Second malignant neoplasms (SMN) in childhood acute lymphoblastic leukemia (ALL): Primitive neuroectodermal tumor of bone (PNET) with p53 mutation

Abstract

8173 Background: About 80% of children treated for ALL will be long term survivors. The estimated cumulative risk of a SMN is 2% to 3.3% 15 yrs after diagnosis. Methods: A review of the literature of 25,907 children treated for ALL revealed 274 SMN (1.07%). Results: The most frequently observed SMN are shown below: Others included CML(3), breast cancer (4), malignant histiocytosis (2), ovarian cancer (2), one case each of nephroblastoma, mucoepidermoid CA, bladder CA, malignant teratoma, leimyosarcoma of lung, and 22 unknown cases. In the lymphoma group there was an equal number of NHL and Hodgkins (10). In the AML/MDS group most were AML(26). Of all cases of SMN 62% recieved RT and the risk of a SMN appears to be dose related. Of significance is the fact that the overall survival rate for those patients with reported long term follow is 57.3% (101/176). The Ewings Family tumors and in particular PNET of bone are rare SMN. Of these 25,901 children treated for ALL there is only one case report of a PNET of bone. Our case of a chest wall PNET developing in an 8-yr-old boy one yr after completing therapy for standard risk ALL is the second case reported and the first one associated with germline and tumor cell p53 mutation. . Our patient did not receive RT and therefore can be excluded as a contributing factor. Exposure to anthracyclines and alkylating agents was minimal (75mg/m2 and 1gm/m2 of adriamycin and cytoxan respectively). Conclusions: We conclude that germline p53 mutation played a major role in the development of this rarely observed SMN and that cases of SMN in pediatric patients should be evaluated for p53 mutation. Overall long term survival for patients with SMN after treatment for ALL is encouraging at 57% and determination of p53 may influence therapeutic and prognostic considerations. One percent of children treated for ALL will develop SMN, the decrease use of RT in children with ALL should result in even a lower number of SMN. No significant financial relationships to disclose.