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. 2021 Jun;87(6):817-826.
doi: 10.1007/s00280-021-04252-y. Epub 2021 Mar 7.

Venous thromboembolism incidence and risk factors in adults with acute lymphoblastic leukemia treated with and without pegylated E. coli asparaginase-containing regimens

Sarah M Kashanian  1 , Noa G Holtzman  2   3 , Ciera L Patzke  3   4 , Jonathan Cornu  4 , Alison Duffy  3   4   5 , Madhurima Koka  6 , Sandrine Niyongere  1   3 , Vu H Duong  1   3 , Maria R Baer  1   3 , Jummai Apata  7 , Farin Kamangar  8 , Ashkan Emadi  9   10   11
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Venous thromboembolism incidence and risk factors in adults with acute lymphoblastic leukemia treated with and without pegylated E. coli asparaginase-containing regimens

Sarah M Kashanian et al. Cancer Chemother Pharmacol. 2021 Jun.

Abstract

Purpose: Asparaginases, key agents in treatment of acute lymphoblastic leukemia (ALL), are associated with venous thromboembolism (VTE). While risks of short-acting asparaginase-related VTE is well-known, we studied VTE incidence and risk factors in adult ALL patients treated with and without long-acting pegylated asparaginase (PegA).

Methods: Single-center, retrospective analysis of 89 ALL patients treated with (n = 61) or without (n = 28) PegA at Greenebaum Comprehensive Cancer Center. Reviewed patient and disease characteristics, treatment, and VTE incidence.

Results: VTE during treatment occurred in 31 patients (35%), and was associated with PegA (p = 0.001) and Philadelphia chromosome negativity (p = 0.002). Among PegA recipients, VTE was associated with a significantly higher mean body mass index (BMI) of 31.3 kg/m2 (p = 0.037), and was more common with pre-T/T cell compared to pre-B/B cell ALL (68.2% vs. 33.3%, p = 0.009). Antithrombin-III (ATIII) levels were measured for 26 patients; 16 (61.5%) were < 50%. Of those, 8 (50%) experienced VTE, while 3 of 10 (30%) patients with ATIII levels ≥ 50% experienced VTE. VTE occurred in 7 of 13 (54%) of patients who received ATIII repletion. There was a trend toward a higher incidence of VTE in the PegA group among patients with non-O compared to O blood type (55.9% vs. 33.3%, p = 0.079) as well as those with a higher hemoglobin at diagnosis (9.3 vs 8.1 g/dL, p = 0.056).

Conclusion: This study confirms PegA as a risk factor for VTE in patients with ALL. Risk factors among those receiving PegA include higher BMI and pre-T/T cell ALL. ATIII repletion was not shown to be protective against VTE. There was a higher incidence of VTE in patients who received PegA with non-O compared to O blood type, but the precise correlation is uncertain.

Keywords: ALL; Acute lymphoblastic leukemia; Pegaspargase; Pegylated-asparaginase; Venous thromboembolism.

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