Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01.
The Dana-Farber Cancer Institute (DFCI) acute lymphoblastic leukemia (ALL) Consortium Protocol 91-01 was designed to improve the outcome of children with newly diagnosed ALL while minimizing toxicity. Compared with prior protocols, post-remission therapy was intensified by substituting dexamethasone for prednisone and prolonging the asparaginase intensification from 20 to 30 weeks. Between 1991 and 1995, 377 patients (age, 0-18 years) were enrolled; 137 patients were considered standard risk (SR), and 240 patients were high risk (HR). Following a 5.0-year median follow-up, the estimated 5-year event-free survival (EFS) +/- SE for all patients was 83% +/- 2%, which is superior to prior DFCI ALL Consortium protocols conducted between 1981 and 1991 (P =.03). There was no significant difference in 5-year EFS based upon risk group (87% +/- 3% for SR and 81% +/- 3% for HR, P =.24). Age at diagnosis was a statistically significant prognostic factor (P =.03), with inferior outcomes observed in infants and children 9 years or older. Patients who tolerated 25 or fewer weeks of asparaginase had a significantly worse outcome than those who received at least 26 weeks of asparaginase (P <.01, both univariate and multivariate). Older children (at least 9 years of age) were significantly more likely to have tolerated 25 or fewer weeks of asparaginase (P <.01). Treatment on Protocol 91-01 significantly improved the outcome of children with ALL, perhaps due to the prolonged asparaginase intensification and/or the use of dexamethasone. The inferior outcome of older children may be due, in part, to increased intolerance of intensive therapy.
Silverman
L B
LB
Department of Pediatric Oncology, Dana-Farber Cancer Institute, the Division of Hematology/Oncology, Children's Hospital, Harvard Medical School, Boston, MA 02215, USA. lewis_silverman@dfci.harvard.edu
Gelber
R D
RD
Dalton
V K
VK
Asselin
B L
BL
Barr
R D
RD
Clavell
L A
LA
Hurwitz
C A
CA
Moghrabi
A
A
Samson
Y
Y
Schorin
M A
MA
Arkin
S
S
Declerck
L
L
Cohen
H J
HJ
Sallan
S E
SE
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000592:standards / Q000627:therapeutic use* / Q000633:toxicity; D001215:Asparaginase / Q000008:administration & dosage / Q000592:standards / Q000633:toxicity; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D003907:Dexamethasone / Q000008:administration & dosage / Q000592:standards / Q000633:toxicity; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000592:standards / Q000633:toxicity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012307:Risk Factors; D016896:Treatment Outcome
D003907:Dexamethasone; D004317:Doxorubicin; D001215:Asparaginase