Schmitz N, Dreger P, Suttorp M, Rohwedder E B, Haferlach T, Löffler H, Hunter A, Russell N H
Department of Internal Medicine II, University of Kiel, Germany.
Blood. 1995 Mar 15;85(6):1666-72.
Transplantation of allogeneic peripheral blood progenitor cells (PBPCs) may have advantages over bone marrow transplantation (BMT) with regards to the speed of hematopoietic and immunologic recovery, which may then shorten the time spent in hospital and decrease costs. The recipient might also profit by an enhanced graft-versus-leukemia reaction exerted by the high number of natural killer cells contained in such grafts. The donor could be spared the discomfort and risks of general anesthesia and marrow harvesting. Primary transplantation of unmanipulated allogeneic PBPCs has not been reported so far because the vast amount of T cells contained in the collection product was thought to cause severe graft-versus-host disease. We present preliminary data on primary transplantation of allogeneic PBPCs in patients who either suffered from advanced leukemia or had a donor unable to undergo general anesthesia. Eight patients with a median age of 42 years suffering from acute myelogenous leukemia (AML) in first remission (n = 3), AML in third remission, AML in relapse (n = 2), acute lymphoblastic leukemia in second remission, or chronic myelogenous leukemia in accelerated phase received myeloablative therapy followed by transplantation of unmanipulated allogeneic PBPCs mobilized with granulocyte colony-stimulating factor (5 to 10 micrograms/kg of body weight of filgrastim administered for 5 to 6 days) in their HLA-identical donors. Hematopoietic reconstitution was achieved in all patients with a median of 15.5 (16.5) days after transplant needed to surpass an absolute neutrophil count of 0.5 (1.0) x 10(9)/L. The median time to an unsupported platelet count greater than 20 (> 50) x 10(9)/L was 19.5 (41) days after grafting. Three patients did not exhibit signs of acute graft-versus-host disease (GVHD), grade I disease was seen in one patient, and three patients experienced grade II disease limited to the skin. The only patient with severe acute GVHD (grade III) refused to take his oral cyclosporin regularly and had ineffective serum levels for most of the time until relapse. Six of eight patients are currently alive without evidence of disease between 61 and 533 days after grafting; two patients grafted for AML in relapse achieved a complete remission after transplantation but relapsed again and died of leukemia on days +48 and +70, respectively. Primary transplantation of unmanipulated allogeneic PBPCs is feasible and results in long-term engraftment without causing detrimental GVHD.
在造血和免疫恢复速度方面，异基因外周血祖细胞（PBPC）移植可能比骨髓移植（BMT）更具优势，这可能会缩短住院时间并降低成本。接受者还可能因这类移植物中所含大量自然杀伤细胞产生的增强的移植物抗白血病反应而获益。供者可免受全身麻醉和骨髓采集的不适与风险。迄今为止，尚未有未经处理的异基因PBPC初次移植的报道，因为采集产物中所含大量T细胞被认为会导致严重的移植物抗宿主病。我们展示了在患有晚期白血病或供者无法接受全身麻醉的患者中进行异基因PBPC初次移植的初步数据。8例患者，中位年龄42岁，分别患有首次缓解期的急性髓性白血病（AML）（n = 3）、第三次缓解期的AML、复发期的AML（n = 2）、第二次缓解期的急性淋巴细胞白血病或加速期的慢性髓性白血病，接受清髓性治疗，随后接受来自其 HLA 匹配供者的未经处理的异基因PBPC移植，这些PBPC是用粒细胞集落刺激因子（非格司亭按5至10微克/千克体重给药5至6天）动员的。所有患者均实现了造血重建，移植后中位15.5（16.5）天中性粒细胞绝对计数超过0.5（1.0）×10⁹/L。移植后血小板计数无支持下大于20（>50）×10⁹/L的中位时间为19.5（41）天。3例患者未表现出急性移植物抗宿主病（GVHD）迹象，1例患者出现I级疾病，3例患者经历了局限于皮肤的II级疾病。唯一患有严重急性GVHD（III级）的患者拒绝规律服用口服环孢素，在复发前大部分时间血清水平无效。8例患者中有6例目前存活，移植后61至533天无疾病证据；2例因复发的AML接受移植的患者移植后实现了完全缓解，但分别在第 +48天和 +70天再次复发并死于白血病。未经处理的异基因PBPC初次移植是可行的，可实现长期植入且不会引起有害的GVHD。
