Patients with refractory severe aplastic anemia (SAA) who lack a matched sibling or unrelated donor need new therapeutic approaches. Hematopoietic SCT (HSCT) using mismatched or haploidentical ...related donors has been used in the past, but was associated with a significant risk of GVHD and mortality. Recently, the use of post-transplant cyclophosphamide (Cy) has been shown to be an effective strategy to prevent GVHD in recipients of haploidentical HSCT, but the majority of reports have focused on patients with hematology malignancies. We describe the outcome of 16 patients who underwent haploidentical transplantation using a reduced-intensity conditioning regimen with post-transplant Cy. Stem cell sources were BM (N=13) or PBSCs (N=3). The rate of neutrophil engraftment was 94% and of platelet engraftment was 75%. Two patients had secondary graft failure and were successfully salvaged with another transplant. Three patients developed acute GVHD being grades 2-4 in two. Five patients have died and the 1-year OS was 67.1% (95% confidence interval: 36.5-86.4%). In our small series, the use of a reduced-intensity conditioning with post-transplant Cy in haploidentical BMT was associated with high rates of engraftment and low risk of GVHD in patients with relapsed/refractory SAA.
To characterize the epidemiology and prognostic factors of invasive fusariosis in hematopoietic stem cell transplant (HSCT) recipients, the records of HSCT recipients from 9 hospitals (7 in Brazil ...and 2 in the United States) were retrospectively reviewed. Sixty-one cases were identified: 54 in allogeneic HSCT recipients and 7 in autologous HSCT recipients. The incidence of fusariosis among allogeneic HSCT recipients varied between a range of 4.21-5.0 cases per 1000 in human leukocyte antigen (HLA)-matched related transplant recipients to 20.19 cases per 1000 in HLA-mismatched transplant recipients. The median time period between transplantation and diagnosis of fusariosis was 48 days. Among allogeneic HSCT recipients, a trimodal distribution was observed: a first peak before engraftment, a second peak at a median of 62 days after transplantation, and a third peak >1 year after transplantation. The actuarial survival was 13% (median, 13 days). Persistent neutropenia was the single prognostic factor for death identified by multivariate analysis.
We developed a haploidentical transplantation protocol with post-transplant cyclophosphamide (CY) for in vivo T-cell depletion (TCD) using a novel adapted-dosing schedule (25 mg/kg on days +3 and +4) ...for Fanconi anemia (FA). With median follow-up of 3 years (range, 37 days to 6.2 years), all six patients engrafted. Two patients with multiple pre-transplant comorbidities died, one from sepsis and one from sepsis with associated chronic GVHD. Four patients without preexisting comorbidities and early transplant referrals are alive with 100% donor chimerism and excellent performance status. We conclude that adjusted-dosing post-transplant CY is effective in in vivo TCD to promote full donor engraftment in patients with FA.
The use of tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), making it possible for patients to have a life expectancy similar to that of the ...healthy population. To improve treatment adherence and effectiveness, it is necessary to understand the side effects that the medications may cause. On the other hand, the importance of TKI discontinuation studies are strengthened by recognition of long term adverse events. The primary objective of this study is to assess the prevalence of renal insufficiency in a cohort of CML patients who use first and second-generation tyrosine kinase inhibitors and compare this prevalence between the two generations of the medication. The secondary objective is to identify risk factors for the development of renal alterations secondary to the use of TKIs. Methods: this is an observational, cross-sectional, and analytical clinical study, with a sample consisting of 160 CML patients at the outpatient clinic of a reference hospital in Brazil between October 2000 and January 2023. Clinical and laboratory data available since the start of hospital follow-up were analyzed from the medical records of these patients. Categorical variables were expressed as counts and percentages, and compared using chi-square tests. The Mann-Whitney test was applied for continuous variables. Logistic regression was used for identifying risk factors for renal disfunction. P-values less than 0.05 were considered statistically significant. Data were collected and tabulated in Microsoft Excel® spreadsheets and analyzed using the Statistical Package for the Social Sciences - SPSS® software (IBM® SPSS® Statistics v. 25.0, SPSS Inc, Chicago, USA). Results: The univariate analyses showed a significant relationship between the presence of renal dysfunction and the use of Imatinib (p = 0.0026), advanced age (p = 0.00001), and presence of comorbidities (p = 0.001), particularly systemic arterial hypertension (SAH) (p = 0.0001). With the multivariate analysis, independent variables for renal dysfunction found were, advanced age (p = 0.0023; OR: 2.08; CI: 1.30-3.32), having SAH (p = 0.0142; OR: 1.91; CI: 1.14 – 3.20), and the use of Imatinib (p = 0.0131; OR: 1.89; CI: 1.14 - 3.14). Conclusion: The study findings suggest that the use of Imatinib therapy in patients with chronic myeloid leukemia may be associated with a reduction in glomerular filtration rate and an increase in the occurrence of chronic kidney disease in this population in the long term, especially when combined with other risk factors such as advanced age and the presence of comorbidities, particularly SAH.
Introduction: Minimal residual disease (MRD) detected before and after hematopoietic stem cell transplantation (HSCT) is associated with poor outcomes in high-risk acute leukemia. This study ...prospectively evaluates the impact of MRD accessed by multiparameter flow cytometry (MFC) in a reference hospital in southern Brazil. Methods: Prospective analysis of 67 consecutive patients transplanted between 2019/Jun and 2022/Jun, with high-sensitive MFC analysis in the month before HSCT. Pre-transplant MRD was negative (MRD-) in 34 (50.7%) and positive (MRD+) in 33 (49.3%) patients (14 ALL and 18 AML). Posttransplant MRD evaluation showed MRD+ in five patients at d30 (5/26, 19.2%), two (2/23, 8.7%) at d60 and 5 (5/57, 8.8%) at d100. Results: There were no differences concerning pretransplant variables between positive and negative MRD pre-HSCT groups. Considering alive patients at d100: Pre-HSCT MRD negative versus posttransplant kinetic: Considering patients available at d100 (n = 57) in relation to pre-transplant MRD status, almost half (n = 30/57, 52.6%) had negative MRD both before and after transplantation. Two AML patients MRD negative became positive and subsequently relapsed, at d488 and d426. Both patients had AML with negative CD34, but this LAIP was not known prior to relapse. Pre-HSCT MRD positive versus posttransplant kinetic: In relation to the 27 patients with positive disease before transplantation who were alive at d100 (n = 27/35, 77.1%), the majority (n = 22/27, 81.5%) became MRD negative, suggesting minimal residual disease clearance in response to treatment. Four patients MRD+ relapsed within the first year after transplantation (d117, d136, d168 and d347) and two other two patients relapsed on d405 and d744. Cumulative incidence of relapse in total cohort was 11.4%, NRM was 22.4% and probabilities of EFS and OS were 64.2% and 70.4%, respectively. MRD positivity before transplantation was associated with decreased OS (88.2% versus 51.5%, p = 0.001) and EFS (82.4% versus 45.5%, p = 0.001), but relapse was not different (5.9% vs 18.2%, p = 0.036); non-relapse mortality was 8.8% vs 36.4% (p = 0.003). Extended follow-up showed a high risk of disease relapse in AML MRD+ subgroup (EFS 78.6% vs 36.8%, p < 0.001, and OS 92.9% vs 47.4%, p = 0.001), and this was associated to MRD positivity at d100. MRD analysis before transplantation had a high sensitivity (75%) in predicting survival, while MRD positivity at d100 was more specific in predicting subsequent relapse (90.5%) in this cohort. Conclusion: A highly sensitive assessment of MRD before HSCT in a real-life setting allowed the correct identification of patients with poor prognosis. Moreover, the persistence of MRD after transplantation identified patients at risk of relapse.
