Introduction
In refractory or relapsed acute leukemia the achievement of a complete
remission by a salvage therapy and the performance of an allogeneic
hematopoietic stem cell transplantation (HSCT) is in most cases the only
treatment by which long term disease-free survival can be accomplished.
With current salvage regimens a 5 year overall survival rate of 29% is
obtained in children with relapsed acute myeloid leukemia (AML) and a 10
year overall survival rate of 36% in children with relapsed acute
lymphoblastic leukemia (ALL) 3,5. It has to be
considered that children with relapsed leukemia have been exposed to
high dose chemotherapy, especially if hematopoietic transplantation and
thus intensive conditioning regimens have already been performed.
Therefore a low toxicity regimen is needed. Melphalan is an alkylating
drug with myeloablative and anti-tumour effect, which has been used in
conditioning regimens prior to stem cell transplantation in different
hematologic and non-hematologic malignancies 6-8. The
dose-limiting toxicity of melphalan is its bone marrow suppression, the
extramedullary toxicity is low including mucosal damage, increase of
liver enzymes and the development of interstitial pneumonia6. Cytarabine is an analogue of deoxycytidine. It is
known to cause myelosuppression and gastrointestinal toxicity, fever and
elevation of hepatic enzymes, neuronal toxicity and cardiac arrhythmia4,9.
In Germany first line treatment for relapsed ALL and AML is conducted
with an induction polychemotherapy, followed by consolidation therapy
and an allogeneic stem cell transplantation in intermediate and high
risk cases of relapsed ALL and in the majority of cases of relapsed AML
according to the ALL-REZ-BFM 2002 protocol and the International
Registry AML Relapse 2009 4,10. In case of second or
third relapse an individualized chemotherapy with the introduction of
new drugs is recommended 4.
In this restrospective case cohort analysis we investigated the outcome
of a salvage therapy with melphalan and cytarabine in refractory or
relapsed acute leukemia in children.