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Absolute lymphocyte counts at end of induction correlate with distinct immune cell compartments in pediatric B cell precursor acute lymphoblastic leukemia

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Abstract

Several retrospective studies in children with B cell precursor (BCP) acute lymphoblastic leukemia (ALL) provided clinical evidence that higher absolute lymphocyte counts (ALC) early into treatment significantly correlated with improved relapse-free and overall survival. It still remains unknown, however, whether the predictive role of higher ALCs reflects general bone marrow recovery or a more specific attribute of immune function. To investigate this question, we implemented a prospective observational cohort study in 20 children with BCP ALL on day 29 (D29) of induction chemotherapy and immunophenotyped their lymphoid (T, B and natural killer cells) and myeloid (neutrophils, monocytes, dendritic cells) compartments. In a first evaluation of a cohort treated with Children’s Oncology Group-based induction chemotherapy, the immune cell compartments were differentially depleted at D29. Neither gender, risk status, minimal residual disease, nor bone marrow recovery markers correlated with D29 ALC. In contrast, both CD3+ T cell and dendritic cell compartments, which did not correlate with age, significantly correlated with D29 ALC (p < 0.0001). In addition, subset complexity of cellular immune compartments was preserved at D29. This study reveals that D29 ALC significantly correlates with distinct immune cell compartments but not with bone marrow recovery markers, suggesting that higher D29 ALCs may contribute to leukemia control by inducing specific host immune activity.

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Abbreviations

ALC:

Absolute lymphocyte count

ALL:

Acute lymphoblastic leukemia

AMC:

Absolute monocyte count

ANC:

Absolute neutrophil count

BCP:

B cell precursor

CBC:

Complete blood cell count

COG:

Children’s Oncology Group

D0:

Day 0 at diagnosis before chemotherapy

D29:

End of induction chemotherapy day 29

HR:

High-risk

mDCs:

Myeloid dendritic cells

NKs:

Natural killer cells

pDCs:

Plasmacytoid dendritic cells

SR:

Standard-risk

WBC:

White blood cell count

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Acknowledgements

The authors would like to thank all the participants in this research study as well as the nurses and physicians involved. We gratefully acknowledge the staff of the BC Children’s Hospital Biobank for their assistance with sample and clinical data acquisition. We also want to thank Kelly D. Getz, PhD for providing statistical expertise, as well as Arnawaz Bashir, Susanna Sung and Sayeh Abdossamadi for their technical assistance.

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Authors and Affiliations

  1. Michael Cuccione Childhood Cancer Research Program, BC Children’s Hospital Research Institute, 950 West 28th Avenue, Reid Lab (Room 3062), Vancouver, BC, V5Z 4H4, Canada

    Nina Rolf, Amina Kariminia, Mario Fidanza & Gregor S. D. Reid

  2. Division of Pediatric Hem/Onc/BMT, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada

    Nina Rolf, Caron Strahlendorf & Gregor S. D. Reid

  3. Experimental Medicine Program, University of British Columbia, Vancouver, BC, Canada

    Kinga K. Smolen & Mario Fidanza

  4. Department of Pathology and Laboratory Medicine, BC Children’s Hospital Biobank, Vancouver, BC, Canada

    Adam Velenosi

  5. Center for Childhood Cancer Research, The Children’s Hospital of Philadelphia and Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA

    Alix E. Seif

Authors
  1. Nina Rolf
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  2. Kinga K. Smolen
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  3. Amina Kariminia
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  4. Adam Velenosi
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  5. Mario Fidanza
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  8. Gregor S. D. Reid
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Contributions

N. Rolf designed the study and performed the research experiments, analyzed the data and wrote the manuscript; K. Smolen contributed to research design; A. Kariminia, M. Fidanza and A. Seif contributed to research analysis; A. Velenosi was the coordinator of the clinical study details; A. Seif performed statistical analyses; C. Strahlendorf, K. Smolen, A. Kariminia, M. Fidanza and A. Seif critically reviewed the manuscript, G. Reid supervised the study and wrote the manuscript.

Corresponding author

Correspondence to Nina Rolf.

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Conflict of interest

The authors have no conflict of interest to disclose. The University of British Columbia Research Ethics Board approved the study (H12-01987). Informed consent of human subjects was obtained in all cases in accordance with the Declaration of Helsinki.

Funding

This work was funded in part by a Leukemia and Lymphoma Society of Canada operating Grant (Gregor SD Reid) and a Canadian Institutes of Health Research (CIHR) Fellowship Award (Nina Rolf).

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Rolf, N., Smolen, K.K., Kariminia, A. et al. Absolute lymphocyte counts at end of induction correlate with distinct immune cell compartments in pediatric B cell precursor acute lymphoblastic leukemia. Cancer Immunol Immunother 67, 225–236 (2018). https://doi.org/10.1007/s00262-017-2070-3

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  • DOI: https://doi.org/10.1007/s00262-017-2070-3

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