Preliminary Results of a Consolidation Therapy Consisting Single Anthracycline Agent and Alternative All-Trans Retinoic Acid in Acute Promyelocytic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4284-4284
Author(s):  
Zhang Jie ◽  
Xiaojian Meng ◽  
Zhen Cai ◽  
Xiujin Ye ◽  
He Huang

Abstract Abstract 4284 Background: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with distinctive biologic and clinical features that is now highly curable. However, there are complicated issues in treatment strategies for induction, consolidation and maintenance that remain to be studied. The optimal regimen and the duration of consolidation is one of the above controversies. Patients and methods: Six patients (4 males, 2 females) were enrolled in this observation with a median age of 28 years (18–36). All were diagnosed de novo APL with demonstration of the abnormal increased promyelocytes of 53–90% accompanied with detection of t(15;17) or PML/RARα rearrangements. At diagnosis, WBC counts were 0.9–4.6×109/L and platelet counts were 13–84×109/L. Induction therapy was composed of all-trans retinoic acid (ATRA) with or without anthracycline or homoharritonine. After achieving complete remission (CR) following the above regimens, consolidation therapy was given monthly consisting single anthracycline agent of idarubincin (8–10 mg/m2/d, day 1–3) or aclarubicin (8–12 mg/m2/d, day 1–7) and alternative ATRA (25 mg/m2/d, day 1–15). After 12–18 months of consolidation, patients received maintenance therapy including methotrexate (12 mg/m2/d, per week) plus 6 mercaptopurine (30 mg/m2/d, qod ×12 days) and alternative ATRA (25 mg/m2/d, day 1–15) for one year. Results and conclusions: At present, all of the six patients are in continuous CR status, four of whom ceased treatment and are undergoing regular monitoring. Preliminary results from our experience demonstrates that single anthracycline and alternative ATRA can act as a valid option with limited toxicity for APL and might be used as a consolidation strategy, particularly for low and intermediate-risk patients. Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 137-137
Author(s):  
Luis Madero ◽  
Pau Montesinos ◽  
Pilar Bastida ◽  
Amparo Verdeguer ◽  
Javier De la Serna ◽  
...  

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 >10×09/l and >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.


1992 ◽  
Vol 65 (3) ◽  
pp. 121-123 ◽  
Author(s):  
P. Hernández ◽  
J. Carnot ◽  
E. Dorticós ◽  
E. Espinosa ◽  
A. González ◽  
...  

Blood ◽  
2010 ◽  
Vol 115 (25) ◽  
pp. 5137-5146 ◽  
Author(s):  
Miguel A. Sanz ◽  
Pau Montesinos ◽  
Chelo Rayón ◽  
Alexandra Holowiecka ◽  
Javier de la Serna ◽  
...  

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.


2005 ◽  
Vol 23 (30) ◽  
pp. 7632-7640 ◽  
Author(s):  
Juan J. Ortega ◽  
Luis Madero ◽  
Guillermo Martín ◽  
Amparo Verdeguer ◽  
Purificación García ◽  
...  

Purpose To analyze the simultaneous combination of all-trans retinoic acid (ATRA) and anthracycline monochemotherapy for children with acute promyelocytic leukemia (APL). Patients and Methods Since November 1996, 66 children (younger than 18 years) with genetically proven APL received induction therapy with ATRA and idarubicin. Consolidation therapy consisted of three courses of anthracycline monochemotherapy. After November 1999, patients with intermediate and high risk of relapse received consolidation therapy with ATRA and slightly reinforced doses of idarubicin. Maintenance therapy consisted of ATRA and low-dose mercaptopurine and methotrexate. Results Thirty-nine girls (59%) and 27 boys (41%) were included in this study. The WBC count at presentation was more than 10 × 109/L in 26 patients (39%). Sixty-one children (92%) achieved complete remission (CR). Early deaths from hemorrhage and retinoic acid syndrome occurred in three patients and two patients, respectively. Toxicity was manageable during consolidation and maintenance therapy. No deaths in CR, clinical cardiomyotoxicity, or secondary malignancy occurred. Two patients had molecular persistence at the end of consolidation. Three clinical relapses and two molecular relapses were also observed. Apart from one molecular relapse, all these events occurred among children with hyperleukocytosis. The 5-year cumulative incidence of relapse was 17%, whereas disease-free and overall survival rates were 82% and 87%, respectively. Conclusion A high incidence of hyperleukocytosis in children with APL was confirmed. Besides low toxicity and a high degree of compliance, a risk-adapted therapy combining ATRA and anthracycline monochemotherapy showed an antileukemic efficacy comparable to those previously reported with other chemotherapy combinations in children.


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