Front-line treatment of acute promyelocytic leukemia with AIDA induction followed by risk-adapted consolidation for adults younger than 61 years: results of the AIDA-2000 trial of the GIMEMA Group

Blood ◽  
2010 ◽  
Vol 116 (17) ◽  
pp. 3171-3179 ◽  
Author(s):  
Francesco Lo-Coco ◽  
Giuseppe Avvisati ◽  
Marco Vignetti ◽  
Massimo Breccia ◽  
Eugenio Gallo ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Promyelocytic Leukemia ◽  
Risk Group ◽  
High Risk Group ◽  
Promyelocytic Leukemia ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
All Trans Retinoic Acid ◽  
Risk Patients

AbstractAfter the identification of discrete relapse-risk categories in patients with acute promyelocytic leukemia (APL) receiving all-trans retinoic and idarubicin (AIDA)–like therapies, the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) designed a protocol for newly diagnosed APL (AIDA-2000) in which postremission treatment was risk-adapted. Patients with low/intermediate risk received remission at 3 anthracycline-based consolidation courses, whereas high-risk patients received the same schedule as in the previous, non–risk-adapted AIDA-0493 trial including cytarabine. In addition, all patients in the AIDA-2000 received all-trans retinoic acid (ATRA) for 15 days during each consolidation. After induction, 600 of 636 (94.3%) and 420 of 445 (94.4%) patients achieved complete remission in the AIDA-0493 and AIDA-2000, respectively. The 6-year overall survival and cumulative incidence of relapse (CIR) rates were 78.1% versus 87.4% (P = .001) and 27.7% versus 10.7% (P < .0001). Significantly lower CIR rates for patients in the AIDA-2000 were most evident in the high-risk group (49.7% vs 9.3%, respectively, P < .0001). Our data confirm that anthracycline-based consolidation is at least equally effective as cytarabine-containing regimens for low-/intermediate-risk patients and suggest that a risk-adapted strategy including ATRA for consolidation improves outcome in newly diagnosed APL. Furthermore, our results highlight the role of cytarabine coupled to anthracyclines and ATRA during consolidation in the high-risk group. This trial was registered at www.clinicaltrials.gov as #NCT 001064570.

scholarly journals Remission in Patients with Acute Promyelocytic Leukemia Treated with Arsenic Trioxide (varitrinox) As the First Line in Colombia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-3
Author(s):  
Gustavo Milone ◽  
Samuel Sarmiento Doncel ◽  
Carol Agudelo Rico ◽  
Fabiola Vizcarra Reyes ◽  
Gina Alejandra Diaz Mosquera ◽  
...  
Keyword(s):  
High Risk ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Conflicts Of Interest ◽  
Promyelocytic Leukemia ◽  
Remission Induction ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
First Line ◽  
Risk Patients

Acute promyelocytic leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML) in which a chromosomal translocation t (15; 17) (q22; q12) is generated by fusing produces a hybrid PML / RARα gene, generating an altered signal . The combination of transretinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of newly diagnosed standard risk patients with acute promyelocytic leukemia (APL) in several countries. The objective of the present study is to describe the frequency of remission in patients with acute promyelocytic leukemia who were administered as a first line Arsenic Trioxide (varitrinox) during the period from November 2017 to June 2020 in Colombian patients. Methods: Retrospective observational and descriptive study of 12 patients diagnosed with acute promyelocytic leukemia treated with ATO Arsenic trioxide (Varitrinox) as first line, the source of information was provided by the treating hematologists (medical records) by filling out the technical concept format. Active pharmacovigilance scientist in Colombia, this format keeps the identification information of the patient anonymized and the confidentiality of the data is guaranteed as well as compliance with the rules of good clinical practice. Results: Twelve patients with age range between 22 and 69 years with a median age of 34.0 were analyzed. It was found in the analysis that 100% had induction hematologic remission with a median of 45 days. 75% of patients received ATO + ATRA and were at low and intermediate risk, the remaining 25% received ATRA + ATO + Chemotherapy and were at high risk, and intermediate risk. 91.7% of molecular remission in consolidation was obtained and it was measured in cycle 3 by means of PCR (undetectable), 8.3% (n = 1) was positive 3% and is finishing consolidation. Regarding the most frequent adverse events, intravascular coagulation (n = 9), neutropenia (n = 6) and thrombocytopenia (n = 6) were observed. 75% of patients are disease-free, 16.7% are on maintenance (they received ATO + ATRA + Induction chemotherapy) and 8.3% are on consolidation. So far, none of the patients under study have died. Conclusions: Our results support the use of ATO (Varitrinox) in newly diagnosed APL patients (as first line), as a care strategy for low, intermediate and high risk patients. The role of ATRA-ATO is guaranteed in other studies where they manage patients of different risks. Key words: Arsenic trioxide, leukemia promyelocytic acute, leukemia myeloid acute, remission induction, tretinoin. Disclosures No relevant conflicts of interest to declare.