Introdução: O surgimento dos Inibidores de Tirosino-Quinase (ITQ), no final da década de 90, revolucionou o tratamento dos pacientes com Leucemia Mieloide Crônica (LMC), impactando diretamente na ...sobrevida desta população nas últimas duas décadas. A maioria dos pacientes tratados com ITQs obtém respostas moleculares profundas, com estudos demonstrando sobrevida similar à população geral. Todavia, alguns pacientes não atingem resposta adequada devido à falha ao tratamento, tanto pela resistência à medicação quanto pela intolerância aos efeitos colaterais. Para pacientes que falham com ITQs, o Transplante de Células-Tronco Hematopoiéticas (TCTH) continua a ser considerado uma terapia eficaz e potencialmente curativa. No entanto, há poucos dados na literatura sobre os resultados dos transplantes realizados após falha com as terapias-alvo. Objetivo: este estudo visa determinar a Sobrevida Global (SG) de pacientes com LMC submetidos ao TCTH após falha aos ITQs em um centro de referência no Brasil, além de analisar as incidências de recaída, mortalidade não relacionada a recaída e incidência cumulativa de DECH aguda (DECHa) ou DECH crônica (DECHc). Métodos: Estudo retrospectivo, observacional e analítico, realizado a partir de registros de prontuários e base de dados do Serviço de Transplante de Medula Óssea. As curvas de sobrevida foram realizadas usando o método de Kaplan Meier e o teste exato de Fisher foi usado para variáveis categóricas. EZR foi usado para análise estatística. Resultados: Foram avaliados 103 pacientes com diagnóstico de LMC, transplantados no período de janeiro de 2001 a maio de 2021, sendo excluídos os pacientes que não utilizaram ITQs previamente, totalizando 70 pacientes na análise final. A idade mediana foi de 38 anos (10‒60) e a maioria dos pacientes eram do sexo masculino (66%). 29 pacientes estavam em fase crônica antes do transplante, 38 em fase acelerada e 3 em crise blástica. 19 pacientes (27%) tiveram mutações identificadas, 5 pacientes com mutação T315I, 3 com mutação G250E e os demais com mutações diversas. 39 pacientes haviam utilizado ITQ de 2ª geração (56%). Quanto às características relacionadas ao TCTH, em 47% a fonte de células foi sangue periférico, 52% tiveram doador aparentado e 93% receberam condicionamento mieloablativo. A sobrevida mediana foi de 11 anos; sendo SG de 1 ano: 70% (57,8‒79,3), SG 5 anos: 57,7% (45,1‒68,5) e SG 10 anos: 51,4% (38,3 -63,1). A SG estimada em 5 anos não foi diferente para CP1 (60%) versus fases avançadas (45%); p = 0,6. Incidência cumulativa de mortalidade Não Relacionada à Recaída (NRM) em 100 dias: 12,9% (6,3‒21,9) e em 1 ano: 21,4 % (12,7‒31,7). Incidência cumulativa de DECHa em 100 dias: 34,3% (23,4‒45,5) e de DECHc em 1 ano: 34,3% (23,3‒45,5). Incidência cumulativa de DECHc em 2 anos: 35,7% (24,6‒47,0). Em relação às taxas de recaída em 1 ano, a incidência cumulativa de recaída foi de 27,1% (17,3‒38) e em 2 anos 34,3 (23,4‒45,5). Conclusão: O estudo teve como objetivo principal a avaliação da sobrevida, sendo encontrada uma taxa superior a 50% em 5 e 10 anos, corroborando o potencial do TCTH no cenário de falha terapêutica. Além disso, foi observada incidência de DECHa, DECHc, recaída e NRM em geral similares a estudos anteriores. Ressalta-se que a busca de doadores deve ser realizada precocemente, assim que observada a resistência a ITQ de 2ª geração, considerando que os melhores resultados são alcançados quando os pacientes ainda estão em fase crônica.
Silvopastoral systems (SPSs) are sustainable alternatives for pasture intensification. Management practices such as thinning are options to diminish competition for resources between pasture and ...trees, ensuring appropriate forage production. The objective of this study was to evaluate the productive and nutritive traits of Piatã palisadegrass (Urochloa brizantha cv. BRS Piatã) after thinning the forest component of a SPS. Forage production and nutritive value, along with microclimate variables were assessed in a SPS and in an intensive system (INT) in São Carlos-SP, Brazil, from 2016 to 2018. The INT was a full sun pasture of Piatã palisadegrass, while the SPS was established with Piatã palisadegrass shaded by eucalyptus (Eucalyptus urograndis clone GG100) spaced 15 × 2 m but thinned to 15 × 4 m before the onset of the experiment. In the SPS, measurements were made under the tree row (SPS_1), 3.75-m (SPS_2), 7.5-m (SPS_3) and 11.25-m (SPS_4) distant from the North row. Forage accumulation in the two systems were similar, whereas the pre-grazing forage mass in most of the SPS positions were smaller than that of the INT during the autumn of 2017 and summer of 2018. Crude protein (CP) content was greater in the SPS than in the INT in most positions and seasons. Forage production was favoured by the thinning of the trees mainly in the seasons close to the event, while forage CP was consistently greater in the understory pasture. Thinning of trees in SPSs can be adopted to provide forage production similar to intensive pastures with higher protein content.
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