Real-life Outcomes on Acute Promyelocytic Leukemia in Brazil – Early Deaths Are Still a Problem

Silva, Wellington F; Rosa, Lidiane Inês da; Marquez, Gabriel Lacerda; Bassolli, Lucas; Tucunduva, Luciana; Silveira, Douglas R. A.; Buccheri, Valéria; Bendit, Israel; Rego, Eduardo Magalhães; Rocha, Vanderson; Velloso, Elvira Drp

doi:10.1016/j.clml.2018.11.004

Cited by 26 publications

(16 citation statements)

References 23 publications

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“…This construction makes it possible to considerably reduce potential for off-target toxicity thanks to its specificity for CD38 and reduced binding affinity of the attenuated IFNα molecules. Non-clinical studies have shown that TAK-573 has robust anti-tumor activity, including complete responses, in MM xenograft models [ 31 ]. Thus, different strategies for increasing CD38 expression on the surface of target cells have improved cytotoxic potential of effector cells in presence of daratumumab.…”

Section: Discussionmentioning

confidence: 99%

Balancing the CD38 Expression on Effector and Target Cells in Daratumumab-Mediated NK Cell ADCC against Multiple Myeloma

Lejeune

Duray

Peipp

et al. 2021

Cancers

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Multiple myeloma (MM) is an incurable cancer characterized by the proliferation and accumulation of monoclonal plasma cells in the bone marrow. The monoclonal anti-CD38 daratumumab has taken a central place in the different treatment regimens for newly diagnosed and relapsed, refractory myeloma. In this study, we correlated the NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and potential fratricide induced by daratumumab with CD38-expression levels on both effector and target cells. We show that CD38 expression can be modulated by adding all-trans retinoic acid (ATRA) or interferon-α to MM cells to further fine-tune these effects. In addition, we observed that ADCC becomes inefficient when fratricide occurs and both ADCC and fratricide depend on the balance between CD38 expression on effector and target cells. However, the addition of adjuvants (retinoic acid or interferon-α) to myeloma cells or the inhibition of fratricide using a CD38-blocking nanobody on NK-cells can reverse this balance towards ADCC and thus promote lysis of target cells by ADCC. ATRA and interferon-α increased the CD38 expression at the surface of MM cells about three-fold and two-fold, respectively. This increase was of interest for MM cells with low CD38 expression, that became susceptible to daratumumab-mediated ADCC after preincubation. A CD38-blocking nanobody prevented the binding of daratumumab to these NK-cells and blunted the fratricidal effect on effector NK cells. In conclusion, our study highlights the importance of a balanced CD38 expression on target and effector cells and attempts to alter this balance will affect the susceptibility of MM cells towards daratumumab-mediated ADCC.

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Section: Discussionmentioning

confidence: 99%

Balancing the CD38 Expression on Effector and Target Cells in Daratumumab-Mediated NK Cell ADCC against Multiple Myeloma

Lejeune

Duray

Peipp

et al. 2021

Cancers

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“…Porém estudos realizados no Brasil e na Europa revelam que há dificuldades de organização do acesso a exames, assistência e tratamentos, para neoplasias hematológicas e não hematológicas, podendo assim corroborar para que as taxas de mortalidades não diminuam (SANZ et al, 2019;SILVA JR et al, 2019). Contradizendo assim com o presente estudo em que apresentou um declínio significativo de mortalidade, causada possivelmente por uma melhora no diagnóstico e tratamento dessas neoplasias no estado do Pará-Brasil durante o período dos anos 2000 a 2017.…”

Section: Discussionunclassified

Leucemia Mieloide E Linfoide: Taxa De Mortalidade No Estado Do Pará-Brasil Entre Os Anos De 2000 E 2017

Weber

2021

RESC

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As leucemias são neoplasias hematopoiéticas heterogêneas, podendo ser classificadas em mieloides e linfoides de acordo com a linhagem celular acometida, e subdivididas em agudas e crônicas. Estudos conduzidos em outros países e no Brasil evidenciam, diminuição de sua mortalidade e aumento da sobrevida. O objetivo do presente estudo foi avaliar as taxas de mortalidades por leucemias no estado do Pará em crianças, adolescentes, adultos e idosos. Os pacientes foram categorizados em grupos de idade de amplitude 0 até 19 anos, conforme o IARC, e os adultos com amplitude 10, até 70 anos acima conforme o IBGE. Foram utilizados dados de óbitos por leucemias obtidos no Sistema de Informação de Mortalidade para o período de 2000 a 2017. O período de análise foi estratificado em triênios e foram calculadas taxas de mortalidade, para o estado do Pará, ajustadas pela população mundial. Quanto as estatísticas foram utilizadas o software minitab versão 18, com análise descritiva dos dados, com intervalo de confiança de 95%, para média populacional tanto do sexo masculino quanto do feminino e raças. No período estudado, ocorreram cerca de 3.632 óbitos por leucemias no estado. Observou-se uma média de óbitos, de 1,01 e 1,58/100 mil habitantes por leucemia linfoide no sexo feminino e masculino, respectivamente. Na leucemia mieloide houve uma média de 1,69 e 1,86/100 mil habitantes para o sexo feminino e masculino. Nas raças houve uma predominância da parda em todas as idades, sexo e leucemias, com 2.390 óbitos de um total de 3.134. Notou-se uma média de mortalidade de 1,52 e 1,51/100 mil habitantes para sexo feminino e masculino, respectivamente, na leucemia linfoide. E na leucemia mieloide houve uma média de 1,06 e 1,35/100 mil habitantes para sexo feminino e masculino. No período de 2000 a 2017, observou-se um decréscimo em todas as leucemias, com o sexo masculino sendo o mais afetado em quase todas as leucemias.

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“…Also, some trials have excluded patients from analyses if they die before receiving treatment [6]. On the other hand, in population-based analyses and single-center experiences from different countries, the rate of induction mortality rate is up to 61.5%, which is higher than expected [11][12][13][14]. Especially populationbased reports from the developed countries emphasize neither ED nor OS improved in the past two decades despite modern therapy methods [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Real-life outcomes of unselected acute promyelocytic leukemia patients: a single-center 14-year experience

Akcay

Yeter

Büyükaşık

2020

Romanian Journal of Internal Medicine

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Background: After the inclusion of all-trans retinoic acid (ATRA) into the treatment of Acute Promyelocytic leukemia (APL), a notable improvement concerning the survival rates of patients with APL has been observed. However, the population-based studies demonstrated that there was no marked improvement in the survival of patients after the 2000s. We aim to describe the clinical response and prognosis of adult patients diagnosed with APL and examine the change in these outcomes by the time period of diagnosis.Methods: We retrospectively reviewed thirty-six unselected APL patients who were diagnosed between September 2003 and February 2016.Results: The probability of survival at two years was 58%, while disease-free survival (DFS) was 87%. The overall early death (ED) rate was 33% and remain stable over time [42% in 2003-2009 vs. 24% in 2010-2016 (p=.20)]. In addition, the 2-year overall survival (OS) rates were 47% in 2003-2009 and 70% in 2010-2016 (p=.29), and no differences were noted. Univariate analyses showed possible predictors of poor OS were defined as leukocytosis (≥10x109/L), high Sanz score, hemorrhage, infection, disseminated intravascular coagulopathy (DIC) at presentation and microgranular morphologic subtype.Conclusion: This study shows that long-term survival remains low in APL patients, particularly related to a high ED rate. Initiatives to reduce ED are exceedingly substantial for improving the survival in APL.

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Real-life Outcomes on Acute Promyelocytic Leukemia in Brazil – Early Deaths Are Still a Problem

Cited by 26 publications

References 23 publications

Balancing the CD38 Expression on Effector and Target Cells in Daratumumab-Mediated NK Cell ADCC against Multiple Myeloma

Balancing the CD38 Expression on Effector and Target Cells in Daratumumab-Mediated NK Cell ADCC against Multiple Myeloma

Leucemia Mieloide E Linfoide: Taxa De Mortalidade No Estado Do Pará-Brasil Entre Os Anos De 2000 E 2017

Real-life outcomes of unselected acute promyelocytic leukemia patients: a single-center 14-year experience

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