Peri-Transplant Toxicity for Pediatric Patients with High-Risk Medulloblastoma Undergoing Tandem Autologous Hematopoietic Cell Transplantation

Background: Medulloblastoma is the most common brain tumor in children and its prognosis is improved by the combination of surgical resection, irradiation, and/or chemotherapy.  Chemotherapy followed by autologous peripheral blood stem cell (auto-PBSC) rescue has been used for the treatment of high-risk medulloblastoma.

Patients & Methods: Between July 2010 and July 2012, 8 patients with high-risk medulloblastoma underwent tandem chemotherapy with stem cell rescue procedures implementing one of two protocols. Four children aged less than 36 months old [median age 30 month old (range 24-33 months old)] (group-A) received the Children's Oncology Group – ACNS0334 protocol. The other 4 patients aged more than 36 months old [median age 12 year old (range 9-15 years old)] (group-B) were treated according to the St. Jude - SJMB03 protocol.

Results: All patients engrafted well and are alive with no evidence of disease. Median follow-up from discharge for last transplant is 6.5 months (range 3-24 months). Neither cardio nor pulmonary toxicities were documented. Gastrointestinal tract: No patient had veno-occlusive disease of the liver. All patients developed mild to moderate mucositis, thus received total parentral nutrition for a median period of 7 days (range 5-12 days). Infections: group-A: all patients experienced at least 1 transplant period without any fever. Bacteremia included staphylococcus Coa. (-), proteus sp. and pseudomonas sp. Neither viral nor fungal infections were documented. Group-B: 2 patients experienced at least 1 transplant without any fever. Bacteremia included staphylococcus Coa. (-), staphylococcus aureus and pseudomonas sp.  Metabolically: 2 group-B patients developed inappropriate anti-diuretic-hormone secretion. All patients developed mild hypomagnesaemia. Neurology: 1 group-B patient developed generalized motor weakness attributed to MESNA he received for the cytoxan. From then on, cytoxan was given without MESNA but with urinary catheterization and hyperhydration. He also developed mastication movements attributed to the resperidal he got, which was stopped with improvement. No patient developed major bleeding. Renal: 1 group-A patient received VP-16 instead of carboplatine on the first transplant due to basic renal impairment. 1 group-B patient suffered from renal impairment with GFR reduction between 25%-50% of baseline following his first transplant. He also demonstrated grade-3 ototoxicity and thus received only 50% cisplatin dose from the third transplant. Another 2 group-B patients suffered from grade 4 ototoxicity before admission and therefore did not get cisplatin at all.

Conclusions: Tandem auto-PBSC transplants are feasible for high-risk medulloblastoma pediatric patients, with excellent engraftment and survival results and acceptable toxicities, applying the ACNS0334 and SJMB03 protocols.