Hematopoietic stem cell transplantation in combination with imatinib mesylate for treatment of Philadelphia-positive leukemia

doi:10.3969/j.issn.2095-4344.2014.50.019

Abstract

Abstract:

BACKGROUND: Hematopoietic stem cell transplantation is recognized as the only method of curing Philadelphia-positive leukemia. Imatinib mesylate is a competitive inhibitor of the BCR/ABL tyrosine kinase, which has been used more and more in the treatment of Philadelphia-positive leukemia．
OBJECTIVE: To observe the curative effect of imatinib mesylate combined with allogeneic hematopoietic stem cell transplantation for treatment of Philadelphia-positive leukemia．
METHODS: We retrospectively analyzed the clinical effect of 12 patients with Philadelphia-positive leukemia who were treated with the combined therapy of imatinib mesylate and allogeneic hematopoietic stem cell transplantation from January 2011 to October 2012, and reviewed the relevant literatures.
RESULTS AND CONCLUSION: Hematopoietic reconstitution was achieved in all 12 patients and the median times of neutrophil recovery and platelet recovery were 15 and 18 days, respectively. Of the 12 patients, 7 patients developed acute graft-versus-host disease II, 1 developed acute graft-versus-host disease III, 7 developed localized chronic graft-versus-host disease, and 3 developed extensive chronic graft-versus-host disease. Leukemia-free survival rate was 66.7%, and transplant-related mortality was 25.0%. The overall survival rate of HLA-matched sibling donors was 75.0%. The mean disease-free survival period was 8.5 months (7-17 months), and the time needed for BCR/ABL becoming negative was 2-5 months. As an effective and safe method for Philadelphia-positive leukemia, allogeneic hematopoietic stem cell transplantation combined with imatinib mesylate before and after transplantation reduces the leukemia cell load before transplantation, inhibits the proliferation of residual leukemia cells, and promotes full chimerism change.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

全文链接：

Key words: stem cells, hematopoietic stem cell transplantation, leukemia

CLC Number:

R394.2

Li Meng-xing, Wang Ji-shi, Zhang Yan, Sun Zhi-qiang, Zhao Peng, Lu Ying-hao. Hematopoietic stem cell transplantation in combination with imatinib mesylate for treatment of Philadelphia-positive leukemia[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(50): 8147-8150.

Figures/Tables 1

2.1 造血干细胞的植入情况 12例患者输注单个核细胞的中位数为4.88×108/kg(3.7×108-7.24×108/kg)，输注CD34+细胞中位数为3.21×106/kg(2.0×106-6.17×106/kg)。移植后均获得造血重建，中性粒细胞植活的中位时间为15 d (12-22 d)，血小板植活的中位时间为18 d(11-35 d)。移植后1个月12例患者均获得不同程度的嵌合状态，9例获得完全嵌合(>95%)，3例获得95%以下的混合嵌合，移植后2个月嵌合均达98%以上。 2.3 移植前后伊马替尼治疗情况移植前经化疗联合伊马替尼治疗4例，达到分子生物学完全缓解(CMR)3例，1例部分缓解(PR)；单用伊马替尼(格列卫)治疗的患者5例，其中3例达血液学完全缓解(CHR)，2例部分缓解。3例诱导化疗失败后，其中2例用伊马替尼挽救治疗，血液学完全缓解1例，部分缓解1例，1例未再进行其他治疗，造血干细胞移植前BCR/ABL融合基因mRNA检查3例阴性，其余均为阳性，2例定量大于10%，所有患者均进行亲缘异基因造血干细胞移植。1例患者为慢粒急髓变未缓解，移植后28 d嵌合体检测18.4%，BCR/ABL阳性，停用免疫抑制剂，加用伊马替尼治疗(400 mg/d)，+59 d获得完全嵌合(98%)。3例患者移植后BCR/ABL定量进行性升高，移植后2个月加用伊马替尼治疗(300 mg/d)，BCR/ABL转阴。4例移植后BCR/ABL未转阴患者均在移植后3个月开始服用伊马替(300-400 mg/d)，BCR/ABL转阴。4例患者移植后BCR/ABL阴性未服用伊马替尼。 2.4 移植物抗宿主病的发生情况 12例异基因移植中，急性移植物抗宿主病的发生率为75%(9/12)，其中Ⅰ度1例，Ⅱ度7例，Ⅲ度1例。存活超过100 d的患者为11例，其慢性移植物抗宿主病的发生率为91%(10/11)，其中局限型7例，广泛型3例，主要累及皮肤、眼及肾。 2.5 其他并发症出血性膀胱炎9例，巨细胞病毒血症7例，细菌血行感染5例，肺部侵袭性真菌感染1例，继发三系减少2例，继发性癫痫1例，急性阑尾炎1例，阴茎部分坏死1例。无患者发生肝静脉闭塞病，无发展为巨细胞病毒间质性肺炎。 2.6 患者的存活及原发病复发情况截至随访结束(2012年10月15日)，8例患者无白血病存活(67%)，多次行骨髓细胞形态学、融合基因检查，维持完全缓解状态，BCR/ABL融合基因阴性，无病存活中位时间为8.5个月(7-17个月)，随访期间死亡3例，1例移植后继发三系减少导致肺部侵袭性真菌感染死亡，1例发生急性肠道移植物抗宿主病而死亡，1例肺部感染死亡；1例患者原发病复发，随访时仍存活。"

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