伊马替尼治疗Ph阳性慢性粒细胞白血病引起的骨髓形态学变化

Bone marrow morphologic features in patients treated with imatinib for Philadelphia chromosome positive chronic myeloid leukemia

目的 观察伊马替尼治疗Ph阳性慢性粒细胞白血病 (CML)引起的骨髓形态学变化 ,并探讨其与血液学、遗传学疗效之间的关系。方法 117例Ph阳性CML患者 ,包括干扰素治疗失败的慢性期 5 4例、加速期 4 1例、急髓变期 2 2例 ,日服伊马替尼 4 0 0或 6 0 0mg,持续 18个月以上。结果 治疗18个月内 ,各期患者骨髓增生程度显著降低、原始粒细胞 +早幼粒细胞显著减少、骨髓无CML特征的比例显著增加 ,慢性期和加速期患者粒、红细胞比例显著降低、巨核细胞数量显著减少 (P值均 <0 0 5 )。获得血液学疗效者骨髓形态持续正常。治疗中发生骨髓增生低下或极度低下还是增生活跃以上与血液学和遗传学疗效密切相关 :慢性期患者其遗传学有效率分别为 5 8.8%和 86 .5 % (P =0 .0 35 ) ,加速期患者血液学完全缓解率分别为 2 6 .3%和 75 .0 % (P =0 .0 0 4 ) ,急变期患者生存期短于 6个月者比例分别为 77.8%和 16 .7% (P =0 .0 0 9)。在CML进展期 ,治疗 1个月时骨髓形态学无CML特征与有CML特征者相比 ,加速期患者 18个月疾病进展率显著降低 (分别为 2 5 .0 %和 75 .0 % ,P =0 .0 2 8)、总生存率显著升高 (分别为 75 .0 %和 11.8% ,P =0 .0 0 4 ) ;急变期患者获得血液学效应的比例显著增加 (分别为 10 0 .0 %和 4 0 .0 % ,P

Objectives To assess bone marrow morphologic changes in Philadelphia-chromosome positive chronic myeloid leukemia (Ph +-CML) patients treated with Imatinib,and to evaluate the correlation of the morphologic changes with hematological or cytogenetic responses. Methods One hundred and seventeen patients with Ph + CML: 54 in chronic phase but failed to interferon-alpha treatment,41 in accelerated phase,22 in blastic phase received oral administration of Imatinib 400 or 600 mg once daily for more than 18 months. Results All of the patients responded to the treatment,including complete hematological response,bone marrow response and return to chronic phase,bone marrow cellularity and myeloblast count reduced significantly to non-CML picture. Myeloid/ erythroid ratio and megkaryocyte count were decreased significantly in most patients in chronic and accelerated phases ( P <0.05). Bone marrow hypoplasia or aplasia was associated with lower cytogenetic response rates in patients in chronic phase (58.8% vs 86.5%,P =0.035),lower complete hematological response in patients in accelerated phase (26.3% vs 75.0%,P =0.004),and 6-month overall survival in patients in blastic phase (77.8% vs 16.7%,P =0.009). Patients in advanced stage obtained non-CML marrow picture in 1 month of treatment had better prognosis. 18-month disease progression rates were lower (25% vs 75%,P =0.028) and overall survival rates higher (75.0% vs 11.8%,P =0.004) in patients obtained non-CML picture marrows than in those with CML marrows picture in accelerated phase. Hematological response rate and overall survival of more than 6 months were higher in patients with non-CML marrows picture than those with CML marrows picture (100.0% vs 40.0%,P =0.017 and 83.3% vs 26.7%,P=0.046 respectively) in blastic phase. Conclusions Normal marrow appearance can be sustained under continuous treatment of Imatinib in CML patients who achieved hematological responses.