetil (MMF/CIs, n = 123) for GVHD prophylaxis after UCBT. The cumulative incidence of neutrophil engraftment was significantly higher in the reduced-MTX/CI (82.3%) and MMF/CI (86.6%) groups than the conv-MTX/CI (71.4%) group (p = 0.014), although there were no differences in platelet recovery or infectious complications among the three groups. The incidence and severity of GVHD were comparable among the three groups, and there were no significant differences in transplantation-related mortality among the three groups. In conclusion, GVHD prophylaxis with reduced-dose methotrexate and MMF was closely associated with high incidence of neutrophil engraftment without an effect on the incidence and severity of GVHD, which was compared to GVHD prophylaxis with conventional-dose methotrexate.


Assuntos
Inibidores de Calcineurina/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores de Calcineurina/administração & dosagem , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Incidência , /etiologia , Japão/epidemiologia , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Neutrófilos , Contagem de Plaquetas , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
4.
Eur J Haematol ; 103(3): 172-177, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31177565

RESUMO

OBJECTIVES: Umbilical cord blood transplantation (UCBT) and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) modalities have been developed to offset the lack of matched donors. In this study, we compare the transfusion requirements of patients undergoing UCBT and haplo-HSCT in a single institution with the aim of providing additional information for clinicians to choose the most adequate alternative graft for HSCT. METHODS: The study reviewed 67 and 46 patients undergoing UCBT and haplo-HSCT, respectively. RESULTS: There were no significant differences for RBC and PLT requirements according to the transplantation modality. Median time to RBC transfusion independence was 35 and 25.5 days in patients who received an UCBT and haplo-HSCT, respectively (P = 0.38), while median time to platelet transfusion independence was 31 days for UCBT patients and 23 for haplo-HSCT patients (P < 0.001). Days until neutrophils > 0.5 × 109 /L were the only variable that significantly influenced RBC and PLT requirements for both transplantation modalities. Cumulative incidence of RBC and PLT transfusion independence at 90 days after transplantation was similar for both UCBT and haplo-HSCT. CONCLUSIONS: Both transplantation platforms require prolonged and intensive supportive RBC and PLT transfusion therapy. Both transplantation platforms require prolonged and intensive supportive RBC and PLT transfusion therapy.


Assuntos
Transfusão de Sangue , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Transplante Haploidêntico , Adolescente , Adulto , Idoso , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Feminino , Doenças Hematológicas/diagnóstico , Doenças Hematológicas/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
5.
Transpl Infect Dis ; 21(3): e13073, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30875143

RESUMO

BACKGROUND: Human leukocyte antigen (HLA) mismatch and the administration of immunosuppressive agents are considered risks for human herpesvirus 6 (HHV-6) reactivation after stem cell transplantation (SCT). However, the incidence of HHV-6 reactivation in HLA-mismatched related SCT remains unknown. METHODS: We monitored plasma HHV-6 DNA loads weekly using real-time quantitative polymerase chain reaction for 5 weeks after SCT and compared serum IL-6 levels in HLA-mismatched SCT groups. RESULTS: Compared with detection in all 11 umbilical cord blood transplantation (CBT) patients (100%), plasma HHV-6 DNA was detected in only 3 of 42 haplo-SCT patients (7.1%) despite the use of methylprednisolone and antithymocyte globulin as graft-vs-host disease prophylaxis and a reduced-intensity conditioning regimen, respectively. Correspondingly, serum IL-6 levels in haplo-SCT patients were significantly lower than those in CBT patients. No HHV-6-associated encephalitis developed in either groups. CONCLUSIONS: Neither HLA disparity nor the use of methylprednisolone and antithymocyte globulin were risk factors for HHV-6 reactivation in our haplo-SCT patients. Rather than increasing risk, the administration of immunosuppressive agents potentially prevented HHV-6 reactivation after haplo-SCT by suppressing IL-6 production.


Assuntos
Corticosteroides/uso terapêutico , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/uso terapêutico , Infecções por Roseolovirus/diagnóstico , Ativação Viral/efeitos dos fármacos , Adolescente , Adulto , Idoso , Soro Antilinfocitário/uso terapêutico , DNA Viral/sangue , Feminino , Antígenos HLA/genética , Herpesvirus Humano 6/fisiologia , Histocompatibilidade , Humanos , Incidência , Interleucina-6/sangue , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante , Adulto Jovem
6.
Transplant Proc ; 51(2): 602-604, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30879599

RESUMO

Hepatitis B virus (HBV) reactivation in patients with prior exposure to HBV and protective levels of hepatitis B surface antibody (HBsAb) is a rare phenomenon and is termed reverse seroconversion. We describe a case of reactivation of HBV infection following reverse seroconversion in a patient who underwent umbilical cord allogeneic hematopoietic cell transplantation (UHCT). The patient developed acute hepatitis with positive hepatitis B surface antigen (HBsAg) and HBV DNA in the context of prior strongly positive HBsAb. The patient was treated with oral tenofovir and liver function tests returned to normal 3 months later. Long-term monitoring for HBV reactivation should be considered in patients with prior exposure to HBV undergoing UHCT regardless of HBsAb status.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Hepatite B/etiologia , Ativação Viral/fisiologia , Idoso , Antivirais/uso terapêutico , Hepatite B/tratamento farmacológico , Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/fisiologia , Humanos , Masculino , Soroconversão , Tenofovir/uso terapêutico
7.
Rinsho Ketsueki ; 60(2): 118-123, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30842378

RESUMO

A 57-year-old man with high-risk myelodysplastic syndrome underwent umbilical cord blood transplantation. He began receiving steroids on day 14 for acute graft-versus-host disease, and experienced dizziness on day 75 during gradual dose reduction. Multiple hemorrhages were observed in the cerebrum, cerebellum, and brainstem. His bleeding increased, and he underwent a brain biopsy on day 91. Subsequently, he was diagnosed with central nervous system vasculitis (CNSV) on the basis of the observed aggregation of mature CD3+ lymphocytes around small vessels and vascular wall invasion by lymphocytes and macrophages. After receiving high-dose steroid therapy, cerebral hemorrhage stopped; however, dysphasia occurred on day 113 and the patient died of cerebral edema on day 128. Toxoplasma DNA and tachyzoites were detected in the brain biopsy specimen during additional examinations; therefore, we suspected that the toxoplasmosis was related to the onset of CNSV. CNSV is a rare, rapidly progressing disease that may present as a fatal post-transplantation central nervous system complication. Investigating the causes of CNSV, including CNSV associated with toxoplasmosis, is critically important for improving the prognosis of patients with CNSV.


Assuntos
Hemorragia Cerebral/diagnóstico , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Toxoplasmose/diagnóstico , Vasculite do Sistema Nervoso Central/diagnóstico , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia
8.
Rinsho Ketsueki ; 60(2): 130-133, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30842380

RESUMO

We managed a patient with acute myeloid leukemia (AML) who showed refractory ascites that developed in late-phase cord blood transplantation (CBT). The ascites obverted 5 months after CBT. The liver was atrophic, and serum hyaluronic acid was elevated at the onset, suggesting fibrotic changes in the liver. The ascites were transiently improved by cell-free and concentrated ascites reinfusion therapy (CART) and corticosteroid administration; however, the patient died from anasarca and recurrent AML 378 d after CBT. The etiology of the ascites is not well understood; therefore, additional studies on similar patients should be explored for proper management.


Assuntos
Ascite/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Humanos , Cirrose Hepática
9.
Rinsho Ketsueki ; 60(2): 93-98, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30842386

