Treating childhood acute lymphoblastic leukemia without cranial irradiation.
BACKGROUND
Prophylactic cranial irradiation has been a standard treatment in children with acute lymphoblastic leukemia (ALL) who are at high risk for central nervous system (CNS) relapse.


METHODS
We conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted from treatment in all children with newly diagnosed ALL. A total of 498 patients who could be evaluated were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission-induction treatment. The duration of continuous complete remission in the 71 patients who previously would have received prophylactic cranial irradiation was compared with that of 56 historical controls who received it.


RESULTS
The 5-year event-free and overall survival probabilities for all 498 patients were 85.6% (95% confidence interval [CI], 79.9 to 91.3) and 93.5% (95% CI, 89.8 to 97.2), respectively. The 5-year cumulative risk of isolated CNS relapse was 2.7% (95% CI, 1.1 to 4.3), and that of any CNS relapse (including isolated relapse and combined relapse) was 3.9% (95% CI, 1.9 to 5.9). The 71 patients had significantly longer continuous complete remission than the 56 historical controls (P=0.04). All 11 patients with isolated CNS relapse remained in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blast cells at diagnosis and a high level of minimal residual disease (> or = 1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the genetic abnormality t(1;19)(TCF3-PBX1), any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection.


CONCLUSIONS
With effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted from the treatment of childhood ALL. (ClinicalTrials.gov number, NCT00137111.)
Pui
Ching-Hon
CH
Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. ching-hon.pui@stjude.org
Campana
Dario
D
Pei
Deqing
D
Bowman
W Paul
WP
Sandlund
John T
JT
Kaste
Sue C
SC
Ribeiro
Raul C
RC
Rubnitz
Jeffrey E
JE
Raimondi
Susana C
SC
Onciu
Mihaela
M
Coustan-Smith
Elaine
E
Kun
Larry E
LE
Jeha
Sima
S
Cheng
Cheng
C
Howard
Scott C
SC
Simmons
Vickey
V
Bayles
Amy
A
Metzger
Monika L
ML
Boyett
James M
JM
Leung
Wing
W
Handgretinger
Rupert
R
Downing
James R
JR
Evans
William E
WE
Relling
Mary V
MV
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D016543:Central Nervous System Neoplasms / Q000188:drug therapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003520:Cyclophosphamide / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D012074:Remission Induction / Q000379:methods; D012307:Risk Factors; D055502:Secondary Prevention; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D003907:Dexamethasone; D003520:Cyclophosphamide; D015122:Mercaptopurine; D001215:Asparaginase; D008727:Methotrexate; D003630:Daunorubicin