Background: Thrombotic thrombocytopenic purpura (TTP) is a rare and severe disease, characterized by thrombocytopenia, microangiopathic anaemia, fever, renal failure, and neurological manifestation ...caused by deposition of von Willebrand factor - platelet rich hyaline thrombi in the arterioles and capillaries. Plasma exchange has decreased the mortality in TTP from almost 100% to 10–30%. However, relapses occur in more than one-third of patients, a subset of whom develop multiple relapses or chronic disease requiring numerous sessions of plasma exchange. This treatment is costly and associated with many adverse reactions. Case
Report: We describe a female patient - diagnosed with TTP in 1996 - who did not achieve a sustained remission with plasma exchange, steroids and vincristine, but who remained in remission after a splenectomy performed in 1997. The patient underwent relapse in 2003 and restarted plasma exchange, with progressive improvement of cytopenias. Plasma exchange was reduced in frequency from daily sessions to every other day. There was a lowering of platelet levels and an increase in LDH levels - steroids and vincristine were re-initiated, but without response. The patient was treated with four, weekly doses (375 mg/m2) of rituximab. Plasma exchange was only required during the first 2 weeks of rituximab treatment, and was discontinued after the second dose of rituximab. The patient remained in complete remission for 9 months, but was then admitted to hospital with femoral thrombosis, and normal LDH and platelet levels. After 40 days of thrombosis therapy, the patient had a further relapse and refused plasma exchange. Treatment with rituximab was restarted as previously, and the patient achieved a complete remission within 2 weeks - now sustained for 11 months.
Conclusion: In comparing this patient with eight previous cases not treated with rituximab, we conclude that rituximab is a very effective treatment for TTP, which is not associated with clinically significant toxicity. Randomized clinical trials are required to confirm these findings.
Glivec was the first tyrosine kinase inhibitor (TKI) approved for chronic myeloid leukemia (CML) treatment and its efficacy has been demonstrated in a large number of trials. Generic formulations ...have been used recently as a more cost effective treatment, but there are few studies that have prospectively evaluated the efficacy and safety of these drugs.Aims: The present study aimed to evaluate the efficacy and safety of generic imatinib in CP-CML in first line therapy. Methods: This is a multicenter, observational, cohort-type study. The prospective cohort consisted of patients who initiated treatment with generic imatinib between January 2015 and September 2017; whereas the retrospective cohort was treated with Glivec between January 2010 and December 2011. All patients started imatinib in CP, less than six months from diagnosis. Patients were managed according to European Leukemia Net (ELN) 2009 and 2013 recommendations. The definition of the responses followed the ELN 2013 criteria. Adverse events were assessed based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.3, 2010. Event-free survival (EFS) was measured from starting date of treatment until loss of complete hematologic response, loss of major cytogenetic response, progression to accelerated (AP) or blast crisis (BC) or death from any cause at any time during initial therapy or discontinuation of imatinib by any cause. Patients that switched from Glivec to generic where censored. Overall survival (OS) was measured from starting date of imatinib until to the date of death from any cause while on therapy or last seen. Progression-free survival (PFS) was measured from starting date of imatinib to transformation to AP or BC or deaths while on therapy. Survival curves were calculated by the Kaplan-Meier method and compared with the log-rank test. Cox regression was used with Backward Wald Method. SPSS version 21.0 was used applying the chi-square and t-test, when adequate. All analysis considered p-value <0.05 as significant.
