Characteristics and outcome of patients with therapy-related acute promyelocytic leukemia front-line treated with or without arsenic trioxide.
Therapy-related acute promyelocytic leukemia (t-APL) is relatively rare, with limited data on outcome after treatment with arsenic trioxide (ATO) compared to standard intensive chemotherapy (CTX). We evaluated 103 adult t-APL patients undergoing treatment with all-trans retinoic acid (ATRA) alone (n=7) or in combination with ATO (n=24), CTX (n=53), or both (n=19). Complete remissions were achieved after induction therapy in 57% with ATRA, 100% with ATO/ATRA, 78% with CTX/ATRA, and 95% with CTX/ATO/ATRA. Early death rates were 43% for ATRA, 0% for ATO/ATRA, 12% for CTX/ATRA and 5% for CTX/ATO/ATRA. Three patients relapsed, two developed therapy-related acute myeloid leukemia and 13 died in remission including seven patients with recurrence of the prior malignancy. Median follow-up for survival was 3.7 years. None of the patients treated with ATRA alone survived beyond one year. Event-free survival was significantly higher after ATO-based therapy (95%, 95% CI, 82-99%) as compared to CTX/ATRA (78%, 95% CI, 64-87%; P=0.042), if deaths due to recurrence of the prior malignancy were censored. The estimated 2-year overall survival in intensively treated patients was 88% (95% CI, 80-93%) without difference according to treatment (P=0.47). ATO when added to ATRA or CTX/ATRA is feasible and leads to better outcomes as compared to CTX/ATRA in t-APL.
Department of Internal Medicine V, University Hospital of Heidelberg, Heidelberg, Germany.|Department of Internal Medicine V, Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ), University of Heidelberg, Heidelberg, Germany.
S
S
Kayser
Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
J
J
Krzykalla
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
M A
MA
Elliott
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA.
K
K
Norsworthy
Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA.
P
P
Gonzales
Cardiff University School of Medicine, Cardiff, UK.
R K
RK
Hills
University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD, USA.|Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
M R
MR
Baer
Department of Internal Medicine, Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic.
Z
Z
Ráčil
Department of Internal Medicine, Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic.
J
J
Mayer
3rd Faculty of Medicine, Department of Internal Medicine and Haematology, Charles University and Faculty Hospital Kralovske Vinohrady, Prague, Czech Republic.
J
J
Novak
Faculty of Medicine, 4th Department of Internal Medicine-Hematology, Charles University and University Hospital Hradec Králové, Hradec Králové, Czech Republic.
P
P
Žák
Faculty of Medicine and Dentistry, Department of Hemato-Oncology, Palacky University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
T
T
Szotkowski
Faculty of Life Sciences and Medicine, Department of Medical & Molecular Genetics, King's College London, London, UK.
D
D
Grimwade
Department of Haematology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
N H
NH
Russell
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Division of Hematology/Department of Medicine, University of Washington, Seattle, WA, USA.|Department of Epidemiology, University of Washington, Seattle, WA, USA.
R B
RB
Walter
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Division of Hematology/Department of Medicine, University of Washington, Seattle, WA, USA.
E H
EH
Estey
Department of Hematology, Oncology and Tumor Immunology, Charité-University Medical Center, Campus Virchow Clinic, Berlin, Germany.
J
J
Westermann
Klinik für Hämatologie, Onkologie und Palliativmedizin, Klinikum Bielefeld Mitte, Bielefeld, Germany.
M
M
Görner
Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
A
A
Benner
Department of Internal Medicine V, University Hospital of Heidelberg, Heidelberg, Germany.|Department of Internal Medicine V, Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ), University of Heidelberg, Heidelberg, Germany.
A
A
Krämer
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA.
B D
BD
Smith
Department of Haematology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
A K
AK
Burnett
Department of Internal Medicine I, University Hospital Carl-Gustav-Carus, Dresden, Germany.
C
C
Thiede
Department of Internal Medicine I, University Hospital Carl-Gustav-Carus, Dresden, Germany.
C
C
Röllig
Department of Internal Medicine V, University Hospital of Heidelberg, Heidelberg, Germany.
A D
AD
Ho
Department of Internal Medicine I, University Hospital Carl-Gustav-Carus, Dresden, Germany.
G
G
Ehninger
National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany.
R F
RF
Schlenk
Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA.
M S
MS
Tallman
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA.
M J
MJ
Levis
Department of Internal Medicine I, University Hospital Carl-Gustav-Carus, Dresden, Germany.
U
U
Platzbecker
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D010087:Oxides / Q000627:therapeutic use*; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide