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1.
Lancet Haematol ; 7(2): e157-e167, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32004485

RESUMO

Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic stem-cell transplantation. Because of the small number of results from well designed, large-scale, clinical studies there is considerable variability in the prevention and treatment of GVHD worldwide. In 2014, to standardise treatment approaches the European Society of Blood and Marrow Transplantation published recommendations on the management of GVHD in the setting of HLA-identical sibling or unrelated donor transplantation in adult patients with haematological malignancies. Here we update these recommendations including the results of study published after 2014. Evidence was searched in three steps: first, a widespread scan of published trials, meta-analyses, and systematic reviews; second, expert opinion was added for specific issues following several rounds of debate; and third, a refined search to target debated or rapidly updating issues. On the basis of this evidence and the 2014 recommendations, five members of the EBMT Transplant Complications Working Party created 38 statements on GVHD prophylaxis, drug management, and treatment of acute and chronic GVHD. Subsequently, they created the EBMT GVHD management recommendation expert panel by recruiting 20 experts with expertise in GVHD management. An email-based, two-round Delphi panel approach was used to manage the consensus. Modified National Comprehensive Cancer Network categories for evidence and consensus were applied to the approved statements. We reached 100% consensus for 29 recommendations and 95% consensus for nine recommendations. Key updates to these recommendations include a broader use of rabbit anti-T-cell globulin; lower steroid doses for the management of grade 2 acute GVHD with isolated skin or upper gastrointestinal tract manifestations; fluticasone, azithromycin, and montelukast should be used for bronchiolitis obliterans syndrome; and the addition of newer treatment options for resteroid-refractory acute and chronic GVHD. In addition, we discuss specific aspects of GVHD prophylaxis and management in the setting of haploidentical transplantation and in paediatric patients, but no formal recommendations on those procedures have been provided in this Review. The European Society of Blood and Marrow Transplantation proposes to use these recommendations as a basis for the routine management of GVHD during stem-cell transplantation.


Assuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco/efeitos adversos , Gerenciamento Clínico , Monitoramento de Medicamentos , Resistência a Medicamentos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressão/métodos , Imunossupressores/administração & dosagem , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Transplante de Células-Tronco/métodos , Condicionamento Pré-Transplante/métodos
2.
Zhonghua Xue Ye Xue Za Zhi ; 41(1): 23-27, 2020 Jan 14.
Artigo em Chinês | MEDLINE | ID: mdl-32023750

RESUMO

Objective: To evaluate possible effects of Gelctin-9 on acute graft versus host disease (aGVHD) development and clinical outcomes in patients before and afer allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood samples were obtained from 29 patients and 15 healthy volunteers with heparin anticoagulant tubes. Samples were analyzed using ELISA kits to measure the serum concentrations of Galectin-9. Results: Patients developing aGVHD had significantly lower level of Galectin-9 [ (7.96±1.18) µg/L] before allo-HSCT compared with those not developing aGVHD [ (12.37±0.97) µg/L, P<0.001]. And after allo-HSCT, the consentration of Galectin-9 increased markedly in patients developing aGVHD [ (17.78±1.78) µg/L] compared with those not developing aGVHD [ (9.45±0.80) µg/L, P<0.001]. Patients developing 3-4 grade aGVHD had significantly higher level of Galectin-9 [ (23.25±2.59) µg/L] compared with those developing 1-2 grade aGVHD [ (14.37±1.45) µg/L, P=0.008] and those without aGVHD [ (9.45±0.80) µg/L, P<0.001]. The patients with lower level of Galectin-9 after allo-HSCT (<13.61 µg/L) showed more favorable clinical outcomes compared with those with higher level of Galectin-9 (≥13.61 µg/L) . The 3-year overall survival rates were (100.00±6.05) % and (69.23±12.80) %, respectively (P=0.009) . The cumulative incidence of non-relapse mortality was significantly higher in high Galectin-9 group [ (23.08±11.69) %] in comparison with low Gaelctin-9 group [ (0.00±7.39) %] (P=0.023) . There was no significant difference between the two groups in terms of the cumulative incidence of relapse. The cumulative incidence of relapse at 3 years were (8.33±7.98) % and (12.50±8.27) % in high and low Galectin-9 groups, respectively (P=0.708) . Conclusions: The serum concentration of Galectin-9 at the time of engraftment after allo-HSCT may be used as a predictor for the development and severity of aGVHD. Galectin-9 might be considered as a potential new approach to regulate transplant rejection to achieve desirable survival.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Galectinas , Humanos , Incidência , Taxa de Sobrevida , Transplante Homólogo
4.
Lancet Haematol ; 7(2): e100-e111, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31958417

RESUMO

BACKGROUND: Previous trials testing prevention strategies for chronic graft versus host disease (GVHD) have measured its cumulative incidence. In this trial of anti-thymocyte globulin, we measured treatment-independence at a long-term timepoint as the primary endpoint. METHODS: This was a randomised, open-label, multicentre, phase 3 trial done at ten centres in Canada and one in Australia. Eligible patients had a haematological malignancy (leukaemia, myelodysplastic syndrome, or lymphoma), were between 16 and 70 years of age, eligible for transplantation with a Karnofsky score of at least 60, and received an unrelated donor (fully matched or one-locus mismatched at HLA-A, HLA-B, HLA-C, or DRB1 loci) graft following myeloablative or non-myeloablative-reduced intensity conditioning. Patients were randomly assigned to receive anti-thymocyte globulin 4·5 mg/kg plus standard GVHD prophylaxis (cyclosporine or tacrolimus plus methotrexate or mycophenolate) or standard GVHD prophylaxis alone. The primary endpoint, freedom from immunosuppressive therapy without resumption at 12 months, was previously reported. Here we report on the prespecified 24-month analysis. Analyses were per-protocol, excluding those patients who did not proceed to transplantation. This trial is registered as ISRCTN 29899028 and NCT01217723, status completed. FINDINGS: Between June 9, 2010, and July 8, 2013, we recruited and randomly assigned 203 eligible patients to receive anti-thymocyte globulin (n=101) or no additional treatment (n=102) along with standard GVHD prophylaxis. 7 (3%) patients did not receive a transplant and were excluded from the analysis. 38 (38%) of 99 evaluable patients in the anti-thymocyte globulin plus GVHD prophylaxis group were free from immunosuppressive therapy at 24 months compared with 18 (19%) of 97 patients in the standard GVHD prophylaxis group (adjusted odds ratio [OR] 3·49 [95% CI 1·60-7·60]; p=0·0016. At 24 months, the cumulative incidence of relapse was 16·3% (95% CI 8·9-23·7) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 17·5 (9·9-25·1) in the standard GVHD prophylaxis group (p=0·73) and non-relapse mortality was 21·2% (95% CI 13·2-29·2) versus 31·3% (21·9-40·7; p=0·15). The cumulative incidence of chronic GVHD at 24 months was 26·3% (95% CI 17·5-35·1) in the anti-thymocyte globulin group and 41·3% (31·3-51·3) in the standard GVHD prophylaxis group (p=0·032). Overall survival at 24 months was 53·3% (95% CI 42·8-62·7) in the anti-thymocyte globulin plus GVHD prophylaxis group compared with 70.6% (95% CI 60·6-78·6) in the standard GVHD prophylaxis group (adjusted hazard ratio [HR] 0·56, 95% CI [0·35-0·90]; p=0·017. Symptoms of chronic GVHD by the Lee Scale were more prevalent in the standard GVHD prophylaxis group, with scores of 13·27 (SD 10·94) in the anti-thymocyte globulin plus GVHD prophylaxis group and 20·38 (SD 14·68) in the standard GVHD prophylaxis group (p=0·040). Depressive symptoms were more prominent in the standard GVHD prophylaxis group, the mean Center for Epidemiological Studies Depression scale (CES-D) scores were 10·40 (SD 9·88) in the anti-thymocyte globulin group and 14·62 (SD 12·26) in the standard GVHD prophylaxis group (p=0·034). Serious adverse events (CTCAE grade 4 or 5) occurred in 38 (38%) patients in the anti-thymocyte globulin group and in 49 (51%) in the standard GVHD prophylaxis group, the most common being infection and GVHD. One patient died of Epstein-Barr virus hepatitis. INTERPRETATION: The results of this prespecified 24-month analysis suggest that pretreatment with anti-thymocyte globulin provides clinically meaningful benefits when added to standard GVHD prophylaxis in patients undergoing unrelated donor transplantation, including a decrease in use of immunosuppressive therapy, chronic GVHD and its symptoms, depressive symptoms, and improved overall survival. Anti-thymocyte globulin could be included in the preparative regimens of patients with haematological malignancies selected for unrelated donor transplantation. FUNDING: Canadian Institutes of Health Research and Sanofi.


Assuntos
Soro Antilinfocitário/uso terapêutico , Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Imunossupressores/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Adolescente , Adulto , Idoso , Ciclosporina/administração & dosagem , Ciclosporina/uso terapêutico , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressores/administração & dosagem , Estimativa de Kaplan-Meier , Masculino , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Linfócitos T/imunologia , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Doadores não Relacionados , Adulto Jovem
5.
Ann Hematol ; 99(1): 147-155, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31786646

RESUMO

Allogeneic hematopoietic stem cell transplantation (HSCT) could be the only curative therapy for patients with relapsed/refractory acute leukemia (RRAL). Many reports have described unmanipulated haploidentical HSCT (HID-HSCT) using high-dose antithymocyte globulin (ATG). However, the transplant outcomes of HID-HSCT using very low-dose ATG (thymoglobulin, 2-2.5 mg/kg) and methylprednisolone (mPSL, 1 mg/kg) for patients with RRAL have not been reported. We compared the outcomes of 46 patients with RRAL who underwent HID-HSCT using very low-dose ATG (thymoglobulin) and mPSL with the outcomes of 72 patients who underwent non-HID-HSCT. Patient characteristics differed regarding conditioning intensity (myeloablative; 19.6% in HID-HSCT vs. 61.1% in non-HID-HSCT, P < 0.001) and having undergone multiple HSCT (26.1% vs. 11.1%, P = 0.045). However, we found no significant differences in the 1-year overall survival (OS, 31.7% vs. 29.1%; P = 0.25), disease-free survival (DFS, 20.5% vs. 23.7%; P = 0.23), cumulative incidence of relapse (CIR, 40.0% vs. 42.8%; P = 0.92), non-relapse mortality (NRM, 39.5% vs. 33.5%; P = 0.22), or 100-day grade II-IV acute graft-versus-host disease (32.6% vs. 34.7%; P = 0.64) following HID-HSCT vs. non-HID-HSCT, respectively. Subgroup analysis stratified by disease and intensity of conditioning regimen demonstrated the same results between HID-HSCT and non-HID-HSCT. Furthermore, multivariate analysis showed that HID-HSCT was not an independent prognostic factor for OS (hazard ratio (HR) = 0.95 [95% confidence interval (CI), 0.58-1.58]), DFS (HR = 1.05 [95%CI, 0.67-1.68]), CIR (HR = 0.84 [95%CI, 0.48-1.47]), or NRM (HR = 1.28 [95%CI, 0.66-2.46]). In summary, transplant outcomes for RRAL were comparable in the HID-HSCT and non-HID-HSCT groups. HID-HSCT using very low-dose ATG and mPSL for RRAL may be a viable alternative to non-HID-HSCT.


Assuntos
Soro Antilinfocitário/administração & dosagem , Efeito Enxerto vs Leucemia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Depleção Linfocítica , Metilprednisolona/administração & dosagem , Adolescente , Adulto , Idoso , Aloenxertos , Ciclofosfamida/administração & dosagem , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Leucemia Mieloide Aguda/sangue , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras , Recidiva
7.
Lancet Haematol ; 7(1): e50-e60, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669248

