Difference between revisions of "Acute promyelocytic leukemia"

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*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
 
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
−
*[[Daunorubicin (Cerubidine)]] 60 mg/m2 IV on days 3-5
+
*[[Daunorubicin (Cerubidine)]] 60 mg/m2 IV on days 3 to 5
−
*[[Cytarabine (Cytosar)]] 200 mg/m2 IV on days 3-9
+
*[[Cytarabine (Cytosar)]] 200 mg/m2 IV on days 3 to 9
  
 
'''9-day course of initial induction chemotherapy, with ongoing use of ATRA'''
 
'''9-day course of initial induction chemotherapy, with ongoing use of ATRA'''
Line 24: Line 24:
 
If >60 years old and WBC <10 x 10^9/L:
 
If >60 years old and WBC <10 x 10^9/L:
 
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
 
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
−
*[[Daunorubicin (Cerubidine)]] 60 mg/m2 IV on days 3-5
+
*[[Daunorubicin (Cerubidine)]] 60 mg/m2 IV on days 3 to 5
  
 
To be followed by [[#APL_2000_.28EAPLG.29_consolidation|APL 2000 (EAPLG) consolidation]] therapy.
 
To be followed by [[#APL_2000_.28EAPLG.29_consolidation|APL 2000 (EAPLG) consolidation]] therapy.
Line 34: Line 34:
 
==North American Leukemia Intergroup Study C9710 induction==
 
==North American Leukemia Intergroup Study C9710 induction==
 
===Regimen===
 
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
 
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m2 IV on days 3-6
+
*[[Daunorubicin (Cerubidine)]] 50 mg/m2 IV on days 3 to 6
−
*[[Cytarabine (Cytosar)]] 200 mg/m2/day IV continuous infusion on days 3-9
+
*[[Cytarabine (Cytosar)]] 200 mg/m2/day IV continuous infusion on days 3 to 9
  
 
'''9-day initial induction chemotherapy, with ongoing use of ATRA'''
 
'''9-day initial induction chemotherapy, with ongoing use of ATRA'''
Line 59: Line 67:
 
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
 
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
 
:*For patients <20 years old, [[All-trans retinoic acid (ATRA)]] dose was 25 mg/m2/day, divided into two equal doses PO BID
 
:*For patients <20 years old, [[All-trans retinoic acid (ATRA)]] dose was 25 mg/m2/day, divided into two equal doses PO BID
−
*[[Idarubicin (Idamycin)]] 12 mg/m2 IV days 2, 4, 6, 8
+
*[[Idarubicin (Idamycin)]] 12 mg/m2 IV once on days 2, 4, 6, 8
  
 
'''8-day initial induction chemotherapy, with ongoing use of ATRA'''
 
'''8-day initial induction chemotherapy, with ongoing use of ATRA'''
Line 88: Line 96:
 
==Arsenic monotherapy==
 
==Arsenic monotherapy==
 
===Regimen===
 
===Regimen===
−
*[[Arsenic trioxide (Trisenox)]] 10 mg (0.15 mg/kg for pediatric patients) IV over 2-3 hours daily  
+
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
 +
*[[Arsenic trioxide (Trisenox)]] 10 mg (0.15 mg/kg for pediatric patients) IV over 2 to 3 hours daily  
  
 
'''given until complete remission (CR) or maximum of 75 days (maximum of 60 days after 2001)'''
 
'''given until complete remission (CR) or maximum of 75 days (maximum of 60 days after 2001)'''
  
 
''If in CR, wait 4 weeks, then:''
 
''If in CR, wait 4 weeks, then:''
−
*[[Arsenic trioxide (Trisenox)]] 10 mg (0.15 mg/kg for pediatric patients) IV over 2-3 hours daily x 28 days
+
*[[Arsenic trioxide (Trisenox)]] 10 mg (0.15 mg/kg for pediatric patients) IV over 2 to 3 hours daily x 28 days
  
 
'''28-day course'''
 
'''28-day course'''
  
 
''If in CR, wait 4 weeks, then:''
 
''If in CR, wait 4 weeks, then:''
−
*[[Arsenic trioxide (Trisenox)]] 10 mg (0.15 mg/kg for pediatric patients) IV over 2-3 hours daily x "10 days a month"
+
*[[Arsenic trioxide (Trisenox)]] 10 mg (0.15 mg/kg for pediatric patients) IV over 2 to 3 hours daily x "10 days a month"
  
 
'''1-month cycles x 6 months'''
 
'''1-month cycles x 6 months'''
  
 
===References===
 
===References===
 +
# Shen ZX, Shi ZZ, Fang J, Gu BW, Li JM, Zhu YM, Shi JY, Zheng PZ, Yan H, Liu YF, Chen Y, Shen Y, Wu W, Tang W, Waxman S, De Thé H, Wang ZY, Chen SJ, Chen Z. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5328-35. Epub 2004 Mar 24. [http://www.pnas.org/content/101/15/5328.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15044693 PubMed]
 
# Mathews V, George B, Lakshmi KM, Viswabandya A, Bajel A, Balasubramanian P, Shaji RV, Srivastava VM, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood. 2006 Apr 1;107(7):2627-32. Epub 2005 Dec 13. [http://bloodjournal.hematologylibrary.org/content/107/7/2627.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16352810 PubMed]
 
