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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
3.
J Cancer Res Clin Oncol ; 145(11): 2823-2834, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31468122

RESUMO

PURPOSE: The optimal dose intensity for conditioning prior to allogeneic hematopoietic stem cell transplantation (alloHSCT) for chronic lymphocytic leukemia (CLL) is unknown. METHODS: We retrospectively compared outcomes of patients who received a first alloHCST after non-myeloablative (NMA) and reduced intensity conditioning (RIC). Data of 432 patients with a median age of 55 years were included, of which 86 patients underwent NMA and 346 RIC. RESULTS: The median follow-up after alloHSCT was 4.3 years. Compared to the RIC group, more NMA patients had purine-analog-sensitive disease, were in complete remission and received matched related donor transplantation. After RIC, the probabilities for 5-year OS, EFS, CIR, and NRM were 46%, 38%, 28%, and 35% and after NMA the respective probabilities were 52%, 43%, 25%, and 32%. In multivariate analysis, remission status prior to conditioning but not RIC versus NMA conditioning had a significant impact on CIR, EFS, and OS. CONCLUSION: Presumed higher anti-leukemic activity of RIC versus NMA conditioning did not translate into better outcomes after alloHSCT, but better remission status prior to conditioning did. Effective pathway inhibitor-based salvage therapies combined with NMA conditioning might thus represent the most attractive contemporary approach for alloHSCT for patients with CLL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Linfocítica Crônica de Células B/mortalidade , Condicionamento Pré-Transplante/mortalidade , Adulto , Idoso , Bussulfano/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Incidência , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfocítica Crônica de Células B/terapia , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Adulto Jovem
4.
Adv Clin Exp Med ; 28(9): 1185-1192, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31430073

RESUMO

BACKGROUND: Acute graft-versus-host disease (aGvHD) is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Identifying its risk factors would enable the proper prophylaxis and management, which may significantly improve the general outcome of children treated with HSCT. OBJECTIVES: The aim of this single-center, retrospective cohort study was to assess the potential risk factors for grades II-IV of aGvHD in children after the 1st allo-HSCT from an unrelated donor (UD), performed as a result of an underlying malignant disease. MATERIAL AND METHODS: From among patients who received HSCT in our center in the years 2004-2015, 237 were included in the study cohort. All the patients received standard aGvHD prophylaxis consisting of cyclosporine (CsA) and a short course of methotrexate (MTX). Various clinical and epidemiological features, the transplant proceedings, graft composition, conditioning regimens, as well as the duration and coherence of aGvHD prophylaxis were analyzed as potential risk factors for aGvHD. RESULTS: The incidence of II-IV aGvHD in the study cohort was 58.6%. The median time of the diagnosis of aGvHD was 18 days post-HSCT. In the multivariate analysis, risk factors significantly associated with grades II-IV of aGvHD were: myeloablative conditioning regimen containing total body irradiation (TBI-MAC) (RR (relative risk): 1.69; p = 0.03), premature termination of CsA administration due to its toxicity (RR: 1.99; p = 0.0003) and HSCT performed before the year 2009 (RR: 1.97; p = 0.0001). Donor and recipient age, donor-recipient sex mismatch, stem cell source, risk of disease, and amount of infused CD34+ cells seem to be insignificant as risk factors for aGvHD. The overall survival (OS) of patients with aGvHD was noticeably worse that in those who were aGvHD-free: 60.8% vs 74.1% (p = 0.08). CONCLUSIONS: The conditioning regimen and the proper aGvHD prophylaxis, including continuous CsA administration, have a major impact on aGvHD occurrence. According to our results, the termination of CsA therapy should be carefully considered, and avoided if possible.


