Stamatović Dragana, Balint Bela, Tukić Ljiljana, Elez Marija, Tarabar Olivera, Todorović Milena, Ostojić Gordana, Tatomirovic Zeljka, Ljubenov Marika, Marjanović Slobodan, Malesević Milomir
Military Medical Academy, Clinic of Hematology, Belgrade, Serbia.
Vojnosanit Pregl. 2011 Dec;68(12):1026-32.
BACKGROUND/AIM: Peripheral blood (PB) is used more frequently as a source of stem cells (SCs) for allogeneic transplantation. However, the influence of cell source on the clinical outcome of SC transplantation is not yet well established. The aim of this study was to compare the results of PBSC transplantation (PBSCT) with bone marrow transplantation (BMT) on the basis of engraftment, frequency and severity of immediate (mucositis, acute Graft versus Host Disease--aGvHD) and delayed (chronic GvHD--cGvHD) complications, as well as transplant-related mortality (TRM), transfusion needs, relapses and overall survival (OS).
We analyzed 158 patients, women/men ratio 64/94 median age 29 (range 9-57), who underwent allogeneic SC transplantation between 1989 and 2009. All included patients had diseases as follows: acute myeloid leukemia (AML)--39, acute lymphoblastic leukemia (ALL) 47, chronic myeloid leukemia (CML)--32, myelodysplastic syndrome (MDS)--10, Hodgkin's lymphoma (HL)- 2, multiple myeloma (MM) 3, granulocytic sarcoma (GrSa) 3, severe aplastic anemia (sAA)--22. The patients underwent transplantations were divided into two groups: BMT group (74 patients) and PBSCT group (84 patients). Each recipient had HLA identical sibling donor. SCs from bone marrow were collected by multiple aspirations of iliac bone and from PB by one "Large Volume Leukapheresis" (after recombinant human granulocyte colony stimulating factor, rHuG-CSF) application (5-12 microg/kgbm, 5 days). Conditioning regimens were applied according to primary disease, GvHD prophylaxis consisted of combination of a cyclosporine A and methotrexate. Results. Engraftment, according to the count of polymorphonuclear and platelets, were significantly (p < 0.001) faster in the PBSCT vs BMT group. The needs for transfusion support were significantly (P < 0.01) higher in the BMT group. Those patients had more frequently oropharingeal mucositis grade 3/4 (33.3% vs 10.0%, p < 0.05). There were no significant differences in the incidence of aGvHD and cGvHD between the two groups. The patients who underwent PBSCT had more frequently extensive cGvHD in comparison with the BMT group (29.1% vs 11.29%, p < 0.05). SC source (SCS) had no significant influence on the TRM (21.62% vs 23.8%, p = 0.64) and the incidence of relapses (21.6% vs 29.7%, p = 0.32). Finally, the patients treated by BMT hd a significantly better OS (logrank 2.33, p < 0.05). Conclusion. SCs harvesting from PB resulted in improved cell yield, faster engraftment, as well as in a decrease of immediate transplantation related complications with a reduced treatment cost. Allogeneic PBSCT were associated with more frequent extensive cGvHD, while the influence of SCS in TRM and relapses was not observed. Finally, the long-term OS was better in the patients treated by BMT. To verify impact of SC source on transplantation (PBSCT vs BMT) overall efficacy, more larger randomized clinical studies are needed.
背景/目的：外周血（PB）作为异基因移植干细胞（SCs）的来源使用得更为频繁。然而，细胞来源对干细胞移植临床结果的影响尚未完全明确。本研究的目的是比较外周血干细胞移植（PBSCT）与骨髓移植（BMT）在植入情况、即刻（粘膜炎、急性移植物抗宿主病——aGvHD）和延迟（慢性移植物抗宿主病——cGvHD）并发症的发生频率及严重程度、移植相关死亡率（TRM）、输血需求、复发率和总生存率（OS）方面的结果。
我们分析了1989年至2009年间接受异基因干细胞移植的158例患者，女性/男性比例为64/94，中位年龄29岁（范围9 - 57岁）。所有纳入患者患有以下疾病：急性髓系白血病（AML）——39例，急性淋巴细胞白血病（ALL）47例，慢性髓系白血病（CML）——32例，骨髓增生异常综合征（MDS）——10例，霍奇金淋巴瘤（HL）——2例，多发性骨髓瘤（MM）3例，粒细胞肉瘤（GrSa）3例，重型再生障碍性贫血（sAA）——22例。接受移植的患者分为两组：BMT组（74例患者）和PBSCT组（84例患者）。每位受者均有HLA配型相同的同胞供者。通过多次髂骨穿刺采集骨髓干细胞，通过一次“大容量白细胞单采术”（应用重组人粒细胞集落刺激因子，rHuG - CSF后）采集外周血干细胞（5 - 12μg/kg体重，共5天）。根据原发疾病应用预处理方案，移植物抗宿主病预防采用环孢素A和甲氨蝶呤联合应用。结果：根据多形核细胞和血小板计数，PBSCT组的植入明显（p < 0.001）快于BMT组。BMT组的输血支持需求明显（P < 0.01）更高。该组患者3/4级口咽粘膜炎更为常见（33.3%对10.0%，p < 0.05）。两组间aGvHD和cGvHD的发生率无显著差异。与BMT组相比，接受PBSCT的患者广泛cGvHD更为常见（29.1%对11.29%，p < 0.05）。干细胞来源（SCS）对TRM（21.62%对23.8%，p = 0.64）和复发率（21.6%对29.7%，p = 0.32）无显著影响。最后，接受BMT治疗的患者总生存率明显更好（对数秩检验2.33，p < 0.05）。结论：从外周血采集干细胞可提高细胞产量、加快植入，并减少即刻移植相关并发症，降低治疗成本。异基因PBSCT与更频繁的广泛cGvHD相关，而未观察到SCS对TRM和复发的影响。最后，接受BMT治疗的患者长期总生存率更好。为验证干细胞来源对移植（PBSCT与BMT）总体疗效的影响，需要更多更大规模的随机临床研究。