Results:A total of 445 patients were analyzed (Glivec=285; Generic=160). The median age was 54 years (18-87) in Glivec and 50 (18-89) in the Generic group (P=0.027). Sokal score stratification in Glivec and generic groups, was respectively: low risk 14.4%/25.7%; intermediate risk 42.3%/38.2% and high risk 43.3%/36.1% (P=0.02). B3a2 frequency was 51.5% vs. 37.7% in Glivec and Generic group, respectively, and b2a2 41.4% vs. 53.8% (P=0.017). There was no significant difference in gender, Hasford, EUTOS scores and ECOG. The median follow-up was 25 months (0-71) and 11 months (0-31) for Glivec and Generic groups, respectively (P<0.0001). The median time between diagnosis and imatinib starting was 18 days (0-119) in Glivec and 27 days (0-168) in the Generic group (P= 0.015). The rate of treatment failure at 3 months according to the ELN 2013 criteria was 6.6% and 14.7% in Glivec vs. Generic (P=0.04); whereas at 6 months there were no significant differences (12.3% vs. 18.9%; P=0.09). There was no significant difference in grade 3 and 4 hematological and non-hematological toxicity during the follow-up. There were 5 and 3 cases of progression in the Glivec and Generic group, respectively. In the Cox regression multivariate analysis, the independent factors for EFS were age at diagnosis (HR=1.03; CI95% 1.00-1.07; P=0.039) and toxicity grade 3-4 (HR 3.37; CI95% 1.08-10.4; P=0.036). The initial therapy was discontinued for the following reasons, in Glivec and generic group respectively: resistance (19.7% vs. 47.5%), intolerance (15.3% vs. 23.7%), non-adherence (4.4% vs. 3.4%), death (2.0% vs. 6.8%), clinical trial (0.5% vs. 10.2%), progression (2.0% vs. 5.0%), pregnancy (0 vs. 3.4%), switch from Glivec to generic (56.1%). OS, PFS and EFS at 24 months were higher in Glivec group in comparison to Generic (99% vs. 96%, P=0.016), (98% vs. 95%, P= 0.026) and (73% vs. 58%; P<0.0001 respectively.
Conclusion: The group treated with generic imatinib presented higher rate of failure at 3 months and lower OS, PFS and EFS at 24 months. Differences between the groups included a longer time to initiate treatment in the Generic group, a higher proportion of patients with b2a2 transcripts, which were related to an inferior rate of molecular responses and survival in other studies. There was no difference in the safety profile. The long-term impact in prognosis will be evaluated after a longer follow-up.
Pagnano:Shire: Other: Lecture; Abbvie: Consultancy; EMS: Other: Financial support for participation in congress; Novartis: Consultancy. Magalhaes:Novartis: Consultancy, Other: Lecture. Clementino:EMS: Other: Financial support for congress. Gaidano:AbbVie: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Morphosys: Honoraria; Amgen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Centrone:EMS: Other: Financial support for congress, Speakers Bureau; Bristol Meiers-Squibb: Other: Financial support for congress, Speakers Bureau; Novartis: Other: Financial support for congress, Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Other: Financial support for congress, Speakers Bureau. Fogliatto:Novartis: Consultancy; Roche: Consultancy, Speakers Bureau; Janssen: Honoraria, Research Funding. Giai:Pfizer: Consultancy; Novartis: Consultancy. Bortolheiro:Abbvie: Consultancy, Speakers Bureau; Sanoffi: Speakers Bureau; Novartis: Consultancy, Speakers Bureau.
Background: The prognostic significance of BCR-ABL1 transcripts in chronic myeloid leukemia (CML) is still controversial. Methods: All consecutive CML patients in chronic phase treated with Glivec ...between January 2010 and December 2011 and generic imatinib between January 2015 and February 2017 from 8 Brazilian centers were analyzed. BCR-ABL1 transcripts were evaluated by multiplex qualitative RT-PCR. Only patients with BCR-ABL transcripts e13a2 and/or e14a2 were included in this analysis. All patients started imatinib less than six months from diagnosis. Study data were collected and managed using REDCap electronic data capture tools. Demographic data were collected at diagnosis: age, gender, blood cell counts, Sokal, Hasford and EUTOS score, cytogenetics and BCR-ABL transcript type. The definition of the responses followed the European Leukemia Net 2013 criteria. Event-free survival (EFS) was measured from starting of treatment until loss of complete hematologic remission, loss of complete cytogenetic response (CCyR), loss of major (MMR), progression to accelerated (AP) or blast phase (BC), or death from any cause at any time after initial therapy. Overall survival (OS) was measured from starting of imatinib until last follow-up or date of death from any cause at any time. Progression-free survival (PFS) was measured from date of imatinib starting to transformation to AP or BC or deaths while on therapy. SPSS 21.0 software (IBM Corp., Armonk, NY, USA) was used for chi-square, t-test, ANOVA, when adequate, considering p-value <0.05 as significant.
Results
191 CML-CP patients treated with imatinib (121 Glivec and 70 generic imatinib) were analyzed. Patient's characteristics are described in Table 1. The median age of patients was 46 (18-89) years. Sokal score: 52.1% low; 33.8% intermediate and 14.1% high risk. BCR-ABL transcripts: 109 (57%) presented e14a2 transcripts, 74 (38.8%) e13a2 and 8 (4.2%) both transcripts. There was no difference between the groups concerning age, gender, Hasford, EUTOS scores, whereas white blood cell counts at diagnosis was higher in patients with e13a2 transcripts (P=0.009). Higher rates of CCyR at 6 months were observed in e14a2 and both transcripts group, compared to e13a2 (58.4%, 60% and 30%, respectively - P=0.003); e14a2 group had higher rates of BCR-ABL transcripts <10% measured by real-time quantitative polymerase chain reaction (RQ-PCR) at 3 months (82.9%, 85.7% and 59.3%; P=0.007) and BCR-ABL <1% at 6 months (78.4% e14a2; 61.7% e13a2 and 43% both transcripts; P=0.039). The groups presented similar OS (89 %, 87% and 83%, P=0.49) and PFS (88%, 84% and 71%, P=0.08). EFS was inferior in the e13a2 group (45% vs. 65% e14a2 vs. 54% both transcripts; P=0.02).
Conclusion: Patients with BCR-ABL transcripts e14a2 presented higher rates of CCyR at 6 months and higher rates of optimal molecular response at 3 and 6 months when compared to e13a2 transcripts, but there was no difference in overall and progression-free survival by 5 years.
Pagnano:Bristol-Meirs Squibb: Consultancy, Speakers Bureau; Roche: Speakers Bureau; Amgen: Consultancy; Novartis: Consultancy.
We report an increased incidence of high relapse risk features in 157 APL Brazilian patients. Out of 134 patients treated with ATRA and anthracyclines, only 91 (67.9%) achieved remission because 43 ...(32%) died during induction. The death rate during consolidation was 10.5%. Bleeding complications were the most frequent cause of failure (21.6%).
A classificação inicial das síndromes mielodisplásicas (SMD) foi realizada em 1976, pelo grupo FAB, e era baseada em parâmetros morfológicos observados no sangue periférico e na medula óssea. A ...classificação FAB foi revisada em 1982 e utilizada nos últimos 25 anos como guia para melhor compreensão desse heterogêneo grupo de doenças. Em 2001, a OMS publicou uma nova classificação, com modificações significativas nos diversos subgrupos da FAB, com o intuito de agrupar melhor subtipos com comportamento clínico semelhante. A mudança mais importante foi a diminuição do número mínimo de blastos para o diagnóstico de LMA de 30% para 20%, causando o desaparecimento do subtipo AREB-T. Esta é também a mudança mais polêmica, havendo inúmeras publicações discutindo as evidentes diferenças clínicas e biológicas entre SMD e LMA, sendo unânime a opinião de que apenas o número de blastos é insuficiente para a escolha da terapêutica. Outro ponto importante foi a diferenciação de grupos com displasia em única e em múltiplas linhagens, que mostra ter grande importância para o prognóstico. Diversos estudos têm sido publicados, comparando as classificações FAB e OMS, reconhecendo a grande contribuição da classificação FAB para a melhor compreensão das SMD, bem como suas falhas e tentando validar as mudanças propostas pela classificação da OMS e identificar pontos passíveis de modificação.
