Abstract
Intensive chemotherapy achieves complete remission in about 75% of patients with acute myeloid leukaemia (AML). For patients refractory to intensive chemotherapy, prognosis is very poor and treatment options are limited. We report a case of AML which was refractory to induction chemotherapy as well as two salvage regimens. The patient then achieved CR through monotherapy with low-dose azacitidine.
The 57-year-old patient was admitted to our hospital with a diagnosis of AML M1. A bone marrow biopsy revealed a blast count of 88%. The karyotype was 48,XX,+8,+11 [4/20]. The patient received induction chemotherapy with idarubicin, cytarabine, and etoposide (ICE). Because her disease was refractory to treatment, with a bone marrow blast count of 66%, the patient received a salvage regimen with high-dose cytarabine, mitoxantrone, and all-trans retinoic acid (A-HAM). Still, AML blasts persisted, with a blast count of 52%. The patient then received FLAMSA (fludarabine, amsacrine, and high-dose cytarabine) as a second salvage regimen, but again failed to achieve remission (medullary blast count 50%). Pancytopenia persisted over a period of approximately 3 months (WBC <100/μl, Hb and platelets transfusion-dependent). We then decided to treat her with 5-azacitidine. During the first cycle, she received additional G-CSF because of fungal pneumonia. Azacitidine was given at a dose of 100mg/m2 subcutaneously for 5 days. Treatment was tolerated without side effects. The patient responded swiftly. After the first cycle, peripheral cell counts normalized and the peripheral blast count decreased to 1%. The bone marrow blast count was 3% after 3 cycles, and <1% after 5 cycles. Peripheral blood counts dropped only slightly during treatment cycles, and the patient required no further transfusions. Cytogenetic analysis, including FISH with a centromeric probe for chromosome 8, gave normal results. With the exception of the first cycle, azacitidine was administered in an outpatient setting. After completing the fifth cycle, the patient went on to receive allogeneic stem cell transplantation.
In the nineteen-seventies and -eighties, conventional (cytotoxic) dosages of 5-azacytidine showed some activity against AML, but did not achieve remission rates comparable to high-dose cytarabine. Treatment-related toxicity was considerable. Recently, low-dose azacitidine, supposedly acting as a demethylating agent, was approved for treatment of myelodysplastic syndromes in the U. S.. According to recent studies, methyltransferase inhibitors seem to achieve good response rates in patients with high-risk MDS. Cytogenetic remissions have been achieved in patients with poor risk karyotypes. Our case report confirms that 5-azacitidine can be effective in AML, even in patients who have a poor prognosis with conventional therapeutic approaches.
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