scholarly journals Acute Promyelocytic Leukemia (APL): Seasonal Behavior in Colombia for the Period 2009-2019

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-39
Author(s):  
Humberto Martínez Cordero ◽  
Juan Ospina Idarraga ◽  
Xiomara Castañeda Contreras ◽  
Alejandro Rico Mendoza ◽  
Henry Idrobo ◽  
...  
Keyword(s):  
Time Series ◽  
Acute Promyelocytic Leukemia ◽  
Progressive Increase ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Main Diagnosis ◽  
Cure Rate ◽  
Seasonal Behavior ◽  
Seasonal Indices ◽  
The Individual

Background Acute promyelocytic leukemia (APL) is a malignant hematologic disease with a high cure rate, but unfortunately it produces several serious complications at the onset of the disease that explain the high early mortality. Based on clinical experience and the papers that precede this document, it has been observed that the incidence of this type of hematological cancer tends to increase at certain times of the year. The present study aims to determine the possible variations in the time intervals of the prevalence of promyelocytic leukemia in Colombia in the decade 2009 to 2019, in order to identify the behavior of the event, seasonality and cyclicality. Methods With data from the individual records of service provision (RIPS) of the official Colombian health system, the prevalence of APL in Colombia from 2009 to 2019 was identified. A filter was made by people attended, main diagnosis, C924 - promyelocytic leukemia acute, by year, semester and month. The analysis was performed with RStudio, R version 4.0.2 (2020-06-22); The fpp2 library was used, the analysis of the monthly and quarterly time series was carried out, the decomposition of the time series was carried out, trying through this process to evaluate the seasonal indices through additive and multiplicative types. Results During the entire period 2009 to 2019, 2,986 APL diagnoses were found throughout the national territory of Colombia. A progressive increase in prevalence was determined in the period studied (Graph 1). Cycles of increasing cases were observed every 10 months in the period 2009 to 2015 and in the cycle from 2016 to 2019 there was a prolongation of the cycle every 17 months, which strongly suggested that APL has cyclical behavior. Quarterly seasonality was identified by the multiplicative method with increases and decreases that behave in a similar way throughout the period studied (Graph 2). Conclusion APL is a highly curable disease that requires adequate support at the onset of the disease to avoid early mortality. The data from this study allow us to conclude that for the period 2009 to 2019 there is a seasonal behavior of this malignant hemopathy. The possibility of predicting during which months of the year the incidence of the disease will increase can serve to properly plan the health services in charge of treating this disease. Additional studies are required to determine what is the cause of the cyclical and seasonal behavior of this APL Disclosures Idrobo: Amgen:Honoraria, Speakers Bureau;Takeda:Honoraria, Speakers Bureau;Janssen:Honoraria, Speakers Bureau;Tecnofarma:Honoraria, Speakers Bureau;Abbvie:Honoraria, Speakers Bureau.

Prognostic Impact Of MLL5 transcript Levels On Outcome Of Patients With Acute Promyelocytic Leukemia Treated With All-Trans Retinoic Acid and Anthracycline-Based Chemotherapy: An International Consortium On Acute Promyelocytic Leukemia Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2586-2586
Author(s):  
Antonio R Lucena-Araujo ◽  
Haesook T. Kim ◽  
Rafael Jacomo ◽  
Raul A Melo ◽  
Rosane Bittencourt ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Induction Therapy ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Prognostic Impact ◽  
Transcript Levels ◽  
Healthy Donors ◽  
Laboratory Features

