Axdorph Ulla, Stenke Leif, Grimfors Gunnar, Carneskog Jan, Hansen Jan, Linder Olle, Ljungman Per, Löfvenberg Eva, Malm Claes, Simonsson Bengt, Turesson Ingemar, Vilén Lars, Udén Anne-Marie, Björkholm Magnus
Division of Haematology, Department of Medicine, Karolinska Hospital and Institutet, Stockholm, Sweden.
Br J Haematol. 2002 Sep;118(4):1048-54. doi: 10.1046/j.1365-2141.2002.03765.x.
In attempting to restore the chronic phase (CP) of chronic myelogenous leukaemia (CML), the Swedish CML group utilized an intensive chemotherapy protocol for 83 patients (aged 16-79 years) in accelerated (AP, n = 22) or blastic phase (BC, n = 61). Most patients received a combination of mitoxantrone (12 mg/m2/d) and etoposide (100 mg/m2/d) together with cytosine arabinoside (1 g/m2 b.i.d) for 4 d. Overall, 39 patients (47%) achieved a second CP (CP2)/partial remission (PR). Responding patients < 65 years were eligible for ablative chemotherapy followed by an allogeneic (SCT) or a double autologous stem cell transplant (ASCT). Seventeen of 34 responders < 65 years failed to proceed to transplantation as a result of early disease progression (n = 15) or disease-related complications (n = 2). The remaining 17 patients underwent SCT (n = 9; including four unrelated donor SCT) or ASCT (n = 8). Only one of the eight ASCT patients had a second ASCT; the remaining seven failed because of progression (n = 5) or hypoplasia (n = 2). The median duration of CP2/PR was 6 months (range 1-72 months). Five patients achieved a longer CP2/PR than CP1. The 1 year survival was 70% for SCT/ASCT patients (median survival 21 months), 50% for responding patients overall, but only 7% for non-responders (P < 0.001). Three SCT/ASCT patients are long-term survivors (65+, 66+ and 73+ months). In conclusion, approximately half of the patients achieved a CP2/PR after intensive chemotherapy, with a clear survival advantage for responders vs non-responders. Subsequent SCT/ASCT was feasible for half of the responders (< 65 years), and one individual underwent double ASCT. Novel therapeutic options for CML patients in AP/BP are needed.
为尝试恢复慢性粒细胞白血病(CML)的慢性期(CP),瑞典CML研究小组对83例处于加速期(AP,n = 22)或急变期(BC,n = 61)的患者(年龄16 - 79岁)采用了强化化疗方案。大多数患者接受米托蒽醌(12 mg/m²/d)和依托泊苷(100 mg/m²/d)联合阿糖胞苷(1 g/m²,每日两次)治疗4天。总体而言,39例患者(47%)实现了第二次慢性期(CP2)/部分缓解(PR)。年龄<65岁的缓解患者有资格接受清髓性化疗,随后进行异基因造血干细胞移植(SCT)或双重自体干细胞移植(ASCT)。34例年龄<65岁的缓解患者中有17例因疾病早期进展(n = 15)或疾病相关并发症(n = 2)未能进行移植。其余17例患者接受了SCT(n = 9;包括4例无关供体SCT)或ASCT(n = 8)。8例ASCT患者中只有1例进行了第二次ASCT;其余7例因病情进展(n = 5)或发育不全(n = 2)失败。CP2/PR的中位持续时间为6个月(范围1 - 72个月)。5例患者的CP2/PR时间长于CP1。SCT/ASCT患者的1年生存率为70%(中位生存期21个月),总体缓解患者为50%,但无反应者仅为7%(P < 0.001)。3例SCT/ASCT患者为长期存活者(65+、66+和73+个月)。总之,约一半的患者在强化化疗后实现了CP2/PR,反应者与无反应者相比有明显的生存优势。随后的SCT/ASCT对一半的反应者(<65岁)是可行的,且有1例患者接受了双重ASCT。AP/BP期CML患者需要新的治疗选择。