Thromboembolic events in children with acute lymphoblastic leukemia (BFM protocols): prednisone versus dexamethasone administration

Abstract

Alterations in hemostasis leading to symptomatic thromboembolism have been observed in patients with acute lymphoblastic leukemia (ALL) receiving Escherichia coli asparaginase (CASP) combined with steroids. Moreover, hereditary prothrombotic risk factors are associated with an increased risk for venous thromboembolism in pediatric ALL patients treated according to the BFM 90/95 protocols (including CASP combined with prednisone during induction therapy). To assess whether the thromboembolic risk associated with established prothrombotic risk factors is modified by treatment modalities (prednisone or dexamethasone), the present analysis was performed. Three hundred thirty-six consecutively recruited leukemic children treated according to different BFM protocols (PRED group, n ‫؍‬ 280, 60 mg/m 2 prednisone; DEXA group, n ‫؍‬ 56, 10 mg/m 2 dexamethasone during induction therapy) were studied. Study end point was the onset of symptomatic vascular accidents during induction therapy. Cumulative thromboembolism-free survival was significantly reduced in children in the PRED group (thrombosis frequency, 10.4%) compared with children in the DEXA group (thrombosis frequency, 1.8%; P ‫؍‬ .028). Although no significant difference was found in the overall prevalence of prothrombotic risk factors, 46.5% of patients in the PRED group who experienced thromboembolic events were carriers of a prothrombotic risk factor, whereas no carrier in the DEXA group had a thromboembolism. At the time of maximum CASP activity, fibrinogen and activities of antithrombin, plasminogen, and protein S were significantly reduced in the PRED group. No significant correlation could be found between CASP activity and levels of coagulation factors. In conclusion, the use of dexamethasone instead of prednisone, administered with CASP, significantly reduced the onset of venous thromboembolism. (Blood. 2003;101:2529-2533)

Dexamethasone versus prednisone for induction therapy in childhood acute lymphoblastic leukemia: a systematic review and meta-analysis

“…The reasons for excluding 15 articles are shown in Figure 1. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] Characteristics of included studies are presented in Table 1 (patients in trial Risk of bias assessment has been hampered by the fact that four of the eight studies, so far, have only published preliminary data in form of conference abstracts (AIEOP-BFM ALL 2000 and ALL-BFM 2000, respectively; COG AALL0232, EORTC 58951). Considering all trials, allocation generation and concealment information were available for one and two trials, respectively.…”

Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children

“…The patients had received a median of three TIT (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), and the seizures occurred a median of 8 days after the last injection.…”

“…Spinal involvement (seven patients, [16][17][18][19][20][21][22]: Two patients had flaccid quadriplegia with sensory and sphincter disorders. The other five patients had solely motor involvement; paraplegia was accompanied in three cases by pyramidal signs (Babinski sign, brisk osteo-tendinous reflexes).…”

“…14,15 The exact incidence of these complications is difficult to determine, as most data come from isolated case reports. [15][16][17][18][19][20] Similarly, the outcome of children with acute neurotoxicity is poorly documented. Yet improvements in outcome in recent years have placed the accent on prevention of treatment sequels.…”

Impaired dexamethasone-related increase of anticoagulants is associated with the development of osteonecrosis in childhood acute lymphoblastic leukemia

“…[3][4][5] Dexamethasone and asparaginase, important drugs in the induction treatment of childhood ALL, can influence the coagulation system. [6][7][8][9][10] Corticosteroids increase most coagulation-protein concentrations, whereas asparaginase can reduce the synthesis of coagulation factors and inhibitors. Micro-thrombi resulting from an imbalance between procoagulant and anticoagulant processes in patients with Legg-Calvé-Perthes disease have been shown to play an important etiological role in the development of ON.…”