# Mathews V, George B, Lakshmi KM, Viswabandya A, Bajel A, Balasubramanian P, Shaji RV, Srivastava VM, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood. 2006 Apr 1;107(7):2627-32. Epub 2005 Dec 13. [http://bloodjournal.hematologylibrary.org/content/107/7/2627.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16352810 PubMed]
 
# Mathews V, George B, Chendamarai E, Lakshmi KM, Desire S, Balasubramanian P,Viswabandya A, Thirugnanam R, Abraham A, Shaji RV, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol. 2010 Aug 20;28(24):3866-71. doi: 10.1200/JCO.2010.28.5031. Epub 2010 Jul 19. [http://jco.ascopubs.org/content/28/24/3866.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/20644086 PubMed]
 
# Mathews V, George B, Chendamarai E, Lakshmi KM, Desire S, Balasubramanian P,Viswabandya A, Thirugnanam R, Abraham A, Shaji RV, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol. 2010 Aug 20;28(24):3866-71. doi: 10.1200/JCO.2010.28.5031. Epub 2010 Jul 19. [http://jco.ascopubs.org/content/28/24/3866.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/20644086 PubMed]
Line 108: Line 125:
 
==ATRA & Arsenic==
 
==ATRA & Arsenic==
 
===Regimen===
 
===Regimen===
 +
Level of Evidence:
 +
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
Estey 2006:
 
Estey 2006:
 
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
 
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.
Line 138: Line 163:
  
 
===Consolidation regimen for patients ≤60 years old and WBC <10 x 10^9/L or age >60 and WBC >10 x 10^9/L===
 
===Consolidation regimen for patients ≤60 years old and WBC <10 x 10^9/L or age >60 and WBC >10 x 10^9/L===
−
*[[Daunorubicin (Cerubidine)]] 60 mg/m2 IV on days 1-3
+
*[[Daunorubicin (Cerubidine)]] 60 mg/m2 IV on days 1 to 3
−
*[[Cytarabine (Cytosar)]] 200 mg/m2 IV on days 1-7
+
*[[Cytarabine (Cytosar)]] 200 mg/m2 IV on days 1 to 7
  
 
Followed by:
 
Followed by:
−
*[[Daunorubicin (Cerubidine)]] 45 mg/m2 IV on days 1-3
+
*[[Daunorubicin (Cerubidine)]] 45 mg/m2 IV on days 1 to 3
−
*[[Cytarabine (Cytosar)]] 1000 mg/m2 IV every 12 hours on days 1-4 (8 total doses)
+
*[[Cytarabine (Cytosar)]] 1000 mg/m2 IV every 12 hours on days 1 to 4 (8 total doses)
  
 
'''Note: Adès, et al. 2006 and Adès, et al. 2008 both do not say that IT chemotherapy is used for patients with age >60 and WBC >10 x 10^9/L, but figure 1 in Adès, et al. 2006 depicts IT chemotherapy in this patient group.  I did not see a reference that clearly resolved this contradiction.'''
 
'''Note: Adès, et al. 2006 and Adès, et al. 2008 both do not say that IT chemotherapy is used for patients with age >60 and WBC >10 x 10^9/L, but figure 1 in Adès, et al. 2006 depicts IT chemotherapy in this patient group.  I did not see a reference that clearly resolved this contradiction.'''
  
 
===Consolidation regimen for patients ≤60 years old and WBC >10 x 10^9/L===
 
===Consolidation regimen for patients ≤60 years old and WBC >10 x 10^9/L===
−
*[[Daunorubicin (Cerubidine)]] 60 mg/m2 IV on days 1-3
+
*[[Daunorubicin (Cerubidine)]] 60 mg/m2 IV on days 1 to 3
−
*[[Cytarabine (Cytosar)]] 200 mg/m2 IV on days 1-7
+
*[[Cytarabine (Cytosar)]] 200 mg/m2 IV on days 1 to 7
 
*3 doses of intrathecal chemotherapy with [[Methotrexate (MTX)]] 15 mg IT, [[Cytarabine (Cytosar)]] 50 mg IT, and corticosteroids
 
*3 doses of intrathecal chemotherapy with [[Methotrexate (MTX)]] 15 mg IT, [[Cytarabine (Cytosar)]] 50 mg IT, and corticosteroids
  
 
Followed by:
 
Followed by:
−
*[[Daunorubicin (Cerubidine)]] 45 mg/m2 IV on days 1-3
+
*[[Daunorubicin (Cerubidine)]] 45 mg/m2 IV on days 1 to 3
−
*If age <50 years old: [[Cytarabine (Cytosar)]] 2000 mg/m2 IV every 12 hours on days 1-5 (10 total doses)
+
*If age <50 years old: [[Cytarabine (Cytosar)]] 2000 mg/m2 IV every 12 hours on days 1 to 5 (10 total doses)
−
*If age 50-60 years old: [[Cytarabine (Cytosar)]] 1500 mg/m2 IV every 12 hours on days 1-5 (10 total doses)
+
*If age 50-60 years old: [[Cytarabine (Cytosar)]] 1500 mg/m2 IV every 12 hours on days 1 to 5 (10 total doses)
 
*2 doses of intrathecal chemotherapy with [[Methotrexate (MTX)]] 15 mg IT, [[Cytarabine (Cytosar)]] 50 mg IT, and corticosteroids
 
