Leda M, Ladon D, Pieczonka A, Boruczkowski D, Jólkowska J, Witt M, Wachowiak J
BMT Unit CIC 641, Institute of Pediatrics, University of Medical Sciences, ul. Szpitalna 27/33, 60-572, Poznan, Poland.
Leuk Res. 2001 Apr;25(4):353-7. doi: 10.1016/s0145-2126(00)00143-0.
A 15-year-old girl with Ph-positive chronic myelogenous leukemia in first chronic phase received bone marrow from her human leukocyte antigen matched brother. Twenty three months after bone marrow transplantation hematological relapse occured which was treated with two infusions of donor lymphocytes (DLI) (0.5x10(8) CD3/kg b.w./infusion). To enforce the graft-versus-leukemia effect (GvL), the first DLI was followed by administration of interferon-alpha (INF-alpha) 6x10(6) U/day for 30 days, whereas, after the second infusion INF-alpha was given at the same dose until hematological remission was achieved (80 doses). Minimal residual disease (MRD) was detected by conventional cytogenetics (Ph chromosome), fluorescence in situ hybridization (FISH) cytogenetics (BCR/ABL translocation) and reverse transcriptase-polymerase chain reaction (RT-PCR) Ecotropic virus integration site-1 (EVI-1 gene expression), whereas cellular chimerism was monitored by assessment of microsatellite markers PCR and Y-chromosomal DNA content FISH. When hematological remission was achieved the pancytopenia was observed and the cytogenetic and molecular investigations revealed only partial remission and mixed chimerism, however, with predominance of donor origin hematopoiesis. To diminish the myelosupressive effect of donor CD3 cells without switching-off the GvL effect, a low dose of cyclosporine A was given. Further observation revealed significant improvement of hematopoiesis with parallel gradual decline of MRD and increase of donor hematopoiesis up to complete chimerism. Graft-versus-host disease was not observed at any stage of the treatment.
一名处于慢性期的15岁Ph阳性慢性粒细胞白血病女孩接受了与其人类白细胞抗原匹配的哥哥的骨髓移植。骨髓移植23个月后发生血液学复发，接受了两次供体淋巴细胞输注（DLI）（0.5x10(8) CD3/kg体重/输注）治疗。为增强移植物抗白血病效应（GvL），第一次DLI后给予α干扰素（INF-α）6x10(6) U/天，共30天，而第二次输注后，以相同剂量给予INF-α直至达到血液学缓解（80剂）。通过常规细胞遗传学（Ph染色体）、荧光原位杂交（FISH）细胞遗传学（BCR/ABL易位）和逆转录聚合酶链反应（RT-PCR）检测嗜亲性病毒整合位点-1（EVI-1基因表达）来检测微小残留病（MRD），而通过评估微卫星标记PCR和Y染色体DNA含量FISH来监测细胞嵌合情况。当达到血液学缓解时，观察到全血细胞减少，细胞遗传学和分子研究仅显示部分缓解和混合嵌合，但以供体来源的造血为主。为减少供体CD3细胞的骨髓抑制作用而不关闭GvL效应，给予低剂量环孢素A。进一步观察发现造血功能显著改善，同时MRD逐渐下降，供体造血增加直至完全嵌合。在治疗的任何阶段均未观察到移植物抗宿主病。
