The best antithymocyte globulin preparation for first-line immune suppression in patients with severe aplastic anemia is still not clear. The aim of this study was to compare hematological response and overall survival in patients submitted to horse or rabbit antithymocyte globulin as first-line treatment for severe aplastic anemia. We retrospectively compared 71 consecutive patients with severe aplastic anemia, classified according to the antithymocyte globulin preparation. Analyses included variables related to patients and to immune suppression. Forty two patients (59.1%) received horse and 29 (40.9%) rabbit antithymocyte globulin. Response rates were higher at 6 months in patients submitted to horse in comparison to rabbit antithymocyte globulin (59.5% versus 34.5% respectively, p = 0.05). Median time to response was similar between the two groups (99 versus 88.5 days, respectively, for horse and rabbit antithymocyte globulin; p = 0.98). Overall survival at 2 years was significantly higher in patients submitted to horse in comparison to rabbit antithymocyte globulin (78.4% versus 55.4%, p = 0.03). Post-treatment response was strongly associated with survival at 2 years (97% in responders versus 41.2% in non-responders, p < 0.001). Use of rabbit antithymocyte globulin was an independent predictor of death (odds ratio 2.5; 95% confidence interval 1.03-6.04; p = 0.04). Rabbit antithymocyte globulin was associated with a significant and prolonged lymphopenia in comparison with horse antithymocyte globulin. Our data suggest the superiority of horse over rabbit antithymocyte globulin as first-line treatment for severe aplastic anemia, both regarding hematological response and survival.
Early lymphocyte recovery (ELR) after autologous peripheral hematopoietic stem cell transplantation (ASCT) is an independent predictor for survival in patients with hematological and non-hematological cancers. Sixty-five ASCT for hematological cancers were retrospectively analyzed to identify the factors associated with ELR and to assess the impact of different mobilization regimens on the pre-collection absolute lymphocyte count (ALC). The CD81 lymphocyte dose in the autograft and the pre-mobilization ALC were independently associated with ELR (P < 0.001 and P 5 0.008, respectively). CD81 lymphocyte doses higher than 0.1 3 10 9 /kg were strongly associated with ELR [P < 0.001, odds ratio 25.22, 95% confidence interval (CI) 4.98-127.69] and this cutoff may be used to predict ELR (P 5 0.001, area under the curve 0.75, 95% CI 0.62-0.88). Mobilization with granulocyte colony-stimulating factor (G-CSF) alone, the pre-collection ALC and the number of apheresis sessions were independently associated with the CD81 lymphocyte dose (P 5 0.04, P 5 0.001, and P < 0.001, respectively). The number of aphereses was the variable with the strongest correlation to the CD81 lymphocyte dose (r s 5 0.68, P < 0.001). Median pre-mobilization ALC was higher than pre-collection ALC in the subgroup of patients without ELR mobilized with chemotherapy followed by G-CSF (1090 vs. 758 lymphocytes/lL; P < 0.001). This reduction was not significant in the subgroup with ELR mobilized with chemotherapy plus G-CSF (1920 vs. 1539/lL, respectively; P 5 0.23). These results suggest that the CD81 lymphocyte dose in the autograft is critical for ELR after ASCT and also demonstrates that mobilization with chemotherapy followed by G-CSF significantly decreases the pre-collection ALC, especially in patients with low pre-mobilization ALC. Am. J. Hematol. 84:21-28, 2009. V
IntroduçãoEm 03 de setembro de 2007 reuniram-se especialistas, usuários, representantes das Forças Armadas e do esporte para traçar diretrizes em relação às condutas a serem adotadas com portadores de traço falciforme e atividades esportivas e militares. A pertinência do tema consiste na alta prevalência do traço falciforme no Brasil (4% da população), da obrigatoriedade do serviço militar no país, e do interesse crescente da população na prática esportiva, quer amadora ou profissional. Além disso, com a inclusão do teste para hemoglobinopatias na triagem neonatal, em nível nacional e, por conseguinte, maior número de portadores identificados, torna- Consenso Brasileiro sobre atividades esportivas e militares e herança falciforme no Brasil -A reunião de consenso brasileiro sobre atividades esportivas e militares e herança falciforme foi realizada no dia 3 de setembro de 2007, no Rio de Janeiro, e reuniu especialistas, representantes das Forças Armadas e de associações de pacientes de doença falciforme. Questões relativas à prática de esporte amador e profissional e do serviço militar foram amplamente discutidas, tendo como base a literatura científica e a experiência de cada um dos participantes. Ao final, algumas recomendações foram assim definidas: 1. O indivíduo portador de traço pode fazer qualquer modalidade de esporte, já que não há dados epidemiológicos consistentes que impeçam a prática de qualquer esporte; 2. Não é necessário fazer triagem para hemoglobinopatias em indivíduos que queiram praticar esportes, quer de natureza amadora ou profissional; 3. Para servir às Forças Armadas não é necessário fazer teste de triagem para hemoglobinopatias, o que equivale dizer que os portadores de traço falciforme podem servir às Forças Armadas; 4. É fundamental que se esclareça entre os mais diferentes segmentos da sociedade que a heterozigose para a hemoglobina S não confere ao seu portador maior risco que a população geral no que tange às atividades físicas, desde que atendidas as condições básicas de hidratação e de descanso. Rev. Bras. Hematol. Hemoter. 2008;30(6):488-495. Palavras-chave: Traço falcêmico; esporte; atividades militares.