GIMEMA-AIEOP AIDA Protocols for the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia (APL) In Children: Analysis of 247 Patients Enrolled In Two Sequential Italian Multicenter Trials

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 871-871 ◽  
Author(s):  
Anna Maria Testi ◽  
Robin Foa ◽  
Gabriella Tomei ◽  
Francesco Lo Coco ◽  
Andrea Biondi ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Therapy ◽  
Acute Promyelocytic Leukemia ◽  
Remission Rate ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
High Risk Patients ◽  
Risk Patients

Abstract Abstract 871 Since 1993, Italian pediatric patients (age <18 years) with newly diagnosed acute promyelocytic leukemia (APL) have been enrolled in two consecutive multicenter Gruppo Italiano per le Malattie Ematologiche dell'Adulto (GIMEMA) - Italian Pediatric Hematology and Oncology Group (AIEOP) AIDA 0493 and 2000 trials. The AIDA 0493 protocol consisted of an induction including ATRA (25 mg/m2/day) and idarubicin, followed by three polychemotherapy consolidation courses without ATRA and a four-arm randomized maintenance therapy for patients who were PCR- after consolidation. The AIDA 2000 trial, which started in September 2000, included the same induction followed by a risk-adapted (Sanz criteria, Blood 2004) consolidation. Low and intermediate risk children received three less intensive anthracycline-based courses plus ATRA; for high risk patients, consolidation was intensified by adding ATRA to the three polychemotherapy consolidation courses of the previous protocol. Maintenance therapy consisted of standard daily mercaptopurine and weekly methotrexate given for two years. ATRA was administered for fifteen days every three months during all maintenance therapy. Between January 1993 and June 2000, 124 children were enrolled in the AIDA 0493 protocol. The results of this study have been previously reported (Testi et al, Blood 2005). From July 2000 to January 2009, 123 children with newly diagnosed APL were enrolled in the AIDA 2000 risk-adapted trial. We have now performed an updated analysis of the results of the first study and compared these results with those achieved with the AIDA 2000 study. The median follow-up is 12 and 5 years for the AIDA 0493 and 2000 studies, respectively. No differences in the main clinical and biologic diagnostic patients' characteristics - M/F ratio, median age, median WBC count, FAB M3/M3v, BCR1/BCR2/BCR3, low-intermediate/high risk - were observed between the two groups; the median platelet count was higher in the AIDA 2000 group (27.5 vs 20 × 109/L, p 0.05). The complete remission rate was 96% and 100% in the AIDA 0493 and 2000 protocols, respectively, with no patient showing resistant disease. No toxic death was recorded during the consolidation phase in both protocols; at recovery from the third consolidation course, 97% and 99% of the two groups of patients, tested by RT-PCR, achieved molecular negativity. The 6-year Kaplan-Meier estimates of overall survival (OS) and disease-free survival (DFS) are 89.7% (CI 95%: 84.7–95) vs 96% (CI 95%: 91.7–100), (p 0.05) and 73.1% (CI 95%: 66.7–80.2) vs 82.5% (CI 95%: 75.9–89.8), (p 0.28) in the AIDA 0493 and 2000 protocols, respectively. For low/intermediate risk children, OS and DFS at 6 years are 94.2% (CI 95%: 89.1–99.5) and 76.7% (CI 95%: 68.9–85.4) in the AIDA 0493 vs 95.6% (CI 95%: 90.0–100) and 82.7% (CI 95% 74.9–91.3) in the AIDA 2000 trial, respectively (p 0.57 and 0.73); considering high risk patients, OS and DFS at 6 years are 81.6% (CI 95%: 72.1–92.3) and 65.2% (CI 95%: 54.7–77.6) in the AIDA 0493 vs 96.8% (CI 95%: 90.9–100) and 82.3% (CI 95%: 70.1–96.5) in the AIDA 2000 trial (p 0.05 and 0.20). These results confirm the high anti-leukemic efficacy of the ATRA + idarubicin induction combination. For low/intermediate risk children, the anthracycline-based plus ATRA consolidation is equally effective as the previous cytarabine-containing regimen. The risk-adapted strategy including ATRA for consolidation resulted into a significant improvement in OS for all children. Furthermore, our results highlight the role of cytarabine coupled to anthracyclines and ATRA during consolidation in the high-risk group. Disclosures: Foa: Roche: Consultancy, Speakers Bureau.

Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome

Blood ◽  
2010 ◽  
Vol 115 (25) ◽  
pp. 5137-5146 ◽  
Author(s):  
Miguel A. Sanz ◽  
Pau Montesinos ◽  
Chelo Rayón ◽  
Alexandra Holowiecka ◽  
Javier de la Serna ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Intermediate Risk ◽  
Consolidation Therapy ◽  
High Risk Patients ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Risk Patients

AbstractA risk-adapted strategy based on all-trans retinoic acid (ATRA) and anthracycline monochemotherapy (PETHEMA LPA99 trial) has demonstrated a high antileukemic efficacy in acute promyelocytic leukemia. We designed a new trial (LPA2005) with the objective of achieving stepwise improvements in outcome. Between July 2005 and April 2009, low- and intermediate-risk patients (leukocytes < 10 × 109/L) received a reduced dose of mitoxantrone for the second consolidation course, whereas high- risk patients younger than 60 years of age received cytarabine combined with ATRA and idarubicin in the first and third consolidation courses. Of 372 patients attaining complete remission after ATRA plus idarubicin (92.5%), 368 proceeded to consolidation therapy. For low- and intermediate-risk patients, duration of neutropenia and thrombocytopenia and hospital stay were significantly reduced without sacrificing antileukemic efficacy, compared with the previous LPA99 trial. For high-risk patients, the 3-year relapse rate was significantly lower in the LPA2005 trial (11%) than in the LPA99 (26%; P = .03). Overall disease-free survival was also better in the LPA2005 trial (P = .04). In conclusion, the lower dose of mitoxantrone resulted in a significant reduction of toxicity and hospital stay while maintaining the antileukemic activity, and the combination of ATRA, idarubicin, and cytarabine for high-risk acute promyelocytic leukemia significantly reduced the relapse rate in this setting. Registered at http://www.clinicaltrials.gov as NCT00408278.

P3609Temporal trends of the management and outcomes of patients after myocardial infarction according to the risk for recurrent cardiovascular events

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Grinberg ◽  
T Bental ◽  
Y Hammer ◽  
A R Assali ◽  
H Vaknin-Assa ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Risk ◽  
Cardiovascular Events ◽  
Risk Group ◽  
Temporal Trends ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
High Risk Patients ◽  
Risk Patients

Abstract Background Following Myocardial Infarction (MI), patients are at increased risk for recurrent cardiovascular events, particularly during the immediate period. Yet some patients are at higher risk than others, owing to their clinical characteristics and comorbidities, these high-risk patients are less often treated with guideline-recommended therapies. Aim To examine temporal trends in treatment and outcomes of patients with MI according to the TIMI risk score for secondary prevention (TRS2°P), a recently validated risk stratification tool. Methods A retrospective cohort study of patients with an acute MI, who underwent percutaneous coronary intervention and were discharged alive between 2004–2016. Temporal trends were examined in the early (2004–2010) and late (2011–2016) time-periods. Patients were stratified by the TRS2°P to a low (≤1), intermediate (2) or high-risk group (≥3). Clinical outcomes included 30-day MACE (death, MI, target vessel revascularization, coronary artery bypass grafting, unstable angina or stroke) and 1-year mortality. Results Among 4921 patients, 31% were low-risk, 27% intermediate-risk and 42% high-risk. Compared to low and intermediate-risk patients, high-risk patients were older, more commonly female, and had more comorbidities such as hypertension, diabetes, peripheral vascular disease, and chronic kidney disease. They presented more often with non ST elevation MI and 3-vessel disease. High-risk patients were less likely to receive drug eluting stents and potent anti-platelet drugs, among other guideline-recommended therapies. Evidently, they experienced higher 30-day MACE (8.1% vs. 3.9% and 2.1% in intermediate and low-risk, respectively, P<0.001) and 1-year mortality (10.4% vs. 3.9% and 1.1% in intermediate and low-risk, respectively, P<0.001). During time, comparing the early to the late-period, the use of potent antiplatelets and statins increased among the entire cohort (P<0.001). However, only the high-risk group demonstrated a significantly lower 30-day MACE (P=0.001). During time, there were no differences in 1-year mortality rate among all risk categories. Temporal trends in 30-day MACE by TRS2°P Conclusion Despite a better application of guideline-recommended therapies, high-risk patients after MI are still relatively undertreated. Nevertheless, they demonstrated the most notable improvement in outcomes over time.

scholarly journals Significance of Modified Risk Stratification Msmart 3.0 and Autologous Stem Cell Transplantation for Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5593-5593
Author(s):  
Andrey Garifullin ◽  
Sergei Voloshin ◽  
Vasily Shuvaev ◽  
Irina Martynkevich ◽  
Elizaveta Kleina ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Risk Stratification ◽  
Risk Group ◽  
High Risk Group ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Genetic Abnormalities ◽  
Standard Risk

Background The risk-stratification systems are repeatedly updated in accordance with the emergence of new information about the prognostic impact of anomalies and other factors. The most extensive and modern system in this time is mSMART risk stratification involving many parameters such as genetic anomalies, albumin, beta-2-microglobulin, LDH, Plasma Cell S-phase and GEP levels. It is possible to use risk-adapted treatment programs with or without ASCT. Nevertheless, the role of complex karyotype, combination of genetic abnormalities and ASCT remains unclear. Aims To estimate the genetic abnormalities in patients with newly diagnosed multiple myeloma and define the role of risk-stratification and ASCT in prognosis of disease. Methods The study included 159 patients (median age 63 years, range 28 - 83; male: female ratio - 1:1.37) with NDMM. Metaphase cytogenetics on bone marrow samples was done by standard GTG-method. FISH analyses were performed according to the manufacturer's protocol for detection primary IgH translocations, 13q (13q14/13q34) deletion, 1p32/1q21 amplification/deletion, P53/cen 17 deletion (MetaSystems DNA probes). We additional searched the t(4;14), t(6;14), t(11;14), t(14;16) and t(14;20) in patients with IgH translocation. All patient was treated by bortezomib-based programs (VD, CVD, VMP, PAD). ASCT was performed at 42% patients. Results The frequency of genetic abnormalities in NDMM patients was 49% (78/159). IgH translocation was detected in 26.4% (42/159) patients: t(11;14) - 16.3% (26/159), t(4;14) - 5.0% (8/159); TP53/del17p - 5.6% (9/159); 1p32/1q21 amp/del - 12% (19/159); hypodiploidy - 3.1% (5/159); hyperdiploidy - 1.25% (2/159); del5q - 0,6% (1/159); other - not found. Combination two aberrations was discovered in 11.9% (19/159) patients, complex abnormalities (>3 aberrations) - in 4.4% (7/159) patients. The median OS in "two aberration" and "complex abnormalities" groups were lower than in standard-risk mSMART 3.0 (normal, t(11;14), hypodiploidy, hyperdiploidy and other): 49 months, 26 months and was not reached, respectively (p=.00015). The median PFS for these groups was 12 months, 11 months and 30 months, respectively (p=.011). Differences between "two aberration" and "complex abnormalities" groups were not find (p> .05). We modified high-risk (gain 1q, p53 mutation, del 17p deletion, t(4;14), t(14;16), t(14;20), R-ISS stage III, double and triple hit myeloma) mSMART 3.0 by adding "two aberration" and "complex abnormalities" groups on based the OS and PFS results. The final analysis was based on the results of the complex examination of 87 patients: 53 patients in standard-risk group and 34 patients in high-risk group. The median OS in standard-risk mSMART 3.0 was not reached, in high-risk mSMART 3.0mod - 48 months; 5-years OS was 62% and 38%, respectively (p=0.0073). The median PFS was 43 and 29 months, respectively (p=.09). The best results of OS and PFS were reach in both groups of patient who performed ASCT. The median OS in standard-risk mSMART 3.0 with ASCT (n=37) was not reached, in high-risk mSMART 3.0mod with ASCT - 48 months (n=20); standard-risk mSMART 3.0 without ASCT - 40 months (n=16); in high-risk mSMART 3.0mod without ASCT - 22 months (n=14); 5-years OS was 81%, 60%, 33% and 28%, respectively (p=0.0015). The median PFS was not reached, 46, 22 and 19 months, respectively (p=.017). Conclusions The combination of two aberrations and complex abnormalities is unfavorable prognostic markers. The median OS and PFS was higher in standard-risk than high-risk group according mSMART 3.0mod. The ASCT can improve treatment's outcomes and life expectancy especially in patients with high-risk. It can be useful for update risk stratification in a future. Disclosures Shuvaev: Novartis: Consultancy; Pfize: Honoraria; Fusion Pharma: Consultancy; BMS: Consultancy.

