Prognostic factors in childhood T-cell acute lymphoblastic leukemia: A pediatric oncology group study

Jonathan J. Shuster, John M. Falletta, D. Jeanette Pullen, William M. Crist, G. Bennett Humphrey, Barry L. Dowell, Moody D. Wharam, Michael J Borowitz

Research output: Contribution to journalArticle

Abstract

Two hundred fifty-three children with newly diagnosed T-cell acute lymphoblastic leukemia (ALL), who were treated uniformly with modified LSA2L2 therapy, were evaluated using univariate and recursive partition analyses to define clinical or biologic features associated with risk of treatment failure. Overall event-free survival (EFS) at 4 years was 43% (SE = 4%). Factors examined included white blood cell (WBC) level, age, gender, race (black v other), presence of a mediastinal mass, hepatomegaly, splenomegaly, marked lymphadenopathy, hemoglobin level, platelet count, blast cell expression of antigens such as the common acute lymphoblastic leukemia antigen (CALLA, CD10), HLA-DR, and T-cell-associated antigens (CD3, CD4, CD8, CD7, CD5, and THY). Univariate analysis showed that age ≤5 or ≤7 years, WBC level 3/μL. and blast cell expression of CD4, CD8, or CALLA were associated with significantly better EFS, while hepatomegaly and splenomegaly were associated with worse EFS. Recursive partitioning analysis showed that the most important single favorable prognostic factor was a WBC level 3/μL and, for patients with WBC counts below this level, the most important predictor of EFS was blast cell expression of the pan-T antigen defined by the monoclonal antibody (MoAb), L17F12 (CD5). For patients with higher WBC levels, the most important predictor of EFS was blast cell expression of THY antigen. The recursive partitioning analysis defined three groups of patients with widely varied prognoses identified as follows (1) those with a WBC count 3 μL. who lacked massive splenomegaly and had blasts expressing CD5 had the best prognosis (66%, SE = 7%, EFS 4 years, n = 84); (2) those with (b1) WBC counts 3/μL with either massive splenomegaly or who had blasts lacking CD5 expression, or (b2) WBC counts >50 × 103/μL with expression of the THY antigen had an intermediate prognosis (39%, SE = 7% EFS at 4 years, n = 94); (3) those with WBC counts 50 × 103/μL and whose blasts lacked expression of THY antigen had the poorest outcome (EFS = 19% at 4 years, SE = 8%, n = 63). A three-way comparison of EFS according to these groupings showed significant differences among the three patient groups (P <.001). The recursive partitioning was able to classify 241 (95%) of the patients. Twelve patients could not be grouped because of missing data. We conclude that this prognostic factor analysis provides information of potential importance for design of randomized clinical trials for children with T-cell ALL (T-ALL), because appropriate stratification depends on results of such analysis to ensure comparability of patient groups. In this study, recursive partitioning analysis provides prognostic insight that was not obtained by the stepwise Cox regression method. However, these results should be considered tentative until confirmed in a prospective clinical trial.

Original languageEnglish (US)
Pages (from-to)166-173
Number of pages8
JournalBlood
Volume75
Issue number1
StatePublished - Jan 1 1990
Externally publishedYes

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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Pediatrics
Oncology
T-cells
Disease-Free Survival
Blood
Leukocyte Count
Splenomegaly
Leukocytes
Antigens
Hepatomegaly
CD3 Antigens
Neprilysin
CD4 Antigens
Viral Tumor Antigens
HLA-DR Antigens
Factor analysis
Platelets
Treatment Failure
Platelet Count

ASJC Scopus subject areas

  • Hematology

Cite this

Shuster, J. J., Falletta, J. M., Pullen, D. J., Crist, W. M., Humphrey, G. B., Dowell, B. L., ... Borowitz, M. J. (1990). Prognostic factors in childhood T-cell acute lymphoblastic leukemia: A pediatric oncology group study. Blood, 75(1), 166-173.

Prognostic factors in childhood T-cell acute lymphoblastic leukemia : A pediatric oncology group study. / Shuster, Jonathan J.; Falletta, John M.; Pullen, D. Jeanette; Crist, William M.; Humphrey, G. Bennett; Dowell, Barry L.; Wharam, Moody D.; Borowitz, Michael J.

In: Blood, Vol. 75, No. 1, 01.01.1990, p. 166-173.