RESUMO

BACKGROUND: The success of unrelated haemopoietic cell transplantation (HCT) is limited by graft-versus-host disease (GVHD), which is the main post-transplantation challenge when HLA-matched donors are unavailable. A sequence dimorphism in exon 1 of HLA-B gives rise to leader peptides containing methionine (Met; M) or threonine (Thr; T), which differentially influence natural killer and T-cell alloresponses. The main aim of the study was to evaluate the role of the leader dimorphism in GVHD after HLA-B-mismatched unrelated HCT. METHODS: We did a retrospective cohort study of 33 982 patients who received an unrelated HCT done in Australia, Europe, Japan, North America, and the UK between Jan 1, 1988, and Dec 31, 2016. Data were contributed by participants of the International Histocompatibility Working Group in Hematopoietic Cell Transplantation. All cases were included and there were no exclusion criteria. Multivariate regression models were used to assess risks associated with HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 mismatching. Among the 33 982 transplantations, the risks of GVHD associated with HLA-B M and T leaders were established in 17 100 (50·3%) HLA-matched and 1457 (4·3%) single HLA-B-mismatched transplantations using multivariate regression models. Leader frequencies were defined in 2 004 742 BeTheMatch US registry donors. FINDINGS: Between Jan 20, 2017, and March 11, 2019, we assessed 33 982 HCTs using multivariate regression models for the role of HLA mismatching on outcome. Median follow-up was 1841 days (IQR 909-2963). Mortality and GVHD increased with increasing numbers of HLA mismatches. A single HLA-B mismatch increased grade 3-4 acute GVHD (odds ratio [OR] 1·89, 95% CI 1·53-2·33; p<0·0001). Among the single HLA-B-mismatched transplantations, acute GVHD risk was higher with leader mismatching than with leader matching (OR 1·73, 1·02-2·94; p=0·042 for grade 2-4) and with an M leader shared allotype compared with a T leader shared allotype (OR 1·98, 1·39-2·81; p=0·0001 for grade 3-4). The preferred HLA-B-mismatched donor is leader-matched and shares a T leader allotype. The majority (1 836 939 [91·6%]) of the 2 004 742 US registry donors have the TT or MT genotype. INTERPRETATION: The HLA-B leader informs GVHD risk after HLA-B-mismatched unrelated HCT and differentiates high-risk HLA-B mismatches from those with lower risk. The leader of the matched allotype could be considered to be as important as the leader of the mismatched allotype for GVHD. Prospective identification of leader-matched donors is feasible for most patients in need of a HCT, and could lower GVHD and increase availability of HCT therapy. These findings are being independently validated and warrant further research in prospective trials. FUNDING: The National Institutes of Health, USA.


Assuntos
Éxons/genética , Doença Enxerto-Hospedeiro/genética , Antígenos HLA-B/genética , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Feminino , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Histocompatibilidade , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos
8.
Ann Hematol ; 99(1): 167-179, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31828376

RESUMO

The optimal rabbit anti-thymocyte globulin (rATG) graft-versus-host disease (GVHD) prophylaxis regimen in matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT) remains to be elucidated. In this prospective study, we used low-dose rATG for GVHD prophylaxis in patients or donors aged ≥ 40 years with hematological malignancies receiving MSD-PBSCT. rATG was administered to 40 patients at an intravenous dose of 5 mg/kg divided over day 5 and day 4 before graft infusion. No graft failure occurred. Median times to leukocyte engraftment and platelet engraftment were 11.0 days and 13.9 days. The cumulative incidence of grades 2-4 and grades 3-4 acute GVHD at day +100 was 30.0% and 2.6%. The 2-year cumulative incidence of extensive chronic GVHD and severe chronic GVHD was 11.4% and 14.7%. 93.5% (29/31) of patients had discontinued immunosuppressive medication within 3 years after transplantation. The 2-year cumulative incidence of transplant-related mortality (TRM) and relapse was 14.0% and 22.6%. The cumulative incidence of cytomegalovirus reactivation, Epstein-Barr virus reactivation, and fungal infection was 22.3%, 12.9%, and 12.5%. Kaplan-Meier estimates for overall survival, disease-free survival, and GVHD-free and relapse-free survival 3 years after transplantation were 68.9%, 68.9%, and 54.0%. rATG for GVHD prophylaxis is tolerable and efficacious at a 5 mg/kg total dose administered over 2 days (days -5 to -4) in patients receiving allogeneic MSD-PBSCT.


