Prognostic impact of absolute lymphocyte counts at the end of remission induction in childhood acute lymphoblastic leukemia

Jeffrey E. Rubnitz, Patrick Campbell, Yinmei Zhou, John T. Sandlund, Sima Jeha, Raul C. Ribeiro, Hiroto Inaba, Deepa Bhojwani, Mary V. Relling, Scott Howard, Dario Campana, Ching Hon Pui

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Abstract

BACKGROUND Absolute lymphocyte counts (ALC) during treatment have been associated with outcome in children and adults with hematologic malignancies. However, the impact of ALC relative to that of other prognostic factors on the outcome of children with acute lymphoblastic leukemia (ALL) treated in recent trials is unknown. METHODS Outcomes of 399 patients aged ≤18 years with newly diagnosed ALL who were enrolled in the Total Therapy XV study at St. Jude Children's Research Hospital were analyzed according to ALC at the end of remission induction therapy. RESULTS An ALC ≥500 cells/μL was significantly more prevalent among patients with B-lineage ALL, in those with favorable presenting features, and in those who achieved negative minimal residual disease (MRD) status on day 43 of treatment. Both overall survival (OS) and event-free survival (EFS) were superior among patients with higher ALC, but only the association with OS was statistically significant in a univariate analysis. In multivariable analyses, ALC was not a significant predictor of outcome after controlling for age, leukocyte count, lineage, risk group, and MRD status at the end of induction (P >.1 for all comparisons). However, among MRD-negative patients, those with low ALC had a 5-year OS rate of 84.2% ± 8.9% versus 97.3% ± 1.0% for patients with higher ALC (P =.036). CONCLUSIONS ALC at the end of induction is related to favorable presenting features and good initial treatment response but does not independently predict outcome in the context of contemporary, MRD-guided therapy.

Original languageEnglish (US)
Pages (from-to)2061-2066
Number of pages6
JournalCancer
Volume119
Issue number11
DOIs
StatePublished - Jun 1 2013

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Remission Induction
Lymphocyte Count
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Residual Neoplasm
Therapeutics
Survival
Hematologic Neoplasms
Leukocyte Count
Disease-Free Survival
Survival Rate

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Rubnitz, J. E., Campbell, P., Zhou, Y., Sandlund, J. T., Jeha, S., Ribeiro, R. C., ... Pui, C. H. (2013). Prognostic impact of absolute lymphocyte counts at the end of remission induction in childhood acute lymphoblastic leukemia. Cancer, 119(11), 2061-2066. https://doi.org/10.1002/cncr.28026

Prognostic impact of absolute lymphocyte counts at the end of remission induction in childhood acute lymphoblastic leukemia. / Rubnitz, Jeffrey E.; Campbell, Patrick; Zhou, Yinmei; Sandlund, John T.; Jeha, Sima; Ribeiro, Raul C.; Inaba, Hiroto; Bhojwani, Deepa; Relling, Mary V.; Howard, Scott; Campana, Dario; Pui, Ching Hon.

In: Cancer, Vol. 119, No. 11, 01.06.2013, p. 2061-2066.

Research output: Contribution to journalArticle

Rubnitz, JE, Campbell, P, Zhou, Y, Sandlund, JT, Jeha, S, Ribeiro, RC, Inaba, H, Bhojwani, D, Relling, MV, Howard, S, Campana, D & Pui, CH 2013, 'Prognostic impact of absolute lymphocyte counts at the end of remission induction in childhood acute lymphoblastic leukemia', Cancer, vol. 119, no. 11, pp. 2061-2066. https://doi.org/10.1002/cncr.28026
Rubnitz, Jeffrey E. ; Campbell, Patrick ; Zhou, Yinmei ; Sandlund, John T. ; Jeha, Sima ; Ribeiro, Raul C. ; Inaba, Hiroto ; Bhojwani, Deepa ; Relling, Mary V. ; Howard, Scott ; Campana, Dario ; Pui, Ching Hon. / Prognostic impact of absolute lymphocyte counts at the end of remission induction in childhood acute lymphoblastic leukemia. In: Cancer. 2013 ; Vol. 119, No. 11. pp. 2061-2066.
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abstract = "BACKGROUND Absolute lymphocyte counts (ALC) during treatment have been associated with outcome in children and adults with hematologic malignancies. However, the impact of ALC relative to that of other prognostic factors on the outcome of children with acute lymphoblastic leukemia (ALL) treated in recent trials is unknown. METHODS Outcomes of 399 patients aged ≤18 years with newly diagnosed ALL who were enrolled in the Total Therapy XV study at St. Jude Children's Research Hospital were analyzed according to ALC at the end of remission induction therapy. RESULTS An ALC ≥500 cells/μL was significantly more prevalent among patients with B-lineage ALL, in those with favorable presenting features, and in those who achieved negative minimal residual disease (MRD) status on day 43 of treatment. Both overall survival (OS) and event-free survival (EFS) were superior among patients with higher ALC, but only the association with OS was statistically significant in a univariate analysis. In multivariable analyses, ALC was not a significant predictor of outcome after controlling for age, leukocyte count, lineage, risk group, and MRD status at the end of induction (P >.1 for all comparisons). However, among MRD-negative patients, those with low ALC had a 5-year OS rate of 84.2{\%} ± 8.9{\%} versus 97.3{\%} ± 1.0{\%} for patients with higher ALC (P =.036). CONCLUSIONS ALC at the end of induction is related to favorable presenting features and good initial treatment response but does not independently predict outcome in the context of contemporary, MRD-guided therapy.",
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AU - Rubnitz, Jeffrey E.

AU - Campbell, Patrick

AU - Zhou, Yinmei

AU - Sandlund, John T.

AU - Jeha, Sima

AU - Ribeiro, Raul C.

AU - Inaba, Hiroto

AU - Bhojwani, Deepa

AU - Relling, Mary V.

AU - Howard, Scott

AU - Campana, Dario

AU - Pui, Ching Hon

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Y1 - 2013/6/1

N2 - BACKGROUND Absolute lymphocyte counts (ALC) during treatment have been associated with outcome in children and adults with hematologic malignancies. However, the impact of ALC relative to that of other prognostic factors on the outcome of children with acute lymphoblastic leukemia (ALL) treated in recent trials is unknown. METHODS Outcomes of 399 patients aged ≤18 years with newly diagnosed ALL who were enrolled in the Total Therapy XV study at St. Jude Children's Research Hospital were analyzed according to ALC at the end of remission induction therapy. RESULTS An ALC ≥500 cells/μL was significantly more prevalent among patients with B-lineage ALL, in those with favorable presenting features, and in those who achieved negative minimal residual disease (MRD) status on day 43 of treatment. Both overall survival (OS) and event-free survival (EFS) were superior among patients with higher ALC, but only the association with OS was statistically significant in a univariate analysis. In multivariable analyses, ALC was not a significant predictor of outcome after controlling for age, leukocyte count, lineage, risk group, and MRD status at the end of induction (P >.1 for all comparisons). However, among MRD-negative patients, those with low ALC had a 5-year OS rate of 84.2% ± 8.9% versus 97.3% ± 1.0% for patients with higher ALC (P =.036). CONCLUSIONS ALC at the end of induction is related to favorable presenting features and good initial treatment response but does not independently predict outcome in the context of contemporary, MRD-guided therapy.

AB - BACKGROUND Absolute lymphocyte counts (ALC) during treatment have been associated with outcome in children and adults with hematologic malignancies. However, the impact of ALC relative to that of other prognostic factors on the outcome of children with acute lymphoblastic leukemia (ALL) treated in recent trials is unknown. METHODS Outcomes of 399 patients aged ≤18 years with newly diagnosed ALL who were enrolled in the Total Therapy XV study at St. Jude Children's Research Hospital were analyzed according to ALC at the end of remission induction therapy. RESULTS An ALC ≥500 cells/μL was significantly more prevalent among patients with B-lineage ALL, in those with favorable presenting features, and in those who achieved negative minimal residual disease (MRD) status on day 43 of treatment. Both overall survival (OS) and event-free survival (EFS) were superior among patients with higher ALC, but only the association with OS was statistically significant in a univariate analysis. In multivariable analyses, ALC was not a significant predictor of outcome after controlling for age, leukocyte count, lineage, risk group, and MRD status at the end of induction (P >.1 for all comparisons). However, among MRD-negative patients, those with low ALC had a 5-year OS rate of 84.2% ± 8.9% versus 97.3% ± 1.0% for patients with higher ALC (P =.036). CONCLUSIONS ALC at the end of induction is related to favorable presenting features and good initial treatment response but does not independently predict outcome in the context of contemporary, MRD-guided therapy.

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