RESUMO

A 68-year-old female with severe aplastic anemia (SAA) refractory to initial immunosuppressive therapy, including anti-thymocyte globulin (ATG) and cyclosporine, received a reduced-intensity cord blood transplant (CBT) in June 2015. Tacrolimus (TAC) and mycophenolate mofetil were administered for graft-versus-host disease (GVHD) prophylaxis, and she received prolonged TAC and prednisolone to treat chronic GVHD. The patient presented with progressive ataxia 14 months after CBT. A brain magnetic resonance image (MRI, FLAIR) detected a high-intensity lesion in the left cerebellar hemisphere, which suggested infarction. Her consciousness level gradually continued to deteriorate and another brain MRI (T2) revealed that the size of the cerebellar lesion had increased and had involved the pons. A cerebrospinal fluid (CSF) examination showed normal cell count and protein levels; however, polymerase chain reaction (PCR) analysis of CSF was positive for JC virus (JCV). Therefore, she was eventually diagnosed with progressive multifocal leukoencephalopathy (PML) and treated with mefloquine. The symptoms were reduced after 3 months, and JCV in CSF disappeared without new lesions after 6 months. This is an unusual case of PML initially involving the cerebellum, and we report here PML after an immunosuppressive therapy and CBT in the patient with SAA.


Assuntos
Anemia Aplástica/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Leucoencefalopatia Multifocal Progressiva/etiologia , Idoso , Feminino , Humanos , Imunossupressores/uso terapêutico , Vírus JC , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Mefloquina/uso terapêutico
10.
Blood Cancer J ; 9(3): 31, 2019 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-30842405

RESUMO

Allogeneic hematopoietic stem cell transplantation is the sole curative therapy for myelodysplastic syndrome (MDS). However, there is concern regarding graft failure and relapse in patients who undergo cord blood transplantation (CBT). We conducted a retrospective study of the CBT outcomes in MDS patients using the Japanese Data Center for Hematopoietic Cell Transplantation database. Seven hundred fifty-two de novo MDS patients of ≥18 years of age (median, 58 years) undergoing their first CBT between 2001 and 2015 were examined. Two-thirds of the patients were male, and were RAEB. The cumulative incidences of neutrophil and platelet engraftment at day 100 were 77 and 59%, respectively. The 3-year overall survival (OS) was 41% and the median survival of the patients was 1.25 years. A multivariate analysis of pre-transplant variables showed that the age, gender, cytogenetic subgroups, number of RBC transfusions, HCT-CI and year of CBT significantly influenced the outcome. The cumulative incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) was 32 and 21%, respectively. A survival benefit was observed in patients who developed cGVHD, but not aGVHD. Our results suggest that CBT is an acceptable alternative graft and that a graft-versus-MDS effect can be expected, especially in patients who develop cGVHD.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Síndromes Mielodisplásicas/complicações , Adulto , Idoso , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Prognóstico , Análise de Sobrevida , Transplante Homólogo
11.
Clin J Gastroenterol ; 12(5): 414-419, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30835083

RESUMO

A 56-year-old man underwent cord blood transplantation for angioimmunoblastic T-cell lymphoma. He developed severe diarrhea and abdominal pain that persisted for more than 4 months. We suspected that he might have cord colitis syndrome (CCS), so metronidazole (MNZ) was administered. The patient's abdominal pain and diarrhea showed some improvement after the initiation of MNZ therapy, but they worsened on the cessation of MNZ, which prompted us to resume MNZ treatment. After the patient had taken MNZ (1500-2000 mg/day) for 78 days, he developed somnolence and dysarthria. We diagnosed him with metronidazole-induced encephalopathy (MIE) based on the characteristic magnetic resonance imaging findings and the clinical course. The patient's dysarthria and somnolence improved within a few days after the discontinuation of MNZ. CCS is a recently proposed clinical entity defined as a persistent diarrheal illness that is culture-negative, antibiotic-responsive, and not attributable to any known cause. Patients with CCS often have recurrent diarrhea after the discontinuation of MNZ and may require prolonged treatment for a median of 120 days. When treating CCS with MNZ, physicians should be alert for the development of MIE.


Assuntos
Antibacterianos/efeitos adversos , Encefalopatias/induzido quimicamente , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Diarreia/tratamento farmacológico , Metronidazol/efeitos adversos , Encéfalo/diagnóstico por imagem , Encefalopatias/diagnóstico por imagem , Colonoscopia , Diarreia/etiologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
14.
J Infect Chemother ; 25(4): 289-292, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30316744

RESUMO

Few cases of cryptococcal infection following umbilical cord blood transplantation (UCBT) have been reported. We report a case, where cryptococcal infection occurred soon after rapidly reducing the dose of tacrolimus in a UCBT recipient who received micafungin prophylaxis during the early phase of transplantation. The etiology of cryptococcal infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including UCBT, might be associated with rapid dose-reduction of calcineurin inhibitors, such as tacrolimus during early phase of allo-HSCT. To our knowledge, this is the first English-language report to describe in detail a case of cryptococcal meningitis with fungemia during early phase of UCBT.


