Myelodysplastic
syndrome/acute myelogenous leukaemia after adjuvant chemotherapy
with pyrimidine anti-metabolites in three patients
V. Pitini, C. Arrigo, G. Aloi, *M. Righi, *M. Falduto, *D.
Teti
Departments of Oncology and *Pathology, University of Messina,
Italy
Correspondence: Dr. Vincenzo Pitini, Oncologia Medica, Pad. H
5° piano, Policlinico UnIversitario, via Consoloare Valeria,
98125 Messina, Italy. Phoe: international +39.090..2213241. Fax:
international +39.2213231. E-mail address:
pitini@ciaoweb.it
Abstract
In recent years therapy-related myelodysplastic syndromes and acute leukemia have been described in patients previously treated with alkylating agents, radiotherapy or topoisomerase II ihibitors. We report three cases of MDS/AML after the administration of Fluorouracil following a curative resection of primary colon cancer.
Text
Therapy-related acute leukemia and Myelodysplastic Syndromes occur in subjects previously treated with cytotoxic agents or radiotherapy. Two major groups are recognized. The first is observed in patients treated with alkylating agents or radiotherapy; the other major type occurs in patients treated with topoisomerase II inhibitors.1 Although, pyrimidine anti-metabolites have been thought to be rarely associated with the development of leukaemia in humans and experimental animals and are generally considered to be less mutagenic, a recent study, however, revealed that pyrimidine anti-metabolites can cause damage to DNA and that the long term administration of large cumulative doses of oral pyrimidine can cause malignant transformation.2,3
In this paper three patients are
reported with multiple cancer, who developed Myelodysplastic
Syndromes (MDS) after adjuvant chemotherapy following a curative
resection of primary colon cancer. The adjuvant regimens were
based on the administration of 5-fluorouracil (5-FU). The patients
were referred to our clinic for a further examination of their
haematological disorders (Figure
1).
A diagnosis of MDS was made in these patients; RAEB-1 for patient
#1, RAEB-2 (WHO) for patients #2 and #3. Cytogenetic analyses of
the bone marrow cells showed unbalanced abnormalities, including
the loss of chromosome 7 or 7q. All patients rapidly developed
overt AML refractory to anti-leukaemic chemotherapy and died 5/8
months later, although the preceding cancers had not relapsed
(Table
1).
The development of therapy-related MDS/AML represents a multistep
process of malignant transformation. All patients had multiple
cancers, implying that they represent a high-risk group with
abnormality of oncogenes or tumour-suppressor genes and they are
more susceptible to malignant transformation by pyrimidine
anti-metabolites. The present cases have warned that the use of
pyrimidine anti-metabolites can result in the development of
lethal MDS/AML especially in susceptible individuals. The
advantages and disadvantages of the agents should be carefully
evaluated in well-organized comparable clinical studies,
especially in an adjuvant setting.
