减低强度预处理造血干细胞移植联合低剂量环孢素A治疗恶性血液病

Haematopoietic stem cell transplantation based on reduced intensity conditioning regimen combined with low-dose cyclosporine A for patients with hematologic malignancies

目的探讨以减低强度的氟达拉滨、白消安（Bu）和环磷酰胺（CTX）为预处理方案的异基因外周血造血干细胞移植（HSCT）联合低剂量环孢素A（CsA）的疗效及并发症发生情况。方法恶性血液病患者11例，接受同胞间HSCT，供、受者间HLA配型，HLA全相合10例，5个抗原相合1例。预处理包括移植前第9～4天给予氟达拉滨30-35mg·m-1·d-1移植前第4、3天给予白消安3．2mg·kg-1·d-1，移植前第2、1天给予CTX60mg·kg-1·d-1移植后联合使用CsA和短程甲氨蝶呤（MTX）预防移植物抗宿主病（GVHD），供者细胞植入后，降低CsA用量。结果移植后早期11例造血功能均获得重建，骨髓细胞为完全供者型。随访3～17个月，9例并发急性GVHD，主要侵犯肝脏和皮肤；9例并发慢性GVHD，均侵犯口腔和肝脏，其中1例为广泛性慢性GVHD，其余为局限性慢性GVHD。增加CsA用量或者加用甲泼尼龙后，急、慢性GVHD均能得到控制，仅1例需加用霉酚酸脂i11例中，2例的原发病复发，其中1例病情得到控制，1例失访。结论HSCT时采用氟达拉滨、白消安和环磷酰胺（CTX）预处理方案，并将白消安的用量减为常用剂量的一半，移植后采用低剂量CsA，细胞的植入率高；急、慢性GVHD的发生率较高，但对糖皮质激素和CsA的治疗反应良好。

Objective To explore the efficacy and complications of reduced intensity of fludarabine, busufan （BU） injection and cyclophosphamide （CY） （FBC） conditioning allogeneic peripheral blood haematopoietic stem cell transplantation （HSCT） combined with the use of low-dose cyclosporine A （CsA） in the treatment of malignant haematologic diseases. Methods Eleven patients with malignant haematologic diseases were subjected to allo-PBSCT. Sibling donor HLA were fully matched exception of one case with one loci mismatched. Conditioning regimen was consisted of fludarabine 30-35 mg·m-2·d-1 for 6 days （ - 9 d- - 4 d）, busulfan injection 3. 2 mg·kg-1·d-1 （ - 4 d--3 d） and cyclophosphamide 60 mg.m 2-d-1 for 2 days （ -2 d- - 1 d）. The prophylaxis of graft-versus-host disease （GVHD） included CsA and short-term methotrexate （MTX）. The low dose of CsA was used after formation of donor chimerism. Results Eleven patients achieved hematopoietic reconstitution with full donor cell chimerism form bone marrow in the early stage. During a median follow-up period of 10 （3-17） months, acute GVHD occurred in 9 cases, mostly involving the skin and liver, chronic GVHD in 9 cases, involving both mouth and liver. Extensive chronic GVHD and local chronic GVHD were found in one case each. Apart from one case needed use of mycophenpolate mofetil （MMF）, all cases were controlled by means of adjustment of CsA or additional use of methylprednisolone. All patients exception of two relapse cases, one of them lost follow-up, remained free disease survival. Conclusion Haematopoietic stem cell transplantation based on reduced intensity conditioning regimen of FBC, reduced half conventional dose of busufan, combined with low dose of CsA post transplantation were characterized by high donor cell engraftment rate and high incidence of acute and chronic GVHD, but GVDH had a good response to CsA and glucocorticoid.