Assuntos
Inibidores de Calcineurina/administração & dosagem , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Fungemia/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Meningite Criptocócica/microbiologia , Tacrolimo/administração & dosagem , Antibioticoprofilaxia/métodos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/isolamento & purificação , Relação Dose-Resposta a Droga , Fungemia/prevenção & controle , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Meningite Criptocócica/prevenção & controle , Micafungina/farmacologia , Micafungina/uso terapêutico , Pessoa de Meia-Idade , Transplante Homólogo/efeitos adversos
15.
J Clin Oncol ; 37(5): 367-374, 2019 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-30523748

RESUMO

PURPOSE: Increasing the number of hematopoietic stem and progenitor cells within an umbilical cord blood (UCB) graft shortens the time to hematopoietic recovery after UCB transplantation. In this study, we assessed the safety and efficacy of a UCB graft that was expanded ex vivo in the presence of nicotinamide and transplanted after myeloablative conditioning as a stand-alone hematopoietic stem-cell graft. METHODS: Thirty-six patients with hematologic malignancies underwent transplantation at 11 sites. RESULTS: The cumulative incidence of neutrophil engraftment at day 42 was 94%. Two patients experienced secondary graft failure attributable to viral infections. Hematopoietic recovery was compared with that observed in recipients of standard UCB transplantation as reported to the Center for International Blood and Marrow Transplant Research (n = 146). The median time to neutrophil recovery was 11.5 days (95% CI, 9 to 14 days) for recipients of nicotinamide-expanded UCB and 21 days (95% CI, 20 to 23 days) for the comparator ( P < .001). The median time to platelet recovery was 34 days (95% CI, 32 to 42 days) and 46 days (95% CI, 42 to 50 days) for the expanded and the comparator cohorts, respectively ( P < .001). The cumulative incidence of grade 2 to 4 acute graft-versus-host disease (GVHD) at day 100 was 44%, and grade 3 and 4 acute GVHD at day 100 was 11%. The cumulative incidence at 2 years of all chronic GVHD was 40%, and moderate/severe chronic GVHD was 10%. The 2-year cumulative incidences of nonrelapse mortality and relapse were 24% and 33%, respectively. The 2-year probabilities of overall and disease-free survival were 51% and 43%, respectively. CONCLUSION: UCB expanded ex vivo with nicotinamide shortens median neutrophil recovery by 9.5 days (95% CI, 7 to 12 days) and median platelet recovery by 12 days (95% CI, 3 to 16.5 days). This trial establishes feasibility, safety, and efficacy of an ex vivo expanded UCB unit as a stand-alone graft.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Sangue Fetal/efeitos dos fármacos , Neoplasias Hematológicas/terapia , Niacinamida/farmacologia , Adolescente , Adulto , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Intervalo Livre de Doença , Feminino , Sangue Fetal/citologia , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/imunologia , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/citologia , Neutrófilos/imunologia , Condicionamento Pré-Transplante/métodos , Adulto Jovem
16.
Transpl Infect Dis ; 21(1): e13024, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30414316

