Randomised trials in pediatric ALL show that multiple doses of E Coli Asparaginase (ASP) are associated with better outcome. In the EORTC 58951 protocol, all the patients except those with high risk features (HR or VHR) had 8 IV doses of ASP during induction Ia and were randomized during induction Ib to receive or not ASP (8 IV doses vs 0) and protocol II (8 IV doses vs 4), respectively long arm and short arm. The aim of this study was to report on safety, asparagine (ASN) depletion and antibody production in 28 consecutive patients with newly diagnosed previously untreated ALL.
Methods. Twenty-eight patients included in the EORTC 58951 protocol were analyzed: one had very low risk features, 22 were average risk patients and 6 had HR features. Thirteen patients were randomized in the short ASP arm and 9 in the long ASP arm. ASN levels were assessed on days 35 of Ia, 27of Ib and 22 of IIa. The amino acid assays employed the HPLC method. Serum samples were taken for antibody titers against ASP analyzed by ELISA on days 12 and 35 of Ia, 17 and 27 of Ib (long arm only) and 8 and 22 of IIa, and before the start of maintenance therapy.
Results. Twenty-eight patients aged 1year 3 months to 14 years 6 months (median 6 years) with newly diagnosed ALL (precursor B-cell: 25 ; T-cell: 3) were assessable. All patients achieved CR after induction phase Ia. Four patients had allogeneic bone marrow transplantation in first CR because of VHR features. Two other patients with HR features had intensified chemotherapy. Preliminary data showed that ASN depletion was obtained in all patients at the end of phase Ia, in all the patients “long arm” at the end of Ib and in one patient ” short arm” at the end of Ib All patients had depletion of ASN after protocol IIa We observed very few severe clinical allergic reactions in this series of patients (10%). Two patients were switched to Erwinia asparaginase because of clinical hypersensitivity. Investigation on correlation between the antibody production against ASP, clinical allergic reaction and depletion of ASN are in progress.
Conclusions. Multiple doses of ASP given intravenously were well tolerated in this series of 28 consecutive patients with previously untreated ALL. Preliminary results reveal that the rate of antibodies production was low and depletion of ASN was obtained in near all the patients. Some patients presented with clinical allergic reactions but had low levels of ASN and no appearance of anti ASP antibodies. Other had antibodies without clinical allergy and with depletion of ASN.
Disclosure: No relevant conflicts of interest to declare.