Abstract Background The MLL5 gene encodes a histone methyltransferase implicated in positive control of several genes related to hematopoiesis. Its close relationship with retinoic acid–induced granulopoiesis suggests that the deregulated expression of MLL5 might lead acute promyelocytic leukemia (APL) blasts to become less susceptible to differentiation-inducing ATRA effects. Here, we retrospectively determined the MLL5 transcript levels in samples from APL patients enrolled in the International Consortium on Acute Promyelocytic Leukemia (IC-APL) trial and analyzed its relationship with clinical and laboratory features, hematologic recovery, relapse, and survival. The results of the IC-APL have been previously reported (Blood 2013, 121(11) pp: 1935). In brief, complete hematological remission (CR) was achieved by 153/180 patients enrolled in Brazil, Mexico, Chile and Uruguay and after a median follow up of 28 months, the 2-year cumulative incidence of relapse (CIR), overall survival (OS) and disease-free survival (DFS) were 4.5%, 80% and 91%, respectively. Design and Methods One hundred and twenty-one APL patients (age, 15-73y) from seven different Brazilian institutions and treated according to the IC-APL protocol were included. The treatment schedule was identical to that adopted in the PETHEMA/HOVON LPA2005 trial, except for the replacement of idarubicin by daunorubicin. ATRA treatment was initiated immediately in all cases in which the diagnosis of APL was suspected based on morphology. As normal controls, total bone marrow (BM, n=8) and peripheral blood (PB, n=101) cells from healthy donors (age, 18-60y) were collected and mononuclear cells were isolated by Ficoll-Hypaque density gradient centrifugation. Additionally, 28 CBF-leukemia samples were included. Gene expression profile was analyzed by real-time quantitative PCR using the ABL FusionQuant Standard Kit as an endogenous control. Based on the continuous distribution of MLL5/ABL expression on APL samples (Figure 1), we adopted the median value of MLL5/ABL expression as cut-off to dichotomize APL patients in “low” and “high” MLL5 transcript levels. Results MLL5 expression was not different between APL, CBF-leukemia and healthy donors samples (Figure 1; P=0.19). There was no relevant difference between APL patients with low (n=62) and high (n=59) MLL5 transcript levels with respect to clinical and laboratory features, although high MLL5 transcript levels were more likely to be present in female gender (P=0.029). Overall, 102 (84%) achieved CR. Patients with low MLL5 transcript levels had significantly lower CR rate than patients with high MLL5 transcript levels (74% vs 95%; P=0.002). Twelve patients (10%) experienced early mortality (i.e., death during induction therapy) due to hemorrhage (n=6; 50%), disease progression (n=1; 8.3%), thrombosis (n=1; 8.3%), therapy-related infection (n=3; 25%) and differentiation syndrome (n=1; 8.3%); MLL5 transcript levels had no impact on early mortality (P=0.155). With a follow-up of 33 months among survivors (range, 1-72 months), patients with low MLL5 transcript levels had significantly lower 2-year OS (P=0.005) and 2-year DFS rate (P=0.037) than patients with high MLL5 transcript levels. Up to January 2013, a total of six relapses (5%) had been recorded. The 2-year CIR among patients with low and high MLL5 transcript levels was 14% (95%CI: 5% to 27%) and 2% (95%CI: 0.1% to 11%), respectively (P=0.04). We have further evaluated the prognostic impact of MLL5 transcript levels in those patients who remain alive after induction therapy (107 patients). Low MLL5 transcript levels were predictive of lower CR rate (P=0.042) and 2-year OS rate (P=0.009), but had no impact on DFS (P=0.106). Conclusion Our results show that MLL5 transcript levels may predict lower remission rate, short survival and higher risk of relapse in APL patients treated with ATRA and anthracycline-based chemotherapy. This is the first report describing the MLL5 expression as a prognostic factor in APL; nevertheless, our results should be confirmed in an independent cohort. Disclosures: No relevant conflicts of interest to declare.

ABO identical and washed blood transfusions as candidate strategies to reduce early mortality in acute promyelocytic leukemia

2017 ◽  
Vol 62 ◽  
pp. 1-3 ◽  
Author(s):  
Tanmay Sahai ◽  
Kelly Henrichs ◽  
Majed Refaai ◽  
Joanna M. Heal ◽  
Scott A. Kirkley ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Blood Transfusions

All-trans retinoic acid and early mortality in acute promyelocytic leukemia

2013 ◽  
Vol 37 (10) ◽  
pp. 1391-1392 ◽  
Author(s):  
Armin Rashidi ◽  
Ranjit K. Goudar ◽  
Farzaneh Sayedian ◽  
Jeffrey A. Vos ◽  
Teresa A. Goldin ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals EPIDEMIOLOGY, DIAGNOSIS AND TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA IN CHILDREN: THE EXPERIENCE IN CHINA

2012 ◽  
Vol 4 (1) ◽  
pp. e2012012 ◽  
Author(s):  
Li Zhang ◽  
Xiaofan Zhu
Keyword(s):  
Developing Countries ◽  
Treatment Failure ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Term Survival ◽  
The Status ◽  
Treatment Abandonment ◽  
Leukemia In Children

The limited available data suggest that the rate of early mortality is high and that long-term survival is poor in many developing countries. Death from bleeding and infection during chemotherapy, relapse and treatment abandonment are among the main cause of treatment failure in APL children. The status of children APL treatment in China is not described in general.

scholarly journals Temporal Trends in Early Mortality in Acute Promyelocytic Leukemia in the United States

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 710-710
Author(s):  
Ana C. Xavier ◽  
Matthew A. Kutny ◽  
Omer Jamy ◽  
Luciano J Costa
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Rural Areas ◽  
Research Funding ◽  
Educational Achievement ◽  
Temporal Trends ◽  
Malignant Neoplasm ◽  
The United States ◽  
Promyelocytic Leukemia ◽  
Early Mortality

Abstract Background: Survival of patients with acute promyelocytic leukemia (APL) has dramatically improved with the use of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Despite this, due to the complexity of initial management and the high risk of fatal thrombotic and hemorrhagic complications at presentation, early mortality (EM) remains the major contributor for treatment failure. It is less known whether advances in treatment, improvements in supportive measures, urgent access to specialized care and broad availability of ATRA and ATO have reduced EM in the last two decades. Methods: We used data from the National Cancer Institute's Surveillance Epidemiology and End Results program (SEER-13) to determine the rates of EM (death within the first 30 days from diagnosis) and overall survival (OS) in patients with APL. Inclusion criteria was the diagnosis of APL as first malignant neoplasm among patients of all ages between 1992 and 2015. Follow up was updated to the end of 2015. Cases were grouped and analyzed according to age, children, adolescent and young adults (< 40 years) and older adults (≥ 40 years), race/ethnicity, gender, county-level income and educational achievement, and residency in rural or urban county. Trends in EM and OS were analyzed across consecutive 4-year eras. Results: A total of 2,224 APL cases (895 <40 and 1,329 ≥ 40 years) were included in the analysis with median follow up of 41 months (range 0-287 months). Median age of patients was 45, and 1,090 (49%) were male. Most patients were White (1,228; 55.2%), 199 (9%) Black, 785 (35.3%) other ethnicity, and 12 (0.5%) unknown. Three-year OS for APL patients diagnosed in 1992-1995 was 49.2% ± 3.5% vs. 76.4 ± 2.1% for patients diagnosed in 2012-2015 (p < 0.001), Figure 1. Early mortality improved for patients < 40 years (27.4% in 1992-1995 vs. 5.4% in 2012-2015, p < 0.001), but not at the same extent for patients ≥ 40 years (35.2% in 1992-1995 vs. 22.2% in 2012-2015, p = 0.02), Figure 2. Improvements in EM are displayed in Table 1. Importantly, improvements in EM were not seen among patients of residents of rural counties. Conclusion: These findings confirm consistent improvements in EM and OS for APL patients in the US and point to the challenge of further extending these improvements in EM rates to older patients and for those living in rural areas. Disclosures Costa: Celgene: Honoraria, Research Funding; Sanofi: Honoraria; Karyopharm: Research Funding; Janssen: Research Funding; BMS: Research Funding; Abbvie: Research Funding; Amgen: Honoraria, Research Funding.

scholarly journals Acute Promyelocytic Leukemia: Simplifying Treatment in a Resource Poor Setting

2021 ◽  
Vol 6 (4) ◽  
pp. 383-387
Author(s):  
Rohan Bhise ◽  
Imtiaz Ahmed ◽  
Sapna Imtiaz
Keyword(s):  
Retinoic Acid ◽  
Supportive Care ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Risk Group ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Resource Poor