*2 doses of intrathecal chemotherapy with [[Methotrexate (MTX)]] 15 mg IT, [[Cytarabine (Cytosar)]] 50 mg IT, and corticosteroids
  
 
===Consolidation regimen for patients >60 years old and WBC <10 x 10^9/L===
 
===Consolidation regimen for patients >60 years old and WBC <10 x 10^9/L===
−
*[[Daunorubicin (Cerubidine)]] 60 mg/m2 IV on days 1-3
+
*[[Daunorubicin (Cerubidine)]] 60 mg/m2 IV on days 1 to 3
  
 
Followed by:
 
Followed by:
−
*[[Daunorubicin (Cerubidine)]] 45 mg/m2 IV on days 1-3
+
*[[Daunorubicin (Cerubidine)]] 45 mg/m2 IV on days 1 to 3
  
 
To be followed by [[#APL_2000_.28EAPLG.29_maintenance|APL 2000 (EAPLG) maintenance]] therapy.
 
To be followed by [[#APL_2000_.28EAPLG.29_maintenance|APL 2000 (EAPLG) maintenance]] therapy.
Line 173: Line 198:
 
Preceded by [[#North_American_Leukemia_Intergroup_Study_C9710_induction|North American Leukemia Intergroup Study C9710 induction]] therapy.
 
Preceded by [[#North_American_Leukemia_Intergroup_Study_C9710_induction|North American Leukemia Intergroup Study C9710 induction]] therapy.
 
===Regimen===
 
===Regimen===
−
Consolidation therapy starts within 2-4 weeks of hematologic remission:
+
Level of Evidence:
−
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV days 1-5, 8-12, 15-19, 22-26, 29-33
+
<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
 
 +
Consolidation therapy starts within 2 to 4 weeks of hematologic remission:
 +
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV once daily on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
  
 
'''7-week cycles (5 weeks of therapy, then 2 weeks off), THEN'''
 
'''7-week cycles (5 weeks of therapy, then 2 weeks off), THEN'''
  
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, starting days 1-7
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, starting days 1 to 7
−
*[[Daunorubicin (Cerubidine)]] 50 mg/m2 IV days 1-3
+
*[[Daunorubicin (Cerubidine)]] 50 mg/m2 IV once daily on days 1 to 3
  
 
'''7-day cycles x 2 cycles'''
 
'''7-day cycles x 2 cycles'''
Line 201: Line 234:
  
 
As detailed in Avvisati, et al., 2002:
 
As detailed in Avvisati, et al., 2002:
−
*[[Idarubicin (Idamycin)]] 5 mg/m2 IV days 1-4 (administered second, 3 hours after cytarabine infusion complete)
+
*[[Idarubicin (Idamycin)]] 5 mg/m2 IV once daily on days 1 to 4 (administered second, 3 hours after cytarabine infusion complete)
−
*[[Cytarabine (Cytosar)]] 1000 mg/m2 IV over 6 hours on days 1-4 (administered first)
+
*[[Cytarabine (Cytosar)]] 1000 mg/m2 IV over 6 hours on days 1 to 4 (administered first)
  
 
'''4-day course of therapy, THEN'''
 
'''4-day course of therapy, THEN'''
  
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV days 1-5 (administered first)
+
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV once daily on days 1 to 5 (administered first)
−
*[[Etoposide (Vepesid)]] 100 mg/m2 IV over 45-60 minutes (administered second, 12 hours after start of mitoxantrone) days 1-5
+
*[[Etoposide (Vepesid)]] 100 mg/m2 IV over 45 to 60 minutes (administered second, 12 hours after start of mitoxantrone) days 1 to 5
  
 
'''5-day course of therapy, THEN'''
 
'''5-day course of therapy, THEN'''
  
 
*[[Idarubicin (Idamycin)]] 12 mg/m2 IV day 1
 
*[[Idarubicin (Idamycin)]] 12 mg/m2 IV day 1
−
*[[Cytarabine (Cytosar)]] 150 mg/m2 SC every 8 hours (450 mg/m2/day total dosage) days 1-5
+
*[[Cytarabine (Cytosar)]] 150 mg/m2 SC every 8 hours (450 mg/m2/day total dosage) days 1 to 5
−
*[[Thioguanine (Tabloid)]] 70 mg/m2 PO every 8 hours (210 mg/m2/day total dosage) days 1-5
+
*[[Thioguanine (Tabloid)]] 70 mg/m2 PO every 8 hours (210 mg/m2/day total dosage) days 1 to 5
  
 
'''5-day course of therapy'''
 
'''5-day course of therapy'''
Line 229: Line 262:
 
===Regimen===
 
===Regimen===
 
High risk:
 
High risk:
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
−
*[[Idarubicin (Idamycin)]] 7 mg/m2 IV days 1-4
+
*[[Idarubicin (Idamycin)]] 7 mg/m2 IV once daily on days 1 to 4
  
 
'''1-month cycle, THEN'''
 
'''1-month cycle, THEN'''
  
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV days 1-5
+
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV once daily on days 1 to 5
  
 
'''1-month cycle, THEN'''
 
'''1-month cycle, THEN'''
  
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
−
*[[Idarubicin (Idamycin)]] 12 mg/m2 IV days 1 & 2
+
*[[Idarubicin (Idamycin)]] 12 mg/m2 IV once on days 1 & 2
  
