Significant improvement in clinical outcomes and remission rates in children has shown the efficacy of asparaginase in childhood acute lymphoblastic leukaemia (ALL). However, asparaginase-induced hypersensitivity reactions (HSR) are the most important side effects that may limit the clinical use of this agent in patients who have reacted [1]. One-third of patients who developed HSR during L-asparaginase administration also experience allergic reactions to PEG-asparaginase [2]. In many countries, there is a shortage of the alternative agents of asparaginase. Therefore, completing the chemotherapy protocol without experiencing another HSR against the available agent is very important.

A 4.5-year-old girl with B-cell ALL underwent IC-BFM 2009 Phase-1A (including eight doses of 5000 U/m² L-asparaginase), Phase-1B, and HR1 phase (including one dose of 25,000 U/m² L-asparaginase), safely. While she was receiving the next 25,000 U/m² L-asparaginase in HR2 protocol, she developed dyspnoea with bilateral rhonchi, nausea and vomiting, and urinary incontinence within a few minutes of initiation of the infusion. With the diagnosis of anaphylaxis, the chemotherapy infusion was immediately terminated, and intramuscular adrenaline (0.01 mg/kg), high-flow oxygen, intravenous dexamethasone, and pheniramine were administered immediately. However, within few minutes, she developed cyanosis, hypotension, bradycardia, and loss of consciousness. Despite repeated doses of adrenaline, positive pressure ventilation, and isotonic saline administrations, the patient’s condition deteriorated. After intubation, she was transferred to the paediatric intensive care unit and adrenaline infusion was initiated. At the end of the 24-hour treatment, the patient’s symptoms resolved and vital signs returned to normal. Asparaginase was still critically importance in her ALL treatment. Because the patient experienced a possibly fatal reaction with L-asparaginase, and due to the risk of recurrence of the HSR, PEG-asparaginase was selected as the treatment of choice, administered with premedication using methylprednisolone, hydroxyzine, montelukast, and famotidine within 1 to 36 h prior to rapid drug desensitisation (RDD) (Supplementary Table S1). She received five more PEG-asparaginase doses with a 16-step desensitisation protocol with 4-week intervals without HSR. She was able to complete all chemotherapy without any disruption, and she is currently in remission of leukaemia.

Patients who develop HSR during L-asparaginase administration may also have hypersensitivity to PEG-asparaginase [2]. In addition, cases of anaphylactic reaction to PEG-asparaginase have also been reported despite both premedication and desensitisation [3]. In the absence of an alternative agent and in the presence of a near fatal HSR, dual implementation of premedication and RDD with PEG-asparaginase becomes a valuable alternative option. Different results have been reported in the literature in regard to desensitisation with PEG- asparaginase (Table 1) [3–10]. It is important to note that some of the patients had previously reacted to PEG-asparaginase after experiencing an HSR to L-asparaginase, PEG-asparaginase, or Erwinia asparaginase. Some of the patients developed HSR during RDD, requiring adrenaline, and their treatments could be completed with treatment modification.

In our case, serum tryptase levels were not assessed during the occurrence of HSR. The reason for this could be the failure to consider the diagnosis of anaphylaxis in the patient, despite meeting the diagnostic criteria. Elevated levels support a diagnosis of anaphylaxis, especially in patients with drug-induced anaphylaxis. However, normal levels do not rule out the occurrence of anaphylaxis, and it should be noted that serum tryptase levels are not able to detect all cases of anaphylactic reactions. Assessing the serum tryptase level in our patient would have been highly beneficial in clarifying the nature of the reaction. Also, skin testing could not performed because of the urgent need for prompt therapeutic intervention; however, it should be noted that skin testing can be considered in elective and clinically stable situations, where feasible. Because our patient experienced a near fatal HSR with L-asparaginase, and due to the possibility of another life-threatening reaction with PEG-asparaginase, we think that the most appropriate treatment method for her was RDD.