Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study
Md. Amylon et al., Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study, LEUKEMIA, 13(3), 1999, pp. 335-342
This study was designed to test the hypothesis that high-dose asparaginase
consolidation therapy improves survival in pediatric patients with T cell a
cute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma. Five
hundred and fifty-two patients (357 patients with T cell acute lymphoblast
ic leukemia (ALL) and 195 patients with advanced stage lymphoblastic lympho
ma) were enrolled in FOG study 8704 (T-3). Treatment included rotating comb
inations of high-dose myelosuppressive chemotherapy agents proven to be eff
ective in T cell ALL in other FOG group-wide or local institutional protoco
ls (including vincristine, doxorubicin, cyclophosphamide, prednisone, aspar
aginase, teniposide, cytarabine and mercaptopurine). After achieving a comp
lete remission (CR), patients were randomized to receive or not receive hig
h-dose intensive asparaginase consolidation (25 000 IU/m(2)) given weekly f
or 20 weeks by intramuscular injection. Intrathecal chemotherapy (methotrex
ate, hydrocortisone and cytarabine) was given to prevent CNS disease, and C
NS irradiation was used only for patients with leukemia and an initial WBC
of >50 000/mu l or patients with active CNS disease at diagnosis. CR was ac
hieved in 96% of patients. The high-dose asparaginase regimen was significa
ntly superior to the control regimen for both the leukemia and lymphoma sub
groups. Four-year continuous complete remission rate (CCR) for the leukemia
patients was 68% (s.e. 4%) with asparaginase as compared to 55% (s.e. 4%)
without. For the lymphoma patients, 4-year CCR was 78% (s.e. 5%) with aspar
aginase and 64% (s.e. 6%) in the controls. The overall one-sided logrank te
st had a P value <0.001 favoring asparaginase, while corresponding values w
ere P = 0.002 for ALL and P = 0.048 lymphoblastic lymphoma. Toxicities were
tolerable, but there were 18 failures due to secondary malignancies (16 wi
th non-lymphocytic leukemia or myelodysplasia). Neither WBC at diagnosis (l
eukemia patients) nor lymphoma stage were major prognostic factors. We conc
lude that when added to a backbone of effective rotating agents, repeated d
oses of asparaginase during early treatment improve the outcome for patient
s with T cell leukemia and advanced stage lymphoblastic lymphoma.