Introduction: Acute promyelocytic leukemia (APL) is a distinct leukemia which can be treated with differentiating agents alone.Treatment without chemotherapy decreases the cost of treatment and the need for supportive care. Here we present analysis of APL patients treated with arsenic trioxide (ATO)-all trans retinoic acid (ATRA) without chemotherapy in our hospital.Patients and Methods: Forty three patients with newly diagnosed APL were treated with arsenic trioxide(ATO ) and All trans retinoic acid (ATRA) during induction treatment. For consolidation ATRA 45 mg /m2 for two weeks every four weeks was administered for twenty eight weeks. ATO was administered for four cycles, with a cycle length of eight weeks. The drug was administered at 0.15 mg/kg/d for five days per week for four weeks during each cycle.Patients were followed up with once in three month hemogram and once in six month reverse-transcriptase polymerase chain reaction (RT-PCR) for two years and yearly thereafter. Results: The morphologic complete remission (CR) rate was 86.04%.The most common cause of remission failure was early death due to bleeding. None of the low risk patients died during induction therapy. The most important prognostic factor for early mortality was a high white blood cell (WBC) count at presentation. The median overall survival (OS) has not been reached.The two year OS was 83.4% and the three year OS was 74.8%.The estimated five year survival was 74.8%. At a median follow up of 42.6 months the estimated five year survival in the low-intermediate risk group was 93.3% and 59.1% in the high risk group Conclusion: ATO –ATRA can be considered as a treatment option for frontline treatment of all risk APL patients in resource poor settings.The results can be better with better supportive care to prevent early mortality and by salvaging patients who relapse.

Clinical Features and Outcome of 148 Patients with Acute Promyelocytic Leukemia in Brazil.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3326-3326 ◽  
Author(s):  
Rafael H. Jácomo ◽  
Raul Melo ◽  
Fernanda Souto ◽  
Éderson Mattos ◽  
Claudia Oliveira ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Promyelocytic Leukemia ◽  
Risk Groups ◽  
Developed Countries ◽  
International Committee ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Life Threatening ◽  
American Society ◽  
Low Dose Chemotherapy

Abstract Acute Promyelocytic Leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) which has a high prevalence in Latinos as well as a different distribution of PML breakpoints with a higher incidence of bcr1 isoform. We describe here the characteristics and outcome of 148 consecutive patients, from 11 centers in Brazil. Induction consisted of ATRA and anthracyclines (ida or daunorubicin). All centers used anthracyclines in consolidation but association with AraC was variable. Maintenance was based on low dose chemotherapy, except in 2 centers, which were excluded from survival analysis. The incidence of APL among AML was 28.2%. According to the risk stratification from PETHEMA/GIMEMA groups, 58 (39.2%) patients were classified as high risk (HR), 63(42.6%) as intermediate (IR) and 27 (18.2%) as low risk (LR), a higher frequency of HR patients than the reported by Sanz et al analyzing 217 APL patients (p=0.003). A relatively high frequency of early complications was observed, with 26 (17.6%) and 68 (45,9%) patients presenting with life threatening hemorrhage and disseminated intravascular coagulation (DIC), respectively. Early mortality (death in the first 14 days of diagnosis) was higher than the described in developed countries - 42 (28.4%) patients; bleeding (37 patients) was the leading cause. Both early mortality and bleeding were more frequent in the HR group (p=0.002 and <0.001 respectively). From 106 patients alive at D+15, 88 patients survived induction and 73 were alive and in remission after consolidation. One patient relapsed before finishing consolidation and six were still in induction. There was no difference among risk groups in mortality after day 14 of induction. Mean overall survival (OS) for the 133 patients available for analysis was 614 days (CI95% 515–712). Excluding early mortality, mean OS was 844 days (CI95% 741–948). Mean OS was different among the risk groups - 928(785–1071), 748(598–898) and 313(187–439) days for LR, IR AND HR, respectively (p<0.001). Our data suggest that risk classification, besides identification of relapse probability, can identify patients with higher incidence of bleeding, laboratorial DIC and also those that are predisposed to death secondary to hemorrhage and this may alert to the necessity of a more intensive supportive care in induction for this group. Despite the fact that ATRA and anthracyclines are available in Brazil hospitals, these results show that Brazilian patients have a worse outcome than the reported by the latest trials. It is possible that late referral partially accounts for an increased number of high-risk APL among these Brazilian patients. Hence, in addition of specific drugs availability, prompt access to care and initiation of specific therapy is necessary to improve outcome. In this regard, the International Consortium in APL (IC APL), created in 2005 by the International Committee of the American Society of Hematology, aims to implement a network to allow the exchange of experiences among hematologists in developing countries and international specialists as well as to offer real time discussion of newly-diagnosed patients with APL and ongoing complications.

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