Radin Arthur I, Kim Haesook T, Grant Barbara W, Bennett John M, Kirkwood John M, Stewart James A, Hahn Richard G, Dutcher Janice P, Wiernik Peter H, Oken Martin M
Department of Internal Medicine, Division of Hematology-Oncology, Cornell University Medical School, New York, New York, USA.
Cancer. 2003 Jul 1;98(1):100-9. doi: 10.1002/cncr.11486.
In vitro and clinical data suggest a therapeutic role for alpha2 interferon (IFN) in the treatment of the chronic myeloproliferative disorders. Accordingly, a multiinstitutional, Phase II trial of IFN in patients with agnogenic myeloid metaplasia (AMM), essential thrombocythemia (ET), and polycythemia rubra vera (PRV) in the spent phase was initiated. The objectives of this study were 1) to investigate the response rates that may be achieved with IFN in the treatment of patients with these disorders, 2) to estimate the durability of the responses, and 3) to assess the toxicities of IFN in these populations.
Enrollment was limited to patients with AMM, ET, or PRV who already had developed 1) anemia or transfusion dependency, 2) thrombocytosis uncontrolled by standard therapy, 3) hemostatic complications, or 4) symptomatic splenomegaly. Initially, patients were started on IFN at a dose of 5 MU/m(2) per day as a subcutaneous injection. After the first 16 patients had been treated, the starting dose of IFN was reduced to 2 MU/m(2) per day because of unexpected toxicities.
IFN demonstrated different levels of efficacy and toxicity in each of the three diseases studied. The overall response rates achieved among the evaluable patients in each category were as follows: ET, 88.2% (n = 17 patients; 1 complete response and 14 partial responses); PRV, 41.7% (n = 12 patients; 1 complete response and 4 partial responses); and AMM, 3.2% (n = 31 patients; 0 complete responses and 1 partial response). Thrombocytosis and leukocytosis were controlled in nearly all patients, with reversal of splenomegaly and resorption of myelofibrosis achieved in fewer patients. The toxicities attributed to IFN differed notably among the three disease groups: patients who had AMM suffered systemic and neurologic toxicities more frequently than patients who had PRV or ET; whereas patients who had ET experienced a greater than expected incidence of hepatic abnormalities, most typically transient elevations of serum amino acid transaminase levels.
The current study demonstrated the safety and efficacy of IFN in patients with ET, PRV, and AMM. Objective responses and/or disease stabilization were obtained in patients with all three disease entities, including the reversal of splenomegaly and resorption of myelofibrosis in some patients.
体外实验和临床数据表明，α2干扰素（IFN）在慢性骨髓增殖性疾病的治疗中具有治疗作用。因此，开展了一项针对无明确病因的骨髓化生（AMM）、原发性血小板增多症（ET）和真性红细胞增多症（PRV）终末期患者的多机构II期IFN试验。本研究的目的是：1）研究IFN治疗这些疾病患者可能达到的缓解率；2）评估缓解的持久性；3）评估IFN在这些人群中的毒性。
入组仅限于已出现以下情况的AMM、ET或PRV患者：1）贫血或输血依赖；2）标准治疗无法控制的血小板增多症；3）止血并发症；4）有症状的脾肿大。最初，患者开始接受IFN治疗，剂量为每日5 MU/m²，皮下注射。在治疗了前16例患者后，由于出现意外毒性，IFN的起始剂量降至每日2 MU/m²。
IFN在研究的三种疾病中表现出不同程度的疗效和毒性。各类别中可评估患者的总体缓解率如下：ET为88.2%（n = 17例患者；1例完全缓解和14例部分缓解）；PRV为41.7%（n = 12例患者；1例完全缓解和4例部分缓解）；AMM为3.2%（n = 31例患者；0例完全缓解和1例部分缓解）。几乎所有患者的血小板增多症和白细胞增多症都得到了控制，较少患者实现了脾肿大的逆转和骨髓纤维化的吸收。IFN引起的毒性在三个疾病组中差异显著：AMM患者比PRV或ET患者更频繁地出现全身和神经毒性；而ET患者出现肝脏异常的发生率高于预期，最常见的是血清氨基酸转氨酶水平短暂升高。
本研究证明了IFN在ET、PRV和AMM患者中的安全性和有效性。所有三种疾病实体的患者均获得了客观缓解和/或疾病稳定，包括部分患者脾肿大的逆转和骨髓纤维化的吸收。