 
'''1-month cycle'''
 
'''1-month cycle'''
  
 
Intermediate risk:
 
Intermediate risk:
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
−
*[[Idarubicin (Idamycin)]] 7 mg/m2 IV days 1-4
+
*[[Idarubicin (Idamycin)]] 7 mg/m2 IV once daily on days 1 to 4
  
 
'''1-month cycle, THEN'''
 
'''1-month cycle, THEN'''
  
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV days 1-5
+
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV once daily on days 1 to 5
  
 
'''1-month cycle, THEN'''
 
'''1-month cycle, THEN'''
  
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
−
*[[Idarubicin (Idamycin)]] 12 mg/m2 IV days 1 & 2
+
*[[Idarubicin (Idamycin)]] 12 mg/m2 IV once on days 1 & 2
  
 
'''1-month cycle'''
 
'''1-month cycle'''
  
 
Low risk:
 
Low risk:
−
*[[Idarubicin (Idamycin)]] 5 mg/m2 IV days 1-4
+
*[[Idarubicin (Idamycin)]] 5 mg/m2 IV once daily on days 1 to 4
  
 
'''1-month cycle, THEN'''
 
'''1-month cycle, THEN'''
  
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV days 1-5
+
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV once daily on days 1 to 5
  
 
'''1-month cycle, THEN'''
 
'''1-month cycle, THEN'''
Line 284: Line 317:
 
===Regimen===
 
===Regimen===
 
High risk:
 
High risk:
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
−
*[[Idarubicin (Idamycin)]] 5 mg/m2 IV days 1-4
+
*[[Idarubicin (Idamycin)]] 5 mg/m2 IV once daily on days 1 to 4
−
*[[Cytarabine (Cytosar)]] 1000 mg/m2 IV days 1-4
+
*[[Cytarabine (Cytosar)]] 1000 mg/m2 IV once daily on days 1 to 4
  
 
'''1-month cycle, THEN'''
 
'''1-month cycle, THEN'''
  
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV days 1-5
+
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV once daily on days 1 to 5
  
 
'''1-month cycle, THEN'''
 
'''1-month cycle, THEN'''
  
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
 
*[[Idarubicin (Idamycin)]] 12 mg/m2 IV day 1
 
*[[Idarubicin (Idamycin)]] 12 mg/m2 IV day 1
−
*[[Cytarabine (Cytosar)]] 150 mg/m2, IV every 8 hours (total dose of 450 mg/m2/day), days 1-4 (12 total doses)
+
*[[Cytarabine (Cytosar)]] 150 mg/m2, IV every 8 hours (total dose of 450 mg/m2/day), days 1 to 4 (12 total doses)
  
 
'''1-month cycle'''
 
'''1-month cycle'''
  
 
Intermediate risk:
 
Intermediate risk:
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
−
*[[Idarubicin (Idamycin)]] 7 mg/m2 IV days 1-4
+
*[[Idarubicin (Idamycin)]] 7 mg/m2 IV once daily on days 1 to 4
  
 
'''1-month cycle, THEN'''
 
'''1-month cycle, THEN'''
  
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV days 1-3
+
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV once daily on days 1 to 3
  
 
'''1-month cycle, THEN'''
 
'''1-month cycle, THEN'''
  
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
−
*[[Idarubicin (Idamycin)]] 12 mg/m2 IV days 1 & 2
+
*[[Idarubicin (Idamycin)]] 12 mg/m2 IV once on days 1 & 2
  
 
'''1-month cycle'''
 
'''1-month cycle'''
  
 
Low risk:
 
Low risk:
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
−
*[[Idarubicin (Idamycin)]] 5 mg/m2 IV days 1-4
+
*[[Idarubicin (Idamycin)]] 5 mg/m2 IV once daily on days 1 to 4
  
 
'''1-month cycle, THEN'''
 
'''1-month cycle, THEN'''
  
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV days 1-3
+
*[[Mitoxantrone (Novantrone)]] 10 mg/m2 IV once daily on days 1 to 3
  
 
'''1-month cycle, THEN'''
 
'''1-month cycle, THEN'''
  
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, days 1 to 15
−
*[[Idarubicin (Idamycin)]] 12 mg/m2 IV day 1
+
*[[Idarubicin (Idamycin)]] 12 mg/m2 IV once on day 1
  
 
'''1-month cycle'''
 
'''1-month cycle'''
Line 342: Line 375:
 
Preceded by [[#ATRA_.26_arsenic|ATRA & arsenic]] induction therapy.
 
Preceded by [[#ATRA_.26_arsenic|ATRA & arsenic]] induction therapy.
 