Treatment with All-Trans Retinoic Acid and Anthracycline Monochemotherapy in Children with Acute Promyelocytic Leukemia: Analysis of Three Sequential Multicenter Trials of the PETHEMA Group

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 137-137
Author(s):  
Luis Madero ◽  
Pau Montesinos ◽  
Pilar Bastida ◽  
Amparo Verdeguer ◽  
Javier De la Serna ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Maintenance Therapy ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Consolidation Therapy ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Risk Patients ◽  
High Degree

Abstract The combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy has been adopted as the standard treatment for children and adults with acute promyelocytic leukemia (APL). However, information about therapy results in pediatric APL patients is scarce, particularly on long-term outcomes. A previous report of the PETHEMA Group (Ortega et al, JCO 2005) showed that a risk-adapted strategy combining a reduced dose of ATRA (25 mg/m2/d) and anthracycline monochemotherapy for induction and consolidation, followed by ATRA and low dose methotrexate and mercaptopurine for maintenance therapy, produced high antileukemic efficacy, moderate toxicity, and a high degree of compliance. We have now performed an updated analysis of a significantly enlarged cohort of 107 consecutive children (younger than 19 years) with APL who were enrolled in three sequential trials of the PETHEMA Group (LPA96, LPA99 and LPA2005) and followed up for a median of 71 months (range, 3–139). Induction consisted of 25 mg/m2 ATRA daily until CR and 12 mg/m2 idarubicin on days 2, 4, 6 and 8. In the LPA96 trial, patients in CR received three monthly chemotherapy courses: idarubicin 5 mg/m2/d × 4 (course #1), mitoxantrone 10 mg/m2/d × 5 (course #2), and idarubicin 12 mg/m2/d × 1 (course #3). Since November 1999 (LPA99 trial), for patients with intermediate or high risk of relapse (Sanz et al, Blood 2000), consolidation was slightly intensified by increasing idarubicin doses in courses #1 and #3, and by simultaneously administering 25 mg/m2 ATRA together with chemotherapy in all three courses. Since July 2005, consolidation therapy in the ongoing LPA 2005 trial included the following modifications: the administration of ATRA for all patients; for low- and intermediate-risk patients, mitoxantrone has been reduced from five to three days in the second course; and for high-risk patients, cytarabine has been added to idarubicin in the first and third course. Maintenance therapy consisted of 50 mg/m2/d mercaptopurine orally, 15 mg/m2/week methotrexate intramuscularly, and 25 mg/m2/d ATRA for 15 days every three months. Of 1031 patients enrolled in three subsequent PETHEMA trials between November 1996 and July 2008, 107 (10%) from 43 Institutions were aged less than 19 years. WBC counts were &gt;10×09/l and &gt;50×109/l in 36 (34%) and 10 (9%), respectively; morphologically, 22 (22%) cases were hypergranular; PML/RARA isoform type was BCR1 or BCR2 in 47 (57%), and BCR3 in 35 (43%). One-hundred and one patients achieved CR (94%). In general, toxicity was manageable during consolidation and maintenance therapy. One patient died in CR during consolidation due to hepatic failure. At the end of consolidation, only 2 patients of 86 patients tested had molecular persistence (defined by positive RT-PCR of PML/RARA at 10−4 sensitivity). Ten additional relapses were observed, 5 molecular and 5 clinical relapses. Apart from 2 clinical relapses and 2 molecular relapses, all these events occurred among high risk patients. The 5-year Kaplan-Meier estimates of overall, disease-free and relapse-free survival were 89%, 86% and 86%, respectively. These results show a higher incidence of hyperleucocytosis in pediatric patients than in adults with genetically proven APL (p=0.05) and confirm the high antileukemic efficacy, low toxicity and high degree of compliance of three subsequent PETHEMA trials using a risk-adapted strategy with ATRA and anthracycline-based chemotherapy for induction and consolidation therapy.

Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1078-1084 ◽  
Author(s):  
Lionel Adès ◽  
Miguel A. Sanz ◽  
Sylvie Chevret ◽  
Pau Montesinos ◽  
Patrice Chevallier ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Cumulative Dose ◽  
Promyelocytic Leukemia ◽  
Joint Analysis ◽  
High Dose ◽  
Newly Diagnosed ◽  
All Trans Retinoic Acid ◽  
High Cumulative Dose ◽  
Wbc Count

Abstract All-trans retinoic acid (ATRA) plus anthracycline chemotherapy is the reference treatment of newly diagnosed acute promyelocytic leukemia (APL), whereas the role of cytosine arabinoside (AraC) remains disputed. We performed a joint analysis of patients younger than 65 years included in Programa para el Estudio de la Terapéutica en Hemopatía Maligna (PETHEMA) LPA 99 trial, where patients received no AraC in addition to ATRA, high cumulative dose idarubicin, and mitoxantrone, and APL 2000 trial, where patients received AraC in addition to ATRA and lower cumulative dose daunorubicin. In patients with white blood cell (WBC) count less than 10 × 109/L, complete remission (CR) rates were similar, but 3-year cumulative incidence of relapse (CIR) was significantly lower in LPA 99 trial: 4.2% versus 14.3% (P = .03), although 3-year survival was similar in both trials. This suggested that AraC is not required in APL with WBC count less than 10 × 109/L, at least in trials with high-dose anthracycline and maintenance treatment. In patients with WBC of 10 × 109/L or more, however, the CR rate (95.1% vs 83.6% P = .018) and 3-year survival (91.5% vs 80.8%, P = .026) were significantly higher in APL 2000 trial, and there was a trend for lower 3-year CIR (9.9% vs 18.5%, P = .12), suggesting a beneficial role for AraC in those patients.

scholarly journals Clinical Investigation of Stratified Therapy in Childhood Acute Promyelocytic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5286-5286 ◽  
Author(s):  
Yuming Zhang ◽  
Xiaoqing Feng ◽  
Cuiling Wu ◽  
Wenling Guo ◽  
Huiping Li ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Promyelocytic Leukemia ◽  
Risk Group ◽  
Disease Free Survival ◽  
High Risk Group ◽  
Promyelocytic Leukemia ◽  
Free Survival ◽  
Standard Risk ◽  
Disease Free