Assuntos
Soro Antilinfocitário/administração & dosagem , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco de Sangue Periférico , Irmãos , Doadores de Tecidos , Adulto , Idoso , Células Alógenas , Doença Crônica , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
9.
Eur J Ophthalmol ; 30(1): 94-103, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30585084

RESUMO

PURPOSE: To evaluate the efficacy and safety of plasma rich in growth factors eye drops for the treatment of corneal and ocular surface disorders in patients with graft versus host disease. METHODS: This retrospective and longitudinal study included graft versus host disease patients with ocular disorders. The resolution of corneal ulcers (area and density staining) was evaluated as primary outcome. Best corrected visual acuity, intraocular pressure, tear film breakup time, Schirmer test, ocular surface disease index, and visual analog score were evaluated as secondary outcomes. All variables were analyzed before and after plasma rich in growth factors treatment. The safety of plasma rich in growth factors treatment was also assessed. RESULTS: Twelve patients (23 eyes) with ocular graft versus host disease were evaluated. Statistically significant improvement in the area (75.7%) and density (73.3%) of the corneal staining, in best corrected visual acuity (74.7%), in ocular surface disease index scale (75.4%), visual analog score frequency (81.4%) and visual analog score severity (81.9%), and an increase of 3.8 s in tear film breakup time and 6 mm in Schirmer test was observed after plasma rich in growth factors treatment (p < 0.001). Some potential modifiers of the therapeutic effect were identified. All patients achieved corneal stability without perforation risk. No adverse events associated with the plasma rich in growth factors were observed. CONCLUSION: Immunosafe plasma rich in growth factors eye drops for the treatment of patients with ocular graft versus host disease could be safe and effective, showing a high rate of corneal ulcer resolution and dry eye disease control. Plasma rich in growth factors eye drops may help to maintain corneal stability and prevent it against higher ocular complications.


Assuntos
Síndromes do Olho Seco/terapia , Doença Enxerto-Hospedeiro/complicações , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Plasma Rico em Plaquetas , Adulto , Idoso , Síndromes do Olho Seco/etiologia , Síndromes do Olho Seco/metabolismo , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/uso terapêutico , Estudos Retrospectivos , Lágrimas/metabolismo
10.
Ann Hematol ; 99(2): 343-349, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31879790

RESUMO

Ruxolitinib is a promising option for treating steroid-refractory acute graft-versus-host disease (SR-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we describe ruxolitinib treatment for SR-aGVHD in HSCT patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) to evaluate its effectiveness. We evaluated the outcomes of 12 patients who received ruxolitinib for SR-aGVHD between January 2017 and March 2019. Of the 12 patients who received ruxolitinib, 7 patients achieved a complete response (CR), 3 had a partial response (PR), and 2 experienced treatment failure (TF). OS and CR rates were 83.3% and 58.3%, respectively. Moreover, CR was achieved by the six patients who had aGVHD with skin involvement. The mean time of steroid application in the patients who received ruxolitinib was 28.1 days. Median survival after HSCT was 64.6 weeks. The adverse effects of ruxolitinib included grades 3 to 4 neutropenia (n = 7) and grades 3 to 4 thrombocytopenia (n = 6). Cytomegalovirus reactivation was observed in three patients. A high rate of CR and short steroid application time of ruxolitinib as a salvage treatment were observed in HSCT patients with EBV-HLH. Consequently, from this study, it was determined that ruxolitinib is an optimal choice to treat SR-aGVHD in patients with EBV-HLH.


Assuntos
Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4 , Linfo-Histiocitose Hemofagocítica , Pirazóis/administração & dosagem , Dermatopatias , Doença Aguda , Adolescente , Adulto , Aloenxertos , Criança , Intervalo Livre de Doença , Resistência a Medicamentos/efeitos dos fármacos , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/terapia , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Estudos Retrospectivos , Dermatopatias/tratamento farmacológico , Dermatopatias/mortalidade , Esteroides/administração & dosagem , Taxa de Sobrevida
11.
J Oncol Pharm Pract ; 26(1): 5-12, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30854922