===Regimen===
 
===Regimen===
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, 7 days per week on weeks 1-2, 5-6, 9-10, 13-14, 17-18, 21-22, 25-26
+
Level of Evidence:
−
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV over 1 hour daily, 5 consecutive days per week on weeks 1-4, 9-12, 17-20, 25-28
+
<span
 +
style="background:#EEEE00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase II</span>
 +
 
 +
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID, 7 days per week on weeks 1 to 2, 5 to 6, 9 to 10, 13 to 14, 17 to 18, 21 to 22, 25 to 26
 +
*[[Arsenic trioxide (Trisenox)]] 0.15 mg/kg IV over 1 hour daily, 5 consecutive days per week on weeks 1 to 4, 9 to 12, 17 to 20, 25 to 28
  
 
'''28 weeks of therapy'''
 
'''28 weeks of therapy'''
Line 365: Line 406:
 
*[[Mercaptopurine (Purinethol)]] 50-90 mg/m2 PO daily  
 
*[[Mercaptopurine (Purinethol)]] 50-90 mg/m2 PO daily  
 
*[[Methotrexate (MTX)]] 15 mg/m2 PO weekly  
 
*[[Methotrexate (MTX)]] 15 mg/m2 PO weekly  
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID on days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID on days 1 to 15
  
 
'''90-day cycles x 2 years'''
 
'''90-day cycles x 2 years'''
Line 376: Line 417:
 
Preceded by [[#North_American_Leukemia_Intergroup_Study_C9710_consolidation|North American Leukemia Intergroup Study C9710 consolidation]] therapy.
 
Preceded by [[#North_American_Leukemia_Intergroup_Study_C9710_consolidation|North American Leukemia Intergroup Study C9710 consolidation]] therapy.
 
===Regimen===
 
===Regimen===
−
Maintenance therapy starts 2-4 weeks after recovery from consolidation therapy:
+
Maintenance therapy starts 2 to 4 weeks after recovery from consolidation therapy:
 
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID x 7 days every other week
 
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID x 7 days every other week
 
With or without:
 
With or without:
Line 406: Line 447:
  
 
Part B:
 
Part B:
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID on days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID on days 1 to 15
  
 
'''15-day course of therapy'''
 
'''15-day course of therapy'''
Line 425: Line 466:
 
<br>Preceded by [[#PETHEMA_LPA99_consolidation|PETHEMA LPA99]] or [[#PETHEMA_LPA2005_consolidation|PETHEMA LPA2005]] consolidation therapy.
 
<br>Preceded by [[#PETHEMA_LPA99_consolidation|PETHEMA LPA99]] or [[#PETHEMA_LPA2005_consolidation|PETHEMA LPA2005]] consolidation therapy.
 
===Regimen===
 
===Regimen===
−
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID on days 1-15
+
*[[All-trans retinoic acid (ATRA)]] 45 mg/m2/day, divided into two equal doses PO BID on days 1 to 15
 
*[[Mercaptopurine (Purinethol)]] 50 mg/m2 PO daily  
 
*[[Mercaptopurine (Purinethol)]] 50 mg/m2 PO daily  
 
*[[Methotrexate (MTX)]] 15 mg/m2 IM weekly
 
*[[Methotrexate (MTX)]] 15 mg/m2 IM weekly
Line 462: Line 503:
  
 
'''Consolidation #3'''
 
'''Consolidation #3'''
−
*[[Cytarabine (Cytosar)]] 2 g/m2 IV over 3 hours twice daily on days 1-4 (8 doses, total)
+
*[[Cytarabine (Cytosar)]] 2 g/m2 IV over 3 hours twice daily on days 1 to 4 (8 doses, total)
 
*[[Filgrastim (Neupogen)]] starting on day 6 (dose, frequency not specified)
 
*[[Filgrastim (Neupogen)]] starting on day 6 (dose, frequency not specified)
  

Revision as of 20:01, 5 July 2013

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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.


Induction therapy

APL 2000 (EAPLG) induction

Regimen

Level of Evidence: Phase III

9-day course of initial induction chemotherapy, with ongoing use of ATRA

If >60 years old and WBC <10 x 10^9/L:

To be followed by APL 2000 (EAPLG) consolidation therapy.

References

  1. Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; European Acute Promyelocytic Leukemia Group. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. Epub 2006 Nov 20. link to original article contains verified protocol PubMed
  2. Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. link to original article contains verified protocol PubMed

North American Leukemia Intergroup Study C9710 induction

Regimen

Level of Evidence: Phase III

9-day initial induction chemotherapy, with ongoing use of ATRA

To be followed by North American Leukemia Intergroup Study C9710 consolidation therapy.

References

  1. Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. link to original article contains verified protocol PubMed

AIDA 0493 induction

AIDA: ATRA, IDArubicin

Regimen

Level of Evidence: Phase II

  • All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, starting day 1 and continuing until remission or maximum of 90 days.

8-day initial induction chemotherapy, with ongoing use of ATRA

To be followed by AIDA 0493 consolidation therapy.

References

  1. Avvisati G, Lo Coco F, Diverio D, Falda M, Ferrara F, Lazzarino M, Russo D, Petti MC, Mandelli F. AIDA (all-trans retinoic acid + idarubicin) in newly diagnosed acute promyelocytic leukemia: a Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) pilot study. Blood. 1996 Aug 15;88(4):1390-8. link to full article contains verified protocol PubMed
  2. Latagliata R, Breccia M, Fazi P, Vignetti M, Di Raimondo F, Sborgia M, Vincelli D, Candoni A, Salvi F, Rupoli S, Martinelli G, Kropp MG, Tonso A, Venditti A, Melillo L, Cimino G, Petti MC, Avvisati G, Lo-Coco F, Mandelli F; GIMEMA Acute Leukaemia Working Party. GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia. Long-term results and prognostic factors. Br J Haematol. 2011 Sep;154(5):564-8. doi: 10.1111/j.1365-2141.2011.08593.x. Epub 2011 Jul 14. link to full article contains verified protocol PubMed
  3. Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA, AIEOP, and EORTC Cooperative Groups. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. link to original article contains verified protocol PubMed

PETHEMA LPA99, LPA2005 induction

PETHEMA: Programa Español de Tratamientos en HEMAtología

Regimen

8-day initial induction chemotherapy, with ongoing use of ATRA

To be followed by PETHEMA LPA99 or PETHEMA LPA2005 consolidation therapy.