RESUMO

BACKGROUND: Human herpesvirus 6 (HHV-6) encephalitis is a known life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, few studies have focused on the occurrence of HHV-6 encephalitis in patients receiving mycophenolate mofetil (MMF) combined with a calcineurin inhibitor as prophylaxis for graft-versus-host disease (GVHD). This study aimed to investigate the impact of MMF administered for GVHD prophylaxis in the occurrence of HHV-6 encephalitis after allo-HSCT and the characteristics of this condition. METHODS AND RESULTS: We retrospectively analyzed 73 patients who underwent allo-HSCT (83 transplants) at our hospital between April 2010 and December 2015. MMF (2-3 g/d) was administered along with a calcineurin inhibitor. Seven patients (8.0%) developed encephalitis due to HHV-6. The median period from allo-HSCT to the onset of HHV-6 encephalitis was 23 days (range, 17-98 days). The cumulative incidence of HHV-6 encephalitis on day 100 after treatment was 12% and 6% in patients who underwent cord blood transplantation (CBT) and non-CBT (ie, bone marrow transplantation and peripheral blood stem cell transplantation), respectively (P = 0.344). Neurological symptoms of encephalitis were more severe in non-CBT cases than those in CBT cases. All patients diagnosed with HHV-6 encephalitis were treated with ganciclovir or foscarnet. None of the enrolled patients died from HHV-6 encephalitis. CONCLUSIONS: Mycophenolate mofetil may have the potential to increase the frequency of severe HHV-6 encephalitis in patients undergoing CBT and non-CBT. Thus, MMF should be administered with caution, and patients should be monitored closely for HHV-6 encephalitis even those who did not undergo CBT.


Assuntos
Encefalite Viral/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/efeitos adversos , Ácido Micofenólico/efeitos adversos , Infecções por Roseolovirus/epidemiologia , Adulto , Idoso , Antivirais/uso terapêutico , Inibidores de Calcineurina/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Encefalite Viral/diagnóstico , Encefalite Viral/tratamento farmacológico , Encefalite Viral/virologia , Feminino , Doença Enxerto-Hospedeiro/imunologia , Neoplasias Hematológicas/cirurgia , Herpesvirus Humano 6/isolamento & purificação , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/tratamento farmacológico , Infecções por Roseolovirus/virologia , Índice de Gravidade de Doença , Transplante Homólogo/efeitos adversos , Adulto Jovem
17.
Eur J Haematol ; 102(4): 331-340, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30506598

RESUMO

OBJECTIVE: Characteristics and risk factors (RFs) of invasive fungal disease (IFD) have been little studied in the setting of umbilical cord blood transplantation (UCBT). METHOD: We retrospectively included 205 single-unit myeloablative UCBT recipients with a median follow-up of 64 months. RESULTS: Fifty-six episodes of IFD were observed in 48 patients (23%) at a median time of 123 days after stem cell infusion. Invasive mold disease (IMD) occurred in 42 cases, 38 of them (90%) caused by invasive aspergillosis whereas invasive yeast disease (IYD) occurred in 14 cases, most of them due to candidemia (n = 12, 86%). The 5-year cumulative incidence of IFD, IMDs, and IYDs was 24% 19%, and 7%, respectively. In multivariate analysis, three RFs for IMDs were identified: age >30 years (HR 3.5, P = 0.017), acute grade II-IV graft-versus-host disease (HR 2.3, P = 0.011), and ≥1 previous transplant (HR 3.1, P = 0.012). The probability of IMDs was 2.5%, 14%, and 33% for recipients with none, 1, or 2-3 RFs, respectively (P < 0.001). Among IFD, IMDs had a negative effect on non-relapse mortality in multivariate analysis (HR 1.6, P = 0.039). IMDs showed a negative impact on overall survival (HR 1.59, P = 0.018). CONCLUSION: Invasive mold disease were very common and serious complication after UCBT.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Micoses/epidemiologia , Micoses/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Adolescente , Adulto , Anti-Infecciosos/uso terapêutico , Causas de Morte , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Micoses/diagnóstico , Micoses/prevenção & controle , Avaliação de Resultados da Assistência ao Paciente , Vigilância em Saúde Pública , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
19.
BMC Infect Dis ; 18(1): 654, 2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30545330

