Ifosfamide in the treatment of childhood lymphomas

Malignant lymphomas are the third most common type of childhood cancer, after acute lymphoblastic leukemias (ALL) and brain tumors. Children’s lymphomas typically present with a diffuse extranodal disease, in contrast to adults, among whom the primary nodal disease is more common. Additionally, the pediatric non-Hodgkin’s lymphomas (NHL) are typically high-grade tumors. The NHLs of childhood are growing very rapidly.
Therefore it is imperative that the diagnosis be established as soon as possible so that appropriate therapy can be started. There have been significant improvements in the treatment outcome for children with newly diagnosed NHL over the past 20 years. In the case of approximately 20-30% of children with NHL frontline therapy fails as manifested by either recurrent or, less commonly, refractory disease. The prognosis for these groups has generally been believed to be quite poor. New drugs are still searched for to improve results in childhood lymphomas. Approximately 23 years ago ifosfamide was introduced in the pediatric oncology arena, especially for the treatment of pediatric soft tissue sarcoma. Several combination chemotherapy regimens including ifosfamide are used to treat NHLs. Although ifosfamide is considered highly effective in lymphomas it is also very toxic, resulting in myelosuppression and immunosuppression and requiring colony-stimulating factors to be incorporated in the treatment regimen. Hemorrhagic cystitis, nephrotoxicity and neurotoxicity can also occur when ifosfamide is used as part of treatment.