References

  1. Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. link to original article contains verified protocol PubMed
  2. Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA and HOVON Groups. 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 Jun 24;115(25):5137-46. Epub 2010 Apr 14. link to original article contains verified protocol PubMed

Arsenic monotherapy

Regimen

Level of Evidence: Phase III

given until complete remission (CR) or maximum of 75 days (maximum of 60 days after 2001)

If in CR, wait 4 weeks, then:

28-day course

If in CR, wait 4 weeks, then:

1-month cycles x 6 months

References

  1. Shen ZX, Shi ZZ, Fang J, Gu BW, Li JM, Zhu YM, Shi JY, Zheng PZ, Yan H, Liu YF, Chen Y, Shen Y, Wu W, Tang W, Waxman S, De Thé H, Wang ZY, Chen SJ, Chen Z. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5328-35. Epub 2004 Mar 24. link to original article contains verified protocol PubMed
  2. Mathews V, George B, Lakshmi KM, Viswabandya A, Bajel A, Balasubramanian P, Shaji RV, Srivastava VM, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood. 2006 Apr 1;107(7):2627-32. Epub 2005 Dec 13. link to original article contains verified protocol PubMed
  3. Mathews V, George B, Chendamarai E, Lakshmi KM, Desire S, Balasubramanian P,Viswabandya A, Thirugnanam R, Abraham A, Shaji RV, Srivastava A, Chandy M. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol. 2010 Aug 20;28(24):3866-71. doi: 10.1200/JCO.2010.28.5031. Epub 2010 Jul 19. link to original article PubMed

ATRA & Arsenic

Regimen

Level of Evidence: Phase III

Estey 2006:

To be followed by ATRA & arsenic consolidation therapy.

Alternate regimen (Shen 2004):

References

  1. Shen ZX, Shi ZZ, Fang J, Gu BW, Li JM, Zhu YM, Shi JY, Zheng PZ, Yan H, Liu YF, Chen Y, Shen Y, Wu W, Tang W, Waxman S, De Thé H, Wang ZY, Chen SJ, Chen Z. All-trans retinoic acid/As2O3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5328-35. Epub 2004 Mar 24. link to original article contains verified protocol PubMed
  2. Estey E, Garcia-Manero G, Ferrajoli A, Faderl S, Verstovsek S, Jones D, Kantarjian H. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006 May 1;107(9):3469-73. Epub 2005 Dec 22. link to original article contains verified protocol PubMed

Consolidation therapy

APL 2000 (EAPLG) consolidation

Preceded by APL 2000 (EAPLG) induction therapy.

Regimen

Level of Evidence: Phase III

Consolidation regimen for patients ≤60 years old and WBC <10 x 10^9/L or age >60 and WBC >10 x 10^9/L

Followed by:

Note: Adès, et al. 2006 and Adès, et al. 2008 both do not say that IT chemotherapy is used for patients with age >60 and WBC >10 x 10^9/L, but figure 1 in Adès, et al. 2006 depicts IT chemotherapy in this patient group. I did not see a reference that clearly resolved this contradiction.

Consolidation regimen for patients ≤60 years old and WBC >10 x 10^9/L

Followed by:

Consolidation regimen for patients >60 years old and WBC <10 x 10^9/L

Followed by:

To be followed by APL 2000 (EAPLG) maintenance therapy.

References

  1. Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; European Acute Promyelocytic Leukemia Group. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. Epub 2006 Nov 20. link to original article contains verified protocol PubMed
  2. Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. link to original article contains verified protocol PubMed

North American Leukemia Intergroup Study C9710 consolidation

Preceded by North American Leukemia Intergroup Study C9710 induction therapy.

Regimen

Level of Evidence: Phase III

Consolidation therapy starts within 2 to 4 weeks of hematologic remission:

7-week cycles (5 weeks of therapy, then 2 weeks off), THEN

7-day cycles x 2 cycles

To be followed by North American Leukemia Intergroup Study C9710 maintenance therapy.

References

  1. Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. link to original article contains verified protocol PubMed

AIDA 0493 consolidation

AIDA: ATRA, IDArubicin
Preceded by AIDA 0493 induction therapy.

Regimen

Level of Evidence: Phase III

As detailed in Avvisati, et al., 2002:

  • Idarubicin (Idamycin) 5 mg/m2 IV once daily on days 1 to 4 (administered second, 3 hours after cytarabine infusion complete)
  • Cytarabine (Cytosar) 1000 mg/m2 IV over 6 hours on days 1 to 4 (administered first)

4-day course of therapy, THEN

5-day course of therapy, THEN

5-day course of therapy

To be followed by AIDA 0493 maintenance therapy.

