Lemoli R M, Bandini G, Leopardi G, Rosti G, Bonini A, Fortuna A, Rondelli D, Mangianti S, Motta M R, Rizzi S, Tassi C, Cavo M, Remiddi C, Curti A, Conte R, Tura S
Institute of Hematology and Medical Oncology L. & A. Seràgnoli, University of Bologna, Italy.
Haematologica. 1998 Jan;83(1):48-55.
Transplantation of mobilized allogeneic peripheral blood stem cells (PBSC) has recently been reported by several groups. However, few patients receiving an allograft in the early stage of their disease have been described so far.
Fifteen patients with early stage hematologic malignancies were transplanted with cryopreserved allogeneic PBSC from HLA-identical siblings. PBSC were collected after priming with 10 micrograms/kg/day of glycosylated granulocyte colony-stimulating factor (G-CSF, lenograstim). Outcomes were compared to a historical control group of 15 patients who received conventional bone marrow transplantation (BMT) from HLA-identical sibling donors. The two groups were matched for diagnosis, stage of disease, age, preparative regimen, graft-versus host (GVHD) prophylaxis, patients' and donors' gender and cytomegalovirus (CMV) serology. Diagnoses in both groups were: chronic myelogenous leukemia (CML) in first chronic phase (= 5), acute leukemia in first complete remission (CR) (= 5), non-Hodgkin's lymphoma in CR (= 1) and multiple myeloma (MM) with sensitive disease (= 4). All patients were given cyclosporin-A (CsA) and methotrexate (MTX) for GVHD prophylaxis. Preparative regimens varied according to diagnosis and included either busulfan/cyclophosphamide combination (BU/Cy) or total body irradiation/cyclophosphamide +/- melphalan (TBI/Cy +/- Mel).
The patients in the PBSC group showed a more rapid hematopoietic reconstitution with a significant difference in the median times to 1 x 10(9) neutrophils/L (19 days vs. 26 days; p = 0.03) and to platelet transfusion independence (18 days versus 22 days; p = 0.02). This finding was associated with a significantly shorter hospitalization (28 days versus 33 days after transplantation; p = 0.01). In the PBSC series, grade II-IV acute GVHD occurred in 3 patients (20%) and grade III-IV in 1 patient (7%). In the BMT control group, grade II-IV aGVHD was reported in 2 cases (13%; p = NS) and 1 case had grade III-IV GVHD. Chronic GVHD developed in 7 patients (47%) (limited = 6; extensive = 1) undergoing PBSC transplantation and 5 patients (33%) (limited = 4; extensive = 1) in the BMT series (p = NS). No difference was found in the incidence of grade II-IV (according to the World Health Organization) mucositis, whereas PBSC recipients did have a significantly lower incidence of additional severe (grade III-IV) organ toxicity. After a median follow-up of 300 days (range 180-630), all PBSC patients are still alive with a median Karnofsky score of 100% (range 80%-100%). Thirteen patients are in CR and 2 myeloma patient are in good partial remission (PR). Also, in the BMT group the peritransplant mortality was absent; two MM patients died due to progressive disease at day +796 and +1,023, respectively; one leukemic patient died of chronic GVHD 407 days after transplantation and one additional leukemic individual relapsed 1,140 days after BMT.
This retrospective comparison suggests that allogeneic PBSC transplantation performed in the early stage of the disease is safe and may be associated with a more rapid hematopoietic reconstitution than BMT, as well as lower transplant-related toxicity and earlier hospital discharge with apparently no increased risk of acute and chronic GVHD.
近期有多个研究小组报道了动员的异基因外周血干细胞(PBSC)移植情况。然而,目前鲜有关于疾病早期接受同种异体移植患者的描述。
15例血液系统恶性肿瘤早期患者接受了来自 HLA 配型相合同胞的冷冻保存异基因 PBSC 移植。PBSC 在给予 10 微克/千克/天的糖基化粒细胞集落刺激因子(G-CSF,来格司亭)动员后采集。将结果与 15 例接受来自 HLA 配型相合同胞供者的传统骨髓移植(BMT)的历史对照组进行比较。两组在诊断、疾病分期、年龄、预处理方案、移植物抗宿主病(GVHD)预防措施、患者及供者性别和巨细胞病毒(CMV)血清学方面进行匹配。两组的诊断情况为:慢性髓性白血病(CML)慢性期(=5 例)、急性白血病首次完全缓解(CR)(=5 例)、非霍奇金淋巴瘤 CR 期(=1 例)和多发性骨髓瘤(MM)敏感疾病(=4 例)。所有患者均给予环孢素 A(CsA)和甲氨蝶呤(MTX)预防 GVHD。预处理方案根据诊断不同而有所变化,包括白消安/环磷酰胺联合方案(BU/Cy)或全身照射/环磷酰胺+/-美法仑(TBI/Cy+/-Mel)。
PBSC 组患者造血重建更快,达到 1×10⁹/升中性粒细胞的中位时间(19 天对 26 天;p = 0.03)和血小板输注独立的中位时间(18 天对 22 天;p = 0.02)有显著差异。这一发现与住院时间显著缩短相关(移植后 28 天对 33 天;p = 0.0