RESUMO

BACKGROUND: Posaconazole reduces the risk of invasive Aspergillus in transplant patients, but significantly inhibits tacrolimus metabolism. One study demonstrated that a three-fold dose reduction of tacrolimus was required to obtain therapeutic concentrations when used with posaconazole. However, with empiric dose reduction, there is a risk of subtherapeutic tacrolimus levels and subsequent graft failure or graft-versus-host disease. Overall, the existing data on the impact of posaconazole on tacrolimus pharmacokinetics is limited. OBJECTIVE: The purpose of this study is to determine whether tacrolimus doses should be decreased upon initiation of posaconazole in patients receiving an allogeneic stem cell transplant. METHODS: This is a retrospective chart review at an academic medical center. All allogeneic stem cell transplant adults who received concomitant posaconazole and tacrolimus from February 2016 through December 2017 were included. RESULTS: Seventy-nine patients identified using an internal electronic database were analyzed. The median time to therapeutic tacrolimus concentration was significantly longer in patients who did not receive an empiric dose reduction (0% DR, 10d; 1-30% DR, 4d; 31-65% DR, 5d; >65% DR, 4d; p = 0.0395). The rate of supratherapeutic levels was highest amongst patients who did not receive an empiric DR, and was noted to be significant compared to the group that had 31-65% DR (p < 0.001). CONCLUSION: This study validates our current practice of instituting an empiric 50% dose reduction of oral tacrolimus to 0.03 mg/kg/day when used concomitantly with posaconazole to achieve therapeutic levels in allogeneic stem cell transplant patients.


Assuntos
Antifúngicos/farmacocinética , Transplante de Células-Tronco Hematopoéticas/tendências , Imunossupressores/farmacocinética , Transplante de Células-Tronco/tendências , Tacrolimo/farmacocinética , Triazóis/farmacocinética , Adulto , Antifúngicos/administração & dosagem , Esquema de Medicação , Interações de Medicamentos/fisiologia , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tacrolimo/administração & dosagem , Triazóis/administração & dosagem
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1973-1978, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839069

RESUMO

OBJECTIVE: To explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed or refractory peripheral T-cell lymphoma(PTCL). METHODS: The clinical data of 6 patients with relapsed or refractory PTCL undergoing allo-HSCT from Sep. 2014 to Sep. 2018 in the department of hematology, aerospace center hospital were retrospectively analyzed. Complications and disease-free survival after HSCT were observed. RESULTS: All the patients could well tolerate the conditioning regimen and acquired hematopoietic recon-struction. Following up till December 2018, with a median time of 11.5 months (1-51); acute GVHD developed in 2 cases and chronic GVHD developed in 5 cases, Among 6 cases one case died of viral pheumonia and the other 5 patients remained disease-free survival. The longest disease-free survival time has reached 51 months. CONCLUSION: allo-HSCT is a safe and effective method for relapsed or refractory peripheral T-cell lymphoma, which can be chosen as salvage treatment method for patients with primary resistance. Optimization of the conditioning regimen may result in better efficacy of allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/terapia , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Homólogo
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1979-1985, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839070

RESUMO

OBJECTIVE: To investigate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of malignant hematopathy and its influencing factors. METHODS: The clinical data of 300 cases received hematopoietic stem cell transplantation due to malignant hematological diseases in Zhu Jiang Hospital of Southern Medical University from January 2010 to June 2018 were analyzed retrospectively, and the factors affecting hematopoietic reconstruction, disease-free survival (DFS) and overall survival (OS) were compared between haploidentical HSCT and HLA matched HSCT. RESULTS: The hematopoietic reconstitution rate, incidence of GVHD, posttransplant recurrence rate and disease-free survival (DFS) were not statistically different between HLA-metched and haploidentical colorts. However, compared with HLA-matched HSCT group the time of platelet implantation was prolonged, the recurrence-related mortality was higher, and the overall survival (OS) rate was lower in the haploidentical HSCT group. Univariate analyses showed that non-remission before transplantation, and grade Ⅲ, Ⅳ aGVHD were the risk factors for OS in both groups (P<0.05). The age than 40 years old at the time of transplantation and unrelated donors were risk factors for OS in haploidentical HSCT group (P<0.05). Multivariate analysis showed that non-remission before transplantation and grade Ⅲ, Ⅳ aGVHD were independent prognostic indictor for OS with relative risk (RR) of 4.4 (95% CI,1.5-13.4), 9.3 (95% CI,2.3-37.0), 11.0 (95% CI,3.2-37.3) (P<0.05) in HLA-matched HSCT group. Unrelated donor, high-risk group, and gradeⅣaGVHD were independent prognostic indictors for OS with relative risk (RR) of 7.4 (95% CI,2.3-23.1), 2.4 (95% CI,1.3-4.5), 4.1(95% CI,1.6-10.5) (P<0.05) in haploidentical HSCT group. CONCLUSION: The comprehensive curative effect of HLA-matched HSCT is better than the haploidentical HSCT in hematological malignancies. In haploidentical HSCT the selecting related donor is better than unrelated donors, which required more platelet transfusion support.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Adulto , Neoplasias Hematológicas/terapia , Humanos , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 2030-2034, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839079