Research output: Contribution to journalArticle

Shuster, JJ, Falletta, JM, Pullen, DJ, Crist, WM, Humphrey, GB, Dowell, BL, Wharam, MD & Borowitz, MJ 1990, 'Prognostic factors in childhood T-cell acute lymphoblastic leukemia: A pediatric oncology group study', Blood, vol. 75, no. 1, pp. 166-173.
Shuster JJ, Falletta JM, Pullen DJ, Crist WM, Humphrey GB, Dowell BL et al. Prognostic factors in childhood T-cell acute lymphoblastic leukemia: A pediatric oncology group study. Blood. 1990 Jan 1;75(1):166-173.
Shuster, Jonathan J. ; Falletta, John M. ; Pullen, D. Jeanette ; Crist, William M. ; Humphrey, G. Bennett ; Dowell, Barry L. ; Wharam, Moody D. ; Borowitz, Michael J. / Prognostic factors in childhood T-cell acute lymphoblastic leukemia : A pediatric oncology group study. In: Blood. 1990 ; Vol. 75, No. 1. pp. 166-173.
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abstract = "Two hundred fifty-three children with newly diagnosed T-cell acute lymphoblastic leukemia (ALL), who were treated uniformly with modified LSA2L2 therapy, were evaluated using univariate and recursive partition analyses to define clinical or biologic features associated with risk of treatment failure. Overall event-free survival (EFS) at 4 years was 43{\%} (SE = 4{\%}). Factors examined included white blood cell (WBC) level, age, gender, race (black v other), presence of a mediastinal mass, hepatomegaly, splenomegaly, marked lymphadenopathy, hemoglobin level, platelet count, blast cell expression of antigens such as the common acute lymphoblastic leukemia antigen (CALLA, CD10), HLA-DR, and T-cell-associated antigens (CD3, CD4, CD8, CD7, CD5, and THY). Univariate analysis showed that age ≤5 or ≤7 years, WBC level 3/μL. and blast cell expression of CD4, CD8, or CALLA were associated with significantly better EFS, while hepatomegaly and splenomegaly were associated with worse EFS. Recursive partitioning analysis showed that the most important single favorable prognostic factor was a WBC level 3/μL and, for patients with WBC counts below this level, the most important predictor of EFS was blast cell expression of the pan-T antigen defined by the monoclonal antibody (MoAb), L17F12 (CD5). For patients with higher WBC levels, the most important predictor of EFS was blast cell expression of THY antigen. The recursive partitioning analysis defined three groups of patients with widely varied prognoses identified as follows (1) those with a WBC count 3 μL. who lacked massive splenomegaly and had blasts expressing CD5 had the best prognosis (66{\%}, SE = 7{\%}, EFS 4 years, n = 84); (2) those with (b1) WBC counts 3/μL with either massive splenomegaly or who had blasts lacking CD5 expression, or (b2) WBC counts >50 × 103/μL with expression of the THY antigen had an intermediate prognosis (39{\%}, SE = 7{\%} EFS at 4 years, n = 94); (3) those with WBC counts 50 × 103/μL and whose blasts lacked expression of THY antigen had the poorest outcome (EFS = 19{\%} at 4 years, SE = 8{\%}, n = 63). A three-way comparison of EFS according to these groupings showed significant differences among the three patient groups (P <.001). The recursive partitioning was able to classify 241 (95{\%}) of the patients. Twelve patients could not be grouped because of missing data. We conclude that this prognostic factor analysis provides information of potential importance for design of randomized clinical trials for children with T-cell ALL (T-ALL), because appropriate stratification depends on results of such analysis to ensure comparability of patient groups. In this study, recursive partitioning analysis provides prognostic insight that was not obtained by the stepwise Cox regression method. However, these results should be considered tentative until confirmed in a prospective clinical trial.",
author = "Shuster, {Jonathan J.} and Falletta, {John M.} and Pullen, {D. Jeanette} and Crist, {William M.} and Humphrey, {G. Bennett} and Dowell, {Barry L.} and Wharam, {Moody D.} and Borowitz, {Michael J}",
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T1 - Prognostic factors in childhood T-cell acute lymphoblastic leukemia

T2 - A pediatric oncology group study

AU - Shuster, Jonathan J.

AU - Falletta, John M.

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AU - Crist, William M.

AU - Humphrey, G. Bennett

AU - Dowell, Barry L.

AU - Wharam, Moody D.

