地西他滨联合BuCy预处理allo-HSCT治疗未缓解的伴T315I突变CML急髓变

Allo-HSCT with decitabine combined with BuCy as conditioning regimenfor a patient with T315I mutation in myeloid blastic phase of chronic myeloid leukemia

目的:伴T315I突变的难治性慢性髓系白血病(CML)急髓变,在未缓解状态下,直接进行地西他滨联合BuCy预处理的无关供体外周血造血干细胞移植(allo-HSCT)。方法:对1例难治性CML急髓变行地西他滨联合BuCy预处理的无关供体allo-HSCT,并持续对其细胞形态学、遗传学及分子生物学进行监测。结果:患者伊马替尼治疗后出现Q252H突变、T315I突变、染色体复杂异常、急髓变,行地西他滨联合BuCy预处理的无关供体allo-HSCT,术后+12d粒系造血重建,+14d骨髓形态缓解,BCR-ABL定量:<10copies/10 000abl copies,后因肠道重度急性移植物抗宿主病(aGVHD)死亡。结论:allo-HSCT是治疗伴有T315I突变的CML患者的有效手段,对于未缓解的患者,行地西他滨联合BuCy预处理临床研究值得探索。

Objective：To report one patient with refractory chronic myeloid leukemia（CML）-blast crisis with T315I mutation directly undergoing unrelated donor peripheral blood stem cell transplantation（allo-HSCT） under conditioning regimen with decitabine and BuCy. Method：The patient with CML-BC who was refractory to imatinib,nilotinib and chemotherapy,directly performed allo-HSCT from a partially mismatched（9/10 HLA allele matched） unrelated donor with conditioning regimen consisting of decitabine and BuCy.The morphology,cytogenetic and molecular biology of bone marrow were continuously monitored. Result：In chronic phase,the patient was diagnosed CML with Ph chromosome and BCR/ABL gene,with no mutation detected.Despite satisfactory hematological remission,the patient failed to achieve complete cytogenetic remission after of 9 months treatment with imatinib.Moreover,the disease progressed rapidly to myeloid blastic phase accompanied by additional chromosomal translocation,Q252H mutation of BCR-ABL fusion and increas ed copies of BCR-ABL.And nilotinib combined with chemotherapy failed with newly appeared complex chromosome karyotype and T315I mutation.Regardless of remission,unrelated donor allo-HSCT was performed with decitabine and BuCy as preparative regimen.White blood cell count was recovered 1.0×109/L at day ＋12 and bone marrow remission and BCR-ABL gene 10 copies/10 000 abl copies were achieved at day ＋14.Unfortunately,the patient developed skin acute graft versus host disease（aGVHD）,and died of grade Ⅳ intestinal aGVHD finally. Conclusion：Allo-HSCT is an effective therapy for patients with CML and T315I mutation.It is essential to explore the effect of decitabine and BuCy combination conditioning regimen for patients undergoing allo-HSCT who do not achieve remission.