RESUMO

Abstract  With the development of transfusion medicine and the mastery of blood transfusion diagnosis and treatment techniques, the application of irradiated blood products in our country is gradually increasing. In recent years, the proportion of blood transfused by γ-rays has been increasing. In some foreign countries, the application rate of blood irradiated by radiotherapy is as high as 95%. At present, it is still in the promotion stage in China. This article summarizes the commonly used methods of blood irradiation, including the choice of irradiation source, the core dose and common irradiation targets, compares the difference of different irradiation methods, and generalizes the common application of blood irradiation. It is proposed that in addition to TA-GVHD application, blood irradiation may have a broad prospects for cancer therapy and microbial killing.


Assuntos
Doença Enxerto-Hospedeiro , Transfusão de Sangue , China , Raios gama , Humanos
15.
Zhonghua Xue Ye Xue Za Zhi ; 40(11): 948-952, 2019 Nov 14.
Artigo em Chinês | MEDLINE | ID: mdl-31856446

RESUMO

Objective: Chronic graft-versus-host disease (cGVHD) is a major long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . It is important to study the changes of serum biomarkers expression in patients for early diagnosis and treatment. Methods: The expression levels of five serum protein markers (IL-1b, IL-16, CXCL9, CCL19, CCL17) in patients with or without cGVHD after allo-HSCT were detected by liquid suspension microarray. Results: Compared with the control group without cGVHD, the expression levels of CXCL9 and CCL17 in serum of patients with cGVHD were significantly increased (P<0.05) . CCL17 was correlated with the severity of cGVHD (P<0.001) . CXCL9 was significantly increased in the serum of patients with skin lesion (P<0.01) , and CCL17 was significantly expressed in cGVHD patients with liver as the target organ (P<0.01) . Conclusion: The combination of CXCL9 and CCL17 can be used as serum biomarkers of cGVHD, which has certain reference value in assisting the diagnosis and evaluation of cGVHD severity.


Assuntos
Doença Enxerto-Hospedeiro , Biomarcadores , Doença Crônica , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante Homólogo
16.
Zhonghua Yi Xue Za Zhi ; 99(48): 3786-3791, 2019 Dec 24.
Artigo em Chinês | MEDLINE | ID: mdl-31874515

RESUMO

Objective: To evaluate the clinical outcomes in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) who had undergone allogeneic hematological stem cell transplantation (allo-HSCT). Methods: From June 2007 to June 2017, the clinical data of PTCL patients who underwent HSCT from eight hospitals were assessed retrospectively. Results: There were 23 patients diagnosed as relapsed or refractory PTCL with chemoresistance who underwent allo-HSCT. Among these patients, 18 were identified as progressive disease (PD) status and 5 patients as stable disease (SD) status before allo-HSCT. Seventeen patients received allo-HSCT from matched sibling donor (MSD),2 patients from matched unrelated donor and 4 patients from related haplo-identical donor (HD). After a median follow-up of 29 months, 21 patients survived longer than 28 days after allo-HSCT. Hematopoietic reconstitution was achieved in 20 of the 21 patients. The median time of myeloid and platelet engraftment were+13 (9-22) d and+16(10-38) d, respectively. The 100-d treatment-related mortality rate was 13.1%. Acute GVHD occurred in 11(47.8%) patients at a median time of 22(6-82) d after transplantation. Grade Ⅱ~Ⅳ aGVHD occurred in 6 patients. Chronic GVHD occurred in 10 patients at a median of 7.9 (3.5-27) months. After a median follow-up of 29 months, 13 patients died after HSCT. Four of them died of complications associated with allo-HSCT, and other 9 patients died of the primary lymphoma. The 3-years cumulative overall survival (OS) and progress-free survival (PFS) were 43.03% (95%CI: 29.79-69.16) and 39.13% (95%CI: 23.50-65.14), respectively. No significant difference was found in the 3-year PFS between patients with PD status and SD status before allo-HSCT (P=0.133). Conclusion: Allo-HSCT can be a promising treatment for relapsed or refractory PTCL with chemoresistance.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico , Resistencia a Medicamentos Antineoplásicos , Humanos , Linfoma de Células T Periférico/tratamento farmacológico , Recidiva Local de Neoplasia , Estudos Retrospectivos
18.
Science ; 366(6469): 1077-1078, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31780546
19.
Zhonghua Xue Ye Xue Za Zhi ; 40(10): 827-830, 2019 Oct 14.
Artigo em Chinês | MEDLINE | ID: mdl-31775481

