Evidence of a Hypercoagulable State in Patients with Acute Lymphoblastic Leukemia Treated with Low Dose of E.coli L-Asparaginase: A GIMEMA Study

Leone, Giuseppe; Gugliotta, Luigi; Mazzucconi, Maria Gabriella; Stefano, V. De; Belmonte, M. Mattioli; Dragoni, Francesco; Specchia, Giorgina; Centra, Antonia; Gamba, G; Camera, Andrea; Mandelli, Franco

doi:10.1055/s-0038-1651179

Cited by 43 publications

(33 citation statements)

References 17 publications

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“…We confirm that L-Ase treatment can induce a latent hypercoagulability state in patients affected by ALL which, in some cases, was evidenced by acute ischemic events [10,11], According to the literature, the frequency of these events ranges from 3 to 5% [12]. We recorded 3 events in the 20 patients considered in the present study (15%).…”

Section: Discussionsupporting

confidence: 83%

<i>L</i>-Asparaginase in Acute Lymphoblastic Leukemia Treatment: The Role of Human Antithrombin III Concentrates in Regulating the Prothrombotic State Induced by Therapy

et al. 1995

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It is well known that L-asparaginase (L-Ase) treatment may cause thrombotic events in patients with acute lymphoblastic leukemia (ALL). The mechanism of this effect is not well understood although a reduction in plasma antithrombin III (AT III) levels is observed. In our study, a group of patients treated with L-Ase received AT III concentrates as adjuvant treatment. This adjuvant treatment reduced the levels of plasma D-dimer and thrombin-antithrombin complex, which are considered as early markers of a hypercoagulability state. These preliminary data suggest that large randomized trials will have to be conducted to improve our understanding of the role of AT III concentrates in ALL therapy.

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Section: Discussionsupporting

confidence: 83%

<i>L</i>-Asparaginase in Acute Lymphoblastic Leukemia Treatment: The Role of Human Antithrombin III Concentrates in Regulating the Prothrombotic State Induced by Therapy

et al. 1995

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“…The main cause of induction death was infection, whereas hemorrhage and thromboembolic events, due to E coli ASP, disappeared when the drug was substituted by Erwinia ASP. 26 Achievement of CR was influenced by age, initial WBC count, and response to PDN pretreatment, but not by immunophenotype or cytogenetic or molecular abnormality. The CR rate in T-lineage ALL was slightly higher (85%); even in this subset, the impact of Cy during induction did not translate into a significantly better disease outcome.…”

Section: Org Frommentioning

confidence: 95%

Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study

Annino

Vegna

Camera

et al. 2002

Blood

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311

196

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The GIMEMA ALL 0288 trial was designed to evaluate the impact of a 7-day prednisone (PDN) pretreatment on complete remission (CR) achievement and length, the influence of the addition of cyclophosphamide (random I) to a conventional 4-drug induction on CR rate and duration, and whether an early post-CR intensification (random II) by an 8-drug consolidation could improve CR duration. Median follow-up of this study was 7.3 years. From January 1988 to April 1994, among 794 adult (> 12 but < 60 years) patients registered, 778 were eligible. Their median age was 27.5 years; 73% had Blineage acute lymphoblastic leukemia (ALL) and 22% had T-lineage disease; 18% showed associated myeloid markers; 47 of 216 analyzed patients (22%) had Philadelphia chromosome-positive ALL. Response to PDN pretreatment was observed in 65% of cases. CR was achieved in 627 patients (82%). Resistant patients and induction death rates were 11% and 7%, respectively. Random II was applied to 388 patients with CR; 201 had maintenance alone and 187 had consolidation followed by maintenance. The relapse rate was 60%; isolated central nervous system relapses were 8% of all

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“…The effects measured in our study are the result of 10 000 IU/ m 2 of L-asparaginase administered every 3 days. In the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) study [32] E. coli L-asparaginase was given daily in a lower dose of 6000 IU/m 2 and also at this dose an increase in hypercoagulability parameters during treatment with E. coli L-asparaginase was found. Nowak-Gottl [33] demonstrated less changes in haemostasis in children treated with 2500 IU/m 2 of the native E. coli L-asparaginase preparation compared with 5000 IU/m 2 of the same L-asparaginase.…”

Section: Discussionmentioning

confidence: 99%

Changes in hypercoagulability by asparaginase: a randomized study between two asparaginases

Appel

Hop²,

Pieters³

2006

Blood Coagulation &Amp; Fibrinolysis

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Alterations in hemostasis have frequently been observed in children with acute lymphoblastic leukemia. Thrombotic events are well documented in patients receiving L-asparaginase as a single agent or in combination with other chemotherapeutic drugs. The present prospective, randomized study evaluated the effect of two different L-asparaginase preparations, native Escherichia coli L-asparaginase (Crasnitin; Bayer AG, Leverkusen, Germany; n = 10) and L-asparaginase derived from Erwinia chrysanthemi (Erwinase; Porton Pruducts, London, UK; n = 10) on the changes in parameters concerning hypercoagulability. Patients were randomized to receive a total of eight doses of 10,000 IU/m2 L-asparaginase intravenously with intervals of 3 days during induction therapy. Before starting L-asparaginase treatment all patients had already demonstrated an increased thrombin generation shown by the elevated levels of prothrombin fragment 1+2 and thrombin antithrombin III, presumably due to therapy with prednisone, daunorubicin and vincristine. A significant decrease in alpha2-antiplasmin and plasminogen levels was measured in the E. coli L-asparaginase but not in Erwinase-treated patients. Increased thrombin generation combined with a decrease in alpha2-antiplasmin and plasminogen levels may lead to a state of increased risk for thrombosis due to a delay in fibrin elimination in E. coli L-asparaginase-treated patients only.

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Evidence of a Hypercoagulable State in Patients with Acute Lymphoblastic Leukemia Treated with Low Dose of E.coli L-Asparaginase: A GIMEMA Study

Cited by 43 publications

References 17 publications

<i>L</i>-Asparaginase in Acute Lymphoblastic Leukemia Treatment: The Role of Human Antithrombin III Concentrates in Regulating the Prothrombotic State Induced by Therapy

<i>L</i>-Asparaginase in Acute Lymphoblastic Leukemia Treatment: The Role of Human Antithrombin III Concentrates in Regulating the Prothrombotic State Induced by Therapy

Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study

Changes in hypercoagulability by asparaginase: a randomized study between two asparaginases

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