The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia: results of the international study Relapsed AML 2001/01.
The prognostic significance of early response to treatment has not been reported in relapsed pediatric acute myeloid leukemia. In order to identify an early and easily applicable prognostic factor allowing subsequent treatment modifications, we assessed leukemic blast counts in the bone marrow by morphology on days 15 and 28 after first reinduction in 338 patients of the international Relapsed-AML2001/01 trial. Both day 15 and day 28 status was classified as good (≤20% leukemic blasts) in 77% of patients. The correlation between day 15 and 28 blast percentages was significant, but not strong (Spearman correlation coefficient = 0.49, P<0.001). Survival probability decreased in a stepwise fashion along with rising blast counts at day 28. Patients with bone marrow blast counts at this time-point of ≤5%, 6-10%, 11-20% and >20% had 4-year probabilities of survival of 52%±3% versus 36%±10% versus 21%±9% versus 14%±4%, respectively, P<0.0001; this trend was not seen for day 15 results. Multivariate analysis showed that early treatment response at day 28 had the strongest prognostic significance, superseding even time to relapse (< or ≥12 months). In conclusion, an early response to treatment, measured on day 28, is a strong and independent prognostic factor potentially useful for treatment stratification in pediatric relapsed acute myeloid leukemia. This study was registered with ISRCTN code: 94206677.
BFM-AML Group, Hannover, c/o Pediatric Hematology/Oncology, Hannover Medical High School, Germany ursula@creutzig.de.
Ursula
U
Creutzig
BFM-AML Group, Hannover, c/o Pediatric Hematology/Oncology, Hannover Medical High School, Germany.
Martin
M
Zimmermann
BFM-AML Group, St. Anna Children's Hospital and Children's Cancer Research Institute, Department of Pediatrics, Medical University of Vienna, Austria.
Michael N
MN
Dworzak
UK NCRI Childhood Leukaemia Group, Department of Paediatric Haematology, Royal Hospital for Sick Children, Glasgow, Scotland, UK.
Brenda
B
Gibson
Pediatric Oncology/Hematology, Beatrix Children's Hospital/UMCG, Groningen, The Netherlands Dutch Childhood Oncology Group, The Hague, The Netherlands.
Rienk
R
Tamminga
NOPHO, Department of Pediatrics, Queen Silvia's Children's Hospital, Göteborg, Sweden.
Jonas
J
Abrahamsson
Hong Kong Paediatric Haematology & Oncology Study Group, c/o Department of Paediatrics & Adolescent Medicine, Queen Mary Hospital, Hong Kong, China.
Shau-Yin
SY
Ha
NOPHO; Department of Pediatrics, Aarhus University Hospital Skejby, Denmark.
Henrik
H
Hasle
Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Alexey
A
Maschan
FRALLE/CLCG, c/o Institut d'Hématologie et d'Oncologie Pédiatrique, Lyon, France.
Yves
Y
Bertrand
FRALLE/CLCG; c/o Unité d'Onco-Hématologie Pédiatrique, Hôpital d'Enfants Armand Trousseau, Paris, France.
Guy
G
Leverger
BFM-AML Group, Hannover, c/o Pediatric Hematology/Oncology, Hannover Medical High School, Germany.
Christine
C
von Neuhoff
St. Jude's Children Research Hospital, Memphis, TN, USA, c/o Children's Center For Cancer and Blood Diseases, Peyton Manning Children's Hospital at St. Vincent, Indianapolis, IN, USA.
Bassem
B
Razzouk
AIEOP, c/o Department of Pediatrics, Hospital S. Gerardo, Monza, Italy.
Carmelo
C
Rizzari
CPH, c/o Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine and University Hospital Motol, Charles University Prague, Czech Republic.
Petr
P
Smisek
UK CCLG; c/o Department of Haematology & Oncology, Our Lady's Children's Hospital, Dublin, Ireland.
Owen P
OP
Smith
Center of Pediatric Hematology/Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Batia
B
Stark
BFM-AML Group, Hannover, c/o Pediatric Hematology/Oncology, Hannover Medical High School, Germany.
Dirk
D
Reinhardt
Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands Dutch Childhood Oncology Group, The Hague, The Netherlands.
Gertjan L
GL
Kaspers
D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000627:therapeutic use*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis
D000903:Antibiotics, Antineoplastic; D003630:Daunorubicin