Favorable outcome in 20-year follow-up of children with very-low-risk ALL and minimal standard therapy, with special reference to TEL-AML1 fusion.
BACKGROUND
As the treatment results of childhood ALL have improved, avoidance of late effects has become increasingly important. Identification of favorable prognostic factors helps to achieve this goal.


METHODS
We studied the prognostic value of TEL-AML1 fusion and a risk factor composed of age, white blood cell count (WBC), lymphomatous features, and hemoglobin level (Hb). We also compared outcome between two cohorts; cohort 1 (n=100) diagnosed 1975-1981, and cohort 2 (n=102) 1989-1991. Both cohorts were retrospectively divided in two groups: very-low-risk (WBC <10 x 10(9)/L, age 2 to <10 years, no lymphomatous features, Hb <90 g/L), and non-low-risk (=the remainder). We performed fluorescent in situ hybridization (FISH) of TEL-AML1 fusion of the marrow samples obtained at diagnosis.


RESULTS
The median follow-up is 20 years in cohort 1, and 8 years in cohort 2. In both cohorts, the very-low-risk category comprised one-fourth of the children. TEL-AML1 fusion was more frequent in the very-low-risk (35%) than in the non-low-risk group (17%) (P=0.03). The 8-year event-free survival (EFS) of children with the fusion was better than of those without, 74 vs. 54% (P=0.040). The 8-year EFS in the very-low-risk group was 76% in cohort 1, and 79% in cohort 2 (n.s.). In the non-low-risk groups, EFS was 39 vs. 64% (P=0.02), respectively.


CONCLUSIONS
Our data support the reported association of TEL-AML1 fusion with a favorable outcome although the risk group had a greater impact. These very-long-term follow-up data also indicate that children with very-low-risk ALL (slow disease) had a favorable outcome already in the late 1970s, and may be over treated with the contemporary ALL protocols.
Kanerva
Jukka
J
Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland. jukka.kanerva@hus.fi
Saarinen-Pihkala
Ulla M
UM
Niini
Tarja
T
Riikonen
Pekka
P
Möttönen
Merja
M
Mäkipernaa
Anne
A
Salmi
Toivo T
TT
Vettenranta
Kim
K
Knuutila
Sakari
S
D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D050676:Core Binding Factor Alpha 2 Subunit; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D000097764:ETS Translocation Variant 6 Protein
D000970:Antineoplastic Agents; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein