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Blood, 15 June 2002, Vol. 99, No. 12, pp. 4257-4264
PLENARY PAPER
Low incidence of second neoplasms among children diagnosed with
acute lymphoblastic leukemia after 1983
Smita Bhatia,
Harland N. Sather,
Olga B. Pabustan,
Michael E. Trigg,
Paul S. Gaynon, and
Leslie L. Robison
From the City of Hope National Medical Center, Duarte,
CA; Dupont Hospital for Children, Wilmington, DE; University of
Minnesota, Minneapolis; Childrens Hospital Los Angeles; and Keck School
of Medicine, University of Southern California, both of Los Angeles,
CA.
Second malignant neoplasms are a serious complication after
successful treatment of childhood acute lymphoblastic leukemia (ALL).
With improvement in survival, it is important to assess the impact of
contemporary risk-based therapies on second neoplasms in ALL survivors.
A cohort of 8831 children diagnosed with ALL and enrolled on
Children's Cancer Group therapeutic protocols between 1983 and 1995 were observed to determine the incidence of second neoplasms and
associated risk factors. The median age at diagnosis of ALL was 4.7 years. The cohort had accrued 54 883 person-years of follow-up.
Sixty-three patients developed second neoplasms, including solid,
nonhematopoietic tumors (n = 39: brain tumors n = 19, other solid
tumors n = 20), myeloid leukemia or myelodysplasia (n = 16), and
lymphoma (n = 8). The cumulative incidence of any second neoplasm was
1.18% at 10 years (95% confidence interval, 0.8%-1.5%),
representing a 7.2-fold increased risk compared with the general
population. The risk was increased significantly for acute myeloid
leukemia (standardized incidence ratio [SIR] 52.3), non-Hodgkin
lymphoma (SIR 8.3), parotid gland tumors (SIR 33.4), thyroid cancer
(SIR 13.3), brain tumors (SIR 10.1), and soft tissue sarcoma (SIR 9.1).
Multivariate analysis revealed female sex (relative risk [RR] 1.8),
radiation to the craniospinal axis (RR 1.6), and relapse of primary
disease (RR 3.5) to be independently associated with increased risk of
all second neoplasms. Risk of second neoplasms increased with radiation
dose (1800 cGy RR 1.5; 2400 cGy RR 3.9). Actuarial survival at 10 years
from diagnosis of second neoplasms was 39%. Follow-up of this large
cohort that was treated with contemporary risk-based therapy showed
that the incidence of second neoplasms remains low after diagnosis of
childhood ALL.
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