Assuntos
Ciclosporina/administração & dosagem , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Criança , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Doadores não Relacionados
5.
Eur J Cancer Care (Engl) ; 28(5): e13122, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31257689

RESUMO

OBJECTIVES: To analyse clinical outcomes comparing two age groups of patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT), and to identify risk factors associated with older patients' mortality. METHODS: In this retrospective study, the medical charts of all consecutive patients admitted in one hospital for allo-HSCT were reviewed. Overall survival (OS) and other outcomes were compared between patients aged up to 55 years (YG) and older than 55 (EG). RESULTS: From January 2007 to August 2014, 111 adult patients were admitted for allo-HSCT and were included 75 in the YG and 36 in the EG group. The OS rate at D+ 100 was 84% for YG individuals in contrast to 75% in the EG (p = 0.01), and 71% vs. 50% at one year after HSCT (p = 0.01) respectively. Therapy-related mortality (TRM) rates for the YG and EG were, respectively, 14% vs. 17% (p = 0.04) at D+ 100 and 17% vs. 32% (p = 0.04) at one year. Haploidentical donor type and active disease status significantly increased mortality risk in the EG (hazard ratio 2.42; p = 0.018; and 2.04; p = 0.033). CONCLUSION: YG and EG have similar TRM rates early after allo-HSCT, but the elderly had higher TRM during the critical period from 100 days to one year.


Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Mortalidade , Recidiva Local de Neoplasia/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Brasil/epidemiologia , Feminino , Haplótipos , Neoplasias Hematológicas/mortalidade , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Recidiva Local de Neoplasia/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Modelos de Riscos Proporcionais , Terapia de Substituição Renal/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Doadores de Tecidos , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
6.
Ann Hematol ; 98(9): 2197-2211, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31321454

RESUMO

Incidence and outcome of microbiologically documented bacterial/viral infections and invasive fungal disease (IFD) in children and adults after hematopoietic cell transplantation (HCT) were compared in 650 children and 3200 adults in multicenter cross-sectional nationwide study. Infections were diagnosed in 60.8% children and 35.0% adults, including respectively 69.1% and 63.5% allo-HCT, and 33.1% and 20.8% auto-HCT patients. The incidence of bacterial infections was higher in children (36.0% vs 27.6%; p < 0.0001). Infections with Gram-negative bacteria were more frequent than Gram-positives in adults (64.6% vs 44.8%; p < 0.0001). Outcome of bacterial infections was better in children (95.5% vs 91.4%; p = 0.0011). The IFD incidence (25.3% vs 6.3%; p < 0.0001) and outcome (88.0% vs 74.9%; p < 0.0001) were higher in children. The incidence of viral infections was higher in children after allo-HCT (56.3% vs 29.3%; p < 0.0001), and auto-HCT (6.6% vs 0.8%; p < 0.0001). Outcome of viral infections was better in children (98.6% vs 92.3%; p = 0.0096). Infection-related mortality was 7.8% in children and 18.4% in adults (p < 0.0001). No child after auto-HCT died of infection. Adult age, mismatched transplants, acute leukemia, chronic GVHD, CMV reactivation, infection with Gram-negatives, and duration of infection > 21 days were risk factors for death from infection. In conclusion, pediatric patients have 2.9-fold higher incidence and 2.5-fold better outcome of infections than adults after HCT.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções por Citomegalovirus/epidemiologia , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Infecções Fúngicas Invasivas/epidemiologia , Doença Aguda , Adolescente , Adulto , Fatores Etários , Idoso , Infecções Bacterianas/etiologia , Criança , Pré-Escolar , Doença Crônica , Estudos Transversais , Infecções por Citomegalovirus/etiologia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Incidência , Lactente , Recém-Nascido , Infecções Fúngicas Invasivas/etiologia , Leucemia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
7.
Eur J Haematol ; 103(4): 402-409, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31332836

RESUMO

BACKGROUND: Oral mucositis (OM) is a common toxicity of stem cell transplantation (SCT). We sought to evaluate OM burden, risk factors, and implications in a cohort of allogeneic-SCT recipients. METHODS: This was a single-center study including 115 adult allogeneic-SCT transplanted between 2016 and 2018 for various hematological conditions. Conditioning intensity was categorized as myeloablative (MAC, 39%), reduced intensity (34%), or reduced toxicity (RTC, 27%) in patients conditioned with fludarabine-treosulfan. OM was prospectively graded using the Common Terminology Criteria for Adverse Events (v.4.0) system. RESULTS: Moderate-to-severe OM (grade 2-4) was experienced by 60% of patients. In a univariate analysis, younger age (P = .023), lower body mass index (P = .01), recent smoking (P = .08), recent antibiotics exposure (P = .018), MAC (P < .001), and methotrexate (P = .009) were associated with moderate-to-severe OM. In a multivariable logistic regression model, conditioning and graft-versus-host disease prophylaxis remained significant. OM risk was lowest with RTC (RTC vs MAC: odd ratio [OR] 0.05, P < .001), and recent antibiotic exposure trended toward increased risk (OR 1.88, P = .168). OM was associated with longer hospitalization, delayed neutrophil engraftment, and gastrointestinal-related infections. CONCLUSION: Oral mucositis remains a leading SCT complication. Treosulfan-based conditioning has low mucosal toxicity and is appealing given previous reports on its high efficacy.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estomatite/etiologia , Idoso , Comorbidade , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doenças Hematológicas/complicações , Doenças Hematológicas/epidemiologia , Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Estomatite/diagnóstico , Estomatite/epidemiologia , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento
8.
Ann Transplant ; 24: 367-373, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31221952

