A Long Survival of a Secondary Acute Myeloid Leukemia Patient under Low-dose Cytosine Arabinoside and Valproic Acid
1University of Sibiu, Romania
The prognosis of elderly patients with acute myeloid leukemia is poor, especially when they have associated diseases that affect their performance status. Azacitidine, decitabine, and low-dose cytosine arabinoside are drugs of choice for the treatment of unfit patients with acute myeloid leukemia. Their combination with other adjuvant drugs worth to be studied, in order to increase the therapeutic effectiveness. We present a female patient who was treated with low-dose cytosine arabinoside and valproic acid. She is alive at 30 months since the diagnosis of acute myeloid leukemia.
Keywords: Acute Myeloid Leukemia; Cytosine Arabinoside, Valproic Acid
Elderly patients with acute leukemia, especially those in which the disease appeared in the evolution of a myelodysplastic syndrome or a myelodysplastic/myeloproliferative neoplasm raise special problems of treatment due to their performance status. The use of low-dose cytosine arabinoside, azacitidine or decitabine in combination with various adjuvant drugs could be a solution for them.
A 76 years old female patient came to the hospital for fatigue, asthenia, anorexia, and weight loss. An ambulatory blood count revealed a leukocytosis with 13% blasts. She was known with diabetes treated with oral antidiabetic agents, ischemic heart disease, essential hypertension, and deteriorative organic psychosyndrome. The physical examination showed: severe pallor, overweight status, liver anterior edge at 1.5 cm below the costal arch and impalpable spleen. She had no fever. Laboratory analysis confirmed the presence of leukocytosis (37,560/mm3); in addition, she had severe anemia (the serum hemoglobin level was 5.3 g/dL), thrombocytopenia (40,000/ mm3), hyperuricemia (13.4mg/dL), and hypertriglyceridemia (229 mg/dL); the erythrocyte sedimentation rate was 152 mm/1 hour, in the absence of any detectable infections; a Coombs test was positive. The two bone marrow aspirations (made in the sternum and iliac crest) were white. The immunophenotypic examination performed from peripheral blood showed a population of atypical cells with the phenotype: CD10-, CD61-, CD41-, CD34-, CD33++, HLA-DR-, CD64-, CD14-, CD22s-, CD20-, CD5- CD4 -, CD8-, MPOic +. The histopathological examination of bone marrow biopsy diagnosed an acute myeloid leukemia (AML) occurred in the evolution of a myelodysplastic / myeloproliferative neoplasia.
During her next hospitalizations she presented two urinary infections that required antibiotics. These were, probably, the cause of a clostridium difficile colitis, that was treated with vancomycin (4x250 mg / day, 10 days) + metronidazole (3x500 mg / day, 10 days) + rifaximin (3x400 mg / day, 10 days). A relapse of her colitis appeared a month later and was treated with the same antibiotics schedule. Colitis has not recurred since then (in the last 3 months). The complete hematological remission persists at 30 months since the establishment of the diagnosis of AML.
Studies that compare the efficacy of low-dose cytosine arabinoside and decytabine administred to elderly patients with AML can be found in the literature. One of them noted that both drugs have similar overall survival and toxicity . We used low-dose cytosine arabinoside as decytabine was not available in Romania at the moment of diagnosis. The reason was that our patient was elderly, with associated diseases (dibetes, ischemic heart disease, arterial hypertension and deteriorative organic psychosyndrome), which gave them an ECOG status of 3. We used the classical schedule „3 + 7” only when the regimen with low-dose cytosine arabinoside + valproic acid was not effective (in relapses). But unlike the cited study, where the median overall survival was 5.5 months for each of the treatment groups , our patient is alive at 30 months since the
It was showed that a histone demethylation encoding gene [UTX (KDM6A)] is able to increase the sensitivity to valproic acid in C. elegans, fact that highlights a functional relationship between the processes of protein acetylation and lysine-specific methylation and offers a promising novel therapeutic target . In the future, a solution for AML patients who are resistant to treatment could be the use of valproic acid associated with a proteasome inhibitor (eg bortezomib), as this combination inhibits in vitro cell proliferation, arrests the cell cycle in G0- G1 phase and promotes apoptosis in some cell lines (HL60 and HL60A) .
Cite this article: Mihaila RG. A Long Survival of a Secondary Acute Myeloid Leukemia Patient under Low-dose Cytosine Arabinoside and Valproic Acid. J J Cancer Sci Res. 2016, 2(6): 045.