AU - Borowitz, Michael J

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N2 - Two hundred fifty-three children with newly diagnosed T-cell acute lymphoblastic leukemia (ALL), who were treated uniformly with modified LSA2L2 therapy, were evaluated using univariate and recursive partition analyses to define clinical or biologic features associated with risk of treatment failure. Overall event-free survival (EFS) at 4 years was 43% (SE = 4%). Factors examined included white blood cell (WBC) level, age, gender, race (black v other), presence of a mediastinal mass, hepatomegaly, splenomegaly, marked lymphadenopathy, hemoglobin level, platelet count, blast cell expression of antigens such as the common acute lymphoblastic leukemia antigen (CALLA, CD10), HLA-DR, and T-cell-associated antigens (CD3, CD4, CD8, CD7, CD5, and THY). Univariate analysis showed that age ≤5 or ≤7 years, WBC level 3/μL. and blast cell expression of CD4, CD8, or CALLA were associated with significantly better EFS, while hepatomegaly and splenomegaly were associated with worse EFS. Recursive partitioning analysis showed that the most important single favorable prognostic factor was a WBC level 3/μL and, for patients with WBC counts below this level, the most important predictor of EFS was blast cell expression of the pan-T antigen defined by the monoclonal antibody (MoAb), L17F12 (CD5). For patients with higher WBC levels, the most important predictor of EFS was blast cell expression of THY antigen. The recursive partitioning analysis defined three groups of patients with widely varied prognoses identified as follows (1) those with a WBC count 3 μL. who lacked massive splenomegaly and had blasts expressing CD5 had the best prognosis (66%, SE = 7%, EFS 4 years, n = 84); (2) those with (b1) WBC counts 3/μL with either massive splenomegaly or who had blasts lacking CD5 expression, or (b2) WBC counts >50 × 103/μL with expression of the THY antigen had an intermediate prognosis (39%, SE = 7% EFS at 4 years, n = 94); (3) those with WBC counts 50 × 103/μL and whose blasts lacked expression of THY antigen had the poorest outcome (EFS = 19% at 4 years, SE = 8%, n = 63). A three-way comparison of EFS according to these groupings showed significant differences among the three patient groups (P <.001). The recursive partitioning was able to classify 241 (95%) of the patients. Twelve patients could not be grouped because of missing data. We conclude that this prognostic factor analysis provides information of potential importance for design of randomized clinical trials for children with T-cell ALL (T-ALL), because appropriate stratification depends on results of such analysis to ensure comparability of patient groups. In this study, recursive partitioning analysis provides prognostic insight that was not obtained by the stepwise Cox regression method. However, these results should be considered tentative until confirmed in a prospective clinical trial.

AB - Two hundred fifty-three children with newly diagnosed T-cell acute lymphoblastic leukemia (ALL), who were treated uniformly with modified LSA2L2 therapy, were evaluated using univariate and recursive partition analyses to define clinical or biologic features associated with risk of treatment failure. Overall event-free survival (EFS) at 4 years was 43% (SE = 4%). Factors examined included white blood cell (WBC) level, age, gender, race (black v other), presence of a mediastinal mass, hepatomegaly, splenomegaly, marked lymphadenopathy, hemoglobin level, platelet count, blast cell expression of antigens such as the common acute lymphoblastic leukemia antigen (CALLA, CD10), HLA-DR, and T-cell-associated antigens (CD3, CD4, CD8, CD7, CD5, and THY). Univariate analysis showed that age ≤5 or ≤7 years, WBC level 3/μL. and blast cell expression of CD4, CD8, or CALLA were associated with significantly better EFS, while hepatomegaly and splenomegaly were associated with worse EFS. Recursive partitioning analysis showed that the most important single favorable prognostic factor was a WBC level 3/μL and, for patients with WBC counts below this level, the most important predictor of EFS was blast cell expression of the pan-T antigen defined by the monoclonal antibody (MoAb), L17F12 (CD5). For patients with higher WBC levels, the most important predictor of EFS was blast cell expression of THY antigen. The recursive partitioning analysis defined three groups of patients with widely varied prognoses identified as follows (1) those with a WBC count 3 μL. who lacked massive splenomegaly and had blasts expressing CD5 had the best prognosis (66%, SE = 7%, EFS 4 years, n = 84); (2) those with (b1) WBC counts 3/μL with either massive splenomegaly or who had blasts lacking CD5 expression, or (b2) WBC counts >50 × 103/μL with expression of the THY antigen had an intermediate prognosis (39%, SE = 7% EFS at 4 years, n = 94); (3) those with WBC counts 50 × 103/μL and whose blasts lacked expression of THY antigen had the poorest outcome (EFS = 19% at 4 years, SE = 8%, n = 63). A three-way comparison of EFS according to these groupings showed significant differences among the three patient groups (P <.001). The recursive partitioning was able to classify 241 (95%) of the patients. Twelve patients could not be grouped because of missing data. We conclude that this prognostic factor analysis provides information of potential importance for design of randomized clinical trials for children with T-cell ALL (T-ALL), because appropriate stratification depends on results of such analysis to ensure comparability of patient groups. In this study, recursive partitioning analysis provides prognostic insight that was not obtained by the stepwise Cox regression method. However, these results should be considered tentative until confirmed in a prospective clinical trial.

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