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Chronic Lymphocytic Leukemia

Risk factors for tumor lysis syndrome in patients with chronic lymphocytic leukemia treated with the cyclin-dependent kinase inhibitor, flavopiridol

Abstract

Tumor lysis syndrome (TLS) has been described in over 40% of patients with chronic lymphocytic leukemia treated with the cyclin-dependent kinase inhibitor, flavopiridol. We conducted a retrospective analysis to determine predictive factors for TLS. In 116 patients, the incidence of TLS was 46% (95% CI: 36–55%). In univariable analysis, female gender, greater number of prior therapies, Rai stages III–IV, adenopathy 10 cm, splenomegaly, del(11q), decreased albumin and increased absolute lymphocyte count, white blood cell count (WBC), β2-microglobulin, and lactate dehydrogenase were associated (P<0.05) with TLS. In multivariable analysis, female gender, adenopathy 10 cm, elevated WBC, increased β2-microglobulin, and decreased albumin were associated with TLS (P<0.05). With respect to patient outcomes, 49 and 44% of patients with and without TLS, respectively, responded to flavopiridol (P=0.71). In a multivariable analysis, controlling for number of prior therapies, cytogenetics, Rai stage, age and gender, progression-free survival (PFS) was inferior in patients with TLS (P=0.01). Female patients and patients with elevated β2-microglobulin, increased WBC, adenopathy 10 cm and decreased albumin were at highest risk and should be monitored for TLS with flavopiridol. TLS does not appear to be predictive of response or improved PFS in patients receiving flavopiridol.

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Acknowledgements

This project was supported by NCI K23 CA109004-01A1, NCI K12 CA133250, NCI U01 CA076576, NCI NO1 CM62207, Leukemia and Lymphoma Society SCOR 7080-06, and the D Warren Brown Foundation.

KAB designed and performed the study, supervised patients enrolled on the described trials, analyzed and interpreted the data, and authored the manuscript. ASR analyzed and interpreted the data, performed statistical analysis, assisted with manuscript preparation, and reviewed and edited the draft manuscript. DW led the patient-care efforts on these trials; collected data on patient response, toxicity and outcomes, and reviewed the draft manuscript. JAW collected and provided the data and reviewed the draft manuscript. JAJ, LA, and JMF supervised and enrolled patients on these studies and reviewed the draft manuscript. BR assisted with the treatment of patients on these studies who developed TLS, providing emergent nephrology support and consultation for the management of these patients, and reviewed the draft manuscript. JJ provided the pharmacokinetic data, assisted with the analysis, and reviewed and edited the draft manuscript. MP validated the pharmacokinetic assay, performed the pharmacokinetic sample analysis and modeling, provided the pharmacokinetic data, and reviewed and edited the draft manuscript. AJJ supervised and performed laboratory correlative work associated with these two trials and reviewed the manuscript. MVC, the principal investigator on NCI NO1 CM62207 that supported this trial, reviewed and edited the draft manuscript. MRG is the principal investigator on NCI U01 CA076576 that supported this trial and he supervised patients enrolled on these studies, assisted with study design and analysis, and reviewed and edited the draft manuscript. JCB served as principal investigator on the described trials, supervised patients enrolled on these studies, assisted with study design and analysis, and reviewed and edited the draft manuscript.

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Correspondence to K A Blum.

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JCB and MRG are both inventors on a use patent related to the administration of flavopiridol. This patent has not been issued and currently has no monetary value.

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Presented: American Society of Hematology 2010, abstract

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Blum, K., Ruppert, A., Woyach, J. et al. Risk factors for tumor lysis syndrome in patients with chronic lymphocytic leukemia treated with the cyclin-dependent kinase inhibitor, flavopiridol. Leukemia 25, 1444–1451 (2011). https://doi.org/10.1038/leu.2011.109

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