ID #591 Direct allergy challenge of cyclophosphamide in a high risk paediatric medulloblastoma patient: a case report

Background

Cyclophosphamide is an alkylating agent that crosses the blood brain barrier, that has been integral to medulloblastoma treatment since the 1980s[1]. Protocol SJMB03 recommends cumulative cyclophosphamide dose of 16g/m2 administrated as eight doses over four chemotherapy cycles[2]. However, preliminary data from Protocol SJMB12 suggests that a reduced cumulative dose of 12g/m2 may maintain comparable five-year progression-free survival[3]. Cyclophosphamide hypersensitivity reactions present a significant challenge, with allergy challenge protocols varying between sites, including skin prick testing or direct drug challenges.

Aim

To describe the outcome of a direct cyclophosphamide allergy challenge in a high-risk medulloblastoma patient to enable continuation of treatment aligned with an evidence based protocols.

Clinical Details

A 16-year-old male with high risk non-WNT/non-SHH medulloblastoma (group 4, subclass V), no previous allergy history experienced a severe reaction post his fifth dose of cyclophosphamide on the SJMB03 protocol. Symptoms included fevers, tachycardia, hypotension, severe facial angioedema, and widespread non-blanching maculopapular rash. Requiring ICU admission with fluid boluses and ionotropic support. He had received 10g/m2 of cyclophosphamide cumulatively (SJMB03 goal of 16g/m2). Thus, the aim was to facilitate a total therapeutic cyclophosphamide dose as per SJMB12 (12g/m2). A graded direct challenge was administered alongside his final chemotherapy cycle as follows: Day 1: full-dose mesna; Day 2: 2.5% cyclophosphamide dose; Day 3: 10% dose. After successful tolerance, cyclophosphamide was administered at 50% of the full dose during cycle 4, with premedication and mesna support.

Outcomes

The challenge was well tolerated, mild transient itch occuring 4 hours post administration on Days 1-2, resolving with antihistamine use. The patient completed treatment, achieving goal cumulative cyclophosphamide dose of 12g/m2.

Conclusion

By undertaking a direct cyclophosphamide challenge, this patient received dosing aligned with an evidence-based protcols without treatment comprimise.

1. Friedman, H. S., Bigner, S. H., & Bigner, D. D. (1995). Cyclophosphamide therapy of medulloblastoma: from the laboratory to the clinic and back again (and again and again). Journal of neuro-oncology, 24(1), 103–108. https://doi.org/10.1007/BF01052667

2. Mushtaq, N., Ul Ain, R., Hamid, S. A., & Bouffet, E. (2023). Evolution of Systemic Therapy in Medulloblastoma Including Irradiation-Sparing Approaches. Diagnostics (Basel, Switzerland), 13(24), 3680. https://doi.org/10.3390/diagnostics13243680

3. Robinson, G. W., Merchant, T. E., Orr, B. A., Bass, J. K., Conklin, H. M., Bag, A., Dhanda, S. K., Pinto, S., Delaney, A., Mikkelsen, M., Reddick, W., Huang, J., Ashford, J., Edwards, A., Christy, L. A., Soans, E., Clarke, M., Strother, D., Fisher, M. J., Bendel, A., Gajjar, A. (2024). MDB-92. EFFECT OF REDUCED-DOSE CRANIOSPINAL IRRADIATION AND REDUCED-DOSE ADJUVANT CHEMOTHERAPY ON CHILDREN AND ADOLESCENTS WITH WNT MEDULLOBLASTOMA WITHOUT RESIDUAL OR METASTATIC DISEASE: RESULTS FROM THE SJMB12 CLINICAL TRIAL. Neuro-Oncology, 26(Suppl 4), 0. https://doi.org/10.1093/neuonc/noae064.540