Early postinduction intensification therapy improves survival for children and adolescents with high-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group.
Longer and more intensive postinduction intensification (PII) improved the outcome of children and adolescents with "higher risk" acute lymphoblastic leukemia (ALL) and a slow marrow response to induction therapy. In the Children's Cancer Group study (CCG-1961), we tested longer versus more intensive PII, using a 2 x 2 factorial design for children with higher risk ALL and a rapid marrow response to induction therapy. Between November 1996 and May 2002, 2078 children and adolescents with newly diagnosed ALL (1 to 9 years old with white blood count 50 000/mm3 or more, or 10 years of age or older with any white blood count) were enrolled. After induction, 1299 patients with marrow blasts less than or equal to 25% on day 7 of induction (rapid early responders) were randomized to standard or longer duration (n = 651 + 648) and standard or increased intensity (n = 649 + 650) PII. Stronger intensity PII improved event-free survival (81% vs 72%, P < .001) and survival (89% vs 83%, P = .003) at 5 years. Differences were most apparent after 2 years from diagnosis. Longer duration PII provided no benefit. Stronger intensity but not prolonged duration PII improved outcome for patients with higher-risk ALL. This study is registered at http://clinicaltrials.gov as NCT00002812.
Seibel
Nita L
NL
Hematology/Oncology, Children's National Medical Center and George Washington University School of Medicine and Public Health, 111 Michigan Avenue NW, Washington, DC 20010, USA. nseibel@cnmc.org
Steinherz
Peter G
PG
Sather
Harland N
HN
Nachman
James B
JB
Delaat
Cynthia
C
Ettinger
Lawrence J
LJ
Freyer
David R
DR
Mattano
Leonard A
LA
Hastings
Caroline A
CA
Rubin
Charles M
CM
Bertolone
Kathy
K
Franklin
Janet L
JL
Heerema
Nyla A
NA
Mitchell
Torrey L
TL
Pyesmany
Allan F
AF
La
Mei K
MK
Edens
Cheryl
C
Gaynon
Paul S
PS
D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality*; D012074:Remission Induction; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents