13 cis- retinoic acid in children with high

Ref ID: 143.1
13 cis- retinoic acid in children with high-risk neuroblastoma: Is more better?
Shifra Ash1, Jerry Stein2, Batia Stark1, Yacov Goshen1, Liora Kornreich3, Zvi Bar-Sever4, Meora Feinmesser5,
Isaac Yaniv1
Pediatric Hematology Oncology1, Bone Marrow Transplantation Unit2, Imaging3, and Nuclear Medicine4, Schneider Children's Medical
Center of Israel, Petah-Tikva, Israel; Pathology5, Rabin Medic Center, Beilinson Campus.
13 cis-retinoic acid (RA) induces differentiation in neuroblastoma (NB) cell lines in-vitro. Administration of highdose RA (two-week pulses for 6 months) improves disease free survival among patients with advanced stage
NB who are in complete remission following standard and myeloablative chemotherapy. We report our
experience with prolonged RA administration in 17 high risk patients with NB. Patients received an average of
11.3 RA courses (range 2 to 26) beginning at a median of 93 days after APBSCT.
In four patients, ganglion cells appeared in bone marrow biopsies obtained during RA treatment. Six year
overall survival is 48% and event free survival is 44%. With a median follow up of 59 months, eight patients
have relapsed. Five of these events occurred during RA administration. One of the patients in whom ganglion
cells appeared in bone marrow biopsy while on RA treatment, relapsed within three months of stopping RA. An
additional relapse occurred in a child who did not tolerate RA due to drug-induced hypercalcemia. Side effects
of treatment included cheilitis and dry skin in all patients and one case of severe hypercalemia as indicated
above. Our cohort of very high-risk patients is exhibiting an unexpectedly good progression free interval after
receiving prolonged RA consolidation therapy. In-vivo demonstration of tumor cell differentiation during therapy
suggests a role for RA as consolidation treatment for patients even in the presence of small amounts of
residual NB. Administration of RA for periods of longer than 6 months should be explored as part of a multimodal approach to the treatment of high-risk NB.
Presentation mode(s): POSTER-PRESENTATION