RESUMO

BACKGROUND Data about application of related haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) on patients with high-risk or intermediate-risk acute myeloid leukemia (AML) in the first complete remission (CR1) are lacking. In this study, we report the outcomes of using unmanipulated haploidentical allogeneic peripheral blood stem cell transplantation (haplo-PBSCT) as post-remission therapy for patients with high-risk or intermediate-risk AML in CR1. MATERIAL AND METHODS From January 2008 to July 2016, 33 patients diagnosed as high-risk or intermediate-risk AML in CR1 undergoing haplo-PBSCT in our institution were enrolled for analysis. The cumulative incidence of platelet and neutrophil recovery, the occurrence of acute graft-versus-host-disease (GVHD) and chronic GVHD, relapse and non-relapse mortality were assessed. Patients' survival rates were estimated using the Kaplan-Meier method. RESULTS The cumulative incidence of grade 2-4 acute GVHD, overall and extensive chronic GVHD was 18.2%, 9.1%, and 6.1%, respectively. 2-year probability of relapse was 9.1%. Disease-free survival and overall survival at 2 years were 72.7% and 75.8%, respectively. CONCLUSIONS Our results showed that unmanipulated haploidentical transplantation with G-CSF primed PBSC alone as a graft source could be an acceptable alternative post-remission treatment for high-risk or intermediate-risk AML patients in CR1 lacking a matched donor.


Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Leucemia Mieloide Aguda/cirurgia , Transplante de Células-Tronco de Sangue Periférico/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Incidência , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Taxa de Sobrevida , Adulto Jovem
9.
Transfus Apher Sci ; 58(3): 300-303, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31036518

RESUMO

Peripheral blood stem cell transplantation (PBSCT) is now widely used in both malignant and non-malignant hematologic diseases as a treatment strategy. Using this approach, a controversial group of donors is children weighing 20 kg or less. The aim of this study was to evaluate results of allogeneic and autologous PBSCT and also the efficacy of our suggested alternative method for a custom prime in cell harvesting of this group. All the participants' demographic and laboratory data were collected before apheresis. A total of 37 individuals participated in this study of which 12 and 25 of them were categorized in autologous and allogeneic groups respectively. For the apheresis procedure, a central venous access was used as well as the custom prime method with some changes. Apheresis details, as well as CD34 and CD3 cell counts in the allogeneic and autologous groups, were calculated. In this study, 91.9% (N = 34) of all individuals achieved the minimal amount of cells for PBSCT (2 × 106 CD34+ cells/kg) in one session. On the other hand, 12% (N = 3) of donors in the allogeneic group achieved the minimal threshold in 2 apheresis sessions. During the leukapheresis a total processed blood volume/total blood volume ratio (TPBV/TBV) was calculated as 4.64 ± 1.06 and 5.18 ± 0.73 fold in the allogeneic and autologous groups respectively. The mean of harvested CD34 cells in allogeneic and autologous groups was 5.28 ± 3.47 × 106 and 3.57 ± 2.9 × 106 cells/kg respectively. Likewise, in the allogeneic group, the mean of the harvested CD3 cell count was 339 ± 141 × 106/kg. Also, the median day of white blood cell (WBC) engraftment was 14 and 13 for allogeneic and autologous groups respectively. Furthermore, the median day of platelet engraftment was 19.5 for both allogeneic and autologous groups. Among the recipients of the allogeneic group, acute graft versus host disease (aGVHD) was detected in 56% (N = 14) of patients and this was also correct for chronic GVHD. Taken together, it was shown, despite the probable complications of peripheral blood stem cell apheresis in donors weighing less than 20 kg; that it is possible to perform this procedure without any complication during the leukapheresis.


