Gemcitabine-Oxaliplatin as a bridge therapy towards autologous hematopoietic stem cell transplantation in Infant-type brain tumors

Barbara Castelli^1,2*Carla Fonte^1,2Marco Tellini^1,2Marco Di Nicola^1,2Milena Guidi^1,2Laura Giunti^1,2Bianca Tirinnanzi^1,2Chiara Marzano^1,2Anna Maria Buccoliero²Ludovico D'Incerti²FLAVIO GIORDANO²Mirko Scagnet²Veronica Tintori²Lorenzo Genitori²Iacopo Sardi^1,2

• ¹Neuro-Oncology Unit, Meyer Children's Hospital, Florence, Italy
• ²Meyer Children's Hospital IRCCS, Florence, Tuscany, Italy

In neuro-oncological pediatric patients under 3 years of age, chemotherapy intensified to high doses (HDC) represents the cornerstone, to avoid the potential toxicity of radiotherapy. Gemcitabineoxaliplatin combined treatment (GemOx) was administered in infant-type cerebral tumors as a bridge towards autologous hematopoietic transplantation, to achieve clinical and neuroradiological permissiveness to HDC and to raise the possibility of second look neurosurgery. From May 2017 to May 2023 at Meyer Children's Hospital IRCSS in Florence (Italy), four patients, median age 19 months (two high-grade gliomas, a metastatic medulloblastoma, a choroid plexus carcinoma CNS WHO grade 3) were subjected to partial neurosurgical removal and induction therapy delivered according to the Italian program for malignant cerebral tumors under 3 years. To delay HDC, for disease reassessment or for temporary unfitness, GemOx cycles were administered. Gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 were provided on day 1 every 21-28 days for 1-6 cycles. Treatment was overall well tolerated, except severe platelet hematological toxicity in a patient, requiring dose reduction to 75%. After GemOx, one patient was also subjected to further neurosurgery. Bridge therapy made it possible to submit patients to HDC in safety, in permissive clinical conditions and after assessment of disease stability. In Infant-type cerebral tumors eligible for HDC, GemOx could be a possible strategy in case of post-induction residual disease to exclude dubious evolution or waiting for clinical suitability for second surgery and intensified treatments. The therapy was overall safe and well tolerated. This approach resulted incisive in the therapeutic or palliative choice for extremely young patients with aggressive brain tumors.