References

  1. Avvisati G, Petti MC, Lo-Coco F, Vegna ML, Amadori S, Baccarani M, Cantore N, Di Bona E, Ferrara F, Fioritoni G, Gallo E, Invernizzi R, Lazzarino M, Liso V, Mariani G, Ricciuti F, Selleri C, Sica S, Veneri D, Mandelli F; GIMEMA (Gruppo Italiano Malattie Ematologische dell'Adulto) Italian Cooperative Group. Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up. Blood. 2002 Nov 1;100(9):3141-6. link to original article contains verified protocol PubMed
  2. Latagliata R, Breccia M, Fazi P, Vignetti M, Di Raimondo F, Sborgia M, Vincelli D, Candoni A, Salvi F, Rupoli S, Martinelli G, Kropp MG, Tonso A, Venditti A, Melillo L, Cimino G, Petti MC, Avvisati G, Lo-Coco F, Mandelli F; GIMEMA Acute Leukaemia Working Party. GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia. Long-term results and prognostic factors. Br J Haematol. 2011 Sep;154(5):564-8. doi: 10.1111/j.1365-2141.2011.08593.x. Epub 2011 Jul 14. link to full article contains verified protocol PubMed
  3. Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA, AIEOP, and EORTC Cooperative Groups. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. link to original article contains verified protocol PubMed

PETHEMA LPA99 consolidation

PETHEMA: Programa Español de Tratamientos en HEMAtología
Preceded by PETHEMA LPA99, LPA2005 induction therapy.

Regimen

High risk:

1-month cycle, THEN

1-month cycle, THEN

1-month cycle

Intermediate risk:

1-month cycle, THEN

1-month cycle, THEN

1-month cycle

Low risk:

1-month cycle, THEN

1-month cycle, THEN

1-month cycle

To be followed by PETHEMA LPA99, LPA2005 maintenance therapy.

References

  1. Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. link to original article contains verified protocol PubMed
  2. Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA and HOVON Groups. 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 Jun 24;115(25):5137-46. Epub 2010 Apr 14. link to original article contains verified protocol PubMed

PETHEMA LPA2005 consolidation

PETHEMA: Programa Español de Tratamientos en HEMAtología
Preceded by PETHEMA LPA99, LPA2005 induction therapy.

Regimen

High risk:

1-month cycle, THEN

1-month cycle, THEN

1-month cycle

Intermediate risk:

1-month cycle, THEN

1-month cycle, THEN

1-month cycle

Low risk:

1-month cycle, THEN

1-month cycle, THEN

1-month cycle

To be followed by PETHEMA LPA99, LPA2005 maintenance therapy.

References

  1. Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. link to original article contains verified protocol PubMed
  2. Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA and HOVON Groups. 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 Jun 24;115(25):5137-46. Epub 2010 Apr 14. link to original article contains verified protocol PubMed

ATRA & arsenic - consolidation

Preceded by ATRA & arsenic induction therapy.

Regimen

Level of Evidence: Phase II

  • All-trans retinoic acid (ATRA) 45 mg/m2/day, divided into two equal doses PO BID, 7 days per week on weeks 1 to 2, 5 to 6, 9 to 10, 13 to 14, 17 to 18, 21 to 22, 25 to 26
  • Arsenic trioxide (Trisenox) 0.15 mg/kg IV over 1 hour daily, 5 consecutive days per week on weeks 1 to 4, 9 to 12, 17 to 20, 25 to 28

28 weeks of therapy

References

  1. Estey E, Garcia-Manero G, Ferrajoli A, Faderl S, Verstovsek S, Jones D, Kantarjian H. Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia. Blood. 2006 May 1;107(9):3469-73. Epub 2005 Dec 22. link to original article contains verified protocol PubMed

Maintenance therapy

APL 2000 (EAPLG) maintenance

Preceded by APL 2000 (EAPLG) consolidation therapy.

Regimen

Level of Evidence: Phase III

90-day cycles x 2 years

References

  1. Adès L, Chevret S, Raffoux E, de Botton S, Guerci A, Pigneux A, Stoppa AM, Lamy T, Rigal-Huguet F, Vekhoff A, Meyer-Monard S, Maloisel F, Deconinck E, Ferrant A, Thomas X, Fegueux N, Chomienne C, Dombret H, Degos L, Fenaux P; European Acute Promyelocytic Leukemia Group. Is cytarabine useful in the treatment of acute promyelocytic leukemia? Results of a randomized trial from the European Acute Promyelocytic Leukemia Group. J Clin Oncol. 2006 Dec 20;24(36):5703-10. Epub 2006 Nov 20. link to original article contains verified protocol PubMed
  2. Adès L, Sanz MA, Chevret S, Montesinos P, Chevallier P, Raffoux E, Vellenga E, Guerci A, Pigneux A, Huguet F, Rayon C, Stoppa AM, de la Serna J, Cahn JY, Meyer-Monard S, Pabst T, Thomas X, de Botton S, Parody R, Bergua J, Lamy T, Vekhoff A, Negri S, Ifrah N, Dombret H, Ferrant A, Bron D, Degos L, Fenaux P. Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results. Blood. 2008 Feb 1;111(3):1078-84. Epub 2007 Nov 1. link to original article contains verified protocol PubMed

North American Leukemia Intergroup Study C9710 maintenance

Preceded by North American Leukemia Intergroup Study C9710 consolidation therapy.