Assuntos
Doenças Hematológicas/terapia , Leucaférese , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico , Doença Aguda , Aloenxertos , Autoenxertos , Peso Corporal , Criança , Pré-Escolar , Estudos Transversais , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doenças Hematológicas/sangue , Doenças Hematológicas/epidemiologia , Humanos , Lactente , Masculino
10.
Medicine (Baltimore) ; 98(19): e15584, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083240

RESUMO

Extramedullary relapse (EMR) rarely occurs after allogeneic hematopoietic stem cell transplantation (HSCT) in leukemia. This study was to investigate the clinical characteristics of EMR.We retrospectively investigated 316 consecutive patients undergoing HSCT for acute leukemia or chronic myeloid leukemia (CML) at 2 institutions between January 2012 and February 2017. Furthermore, we analyzed and compared the risk factors and outcomes between EMR and bone marrow relapse (BMR).The 5-year cumulative incidence of EMR was 14.1%. The EMR incidence in acute myeloid leukemia, lymphoblastic leukemia, and CML was 17.5%, 18.9%, and 5.3%, respectively. CML had a lower EMR incidence rate. Compared to the BMR group, the EMR group had a longer median relapse-free time (10.5 months vs 5 months, P = .02), and the EMR group had a higher incidence rate of chronic graft-versus-host disease (50.0% vs 20.9%, P = .009). EMR had better estimated 3-year survival rates post-HSCT, and post-relapse, than did BMR (39.5% vs 9.5%, P < .001, and 21.9% vs 10.8%, P = .001). Multivariate analysis identified that adverse cytogenetics (hazard ratio [HR] = 9.034, P < .001) and extramedullary leukemia before HSCT (HR = 2.685, P = .027) were the independent risk factors for EMR after HSCT. In the EMR group, patients who achieved complete remission (CR) had a significantly better, estimated 3-year survival than did patients who did not achieve CR (38.4% vs 14.3%, P = .014).EMR is a significant contributor to mortality after HSCT, which appears to be resistant to most of the current therapies. Establishing effective strategies for EMR is important in improving outcomes after HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia/cirurgia , Transplante Homólogo , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Incidência , Leucemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Recidiva , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
11.
Exp Hematol ; 74: 33-41, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31047963

RESUMO

Both primary disease relapse (PDR) and chronic graft-versus-host disease (cGVHD) have long been the dreaded outcomes for patients with hematologic malignancies. Previous theories have speculated an inverse relationship between the two; therefore, we attempted to verify the described association. We searched for titles of articles in MEDLINE (PubMed), Cochrane library, and EMBASE database that evaluated the association between PDR and cGVHD and conducted a random effect meta-analysis of 11 studies involving a total of 64,239 participants. We found a significantly decreased risk of developing PDR in patients with cGVHD, with a pooled risk ratio of 0.49 (95% confidence interval: 0.40-0.61, I2 = 69.3%). We concluded that patients with cGVHD have a significantly lower risk of developing PDR compared with patients without cGVHD.


Assuntos
Doença Enxerto-Hospedeiro/epidemiologia , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/terapia , Humanos , Masculino , Recidiva , Fatores de Risco
12.
Eur J Haematol ; 103(1): 10-17, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30958904

RESUMO

OBJECTIVES: This retrospective study analyzed the impact of early cyclosporine A (CsA) initiation (day -3) on the risk of acute graft-vs-host disease (aGvHD) after haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplant cyclophosphamide. METHODS: Sixty-one consecutives patients who underwent Haplo-HCT were analyzed. RESULTS: At day +180, the cumulative incidences of grade II-IV and grade III-IV aGvHD were 39% and 18%, respectively. Patients having a lowest CsA concentration (<301 ng/mL; the cutoff value used to segregate the patients between low and high CsA concentrations) in the first week after Haplo-HCT had a significantly higher risk of grade II-IV aGvHD (P = 0.02), severe grade III-IV aGvHD (P = 0.03), cGvHD (P = 0.02), and extensive cGvHD (P = 0.04). In multivariate analysis, a higher CsA concentration (≥301 ng/mL) during the first week following Haplo-HCT was the only parameter significantly associated with a reduced risk of grade II-IV and grade III-IV aGvHD (RR = 0.21; P = 0.049 and RR < 0.001; P < 0.0001, respectively). We find no correlation between CsA concentration and relapse, non-relapse mortality, progression-free survival, GvHD-free and progression-free survival, or overall survival. CONCLUSIONS: CsA could be initiated early before Haplo-HCT with achievement of high CsA concentration to reduce the risk of aGvHD without any detrimental effect on relapse.


