格列卫治疗慢性粒细胞白血病Ph染色体转阴后进行自体外周血干细胞移植的结果

Autogeneic peripheral blood hemopoietic stem cell transplantation for chronic myeloid leukemia with imatinib mesylate-induced negavitation of Philadelphia chromosome

目的探讨格列卫治疗慢性粒细胞白血病Ph染色体阴性后自体外周血干细胞移植的可行性.方法对2例成人慢性粒细胞白血病(CML)慢性期患者采用Ph染色体阳性细胞和间期荧光原位杂交(I-FISH)检查bcr/abl融合基因阳性细胞均≥90%,IFN-α治疗半年耐药,改用格列卫0.3～0.4 g/d分别治疗130和168 d,期间3次复查Ph染色体和FISH检测bcr/abl融合基因均示阴性,此后应用阿糖胞苷2.0 g/d和足叶乙甙0.2 g/d分别静脉注射3 d,环磷酰胺1.0 g静脉注射1次.当白细胞＜1.0×109/L时,应用G-CSF 300μg/d,至白细胞＞10×109/L时应用CS 3000Plus分离外周血单个核细胞并用液氮保存待用.应用MiniMAC富集的CD34+细胞(纯度分别为83%和93%)的bcr/abl阳性率分别为11%和14%.动员完成后3～4周给予全身照射9Gy,分2次照射,每天以环磷酰胺60mg/kg@b.w.和足叶乙甙300 mg分别静脉注射2 d,静脉输注液氮保存的外周血干细胞,单个核细胞分别为4.17和3.9×108/kg@b.w.、CD34+细胞为4.89和4.8×106/kg@b.w.,移植-1～14 d应用CsA联合IL-2诱导移植物抗宿主病(GVHD).结果移植后中性粒细胞绝对值＞0.5×109/L平均需要11d,血小板＞20×109/L平均需要20 d,无GVHD样表现.随访观察120d和300d,患者血液学持续缓解,但I-FISH检测骨髓细胞bcr/abl融合基因阳性率分别为20%和40%.结论格列卫治疗CML获细胞遗传学完全缓解后进行自体外周血干细胞移植,白血病还可以复发.

Objective To study the possibility of curing chronic myeloid leukemia with autogeneic hemopoietic stem celltransplantation in patients with negative Philadelphia (Ph) chromosome induced by imatinib mesylate (STI 571) tretament.Methods Two patients with chronic myeloid leukemia in chronic phase, who had 90% Ph chromosome-positive cells andbcr/abl fusion gene- positive cells as shown by interphase fluorescence in situ hybridization (I-FISH), failed to respond favorablyto interferon-αtherapy in the treatment courses of 7 and 8 months, respectively. Treatment with STI 571 at a daily dose of 300to 400 mg for 5 months to 8 months was subsequently implemented, after which the Ph chromosome and bcr/abl fusion genesbecame normal in detection for 3 times. Peripheral blood haemopoietic stem cell mobilization was then initiated by intravenousinjection of cytarabine (2.0 g/d) for 3 days, etoposide (0.2 g/d) for 3 d and cyclophosphamide (1.0 g/d) for one day. When thewhite blood cell was below 1.0×109/L, the G-CSF (300 μg/d) was administered subcutaneously for 5 or 6 d, and the peripheralblood mononuclear cells were collected by CS3000 Plus blood cell separator. The percentage of bcr/abl fusion gene-positivecells among CD34+ cells enriched by MiniMAC ranged from 11% to 14%. After 3 or 4 weeks, the patients received total body irradiationat 9 Gy given in 2 fractions, with intravenous injection of cyclophosphamide (60 mg/kg daily) and etoposide (300 mg/d) for 2 d.On the day of transplantation, the collected mononuclear cells were 4.17×108/kg and 3.9×108/kg, with CD34+ cells reaching 4.89×106/kg·b.wand 4.89×106/kg.CsAwasalsousedsinceday -1today +13ofthetransplantationforpreventionofgraft-versus-hostdisease. G-CSF was administrated daily at the dose of 300 μg subcutaneously from day +3 to +12. Results After the transplantation, the absolute neutrophil count (ANC) took a mean of 11 d to exceed 0.5×109/L in these two patients,and 19 and 21 d, respectively, were needed for the pletelet count to exceed 20×109/L. The two patients showed cytogeneticrelapse at 120 and 300 d after the transplantation, respectively. Conclusion Autogeneic prepherial blood stem cells transplan-tation after Ph chromosome is negative in patients with chronic myeloid leukemia, who receive STI 571 treatment, may alsorelapse, and more radical elimination of Ph chromosome-positive cells is needed.