Regimen

Maintenance therapy starts 2 to 4 weeks after recovery from consolidation therapy:

With or without:

1 year of therapy

References

  1. Powell BL, Moser B, Stock W, Gallagher RE, Willman CL, Stone RM, Rowe JM, Coutre S, Feusner JH, Gregory J, Couban S, Appelbaum FR, Tallman MS, Larson RA. Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710. Blood. 2010 Nov 11;116(19):3751-7. Epub 2010 Aug 12. link to original article contains verified protocol PubMed

AIDA 0493 maintenance

Preceded by AIDA 0493 consolidation therapy.

Regimen

Level of Evidence: Phase III

See Avvisati, et al. 2011 for details about outcomes with or without maintenance therapy. Treatment options investigated included only using Part A, only using Part B, or alternating between the two, in all cases for a total of 2 years.
Part A:

90-day course of therapy, THEN

Part B:

15-day course of therapy

Alternate regimen (Avvisati, et al. 2002)

2-year course of therapy

References

  1. Avvisati G, Petti MC, Lo-Coco F, Vegna ML, Amadori S, Baccarani M, Cantore N, Di Bona E, Ferrara F, Fioritoni G, Gallo E, Invernizzi R, Lazzarino M, Liso V, Mariani G, Ricciuti F, Selleri C, Sica S, Veneri D, Mandelli F; GIMEMA (Gruppo Italiano Malattie Ematologische dell'Adulto) Italian Cooperative Group. Induction therapy with idarubicin alone significantly influences event-free survival duration in patients with newly diagnosed hypergranular acute promyelocytic leukemia: final results of the GIMEMA randomized study LAP 0389 with 7 years of minimal follow-up. Blood. 2002 Nov 1;100(9):3141-6. link to original article contains verified protocol PubMed
  2. Avvisati G, Lo-Coco F, Paoloni FP, Petti MC, Diverio D, Vignetti M, Latagliata R, Specchia G, Baccarani M, Di Bona E, Fioritoni G, Marmont F, Rambaldi A, Di Raimondo F, Kropp MG, Pizzolo G, Pogliani EM, Rossi G, Cantore N, Nobile F, Gabbas A, Ferrara F, Fazi P, Amadori S, Mandelli F; GIMEMA, AIEOP, and EORTC Cooperative Groups. AIDA 0493 protocol for newly diagnosed acute promyelocytic leukemia: very long-term results and role of maintenance. Blood. 2011 May 5;117(18):4716-25. Epub 2011 Mar 8. link to original article contains verified protocol PubMed
  3. Latagliata R, Breccia M, Fazi P, Vignetti M, Di Raimondo F, Sborgia M, Vincelli D, Candoni A, Salvi F, Rupoli S, Martinelli G, Kropp MG, Tonso A, Venditti A, Melillo L, Cimino G, Petti MC, Avvisati G, Lo-Coco F, Mandelli F; GIMEMA Acute Leukaemia Working Party. GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia. Long-term results and prognostic factors. Br J Haematol. 2011 Sep;154(5):564-8. doi: 10.1111/j.1365-2141.2011.08593.x. Epub 2011 Jul 14. link to original article contains verified protocol PubMed

PETHEMA LPA99, LPA2005 maintenance

PETHEMA: Programa Español de Tratamientos en HEMAtología
Preceded by PETHEMA LPA99 or PETHEMA LPA2005 consolidation therapy.

Regimen

90-day cycles x 2 years

References

  1. Sanz MA, Martín G, González M, León A, Rayón C, Rivas C, Colomer D, Amutio E, Capote FJ, Milone GA, De La Serna J, Román J, Barragán E, Bergua J, Escoda L, Parody R, Negri S, Calasanz MJ, Bolufer P; Programa de Estudio y Traitmiento de las Hemopatías Malignas. Risk-adapted treatment of acute promyelocytic leukemia with all-trans-retinoic acid and anthracycline monochemotherapy: a multicenter study by the PETHEMA group. Blood. 2004 Feb 15;103(4):1237-43. Epub 2003 Oct 23. link to original article contains verified protocol PubMed
  2. Sanz MA, Montesinos P, Rayón C, Holowiecka A, de la Serna J, Milone G, de Lisa E, Brunet S, Rubio V, Ribera JM, Rivas C, Krsnik I, Bergua J, González J, Díaz-Mediavilla J, Rojas R, Manso F, Ossenkoppele G, González JD, Lowenberg B; PETHEMA and HOVON Groups. 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 Jun 24;115(25):5137-46. Epub 2010 Apr 14. link to original article PubMed

Relapsed/refractory

Arsenic-based re-induction followed by consolidation and autologous stem cell transplant

Regimen

Level of Evidence: Phase II

Induction

Special notes: [*] Arsenic was continued until complete remission or maximum of 60 days [**] Idarubicin was added under special conditions, see text for details

Consolidation #1 and #2

Consolidation #3

Peripheral blood stem cells collected upon WBC recovery, followed by:

References

  1. Yanada M, Tsuzuki M, Fujita H, Fujimaki K, Fujisawa S, Sunami K, Taniwaki M, Ohwada A, Tsuboi K, Maeda A, Takeshita A, Ohtake S, Miyazaki Y, Atsuta Y, Kobayashi Y, Naoe T, Emi N; Japan Adult Leukemia Study Group. Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. Blood. 2013 Apr 18;121(16):3095-102. doi: 10.1182/blood-2012-11-466862. Epub 2013 Feb 14. link to original article Contains verified protocol PubMed
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