Aichberger K J, Sperr W R, Gleixner K V, Kretschmer A, Valent P
Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Austria.
Eur J Clin Invest. 2008 Nov;38(11):869-73. doi: 10.1111/j.1365-2362.2008.02036.x.
Systemic mastocytosis (SM) is a mast cell neoplasm in which neoplastic cells usually display the D816V-mutated variant of KIT. Cladribine (2CdA) and dasatinib are two drugs that counteract the in vitro growth of neoplastic mast cells in SM. However, only little is known about the in vivo effects of these drugs in SM.
We report on a patient with highly aggressive interferon-alpha-resistant SM who was treated with 2CdA and dasatinib. In vitro pretesting revealed a response of neoplastic mast cells to both compounds with reasonable IC(50) values.
The patient was treated with six cycles of 2CdA (0.13 mg kg(-1) intravenously daily on 5 consecutive days). Despite a short-lived major clinical response and a decrease in serum tryptase, the patient progressed to mast cell leukaemia after the sixth cycle of 2CdA. The patient then received two further courses of 2CdA followed by treatment with dasatinib (100 mg per os daily). However, no major response was obtained and the patient died from disease progression after 2 months.
In a patient with rapidly progressing aggressive SM, neither 2CdA nor dasatinib produced a long-lasting response in vivo, despite encouraging in vitro results. For such patients, alternative treatment strategies have to be developed.
系统性肥大细胞增多症（SM）是一种肥大细胞肿瘤，其中肿瘤细胞通常表现为KIT的D816V突变变体。克拉屈滨（2CdA）和达沙替尼是两种可对抗SM中肿瘤性肥大细胞体外生长的药物。然而，关于这些药物在SM中的体内作用知之甚少。
我们报告了一名对α干扰素耐药的高度侵袭性SM患者，该患者接受了2CdA和达沙替尼治疗。体外预试验显示肿瘤性肥大细胞对这两种化合物均有反应，且IC（50）值合理。
该患者接受了六个周期的2CdA治疗（0.13 mg kg⁻¹，连续5天每日静脉注射）。尽管出现了短暂的主要临床反应且血清类胰蛋白酶降低，但该患者在接受第六个周期的2CdA治疗后进展为肥大细胞白血病。该患者随后又接受了两个疗程的2CdA治疗，之后接受达沙替尼治疗（每日口服100 mg）。然而，未获得主要反应，患者在2个月后因疾病进展死亡。
在一名快速进展的侵袭性SM患者中，尽管体外结果令人鼓舞，但2CdA和达沙替尼在体内均未产生持久反应。对于此类患者，必须制定替代治疗策略。
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