Abstract OBJECTIVE: The aim of this study was to investigate the clinical biological features, treatment strategy, prognosis and long-term survival in children with acute promyelocytic leukemia（APL）. Focus on the effect of stratified therapy in childhood APL. METHODS: The clinical data of 42 cases of APL with t (15;17) from April 2004 to December 2012 were analyzed retrospectively. Patients were stratified into three risk-group based on white blood cell count and platelet count at diagnosis: standard, intermediate and high-risk group. Induction treatment consisted of all-trans retinoic acid（ATRA）and Idarubicin（IDA）), followed by multi-drug chemotherapy consolidation and a long term maintenance therapy including ATRA,6-Mercaptopurine（6-MP), Methotrexate（MTX）. The complete remission (CR) rate, overall survival (OS) rate, disease free survival (DFS) rate, hematologic and cytogenetic cumulative incidence of relapse (CIR) were compared among the three groups, the stratified therapy in childhood APL and its correlation with clinical prognosis was analyzed. The statistical analyses were performed by SPSS. RESULTS: 42 patients were enrolled (median age 5.8 years, range 1.5-14, 64% males and 36% females), 11 in standard-risk group, 18 in intermediate-risk group, 13 in high-risk group. Immunophenotyping analysis indicated that MPO, CD33, CD13 and CD117 were commonly expressed antigens while HLA-DR and CD34 were mostly the negative markers on APL cells. Of the 42 patients receiving treatment, 38 children (90.5%) achieve complete remission. 1 patient from the high risk group died of intracranial hemorrhage, 1 patient from the Standard Risk group died of anthracycline cardiotoxicity, 1 patient from the intermediate group died of severe infection. The estimated overall survival (OS) rates at 3 and 5 years were （74.2±6.7%）and（70±7.4%）respectively, the disease free survival (DFS) rates were（71±3.8%）and（57±8.1%）respectively. The 3 and 5-year cumulative incidence of relapse (CIR) were 18% and 27%. OS for three groups were (86±7.4%),（71±4、8%）and（57±4.7%）respectively, the 5-year DFS were (82±6.3%), (61±5.3%)and(50±7.2%) and 5-year CIR were 6.7%、18%、35%.There were significant differences in 5-year OS, DFS and CIR rates of three groups (P< 0.05). CONCLUSION: The results indicated that ATRA combined with Anthracycline is effective and safe for treatment of newly diagnosed childhood APL. Prognosis of childhood APL was associated with clinical types. It indicates that stratified therapy according to different risk group can improve the OS and EFS rate and decrease the CIR rate while minimizing chemotherapy-related toxicity. Now, real-time quantitative polymerase chain reaction (RQ-PCR), which can performed to detect PML-RARα fusion transcripts, has become an important means for minimal residual disease (MRD) assays, but it is rarely used in children. Compared with RQ-PCR, clinical risk-adapted classification is a simple, validated and highly predictive index for the determination of stratified therapy in childhood acute promyelocytic leukemia. Disclosures No relevant conflicts of interest to declare.

scholarly journals A novel hyperinflammation clinical risk tool, HI5-NEWS2, predicts mortality following early dexamethasone use in an observational cohort of hospitalised COVID-19 patients.

2021 ◽  
Author(s):  
Michael R Ardern-Jones ◽  
Hang T.T. Phan ◽  
Florina Borca ◽  
Matthew Stammers ◽  
James Batchelor ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Group ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk ◽  
Intermediate Risk ◽  
Dexamethasone Treatment ◽  
Dexamethasone Therapy ◽  
Risk Patients ◽  
Anti Inflammatory

Background The success of early dexamethasone therapy for hospitalised COVID-19 cases in treatment of Sars-CoV-2 infection may predominantly reflect its anti-inflammatory action against a hyperinflammation (HI) response. It is likely that there is substantial heterogeneity in HI responses in COVID-19. Methods Blood CRP, ferritin, neutrophil, lymphocyte and platelet counts were scored to assess HI (HI5) and combined with a validated measure of generalised medical deterioration (NEWS2) before day 2. Our primary outcome was 28 day mortality from early treatment with dexamethasone stratified by HI5-NEWS2 status. Findings Of 1265 patients, high risk of HI (high HI5-NEWS2) (n=367, 29.0%) conferred a strikingly increased mortality (36.0% vs 7.8%; Age adjusted hazard ratio (aHR) 5.9; 95% CI 3.6-9.8, p<0.001) compared to the low risk group (n= 455, 36.0%). An intermediate risk group (n= 443, 35.0%) also showed significantly higher mortality than the low risk group (17.6% vs 7.8%), aHR 2.2, p=0.005). Early dexamethasone treatment conferred a 50.0% reduction in mortality in the high risk group (36.0% to 18.0%, aHR 0.56, p=0.007). The intermediate risk group showed a trend to reduction in mortality (17.8% to 10.3%, aHR 0.82, p=0.46) which was not observed in the low risk group (7.8% to 9.2%, aHR 1.4, p =0.31). Interpretation The HI5-NEWS2 measured at COVID-19 diagnosis, strongly predicts mortality at 28 days. Significant reduction in mortality with early dexamethasone treatment was only observed in the high risk group. Therefore, the HI5-NEWS2 score could be utilised to stratify randomised clinical trials to test whether intensified anti-inflammatory therapy would further benefit high risk patients and whether alternative approaches would benefit low risk groups. Considering its recognised morbidity, we suggest that early dexamethasone should not be routinely prescribed for HI5-NEWS2 low risk individuals with COVID-19 and clinicians should cautiously assess the risk benefit of this intervention. Funding No external funding.

