Allo-HSCT with decitabine combined with BuCy as conditioning regimenfor a patient with T315I mutation in myeloid blastic phase of chronic myeloid leukemia
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摘要: 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+12 d粒系造血重建，+14 d骨髓形态缓解，BCR-ABL定量：<10 copies/10 000 abl 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。Abstract: 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.
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