The Effect of CAHB on Myelodysplastic Syndrome In Vitro and Its Application in a Prospective Clinical Trial

Autor: Maofang Lin, Jingsong He, He Huang, Xiaoyan Han, Qunyi Guo, Li Li, Zhen Cai, Jiming Shi, Hui Zhou, Buwen Zhang
Rok vydání: 2007
Předmět:
Zdroj: Blood. 110:4628-4628
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood.v110.11.4628.4628
Popis: Introduction: Despite recent advances, myelodysplastic syndrome (MDS) is still a therapeutic challenge. CAHB is a novel differentiation inducer which showed early evidence of efficacy in a phase I clinical trial. We used this agent to treat cultured MDS cells in vitro in our research laboratory and then, in a prospective clinical trial in our clinic. Preclinical data: We first investigated the effect of CAHB in vitro in human MDS-RAEB cell line MUTZ-1 cells. Treatment with CAHB remarkably inhibited the growth of MUTZ-1 cells in a dose-dependent and time-dependent manner with IC50 at 5.6 mmol/L at 48 hours. CAHB treatment decreased S phase cells, increased G2/M phase cells, but did not change G0/G1 phase cells, which indicated arrest in G2 phase. When treated with different concentrations of CAHB (0, 2.5, 5, 10 mmol/L) for 24 hours, the expressions of survivin mRNA decreased in a dose-dependent fashion. Patients and method: Eligible patients with MDS had organ functions and were without significant cormobidities. Data from 3 pancytopenic patients on this trial were analyzed. Their whole blood counts were 1.1, 2.3, and 2.5 k/uL, respectively. Their hemoglobins were 7, 9, and 7 g/dL, respectively. Their platelets counts were 10, 31, and 20 k/uL, respectively. The blasts form all 3 patients were of myeloid immunophenotype and diploid chromosomal karyotype. All 3 patients received 0.45g/m2 CAHB for eight hours daily for 10 days every 5 weeks as 1 cycle. Clinical Results: Upon the completion of the two courses, all had fatigue. Their bone marrow blasts decreased from 13.5% to7% (48% decrease), 26.5% to12% (55% decrease), and 11% to 2% (82% decrease), respectively. No grade 3–4 toxicities were observed after 2 months. Grade 1–2 toxicities included nausea and vomiting. Two patients had EKG changes with ST-segment depressions, u wave and bundle branch block which disappeared after the drug was stopped. There was no significant change in the peripheral blood cell counts in all 3 patients. Conclusion: CAHB inhibited cell growth and induced apoptosis of MUTZ-1 cells in vitro. CAHB reduced blast cells in 3 MDS patients. Two patients had transient EKG changes. Our preliminary clincial data showed early evidence of efficacy of CHAB in treating MDS with a tolerable toxicity profile. Its mechnism of action is under further investigation.
Databáze: OpenAIRE
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