Prognostic significance of T-lineage leukemic cell growth in SCID mice: a Children's Cancer Group study.
Contemporary intensive therapies are effective for the majority of pediatric T-lineage acute lymphoblastic leukemia (ALL) patients, thus current challenge is to identify patients who may benefit from alternative treatment modalities. Previously, we demonstrated that human leukemic cell growth in the severe combined immunodeficiency (SCID) mouse was a significant prognostic factor for very high risk B-lineage ALL patients. In the current report we show that primary leukemic cells from 24 of 88 (27%) T-lineage ALL patients (SCID+) caused histopathologically detectable leukemia in SCID mice. These SCID+ patients were similar to SCID- (n = 64) patients with respect to virtually all presenting features, including age, sex, race, and leukocyte count. Growth of primary leukemic cells in SCID mice was not a significant predictor of outcome for the aggregate population of T-lineage ALL patients. Two-year event-free survival (EFS) outcomes for SCID+ patient and SCID- patients were 76.2% (SD = 5.6%) and a 64.0% (SD = 10.4%; p = 0.20). Overall survival also was similar between the two groups (p = 0.36). Among the subset of patients with M1 or M2 marrow status by day 7 of induction chemotherapy (rapid early responders), those who were SCID+ had poorer outcomes than those who were SCID-, with a 2-year EFS of 68.4% (SD = 11.9%) vs. 85.7% (SD = 6.0%) and relative hazard rate of 3.06 (p = 0.06). These data suggest that leukemic cell growth in SCID mice may identify a subset of T-lineage ALL patients who are at higher risk for relapse despite achieving a rapid early response to induction chemotherapy.
Uckun
F M
FM
Parker Hughes Cancer Center, Children's Cancer Group ALL Biology Reference Laboratory, and Hughes Institute, St. Paul, MN 55113, USA.
Waurzyniak
B J
BJ
Sather
H N
HN
Sensel
M G
MG
Chelstrom
L
L
Nachman
J
J
Gaynon
P S
PS
Bostrom
B
B
Ek
O
O
Sarquis
M
M
Steinherz
P G
PG
Reaman
G H
GH
D000818:Animals; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome