Hohaus S, Goldschmidt H, Ehrhardt R, Haas R
Department of Internal Medicine V, University of Heidelberg, Germany.
Exp Hematol. 1993 Apr;21(4):508-14.
High-dose conditioning therapy followed by autografting with blood stem cells rather than bone marrow has become an increasingly used transplantation modality for patients with chemosensitive malignancies. We treated 10 patients with malignant lymphoma in sensitive relapse with recombinant human granulocyte colony-stimulating factor (rhG-CSF) following salvage therapy. rhG-CSF was given subcutaneously (5 micrograms/kg/day) starting 24 hours after chemotherapy and stem cell collection was performed by repeated leukaphereses during leukocyte recovery. The yield of myeloid progenitors varied between 0.79 and 38.36 x 10(4) CFU-GM/kg body weight (median 4.1 x 10(4). A strong correlation was found between the number of granulocyte-macrophage colony-forming cells (CFU-GM) plus blast-forming erythroid cells (BFU-E) and CD34-positive (CD34+) cells (R = 0.80; p < 0.001). The majority of CD34+ cells (> 95%) strongly coexpressed human lymphocyte antigen-DR (HLA-DR) and CD38, whereas CD33 varied between 20% and 94%. Costaining of CD34+ cells for CD19 above the control level could not be detected, suggesting that early B lymphoid progenitors are not expanded or released into the circulation by rhG-CSF. Following total body irradiation (TBI)/cyclophosphamide or the CBV regimen (cyclophosphamide, BCNU, VP-16), all patients achieved complete engraftment with a median of 14 days for 1.0 x 10(9)/L white blood cells (WBC), 15 days for 0.5 x 10(9)/L polymorphonuclear cells (PMN) and 22 days for 20 x 10(9)/L platelets. The quantity of CFU-GM/kg transplanted was predictive for neutrophil and platelet recovery. The strongest correlation, however, was found between the number of CD34+ cells/kg autografted and platelet recovery (R = -0.86; p < 0.001). The patients transplanted with more than 5 x 10(6)/kg CD34+ cells reached an unsubstituted platelet count > 20 x 10(9)/L within 8 to 12 days. Our data demonstrate that rapid and complete engraftment can be achieved following myeloablative conditioning therapy with rhG-CSF-exposed blood stem cells without the need for additional bone marrow support or growth factor administration posttransplantation.
对于化疗敏感的恶性肿瘤患者，大剂量预处理疗法后进行血干细胞而非骨髓的自体移植已成为一种越来越常用的移植方式。我们对10例恶性淋巴瘤敏感复发患者在挽救性治疗后用重组人粒细胞集落刺激因子（rhG-CSF）进行治疗。rhG-CSF在化疗后24小时开始皮下注射（5微克/千克/天），在白细胞恢复期间通过反复白细胞单采术进行干细胞采集。髓系祖细胞产量在0.79至38.36×10⁴集落形成单位-粒细胞/巨噬细胞（CFU-GM）/千克体重之间（中位数为4.1×10⁴）。发现粒细胞-巨噬细胞集落形成细胞（CFU-GM）加爆式红系集落形成细胞（BFU-E）的数量与CD34阳性（CD34⁺）细胞之间存在强相关性（R = 0.80；p < 0.001）。大多数CD34⁺细胞（> 95%）强烈共表达人淋巴细胞抗原-DR（HLA-DR）和CD38，而CD33在20%至94%之间。未检测到CD34⁺细胞上CD19的共染色高于对照水平，这表明rhG-CSF不会使早期B淋巴细胞祖细胞扩增或释放到循环中。在全身照射（TBI）/环磷酰胺或CBV方案（环磷酰胺、卡氮芥、依托泊苷）后，所有患者均实现完全植入，白细胞（WBC）达到1.0×10⁹/L的中位数时间为14天，多形核细胞（PMN）达到0.5×10⁹/L的中位数时间为15天，血小板达到20×10⁹/L的中位数时间为22天。每千克移植的CFU-GM数量可预测中性粒细胞和血小板的恢复。然而，发现每千克自体移植的CD34⁺细胞数量与血小板恢复之间的相关性最强（R = -0.86；p < 0.001）。移植超过5×10⁶/kg CD34⁺细胞的患者在8至12天内血小板计数达到> 20×10⁹/L且无需替代。我们的数据表明，用rhG-CSF处理的血干细胞进行清髓性预处理治疗后可实现快速完全植入，无需额外的骨髓支持或移植后给予生长因子。