RESUMO

Objective: To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) containing cladribine sequential busulfan regimen for refractory/relapsed acute myeloid leukemia (AML) . Methods: The clinical data of 12 refractory/relapsed AML patients received allo-HSCT with cladribine sequential busulfan regimen. Results: ① Of the 12 patients, 9 were males and 3 females, with a median age of 36 (27-50) years. The donors were identical sibling (3) , matched unrelated (1) and haploidentical family member (9) respectively. Nine patients reached partial remission and other remained no remission after chemotherapy before allo-HSCT. The median previous chemotherapy courses before allo-HSCT were 6 (2-13) . ② Conditioning regimen: Smostine 250 mg·m(-2)·d(-1), d-7; Cladribine 5 mg·m(-2)·d(-1), d-6 to d-2; Cytarabine Arabinoside 2 g·m(-2)·d(-1), d-6 to d-2; Busulfan 3.2 mg·m(-2)·d(-1), d-6 to d-3; Rabbit anti-human thymocyte immunoglobulin (ATG) 1.5 mg·m(-2)·d(-1) (unrelated donor transplantation) or 2.0-2.5 mg·m(-2)·d(-1) (haplo-HSCT) , d-4 to d-1. ③ Of the 12 patients, 11 patients attained complete haploidentical engraftment, one case occurred primary graft failure. The median durations for neutrophils and platelet implantations were 15 (15-21) and 19 (17-30) days respectively. ④After conditioning, no hepatic veno-occlusive diseases were observed, hemorrhagic cystitis occurred in 2 patients, 8 patients had fever, 3 cases experienced acute GVHD grade II, localized chronic GVHD occurred in 8 patients. ⑤The median follow-up was 8 (4-12) months. Leukemia relapse occurred in 2 patients at time of 6, 12 months after allo-HSCT. The estimated 1-year OS and DFS were (71.1±1.8) % and (62.2±1.8) %, respectively. Conclusions: allo-HSCT with cladribine sequential busulfan regimen was a feasible choice with favorable outcome for refractory/relapsed AML.


Assuntos
Cladribina/uso terapêutico , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Bussulfano , Feminino , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Condicionamento Pré-Transplante
20.
Zhonghua Xue Ye Xue Za Zhi ; 40(10): 853-855, 2019 Oct 14.
Artigo em Chinês | MEDLINE | ID: mdl-31775486

RESUMO

Objective: To explore the availability and safety of fecal microbiota transplantation for patients with refractory diarrhea after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Four acute leukemia patients suffered from refractory diarrhea after allo-HSCT. One of them was refractory intestinal infection, the others were intestinal graft versus host disease. One or two doses of fecal microbiota, 3.4-6.0 U for one dose, were infused via nasal-jejunal tube. The curative effect and side effects were reviewed. Results: Three cases achieved complete remission while 1 was stable disease. The side effects included fever, abdominal pain and diarrhea, which all were Ⅰ grade. Conclusion: Fecal microbiota transplantation was effective and safe for refractory diarrhea after allo-HSCT.


Assuntos
Diarreia/terapia , Transplante de Microbiota Fecal , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Diarreia/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos
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