Background: Early absolute lymphocyte count (ALC) recovery after autologous peripheral hematopoietic stem cell transplantation (ASCT) has been reported as an independent prognostic factor for overall survival and progression-free survival for patients with hematological and non-hematological cancers. Early immune reconstitution appears to have a protective effect against residual disease after ASCT. End points: Assessment of factors impacting on early ALC recovery after ASCT. Methods: Retrospective analysis of the ASCT procedures done between 2000 and 2007 in Hemorio. Early lymphocyte recovery (ELR) was defined as an ALC ≥500/μL at day 12 after ASCT. Results: A total of 53 of 66 consecutive ASCT (80,3%) were eligible for this study. Of the 53 ASCT, 9 were for lymphoma, 22 for multiple myeloma and 22 for acute myelogenous leukemia. Median age of the group was 34 years (range: 13–65). All patients except one were mobilized with chemotherapy plus granulocyte colony-stimulating factor (G-CSF). ELR was observed in 41% of the patients. Univariate analysis identified an association between the following factors and ELR: median pre-mobilization ALC (1920 vs 1060 lymphocytes/μL; p=0.003), pre-collection ALC (1637 vs 747 lymphocytes/μL; p<0.001), dose of leukocytes infused (1.21 x 109 vs 0.65 x 109 leukocytes/kg; p=0.002), dose of lymphocytes infused (0.26 x 109 vs 0.10 x 109 lymphocytes/kg; p<0.001), dose of CD4+ lymphocytes infused (0.075 x 109 vs 0.034 x 109 CD4+ lymphocytes/kg; p<0.001) and dose of CD8+ lymphocytes infused (0.11 x 109 vs 0.03 x 109 CD8+ lymphocytes/kg; p<0.001) were all higher in the ELR group. Patient diagnosis, number of previous cycles of chemotherapy and number of CD34+ cells collected were not correlated with ELR. Forward stepwise regression identified the pre-mobilization ALC and the number of lymphocytes in the autograft as factors related to ELR (p=0.013 and p<0.001; respectively). Multivariate analysis demonstrated that the lymphocyte dose in the graft can be predicted by the pre-collection ALC and the number of aphereses carried out (p<0.001 for both). Median pre-mobilization ALC was higher than pre-collection ALC (1335 vs 975 lymphocytes/μL respectively; p=0.013). This difference was most significant in the group of patients without ELR (1060 vs 747 lymphocytes/μL respectively; p=0.004). Among patients with ELR, the difference was not significant (1920 vs 1637 lymphocytes/μL respectively; p=0.53). Conclusions: These results indicate that ELR after ASCT depends on the pre-mobilization ALC and the lymphocyte dose in the autograft. The number of aphereses performed for stem cell collection and the pre-collection ALC predict the number of lymphocytes collected. Stem cell mobilization with chemotherapy and G-CSF significantly reduces the ALC at the time of collection, specially in patients with lower ALC at the time of the mobilization. Strategies to improve immunologic recovery may have an impact on the results of ASCT. Figure Figure
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