Siena S, Bregni M, Bonsi L, Sklenar I, Bagnara G P, Bonadonna G, Gianni A M
Cristina Gandini Unit, Istituto Nazionale Tumori, Milan, Italy.
Exp Hematol. 1993 Nov;21(12):1583-90.
Seven patients received cancer chemotherapy with high-dose cyclophosphamide (HD-CTX) associated with either recombinant human granulocyte colony-stimulating factor (rhG-CSF), rh interleukin-3 (rhIL-3), rh granulocyte-macrophage CSF (rhGM-CSF) plus rh erythropoietin (rhEpo), rhIL-3 plus rhGM-CSF, or rhIL-3 plus rhG-CSF. In the steady-state blood samples (before HD-CTX), megakaryocyte burst-forming units (BFU-Meg) and megakaryocyte colony-forming units (CFU-Meg) were virtually undetectable (< or = 1/mL BFU-Meg and CFU-Meg, range 0 to 1) by assaying unfractionated leukocytes. In contrast, in the recovery-phase blood samples (after HD-CTX), BFU-Meg and CFU-Meg increased several hundred-fold over steady-state values. This occurred regardless of the in vivo growth factors used and in parallel with increases in mixed, erythroid, and myeloid progenitors. In vitro, recovery-phase BFU-Meg and CFU-Meg responded to the novel GM-CSF/IL-3 fusion protein PIXY321 similarly as to optimal concentrations of rhIL-3 and rhGM-CSF. However, these progenitors differed from those in the steady state because BFU-Meg had faster duplication time and CFU-Meg prevailed numerically (CFU-Meg to BFU-Meg ratio 3.4 [recovery] vs. 0.52 [steady state]). Furthermore, soluble c-kit ligand/rh stem cell factor (rhSCF), in vitro in combination with rhIL-3 and rhGM-CSF or PIXY321, increased the size but not the number of colonies derived from recovery-phase BFU-Meg and CFU-Meg. These quantitative and qualitative changes occurring in circulating megakaryocyte progenitors contribute to the understanding of the rapid platelet recovery that occurs when peripheral blood hematopoietic progenitors elicited by HD-CTX and growth factor(s) are transplanted into patients treated with myeloablative chemoradiotherapy.
7例患者接受了高剂量环磷酰胺（HD-CTX）联合重组人粒细胞集落刺激因子（rhG-CSF）、rh白细胞介素-3（rhIL-3）、rh粒细胞-巨噬细胞集落刺激因子（rhGM-CSF）加rh促红细胞生成素（rhEpo）、rhIL-3加rhGM-CSF或rhIL-3加rhG-CSF的癌症化疗。在稳态血样（HD-CTX治疗前）中，通过检测未分离的白细胞，巨核细胞爆式集落形成单位（BFU-Meg）和巨核细胞集落形成单位（CFU-Meg）几乎检测不到（<或=1/mL BFU-Meg和CFU-Meg，范围0至1）。相比之下，在恢复阶段血样（HD-CTX治疗后）中，BFU-Meg和CFU-Meg比稳态值增加了数百倍。无论使用何种体内生长因子，这种情况都会发生，并且与混合、红系和髓系祖细胞的增加同时出现。在体外，恢复阶段的BFU-Meg和CFU-Meg对新型GM-CSF/IL-3融合蛋白PIXY321的反应与对rhIL-3和rhGM-CSF最佳浓度的反应相似。然而，这些祖细胞与稳态时的祖细胞不同，因为BFU-Meg有更快的复制时间，并且CFU-Meg在数量上占优势（CFU-Meg与BFU-Meg的比率为3.4[恢复]对0.52[稳态]）。此外，可溶性c-kit配体/rh干细胞因子（rhSCF）在体外与rhIL-3和rhGM-CSF或PIXY321联合使用时，增加了源自恢复阶段BFU-Meg和CFU-Meg的集落大小，但没有增加集落数量。循环中的巨核细胞祖细胞发生的这些定量和定性变化有助于理解当HD-CTX和生长因子引发的外周血造血祖细胞被移植到接受清髓性放化疗的患者体内时发生的快速血小板恢复。