scholarly journals MO315CLINICAL AND PATHOLOGICAL FEATURES OF IGA NEPHROPATHY: A REPORT FROM A SINGLE CENTER

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Anna Lima ◽  
Afonso Santos ◽  
Catarina Brás ◽  
Rita Manso ◽  
Pedro Campos ◽  
...  
Keyword(s):  
High Risk ◽  
Iga Nephropathy ◽  
Risk Group ◽  
Immunosuppressive Treatment ◽  
High Risk Group ◽  
Intermediate Risk ◽  
Risk Patients ◽  
Kidney Disease Progression ◽  
Predicted Risk

Abstract Background and Aims IgA nephropathy (IgAN) is one of the most prevalent glomerulopathies worldwide with broad variable clinical presentation and extremely heterogeneous risk of progressive CKD and ESKD. It was recommended risk stratifying patients in order to target immunosuppressive treatment to high-risk patients. The OXFORD MEST classification and, more recently, a new international risk-prediction tool for IgAN (IgANPT) help to predict kidney outcomes and stratify patient risk, eventually aiding in treatment decision. Here, we analyzed a single center cohort of IgAN to investigate if treatment decisions were accurately accomplished using individualized risk from the IgANPT. Method A retrospective analysis of all kidney biopsies performed from January 2010 to December 2019 in a Nephrology Department was performed and adult patients with IgAN diagnosis were selected. The presence of IgA vasculitis and Henoch-Schönlein purpura as well as lack of follow-up data were exclusion criteria. Clinical, laboratorial and pathological data were collected, including treatment and kidney outcome. Risk of kidney progression decline was assessed by using the on-line web-based calculator of the IgANPT. Results A total of 33 patients met the study criteria, with median age at diagnosis of 58 (IQR 38 - 68) years-old, mostly male (84,8%, N=28) and all Caucasian. At biopsy time 60,6% (N=20) had hypertension, only 15,5% (N=5) diabetes mellitus and 57,6% (N=19) were under ACE inhibitors/ARBs. Median GFR at biopsy time was 57 (IQR 20 - 78,5) ml/min/1.73m2. More than half of the patients (57,6%, N=19) had GFR &lt;60ml/min/1.73m2. All patients had proteinuria (UACR &gt; 300mg/g), with 18,2% (N=6) in the nephrotic range. Hematuria was present in almost all patients. Overall MEST classification was: 51,5% (N= 17) with M1 score, 39,4% (N=13) E1, 66,7% (N=22) S1 and 45,5% (N=15) had T ≥1 score (2 patients with T2). Crescents were present in 27,3% of the biopsies (N=9). Near one-half of the patients (45,5%, N=15) presented IgA deposits on both mesangium and capillary wall. Around one-third of patients (30,3%, N=10) progressed to ESKD during follow up. According to the risk of kidney disease progression in 60-months calculated with IgANPT, patients were stratified into low/intermediate risk in 21,2% (N=7) of cases (mean predicted risk &lt; 4,7%) and high risk in 78,8% (N=26) of cases (mean predicted risk &gt; 4,7%). Using the chi-squared test the high-risk group was associated with progression to ESKD(p=0,019). On the contrary none of the low-risk group progressed to ESKD. The majority of patients received supportive treatment (87,9%, N= 29), mainly with ACEi/ARB (N=31) and omega (15,2%, N=5). Immunosuppressive treatment included mainly corticosteroids (51,5%, N=17), with other options being (12,1% N=4): cyclophosphamide (N=2), ciclosporin (N=1) and MMF (N=1). From the group of low/intermediate risk patients, only two (28,5%) received immunosuppressive treatment with either oral or intravenous corticosteroids. On the other hand, from the high-risk group, more than one third of patients (38,4%, N=10) did not receive immunosuppressive treatment. Conclusion A better prediction of kidney outcomes and consequent better patient selection for IS therapy may be challenging in IgA nephropathy. In spite of the existent tools, it is still difficult to determine which patients benefit from immunosuppressive treatment. In this case series we stratified our patients by using the IgANPT identifying who was at higher risk of progression to ESKD, in whom, a more aggressive treatment could have potentially benefit avoiding kidney disease progression. It was also important to stratify patients at low-risk, in whom immunosuppressive treatment could carry risk of adverse events with no additional advantage in kidney outcomes.

Sign in / Sign up

Export Citation Format

Share Document