The Challenges of Crizotinib Treatment in a Child With Anaplastic Large Cell Lymphoma

Abstract

Survival in cases involving childhood malignancy is reaching nearly 80% in high-income countries, yet cancer remains one of the leading disease-related causes of death in children. In adult oncology the role of targeted therapies is established, but information regarding the use of these therapies in children is limited, largely because targeted therapies were developed in the context of adult pathologies. The few pediatric reports regarding crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, seem promising. This case of an 8-year-old male with an ALK-positive anaplastic large cell lymphoma highlights the challenges of treating children with crizotinib. Our experience with crizotinib was more challenging than described in the limited pediatric reports. Not only was the tumor response poorer than described in the reports, but a substantial amount of side-effects and practical difficulties, such as the method of administration and dosing, made management challenging. Many challenges for the use of targeted therapy in pediatric care currently persist. The limited research in pediatric populations leaves uncertainty regarding efficacy and short- and long-term side effects as well as practical difficulties. Despite a clear underlying biological rationale for certain targeted therapies, their contribution toward improving the outcome of childhood cancer remains largely unclear.

Keywords: anaplastic large cell lymphoma; crizotinib; molecular targeted therapy; off-label use; oncology; pediatrics.

Figure 1.

Intermittent treatment response of the mediastinal tumor mass on crizotinib, as seen on chest x-ray. A) Apical (AP) chest x-ray before administration of crizotinib; B) Stable disease after 7 days of daily crizotinib (oral capsules) on AP chest x-ray; C) Improved anti-tumor effect on day 28 after 14 days of crizotinib via nasogastric tube and intravenous vinblastine.

Figure 2.

Esophageal crizotinib crystal residue on gastroscopy and reported after a tissue biopsy.

Figure 3.

Magnetic resonance imaging demonstrating cerebral lesions suspected to represent brain metastases.

Figure 4.

Staphylococcal scalded skin syndrome.

Figure 5.

Timeline of the disease process.