Acute promyelocytic leukemia - null regimens

The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main APL page for regimens that include active anticancer treatment.
=Maintenance after upfront therapy=
==Observation==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Avvisati et al. 2002 (GIMEMA LAP 0389) 	1989-1993 	Phase 3 (C)	6-MP & MTX 	Did not meet primary endpoint of EFS
Mandelli et al. 1997 (GIMEMA AIDA 0493)	1993-1996 	Phase 3 (C)	1. ATRA 	Did not meet primary endpoint of molecular DFS
Mandelli et al. 1997 (GIMEMA AIDA 0493)	1993-1996 	Phase 3 (C)	2. ATRA, 6-MP, MTX 	Did not meet primary endpoint of molecular DFS
Mandelli et al. 1997 (GIMEMA AIDA 0493)	1993-1996 	Phase 3 (C)	3. 6-MP & MTX 	Did not meet primary endpoint of molecular DFS
Fenaux et al. 1999 (EAPLG APL 93) 	1993-1996 	Phase 3 (C)	1. ATRA 	Seems to have lower 2-year relapse rate
Fenaux et al. 1999 (EAPLG APL 93) 	1993-1996 	Phase 3 (C)	2. ATRA, 6-MP, MTX 3. 6-MP & MTX	Lower 2-year relapse rate
Coutre et al. 2014 (SWOG S0521) 	2007-06 to 2010-05 	Phase 3 (C)	ATRA, 6-MP, MTX 	Inconclusive whether non-inferior DFS36 (primary endpoint)DFS36: 100% vs 96%(HR not reported)
No further treatment given after consolidation. Note that this arm was dropped from AIDA 0493 from February 1997.
====Preceding treatment====
*EAPLG APL 93: Cytarabine & daunorubicin consolidation
*GIMEMA AIDA 0493 & LAP 0389: Cytarabine & idarubicin, then etoposide & mitoxantrone, then cytarabine, idarubicin, thioguanine consolidation
===References===
# GIMEMA AIDA 0493: Mandelli F, Diverio D, Avvisati G, Luciano A, Barbui T, Bernasconi C, Broccia G, Cerri R, Falda M, Fioritoni G, Leoni F, Liso V, Petti MC, Rodeghiero F, Saglio G, Vegna ML, Visani G, Jehn U, Willemze R, Muus P, Pelicci PG, Biondi A, Lo Coco F; Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto; Associazione Italiana di Ematologia ed Oncologia Pediatrica Cooperative Groups. Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Blood. 1997 Aug 1;90(3):1014-21. link to original article EuroPMC
## Update: 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; EORTC. 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 EuroPMC
# EAPLG APL 93: Fenaux P, Chastang C, Chevret S, Sanz M, Dombret H, Archimbaud E, Fey M, Rayon C, Huguet F, Sotto JJ, Gardin C, Makhoul PC, Travade P, Solary E, Fegueux N, Bordessoule D, Miguel JS, Link H, Desablens B, Stamatoullas A, Deconinck E, Maloisel F, Castaigne S, Preudhomme C, Degos L. A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia; European APL Group. Blood. 1999 Aug 15;94(4):1192-200. link to original article EuroPMC
## Update: Adès L, Guerci A, Raffoux E, Sanz M, Chevallier P, Lapusan S, Recher C, Thomas X, Rayon C, Castaigne S, Tournilhac O, de Botton S, Ifrah N, Cahn JY, Solary E, Gardin C, Fegeux N, Bordessoule D, Ferrant A, Meyer-Monard S, Vey N, Dombret H, Degos L, Chevret S, Fenaux P; European APL Group. Very long-term outcome of acute promyelocytic leukemia after treatment with all-trans retinoic acid and chemotherapy: the European APL Group experience. Blood. 2010 Mar 4;115(9):1690-6. Epub 2009 Dec 17. link to original article EuroPMC
# GIMEMA LAP 0389: 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. 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 EuroPMC
#SWOG S0521: Coutre SE, Othus M, Powell B, Willman CL, Stock W, Paietta E, Levitan D, Wetzler M, Attar EC, Altman JK, Gore SD, Maher T, Kopecky KJ, Tallman MS, Larson RA, Appelbaum FR. Arsenic trioxide during consolidation for patients with previously untreated low/intermediate risk acute promyelocytic leukaemia may eliminate the need for maintenance therapy. Br J Haematol. 2014 May;165(4):497-503. Epub 2014 Feb 14. link to original article link to PMC article EuroPMC NCT00492856
Category:Acute promyelocytic leukemia regimens
Category:Disease-specific pages
Category:Acute leukemias
Category:Null regimens