Assuntos
Ciclosporina/administração & dosagem , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunossupressores/administração & dosagem , Doença Aguda , Adolescente , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Ciclosporina/farmacocinética , Monitoramento de Medicamentos , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Humanos , Imunossupressores/farmacocinética , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Tempo para o Tratamento , Condicionamento Pré-Transplante , Transplante Haploidêntico , Resultado do Tratamento , Adulto Jovem
13.
Pediatr Hematol Oncol ; 36(2): 86-102, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30978121

RESUMO

This study consists of a retrospective study including 71 childhood leukemia survivors (36 females) treated with allo-HSCT 12 Gy fractionated total body irradiation (fTBI) conditioning, with a median age of 25.0 y at time of follow-up and a median delay of 14.8 y since the graft. The recovery ratio was 90%. The number of severe late-effects was specified for each patient: 21 with growth deficiency (final height <162.5 cm for 12/35 men and <152.0 cm for 9/36 women - Growth deficiency was correlated to young age at the time of the allograft); 5 with sclerodermic chronic graft vs. host disease; 9 with osteonecrosis; risk of impaired fertility for 25 women and 28 men (only 2 women had a child); 8 with diabetes; 5 with pulmonary late-effects including 1 death; 5 with chronic renal insufficiency including 1 death; 2 with cardiac late-effects; 2 with arterial high blood pressure; 11 (8 women) declared 14 subsequent cancers (7 with thyroid carcinomas, 3 with multiple squamous cell carcinomas, 2 with epidermoïdis carcinomas of the tongue or the lip, 1 with bone sarcoma, and 1 with carcinoma of the breast); 6 with chelating treatments of hemochromatosis; 14 with important educational underachievement; 11 with depression at adult age; 1 with hepatitis B virus infection; 4 with other severe late-effects, including 2 with blindness. The average number of severe late-effects was 2.3 with a positive correlation according to delay from fTBI (p < 0.0002). Two-thirds had at least 2 late-effects. These results emphasize the urgent abandonment of conditioning by TBI in children.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia/terapia , Síndromes Mielodisplásicas/terapia , Lesões por Radiação/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Irradiação Corporal Total/efeitos adversos , Adolescente , Aloenxertos , Criança , Pré-Escolar , Fracionamento da Dose de Radiação , Doenças do Sistema Endócrino/epidemiologia , Doenças do Sistema Endócrino/etiologia , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/etiologia , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Lactente , Infertilidade/epidemiologia , Infertilidade/etiologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , /etiologia , Hepatopatias/epidemiologia , Hepatopatias/etiologia , Pneumopatias/epidemiologia , Pneumopatias/etiologia , Masculino , Lesões por Radiação/epidemiologia , Indução de Remissão , Estudos Retrospectivos , Sobreviventes
14.
Ann Hematol ; 98(6): 1449-1455, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30868307

RESUMO

This study reports a retrospective multicenter experience by the Rete Ematologica Pugliese (REP) over the past 16 years, aiming to compare the patients characteristics and outcomes of 21 brentuximab vedotin (BV)-pre-treated patients to 51 patients who received reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT) without prior BV. In total, 72 patients with classical Hodgkin's lymphomas who received allogeneic SCT were retrospectively studied. Prior use of BV had no effect on either engraftment or the incidence and severity of acute graft versus host disease (GVHD). Indeed, a lower incidence of chronic GVHD was observed in the BV group, with a 43% cumulative incidence at 3 years versus 47% in the no BV group, although this was not statistically significant. Despite the low incidence of chronic GVHD, survival was not worse in the BV-treated group: 3-year progression-free survival (PFS) was 53%, 3-year overall survival (OS) was 62%, 3-year non-relapse mortality (NRM) was 24%. In the no BV group, the 3-year PFS was 33%, 3-year OS was 44%, and 3-year NRM was 14%. In chemorefractory patients at the time of transplant, we found a statistically significant difference in PFS between the BV and no BV groups (51% vs. 10%, p = 0.013).