A classificação inicial das síndromes mielodisplásicas (SMD) foi realizada em 1976, pelo grupo FAB, e era baseada em parâmetros morfológicos observados no sangue periférico e na medula óssea. A ...classificação FAB foi revisada em 1982 e utilizada nos últimos 25 anos como guia para melhor compreensão desse heterogêneo grupo de doenças. Em 2001, a OMS publicou uma nova classificação, com modificações significativas nos diversos subgrupos da FAB, com o intuito de agrupar melhor subtipos com comportamento clínico semelhante. A mudança mais importante foi a diminuição do número mínimo de blastos para o diagnóstico de LMA de 30% para 20%, causando o desaparecimento do subtipo AREB-T. Esta é também a mudança mais polêmica, havendo inúmeras publicações discutindo as evidentes diferenças clínicas e biológicas entre SMD e LMA, sendo unânime a opinião de que apenas o número de blastos é insuficiente para a escolha da terapêutica. Outro ponto importante foi a diferenciação de grupos com displasia em única e em múltiplas linhagens, que mostra ter grande importância para o prognóstico. Diversos estudos têm sido publicados, comparando as classificações FAB e OMS, reconhecendo a grande contribuição da classificação FAB para a melhor compreensão das SMD, bem como suas falhas e tentando validar as mudanças propostas pela classificação da OMS e identificar pontos passíveis de modificação.The initial classification of the myelodisplastic syndromes (MDS) was compiled in 1976 by the FAB group and was based on morphological parameters observed in the peripheral blood and in the bone marrow. The FAB classification was revised in 1982 and has been used in the last 25 years as a guide for a better understanding of this heterogeneous group of diseases. In 2001, the WHO published a new classification with significant modifications in the diverse subgroups of FAB with the intention of obtaining a better grouping of the subtypes with similar clinical behaviors. The most important modification was the decrease in the minimum number of blasts for the AML diagnosis from 30% to 20%, resulting in the disappearance of the subtype RAEB-T. This is also the most polemic alteration, as there are innumerable publications discussing the evident clinical and biological differences between the MDS and AML, with the opinion that the number of blasts alone is insufficient for the choice of therapy being unanimous. Another important point was the differentiation of the groups with dysplasia in single and multiple strains, which has been demonstrated as having great importance in the prognosis. Several studies have been published comparing the FAB and WHO classifications, recognizing the great contribution of the FAB classification for the better understanding of the MDS, as well as its shortcomings, and attempting to validate the modifications proposed by the WHO classification and identify the points liable to modification.
A doença de Gaucher (DG) é um erro inato do metabolismo do grupo das doenças lisossômicas de depósito, sendo a mais freqüente do referido grupo. É de herança autossômica recessiva, portanto com risco ...de 25% a cada gestação de casal heterozigoto. A doença é resultante da deficiência da beta-glicosidase ácida ou beta-glicocerebrosidase, que leva ao acúmulo de glicolipídios nos macrófagos principalmente em baço, fígado, medula óssea e pulmão. As manifestações clínicas ou fenotípicas da DG vão depender do grau de deficiência da enzima, existindo três tipos: Tipo I, forma não neuropática, afeta crianças e adultos com hepatoesplenomegalia, anemia, trombocitopenia, leucopenia e lesões ósseas; Tipo II, forma neuropática aguda, afeta crianças com 4-5 meses com quadro neurológico grave, hepatoesplenomegalia e comprometimento pulmonar e o Tipo III, forma neuropática crônica, afeta crianças e adolescentes com quadro neurológico menos grave que o Tipo II e ainda pode comprometer fígado, baço e ossos. Um grupo de catorze médicos com experiência no tratamento da DG com reposição enzimática realizaram extensa revisão da literatura, confrontaram com os dados evolutivos dos pacientes brasileiros e chegaram a um consenso quanto aos critérios para iniciar o tratamento, a dose da enzima e freqüência das infusões, do acompanhamento ambulatorial, laboratorial e radiológico. O Grupo Brasileiro de Estudos em Doença de Gaucher e outras Doenças de Depósito Lisossômico (GBDDL) tem o objetivo de estabelecer diretrizes para o diagnostico, tratamento e acompanhamento de pacientes com doença de Gaucher no Brasil. Esta iniciativa pioneira visa uniformizar a conduta no país com relação ao tratamento de DG com reposição enzimática, tratamento de alto custo porém de grande eficácia.
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