Tandem High Dose Chemotherapy and Autologous Stem Cell Rescue for High Risk Pediatric Brain Tumors

The investigators plan to improve event free survival rate and reduce treatment related toxicities of pediatric patients with high risk/recurrent CNS tumors by administrating tandem high dose chemotherapy and autologous stem cell rescue.

High risk/recurrent central nervous system (CNS) tumors have a poor prognosis so that tandem high dose chemotherapy (HDCT) with hematopoietic progenitor stem cell rescues has been chosen as potentially curative therapy. Many institutions have used carboplatin, thiotepa, etoposide (CTE) for conditioning regimen of 1st HDCT and cyclophosphamide, melphalan (CM) for conditioning regimen of 2nd HDCT. Our institution applied this regimen to the 38 pediatric patients with high risk brain tumor since 1996. Although the 3 year overall survival rate and event free survival rate were improved to 69% and 47.9%, respectively, the results showed relatively high treatment related mortality (TRM) rate of 21%. Toxicity of this tandem regimen was also reported as being high up to 32% in other researches as well so that this regimen is considered not feasible due to toxicity. In this study, the investigators plan to improve event free survival rate and reduce treatment related toxicities of pediatric patients with high risk/recurrent CNS tumors by administrating tandem high dose chemotherapy and autologous stem cell rescue with topotecan, thiotepa, carboplatin (TTC) for 1st HDCT and melphalan, etoposide, carboplatin (MEC) for 2nd HDCT.

Inclusion Criteria:

1. High risk pediatric brain tumors Newly diagnosed medulloblastoma, CNS PNET, ATRT, Choroid plexus carcinoma, pineoblastoma with residual tumor over 1.5cm2 after operation or with leptomeningeal seeding at diagnosis

2. All high grade or malignant brain tumor, age < 3 years

3. Recurrent embryonal brain tumors, recurrent CNS germ cell tumor

4. Age : no limitation

5. Performance status : ECOG 0-2.

6. Patients must be free of significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases.

   Heart: a shortening fraction ≥ 28%. Liver: total bilirubin < 2 ⅹ upper limit of normal; ALT < 3 ⅹ upper limit of normal. Kidney: creatinine < 2 ⅹ normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2.

7. Patients must lack any active viral infections or active fungal infection.

8. Patients (or one of parents if patients age < 20) should sign informed.

Exclusion Criteria:

1. Patients who do not reach partial response prior to high dose chemotherapy.
2. Pregnant or nursing women.
3. Malignant (except brain tumor) or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
4. Psychiatric disorder that would preclude compliance.
5. Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.