RESUMO

BACKGROUND: Bloodstream infection (BSI) is one of the major causes of morbidity and mortality for patients undergoing hematopoietic stem cell transplantation (HSCT). The unrelated cord blood transplantation (UCBT) can provided opportunities for patients without suitable donors for bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT), while few studies have addressed BSI after UCBT. The aim of this study was to analyse the incidence and risk factors of BSI, causative organisms, microbial resistance, and its impact on the clinical outcomes and survival of patients. METHODS: There are 336 patients, were divided into two groups depending on whether developing BSI. Demographic characteristics, laboratory data, and clinical outcome were compared between different groups. The risk factors of BSI was examined using logistic regression and the survival was examined using the Kaplan-Meier method and log-rank test. RESULTS: Ninety-two patients (27.4%) developed early BSI with 101 pathogenic bacteria isolated, and the median day of developing initial BSI was 4.5 d. Gram-negative bacteria were the most common isolate (60, 59.4%), followed by Gram-positive bacteria (40, 39.6%) and fungi (1, 1.0%). Thirty-seven (36.6%) isolates were documented as having multiple drug resistance (MDR). Myeloid malignancies, conditioning regimens including total body irradiation (TBI), and prolonged neutropenia were identified as the independent risk factors for early BSI. The 3-year OS was 59.9% versus 69.2% in the BSI group and no-BSI group (P = 0.0574), respectively. The 3-year OS of the MDR group was significantly lower than that of the non-BSI group (51.1% versus 69.2%, p = 0.013). CONCLUSIONS: Our data indicate that the incidence of early BSI after UCBT was high, especially in patients with myeloid disease and a conditioning regimen including TBI and prolonged neutropenia. Early BSI with MDR after UCBT had a negative impact on long-term survival.


Assuntos
Bacteriemia/epidemiologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/etiologia , Bacteriemia/microbiologia , Criança , Transplante de Células-Tronco de Sangue do Cordão Umbilical/estatística & dados numéricos , Feminino , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Doadores não Relacionados/estatística & dados numéricos , Adulto Jovem
20.
Haematologica ; 103(12): 2109-2115, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30076172

RESUMO

Diffuse alveolar hemorrhage after hematopoietic stem cell transplantation is a frequently fatal complication with no standard therapy. Although significant changes in supportive and intensive care measures for patients undergoing hematopoietic stem cell transplantation have been made over the past decades, the impact of these changes on the incidence and outcome of patients with diffuse alveolar hemorrhage has not been examined. We analyzed 1228 patients who underwent allogeneic hematopoietic stem cell transplantation between 2008-2015 at the University of Minnesota to study the incidence, risk factors, and outcomes of diffuse alveolar hemorrhage. Diffuse alveolar hemorrhage developed in 5% of allogeneic hematopoietic stem cell transplant recipients, at a median of 30 days (range +3 to +168 days) after transplantation. The incidence of diffuse alveolar hemorrhage was significantly greater in recipients of umbilical cord blood than peripheral blood or bone marrow grafts (HR: 2.08, 95% CI: 1.16-3.74; P=0.01). In multivariate analysis, delayed neutrophil engraftment or primary graft failure was a risk factor for diffuse alveolar hemorrhage following peripheral blood or bone marrow hematopoietic stem cell transplants (HR: 5.51, 95% CI: 1.26-24; P=0.02) and delayed platelet engraftment was associated with significantly increased diffuse alveolar hemorrhage in umbilical cord blood transplant recipients (HR: 6.96, 95% CI: 2.39-20.29; P<0.05). Myeloablative regimens including total body irradiation were also risk factors for diffuse alveolar hemorrhage (HR: 1.8, 95% CI: 1.03-3.13, P=0.05) in both peripheral blood or bone marrow and umbilical cord blood hematopoietic stem cell transplants (HR: 1.87, 95% CI: 0.95-3.71). Patients with diffuse alveolar hemorrhage had an inferior 6-month treatment-related mortality (HR: 6.09, 95% CI: 4.33-8.56, P<0.01) and 2-year overall survival (HR: 4.16, 95% CI: 3.06-5.64; P<0.01) using either graft source. The etiology of diffuse alveolar hemorrhage is multifactorial, involving lung injury influenced by high-dose total body irradiation, graft source, and delayed engraftment or graft failure. The survival of patients with diffuse alveolar hemorrhage after hematopoietic stem cell transplantation remains poor. Clinical interventions or experimental studies (e.g., cell expansion for umbilical cord blood transplants or thrombopoietin use) that modulate these risk factors may limit the incidence and improve the outcomes of diffuse alveolar hemorrhage.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Hemorragia/diagnóstico , Alvéolos Pulmonares/patologia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/métodos , Criança , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Humanos , Lactente , Recém-Nascido , Cinética , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo , Adulto Jovem
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