Lambertenghi-Deliliers G, Annaloro C, Cortellaro M, Pozzoli E, Oriani A, Polli E E
Istituto di Scienze Mediche, Università, Milano, Italy.
Haematologica. 1991 Sep-Oct;76(5):406-8.
Blastic crisis (BC) is the terminal event in the natural history of most chronic myelogenous leukemia (CML) patients. Depletion of the normal stem cell compartment, as well as the proliferative advantage and frequent pharmacoresistance of the blastic clone, contribute to the poor prognosis of CML patients in this phase. Recent clinical trials have shown that idarubicin (IDR) in combination with cytosine arabinoside (ARA-C) is more active than daunorubicin at comparable doses in acute myelogenous leukemia (AML). Furthermore, IDR alone also exhibits antitumoral activity in the BC of CML.
Twelve Ph+ CML patients in BC (male 8, female 4; median age 45 yrs., range 19-55 yrs.) were treated with IDR 12 mg/m2/die for 3 consecutive days in sequential combination with Ara-C (1 hour i.v. infusion) 120 mg/m2/12 hrs. for 7 consecutive days. BC exhibited a myeloid phenotype in 9 and a lymphoid phenotype in 3 cases. Median duration of the previous chronic phase had been 36 months (range 6-180).
Clearing of peripheral and bone marrow blasts was achieved in all but one patient. Three other patients were classified as resistant because of blastic regrowth, and 3 died of infection during postchemotherapeutic aplasia. Two patients achieved complete remission (CR) and 3 partial remission (PR). The median duration of response was 11 months (range 6-32).
In BC of CML the IDR/Ara-C combination led to an encouraging rate of either partial or complete responses. The relatively long duration of unmaintained response was even more interesting, with the duration of PR approaching that of CR. These data suggest that IDR should be considered as one of the first-line drugs in the treatment of BC of CML.
急变期(BC)是大多数慢性粒细胞白血病(CML)患者自然病程中的终末期事件。正常干细胞池的耗竭,以及急变期克隆的增殖优势和频繁的耐药性,导致了此阶段CML患者的预后不良。最近的临床试验表明,在急性髓性白血病(AML)中,同等剂量下伊达比星(IDR)联合阿糖胞苷(ARA-C)比柔红霉素更具活性。此外,单独使用IDR在CML的急变期也表现出抗肿瘤活性。
12例处于急变期的Ph+ CML患者(男性8例,女性4例;中位年龄45岁,范围19 - 55岁)接受IDR 12 mg/m²/天,连续3天,随后与阿糖胞苷(静脉输注1小时)120 mg/m²/12小时连续7天序贯联合治疗。9例急变期表现为髓系表型,3例为淋巴系表型。之前慢性期的中位持续时间为36个月(范围6 - 180个月)。
除1例患者外,所有患者的外周血和骨髓原始细胞均清除。另外3例患者因原始细胞再生而被归类为耐药,3例在化疗后再生障碍期间死于感染。2例患者达到完全缓解(CR),3例部分缓解(PR)。缓解的中位持续时间为11个月(范围6 - 32个月)。
在CML的急变期,IDR/阿糖胞苷联合治疗导致了令人鼓舞的部分或完全缓解率。未维持缓解的相对较长持续时间更令人关注,部分缓解的持续时间接近完全缓解。这些数据表明,IDR应被视为治疗CML急变期的一线药物之一。