Yoshimitsu Makoto, Fujiwara Hiroshi, Ozaki Atsuo, Hamada Heiichiro, Matsushita Kakushi, Arima Naomichi, Tei Chuwa
Department of Hematology and Immunology, Kagoshima University Hospital, Kagoshima, Japan.
Department of Bioregulatory Medicine, Graduate School of Medicine, Ehime University, Shitsukawa, Toh-on, Ehime, 791-0295, Japan.
Int J Hematol. 2008 Oct;88(3):331-335. doi: 10.1007/s12185-008-0150-z. Epub 2008 Aug 12.
A 23-year-old man with Philadelphia-chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) underwent myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) from his HLA-identical brother in first hematological remission following induction chemotherapy which included imatinib. He had no acute graft-versus-host disease (GVHD), and 4.5 months after HSCT, he had a molecular relapse (180,000 copies/mug RNA of minor bcr/abl transcripts (m-bcr/abl) without mutation in 22 sites including the p-loop region). Following discontinuation of cyclosporine A, imatinib (600 mg daily) was restarted and 4 days later donor lymphocyte infusion (DLI) (5 x 10(7)/kg of CD3(+) cells) was given. In 2 weeks, the marrow m-bcr/abl became undetectable. He received two further DLIs and imatinib was continued at a reduced dose of 400 mg a day. At the time of this report, he remains in complete hematological remission more than 33 months after allo-HSCT and persists in the second molecular remission for longer than 24 months. During this clinical course, he became positive for anti-nuclear antibody after second DLI, without any other manifestations of GVHD. The standard treatment for Ph(+) ALL relapsing after allo-HSCT still remains to be established. Imatinib in combination with DLI for early molecular relapse may be a promising option.
一名23岁费城染色体阳性(Ph(+))急性淋巴细胞白血病(ALL)患者,在接受包括伊马替尼在内的诱导化疗后首次血液学缓解期,接受了来自其HLA全相合兄弟的清髓性异基因造血干细胞移植(allo-HSCT)。他未发生急性移植物抗宿主病(GVHD),HSCT后4.5个月出现分子复发(微小bcr/abl转录本(m-bcr/abl)为180,000拷贝/μg RNA,22个位点包括p环区域无突变)。停用环孢素A后,重新开始使用伊马替尼(每日600 mg),4天后给予供者淋巴细胞输注(DLI)(5×10(7)/kg CD3(+)细胞)。2周内,骨髓中m-bcr/abl变得无法检测到。他又接受了两次DLI,伊马替尼继续以每日400 mg的减量服用。在本报告发布时,allo-HSCT后33个月以上他仍处于完全血液学缓解状态,且持续第二次分子缓解状态超过24个月。在此临床过程中,第二次DLI后他抗核抗体呈阳性,无GVHD的任何其他表现。allo-HSCT后复发的Ph(+) ALL的标准治疗仍有待确定。伊马替尼联合DLI治疗早期分子复发可能是一个有前景的选择。