Pilot Study: Favorable Outcomes with Addition of Topotecan to Busulfan/Melphalan As High-Dose Myeloablative Therapy Followed by Autologous Hematopoietic Cell Transplantation

Patients with NBL, stage III or IV were eligible and consented to participate in the study. Seven patients were enrolled, the median age was 2.65 yrs (range 2.3 – 4.x yrs), and there were 4 males (57%). All patients were initially treated on COG protocols and in all cases a complete response was documented prior to proceeding with AHCT. Autologous hematopoietic cells were collected, following mobilization with G-CSF, after 2 (n=6) or 3 (n=1) cycles of chemotherapy. All patients were given post transplant radiation therapy to the primary tumor bed and cis-retinoic acid, 3 patients were also given monoclonal antibodies. Data on engraftment, toxicities, event free survival (EFS) and overall survival (OS) were analyzed.

The median cell dose was 6.62 × 10⁶ CD34+/kg (5.57×10⁶−7.33 × 10⁷). Engraftment occurred promptly in all patients. Myeloid and platelet recovery occurred at a median of 12 (8–17 days) and 22 (17–41 days), respectively. The treatment was well tolerated with no grade 4 or higher toxicities. Grade 3 toxicities included; mucositis (n=7, 100%), electrolyte imbalance (n=3), diarrhea (n=3), autoimmune hemolysis (n=1) and epistaxis (n=1). Three patients suffered disease recurrence, 156, 821 and 899 days post AHCT. One patient is dead and two continue salvage therapy 55 and 52 months, post transplant, respectively. The 4-year OS and EFS were 87% to 57%, respectively.

This novel regimen of Topo/Bu/Mel appears to be well tolerated with low TRM and promising EFS and OS. Further and larger studies are required to establish its role as HD therapy prior to AHCT in patients with advanced NBL.

No relevant conflicts of interest to declare.