Neudorf S M, Rybka W, Ball E, Blatt J, Bloom E, Corey S, deMagalhaes-Silverman M, Koehler M, Lister J, Mierski J, Mirro J, Pincus S, Wilson J, Wollman M, Donnenberg A D
Bone Marrow Transplantation Program, Pittsburgh Cancer Institute, University of Pittsburgh Medical Center, PA, USA.
J Hematother. 1997 Aug;6(4):351-9. doi: 10.1089/scd.1.1997.6.351.
Transplantation of marrow from unrelated donors is associated with an increased incidence and severity of graft-versus-host disease (GVHD). In an attempt to minimize GVHD without compromising engraftment, unrelated donor marrow was depleted of lymphocytes by counterflow centrifugal elutriation (CCE), and a fixed dose of 0.5 x 10(6) CD3+ T cells/kg, as measured in real time by flow cytometry, was added back to the graft. Patients received cyclosporine (CYA) and corticosteroids for GVHD prophylaxis and to facilitate engraftment. In the first cohort (study I), 7 patients received busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (CY) and one patient received CY (200 mg/kg) + 1260 cGy fractionated TBI. Of 6 who were evaluable for both engraftment and rejection, 4 rejected their graft. The study was terminated, and the protocol was modified (study II) by the addition of antithymocyte globulin (ATG) to the pre-BMT and post-BMT therapy. Twelve patients received CY + TBI as above plus ATG given pre-BMT and post-BMT. Ten of twelve who received ATG engrafted. Twelve patients from studies I and II were evaluable for acute GVHD. Two developed grade I acute GVHD. Two patients developed grade II acute GVHD, 2 patients developed grade III GVHD, and 1 patient developed grade IV acute GVHD. Two of three cases of acute GVHD (> grade II) occurred later than day 100 after BMT concomitant with reduction of immunosuppressive therapy. The rate of engraftment was significantly higher in study II (p = .054). In numbers of CD34+ cells infused, numbers of CFU-GM infused, and numbers of nucleated cells did not correlate with engraftment. We conclude that (a) in contrast to the results seen in recipients of marrow from HLA-matched sibling donors, the depletion of unrelated donor marrow of all but 0.5 x 10(6) CD34+ cells/kg together with CYA + corticosteroids was not sufficient to facilitate engraftment. The use of a more immunosuppressive regimen containing TBI and ATG appeared to improve engraftment. (b) The reduction of the graft T cell dose to 0.5 x 10(6) CD34+ cells/kg resulted in a higher incidence of acute GVHD than that seen in recipients of marrow from genotypically identical donors whose marrow was similarly processed.
来自无关供者的骨髓移植与移植物抗宿主病（GVHD）的发生率和严重程度增加相关。为了在不影响植入的情况下尽量减少GVHD，通过逆流离心淘析法（CCE）去除无关供者骨髓中的淋巴细胞，并将通过流式细胞术实时检测的固定剂量0.5×10⁶个CD3⁺T细胞/kg回输到移植物中。患者接受环孢素（CYA）和皮质类固醇以预防GVHD并促进植入。在第一个队列（研究I）中，7例患者接受白消安（16mg/kg）和环磷酰胺（120mg/kg）（CY），1例患者接受CY（200mg/kg）+1260cGy分次全身照射（TBI）。在6例可评估植入和排斥反应的患者中，4例发生了移植物排斥。该研究终止，方案进行了修改（研究II），在预处理和移植后治疗中加入抗胸腺细胞球蛋白（ATG）。12例患者接受上述CY+TBI治疗，并在预处理和移植后给予ATG。接受ATG的12例患者中有10例植入成功。研究I和II中的12例患者可评估急性GVHD情况。2例发生I级急性GVHD。2例患者发生II级急性GVHD，2例患者发生III级GVHD，1例患者发生IV级急性GVHD。3例急性GVHD（>II级）中有2例发生在BMT后100天以后，同时免疫抑制治疗减少。研究II中的植入率显著更高（p=0.054）。输入的CD34⁺细胞数量、输入的CFU-GM数量和有核细胞数量与植入无关。我们得出结论：（a）与HLA匹配的同胞供者骨髓受者的结果相反，除0.5×10⁶个CD3⁺细胞/kg外去除无关供者骨髓中的所有细胞并联合CYA+皮质类固醇不足以促进植入。使用包含TBI和ATG的更强免疫抑制方案似乎可改善植入情况。（b）将移植物T细胞剂量减少至0.5×10⁶个CD3⁺细胞/kg导致急性GVHD的发生率高于基因型相同供者骨髓经过类似处理的受者。
