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ACUTE LYMPHOBLASTIC LEUKEMIA

Association between CEP72 genotype and persistent neuropathy in survivors of childhood acute lymphoblastic leukemia

Leukemia volume 36, pages 1160–1163 (2022)Cite this article

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Five-year survival rates for childhood acute lymphoblastic leukemia exceed 90% [1]. However, acute treatment-related adverse events are common and are not always transient. Over 40% of long-term ALL survivors report sensory and/or motor neuropathy symptoms that interfere with movement [2] and quality of life [3]. Identifying risk factors for persistent neuropathy is needed to target survivors who will benefit from preventive or restorative interventions. Recent data indicate that a single nucleotide polymorphism (rs924607) in the promoter region of the CEP72 gene is associated with incidence and severity of acute peripheral neuropathy [4, 5], where those homozygous for the rs924607 risk allele (TT) are at greatest risk for acute neuropathy [4]. It is unknown whether this variant predisposes to persistent neuropathy. Thus, the purpose of this study was to determine associations between the CEP72 genotype (rs924607) and prevalence and severity of persistent motor and sensory neuropathy in childhood ALL survivors ≥5 years from diagnosis.

Participants were enrolled in the Institutional Review Board approved St. Jude Lifetime Cohort Study (NCT00760656) [6], treated at St Jude Children’s Research Hospital 1962–2012, and ≥5 years post-diagnosis. Participants completed questionnaires, medical and physical assessments and provided biospecimens for genetic studies. Medical records were abstracted for treatment exposures and significant health events (including acute neuropathy) (Supplemental Methods). Survivors eligible for these analyses had a primary diagnosis of ALL and no history of peripheral vascular disease, diabetes, or non-digit amputation. Of 1361 potentially eligible participants, 253 (18.6%) were excluded because existing conditions precluded accurate neuropathy ascertainment or germline DNA was unavailable (received hematopoietic stem cell transplant). An additional 118 (10.6%) had missing genomic or assessment data, resulting in a final sample size of 990 (Fig. S1).

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Fig. 1: Proportions of survivors with persistent neuropathy (CTCAE Grade ≥2).
Fig. 2: Results of multivariate logistic regression models evaluating predictors of persistent neuropathy phenotypes (CTCAE Grade ≥2) among 990 survivors.

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Acknowledgements

This work was supported by grants provided by the National Cancer Institute (CA036401, Evans; CA195547, Hudson and Robison), the Cancer Center Support Grant No. CA21765, Roberts), and the American Lebanese Syrian Associated Charities (ALSAC). None of the authors have a relevant financial conflict of interest to disclose. The content of this publication does not reflect the views or policies of the National Institutes of Health or the United States government.

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Authors and Affiliations

  1. Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Chelsea G. Goodenough, Yadav Sapkota, Emily R. Finch, Lu Lu, Robyn E. Partin, Matthew D. Wogksch, Melissa M. Hudson, Leslie L. Robison, Zhaoming Wang & Kirsten K. Ness

  2. Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Barthelemy Diouf, Wenjian Yang & William E. Evans

  3. Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Melissa M. Hudson

  4. Department of Computational Biology, St Jude Children’s Research Hospital, Memphis, TN, USA

    Zhaoming Wang

  5. Department of Global and Pediatric Medicine, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Sima Jeha

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  1. Chelsea G. Goodenough
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  2. Barthelemy Diouf
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Contributions

C.G.G. contributed to data collection, analyzed and interpreted data, wrote and revised the manuscript. B.D. and W.Y. contributed to conceptualizing the study, interpreted data, and reviewed the manuscript. Y.S. contributed to data collection, provided analysis support, and reviewed the manuscript. E.R.F. contributed to data interpretation and manuscript review. R.E.P. and M.D.W. contributed to data collection and manuscript review. M.M.H., Z.W., and S.J. supervised data collection, interpreted data, and reviewed the manuscript. L.L.R. provided administrative and material support, interpreted data, and reviewed the manuscript. W.E.E. conceptualized and designed the study, interpreted data, and reviewed the manuscript. K.K.N. conceptualized and designed the study, supervised data collection, analyzed and interpreted data, wrote and revised the manuscript.

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Correspondence to Kirsten K. Ness.

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Goodenough, C.G., Diouf, B., Yang, W. et al. Association between CEP72 genotype and persistent neuropathy in survivors of childhood acute lymphoblastic leukemia. Leukemia 36, 1160–1163 (2022). https://doi.org/10.1038/s41375-021-01484-y

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