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Imunoconjugados/uso terapêutico , Adolescente , Adulto , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Imunoconjugados/administração & dosagem , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico , Pré-Medicação , Intervalo Livre de Progressão , Estudos Retrospectivos , Terapia de Salvação , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
15.
Int J Hematol ; 109(6): 684-693, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30877606

RESUMO

In Japan, use of unrelated peripheral blood stem cell transplantation (uPBSCT) from HLA-mismatched unrelated donors has recently been approved. We compared outcomes between HLA-matched and 1-locus mismatched uPBSCT, as well as the impact of HLA disparity in uPBSCT and in unrelated bone marrow transplantation (uBMT). In total, 5862 uBMT recipients and 234 uPBSCT recipients were included. In terms of HLA allele disparity, 185 uPBSCT patients (79.1%) had no HLA mismatch, and 49 (20.9%) had 1-locus mismatch; in comparison, 3585 uBMT patients (61.2%) had no HLA mismatch, and 2277 (38.8%) had 1-locus mismatch. The impact of 1-locus mismatch as compared with match in uPBSCT was not significantly higher than in uBMT [hazard ratio (HR) = 1.02 and 1.27 for grade III-IV acute graft-versus-host disease, HR = 0.98 and 1.14 for non-relapse mortality, and HR = 0.87 and 1.06 for overall survival, respectively]. In conclusion, the impact of single-locus mismatch on short-term outcomes was comparable in uPBSCT and uBMT. Larger studies with longer follow-up are needed to assess long-term outcomes.


Assuntos
Transplante de Medula Óssea , Antígenos HLA , Transplante de Células-Tronco de Sangue Periférico , Doadores não Relacionados , Doença Aguda , Adolescente , Adulto , Idoso , Alelos , Soro Antilinfocitário , Transplante de Medula Óssea/mortalidade , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Ann Hematol ; 98(6): 1477-1483, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30919074

RESUMO

In the pathway inhibitor era, the number of allogeneic stem cell transplantation (ASCT) for chronic lymphocytic leukemia (CLL) continues to decrease and this approach should be offered only after careful risk-benefit assessment. Nevertheless, ASCT still remains only curative therapeutic modality for CLL, especially in countries with limited access to novel agents. Thirty patients with CLL at median age of 42 years at diagnosis (range 29-64) underwent ASCT between years 2002 and 2018. Thirteen patients were transplanted in complete remission (CR), ten patients achieved partial response (PR), and seven had stable disease. The median time from diagnosis to transplant was 4 years (range 0.5-12). Twenty-three patients received HLA-matched related donor stem cell grafts, and seven patients received either matched unrelated donor or HLA-mismatched grafts. Reduced intensity conditioning (RIC) and myeloablative regimen (MAC) were used in 24 and 6 patients, respectively. Mortality to day + 100 after transplant was 16% (8% for RIC only). Acute and chronic graft versus host disease (GVHD) developed in 40% and 63% of patients, respectively. Fifteen patients relapsed or progressed after transplant. Thirteen patients (43%) are alive at last follow-up and 10 (77%) remain in clinical CR. Median follow-up for survivors was 6.8 years (range 0.4-15.2). Three-year progression-free and overall survivals were 56% and 60%, respectively. These outcomes were better for patients who received RIC conditioning: 64% and 72%, respectively. CR at transplant was found to have favorable impact on post-allograft survival. RIC should be preferred over MAC. ASCT may remain a valuable option for some CLL patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Crônica de Células B/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento
17.
Breastfeed Med ; 14(3): 193-202, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30916575

RESUMO

OBJECTIVE: Human milk administration in the early peritransplant period would lower intestinal inflammation after bone marrow transplant (BMT). MATERIALS AND METHODS: Children 0-5 years undergoing BMT received either a ready-to-feed human milk preparation designed for these children (Prolacta Bioscience, Duarte, CA) or standard formula. Babies breastfeeding at the time of BMT were also enrolled on the human milk arm. Human milk was administered from day -3 until day +14 after BMT. Metagenomic shotgun sequencing and metabolomics of stool, plasma cytokines, and regenerating islet-derived 3α (REG3α) levels were measured at enrollment and day +14. Human leukocyte antigen-DR isotype (HLA-DR), CD38, and CD69 expression on T cells were evaluated at day +21. RESULTS: Forty-six children were enrolled, 32 received human milk (donor milk n = 23, breastfeeding babies n = 9), and 14 were controls who received standard feeds supervised by a BMT dietician. Twenty-four patients received at least 60% of goal human milk and were evaluable. Plasma interleukin (IL)-8 (p = 0.04), IL-10 (p = 0.02), and REG3α (p = 0.03) were decreased in the human milk cohort. Peripheral blood CD69+ CD8+ T cells were higher in controls (p = 0.01). Species abundance of Adenovirus (p = 0.00034), Escherichia coli (p = 0.0017), Cryptosporidium parvum (p = 0.0006), Dialister invisus (p = 0.01), and Pseudomonas aeruginosa (p = 0.05) from stool was higher in controls. Stool alanine, tyrosine, methionine, and the ratio of fecal alanine to choline and phosphocholine were higher in controls (p < 0.05). No difference was observed in stool propionate and butyrate levels as measures of short-chain fatty acids between the two cohorts. CONCLUSIONS: Administration of human milk resulted in decreased markers of intestinal inflammation and could be a valuable adjunct for patients after BMT.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Nutrição Enteral , Inflamação/prevenção & controle , Intestinos/patologia , Leite Humano , Animais , Bacteriemia/epidemiologia , Bacteriemia/prevenção & controle , Pré-Escolar , Citocinas/metabolismo , Feminino , Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Lactente , Intestinos/microbiologia , Masculino , Ohio , Projetos Piloto , Cicatrização
18.
Medicine (Baltimore) ; 98(8): e14474, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813150

RESUMO

BACKGROUND: Numerous reports have explored the prognostic value of pretransplant serum C-reactive protein (CRP) in patients receiving allogeneic stem cell transplant (ASCT), but the results remain conflicting. Therefore, we performed a meta-analysis to comprehensively assess the prognostic value of pretransplant serum CRP in patients receiving ASCT. METHODS: We systematically searched eligible studies in PubMed, Embase, and Web of Science from 1999 to September 2018. The pooled hazard ratios (HRs) and their corresponding 95% CIs were used to synthetically assess the prognostic value of pre-ASCT CRP in terms of overall survival (OS), non-relapse mortality (NRM), and acute graft versus host disease (aGVHD). RESULTS: A total of 14 articles with 15 studies containing 3458 patients were included in this meta-analysis. The pooled results showed that high pre-ASCT CRP level was significantly related to worse OS (HR = 1.63; 95% CI: 1.34-1.98; P < .05), to an increased risk of NRM (HR = 2.06; 95% CI: 1.62-2.62; P < .05), and aGVHD (HR = 1.35; 95% CI: 1.07-1.71; P < .05). Additionally, sensitivity and subgroup analyses demonstrated that our pooled results were stable and reliable. CONCLUSIONS: High pre-ASCT serum CRP was significantly associated with worse OS, as well as higher risk of NRM and aGVHD. CRP may be a candidate factor of updating the existing risk scoring systems or establishing a novel risk scoring systems, which has the potential of guiding patient selection for ASCT and proceeding with risk-adapted therapeutic strategies. However, more high-quality clinical studies and basic research are required to further validate our findings in view of several limitations in our meta-analysis.


