Hassan H T, Krog C, Stockschläder M, Schleimer B, Zeller W, Krüger W, Erttmann R, Zander A R
Bone Marrow Transplantation Center, Hamburg University Hospital Eppendorf, Germany.
Anticancer Res. 1997 Jan-Feb;17(1B):589-99.
In the present single institution study of 66 leukaemia patients (28 AML, 23 ALL, 15 CML), the factors influencing haematological recovery after allogeneic bone marrow transplantation (alloBMT) were analysed retrospectively in order to identify the optimal conditions required for a rapid haematological recovery after alloBMT. All patients received GVHD prophylaxis with cyclosporine A plus methotrexate. The mean number of days required to achieve > or = 0.5 x 109/l neutrophil count after alloBMT was 17 (median 17, range 9 to 27 days) and 19 patients (28.8%) had rapid neutrophil recovery within 15 days after alloBMT. The haematological recovery was more rapid in the 38 patients without GVHD or with only grade I GVHD. Furthermore, 50% and 40% of patients receiving 10 (n = 18) or 5 (n = 20) micrograms/kg/day G-CSF had rapid neutrophil recovery within 15 days after alloBMT, versus only 7.1% of patients not receiving G-CSF post-transplant (n = 28), p < 0.001. The neutrophil recovery was similar in patients receiving either fresh or cryopreserved allografts and either TBI-containing or busulfan-containing conditioning regimen. A significant correlation was found between neutrophil recovery and either the MNC or CFU-GM content of the allografts, r = 0.33, p < 0.01. The mean number of days required for neutrophil recovery was only 16 days (median 16, range 9 to 24 days) in patients receiving allografts containing > 1 x 10(5) CFU-GM/kg (n = 28) versus 19 days (median 19, range 13 to 27 days) in patients receiving allografts containing < 1 x 10(5) CFU-GM/kg (n = 35). Three patients receiving allografts containing less than 0.5 x 10(5) CFU-GM/kg had primary neutrophil engraftment failure. The mean number of days required to achieve 20 x 109/l platelet count was 21 (median 20, range 11 to 50 days) and 30 patients (46.9%) had platelet recovery within 20 days after alloBMT. The platelet recovery after alloBMT was not significantly affected by the type of leukaemia, conditioning regimen, or G-CSF administration. The mean number of days required for platelet recovery after alloBMT was only 20 days (median 18 days) in patients receiving allografts containing > 1.0 x 10(5) BFU-E/kg (n = 35) versus 23 days (median 20 days) in patients receiving allografts containing < 1.0 x 10(5) BFU-E/kg (n = 24). Seven patients receiving allografts containing less than 0.5 x 10(5) BFU-E/kg had primary platelet engraftment failure. The present study has identified the high number of progenitor cells in the allografts infused and the daily administration of G-CSF post-transplant as the optimal combination for a rapid neutrophil recovery after alloBMT. More significantly, the number of BFU-E in allografts was the most significant factor to determine platelet recovery after alloBMT. The development of GVHD of grade II or more during the first weeks after alloBMT was associated with slower haematological recovery and longer period of fever during neutropenia and hospitalisation.
在本项针对66例白血病患者（28例急性髓系白血病、23例急性淋巴细胞白血病、15例慢性髓系白血病）的单中心研究中，对异基因骨髓移植（alloBMT）后影响血液学恢复的因素进行了回顾性分析，以确定alloBMT后血液学快速恢复所需的最佳条件。所有患者均接受环孢素A加甲氨蝶呤预防移植物抗宿主病（GVHD）。alloBMT后中性粒细胞计数达到≥0.5×10⁹/L所需的平均天数为17天（中位数17天，范围9至27天），19例患者（28.8%）在alloBMT后15天内中性粒细胞快速恢复。38例无GVHD或仅有I级GVHD的患者血液学恢复更快。此外，接受10（n = 18）或5（n = 20）μg/kg/天粒细胞集落刺激因子（G-CSF）的患者中，分别有50%和40%在alloBMT后15天内中性粒细胞快速恢复，而移植后未接受G-CSF的患者（n = 28）中只有7.1%，p < 0.001。接受新鲜或冷冻保存的同种异体移植物以及含全身照射（TBI）或含白消安预处理方案的患者中性粒细胞恢复情况相似。发现中性粒细胞恢复与同种异体移植物的单个核细胞（MNC）或粒系集落生成单位（CFU-GM）含量之间存在显著相关性，r = 0.33，p < 0.01。接受含>1×10⁵CFU-GM/kg同种异体移植物的患者（n = 28）中性粒细胞恢复所需的平均天数仅为16天（中位数16天，范围9至24天），而接受含<1×10⁵CFU-GM/kg同种异体移植物的患者（n = 35）为19天（中位数19天，范围13至27天）。3例接受含<0.5×10⁵CFU-GM/kg同种异体移植物的患者出现原发性中性粒细胞植入失败。达到20×10⁹/L血小板计数所需的平均天数为21天（中位数20天，范围11至50天），30例患者（46.9%）在alloBMT后20天内血小板恢复。alloBMT后的血小板恢复不受白血病类型、预处理方案或G-CSF给药的显著影响。接受含>1.0×10⁵红系爆式集落形成单位（BFU-E）/kg同种异体移植物的患者（n = 35）alloBMT后血小板恢复所需的平均天数仅为20天（中位数18天），而接受含<1.0×10⁵BFU-E/kg同种异体移植物的患者（n = 24）为23天（中位数20天）。7例接受含<0.5×10⁵BFU-E/kg同种异体移植物的患者出现原发性血小板植入失败。本研究确定，输注的同种异体移植物中祖细胞数量多以及移植后每日给予G-CSF是alloBMT后中性粒细胞快速恢复的最佳组合。更显著的是，同种异体移植物中BFU-E的数量是决定alloBMT后血小板恢复的最显著因素。alloBMT后最初几周内发生II级或更高级别的GVHD与血液学恢复较慢、中性粒细胞减少期间发热时间延长和住院时间延长有关。
