Therapy-related Myelodysplasia (T-MDS/T-AML) Following Treatment Of Children With Osteosarcoma
Diana Stripp, MD
University of Pennsylvania Cancer
Last Modified: May 15, 2001
Presenter: Smita Bhatia Affiliation: City of Hope Comprehensive Cancer Center, Duarte, CA
T-MDS/T-AML is known to be associated with anti-neoplastic treatment.
With alkylating agents, T-MDS/T-AML is associated with deletion of chromosome 5 and/or 7, with a long latency (4-7 yrs) and MDS.
With Topoisomerase II, abnormality of 11q23, shorter latency period (2-3 yrs) and lack MDS feature.
This trial is designed to study T-MDS/T-AML in children treated for osteosarcoma, to identify risk factors and evaluate the effect of ifosfomide.
Materials and Methods:
778 children and adolescents diagnosed with osteosarcoma between 1992 and 1997 (and treated according to a therapeutic protocol: CCG-7921/POG- 9351) were entered to this phase III, prospective, randomized trial of two chemotherapy regimens:
A - high-dose methotrexate (cumulative dose: 144 g/m2), doxorubicin (450 mg/m2) and cisplatin (480 mg/m2).
B - called for the administration of these agents plus ifosfamide (45 g/m2).
Median age at diagnosis (dx) was 14.0 yr. (range: 6.2-26.2), and median follow up was 2.6 years (yrs) (range: 0-6.1).
Thirteen patients (pts.) developed T-MDS/T- AML, and 11 had cytogenetic abnormalities.
3 pts suffered a relapse of the primary disease prior to developement of T-MDS/T-AML and only those pts developed T-MDS/T-AML were subsequently analysed.
The cumulative incidence of T-MDS/T-AML, was 3.3±1.2% at 6 yr. The median time to development of T-MDS/T-AML was 3.1 yr. (range 1.7-4.7 yr.)
Relative risk of developing T-MDS/T-AML was no different between age of diagnosis, genders, treatment regimens, or between cytogenetic abnormalities.
Overall, the risk was similar for patients in both regimens.
The addition of ifosfamide at a cumulative dose of 45 g/m2 (Regimen B) did not increase the risk of T-MDS/T-AML.
Continued follow-up of this cohort is necessary to determine the incidence of late occurance of T-MDS/T-AML in this cohort.
Even though this trial showed the addition of ifosfamide did not increased the risk of developing T-MDS/T-AML, the follow-up period of this study is short.
The findings of this study are similar to other studies that showed a cummulative risk of developing a secondary malignancy is 2-3% at 4 yrs.