Assuntos
Biomarcadores/sangue , Proteína C-Reativa/análise , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Prognóstico , Medição de Risco/métodos , Taxa de Sobrevida , Transplante Homólogo/efeitos adversos , Transplante Homólogo/mortalidade
19.
Ann Hematol ; 98(6): 1485-1493, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30915500

RESUMO

Post-transplantation cyclophosphamide (PTCy) demonstrated effectiveness to prevent GVHD after haploidentical hematopoietic cell transplantation (HCT). Reducing toxicities with a maximized efficacy is still challenging in HCT. In this retrospective study, we analyzed the safety and efficacy of transplantation from a 1-antigen HLA-mismatched unrelated donor (9/10 MMUD) in 80 patients with hematological disorders between 2010 and 2018; 22 patients received PTCy with a reduced dose of 40 mg/kg, cyclosporine A, and mycophenolate mofetil (MMF); 58 patients received anti-thymocyte globulin (ATG), cyclosporine A, and either methotrexate or MMF for GVHD prophylaxis. Cumulative incidence (CI) of acute GVHD grades II-IV in the PTCy group was significantly lower (15% vs. 50%, p = 0.006); however, CI of chronic GVHD was (not significantly) lower in the PTCy group (26% vs. 35%, p = 0.137). One-year OS was significantly longer (p = 0.008) in the PTCy group with a similar 1-year PFS (p = 0.114) in both groups. Rates of 1-year relapse and non-relapse mortality were similar. Median time to neutrophil engraftment was comparable in both GVHD prophylaxis groups (14 days vs. 16 days, respectively, p = 0.107). Our results show that a lower dose of PTCy-based prophylaxis is an effective and safe strategy to prevent acute GVHD in HCT with 9/10 MMUD compared to ATG.


Assuntos
Soro Antilinfocitário/uso terapêutico , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Adulto , Idoso , Anemia Aplástica/terapia , Doenças da Medula Óssea/terapia , Ciclofosfamida/administração & dosagem , Ciclosporina/uso terapêutico , Avaliação de Medicamentos , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Antígenos HLA/análise , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemoglobinúria Paroxística/terapia , Histocompatibilidade , Humanos , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Neoplasias/terapia , Estudos Retrospectivos , Linfócitos T/imunologia , Doadores de Tecidos
20.
Am J Respir Crit Care Med ; 200(1): 63-74, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30742492

RESUMO

Rationale: "Noninfectious" pulmonary complications are significant causes of morbidity and mortality after allogeneic hematopoietic cell transplant. Early-onset viral reactivations or infections are common after transplant. Whether the first-onset viral infection causes noninfectious pulmonary complications is unknown. Objectives: To determine whether the first-onset viral infection within 100 days after transplant predisposes to development of noninfectious pulmonary complications. Methods: We performed a retrospective review of 738 allogeneic hematopoietic cell transplant patients enrolled from 2005 to 2011. We also established a novel bone marrow transplantation mouse model to test whether herpesviral reactivation after transplant causes organ injury. Measurements and Main Results: First-onset viral infections with human herpesvirus 6 or Epstein-Barr virus within 100 days after transplant increase the risk of developing idiopathic pneumonia syndrome (adjusted hazard ratio [aHR], 5.52; 95% confidence interval [CI], 1.61-18.96; P = 0.007; and aHR, 9.21; 95% CI, 2.63-32.18; P = 0.001, respectively). First infection with human cytomegalovirus increases risk of bronchiolitis obliterans syndrome (aHR, 2.88; 95% CI, 1.50-5.55; P = 0.002) and grade II-IV acute graft-versus-host disease (aHR, 1.59; 95% CI, 1.06-2.39; P = 0.02). Murine roseolovirus, a homolog of human herpesvirus 6, can also be reactivated in the lung and other organs after bone marrow transplantation. Reactivation of murine roseolovirus induced an idiopathic pneumonia syndrome-like phenotype and aggravated acute graft-versus-host disease. Conclusions: First-onset herpesviral infection within 100 days after allogeneic hematopoietic cell transplant increases risk of pulmonary complications. Experimentally reactivating murine roseolovirus causes organ injury similar to phenotypes seen in human transplant recipients.


Assuntos
Bronquiolite Obliterante/epidemiologia , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Infecções por Herpesviridae/epidemiologia , Lesão Pulmonar/epidemiologia , Pneumonia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Transplante Homólogo , Adolescente , Adulto , Idoso , Animais , Criança , Pré-Escolar , Infecções por Citomegalovirus/epidemiologia , Modelos Animais de Doenças , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Herpes Simples/epidemiologia , Humanos , Lactente , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Infecções por Roseolovirus/epidemiologia , Ativação Viral , Adulto Jovem
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