van der Wall E, Richel D J, Holtkamp M J, Slaper-Cortenbach I C, van der Schoot C E, Dalesio O, Nooijen W J, Schornagel J H, Rodenhuis S
Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam.
Ann Oncol. 1994 Nov;5(9):795-802. doi: 10.1093/oxfordjournals.annonc.a059007.
Peripheral blood progenitor cell transplantation is rapidly replacing autologous bone marrow transplantation as hematological support after high-dose chemotherapy for lymphoma or solid tumors. Controversy exists concerning the number of progenitor cells required for rapid and sustained bone marrow recovery, and as to which of the widely available methods for estimating this number should be employed.
Forty consecutive patients with solid tumors or lymphomas received high-dose chemotherapy followed by autologous peripheral stem cell reinfusion. All stem cell harvests had been performed after mobilization with standard-dose chemotherapy followed by 300 micrograms G-CSF daily. Hematopoietic reconstitution was studied in relation to pertinent patient characteristics, to the size of the graft (in terms of the total number of mononuclear cells (MNC), the number of granulocyte/macrophage colony-forming units (CFU-GM) and the number of CD34+ cells, and to the use of G-CSF after stem cell reinfusion.
Both the numbers of CFU-GM and CD34+ cells reinfused, but not those of the MNC, correlated with granulocyte and platelet recovery. Patients who received at least 5 x 10(6) CD34+ cells/kg body weight achieved platelet transfusion independence on day 12 after reinfusion (range: day 7-37), significantly earlier than patients who had received less (p = 0.001). Thirty patients who received G-CSF (300 micrograms s.c. daily) after reinfusion achieved granulocyte recovery (> or = 500 x 10(6)/l) on day 9 (range: day 8-12), while this took a median of 15 days (range: day 10-28) in 10 consecutive patients not receiving G-CSF (p = 0.0003). In one patient who had received 1.4 x 10(6) CD34+ cells/kg, secondary bone marrow failure developed 3 months after transplantation. Reinfusion of cryopreserved autologous bone marrow was followed by prompt recovery.
Peripheral stem cells, mobilized by moderate-dose chemotherapy and G-CSF, lead to rapid and durable engraftment after high-dose chemotherapy when at least 3-5 x 10(6) CD34+ cells/kg are reinfused. Lower numbers may also be satisfactory, but are associated with slower granulocyte and platelet recoveries. A moderate dose of G-CSF after reinfusion significantly hastens granulocyte recovery without interfering with platelet recovery.
外周血祖细胞移植正迅速取代自体骨髓移植，成为淋巴瘤或实体瘤大剂量化疗后的血液学支持手段。关于骨髓快速且持续恢复所需的祖细胞数量，以及应采用哪种广泛可用的方法来估算该数量，目前仍存在争议。
40例连续的实体瘤或淋巴瘤患者接受了大剂量化疗，随后进行自体外周干细胞回输。所有干细胞采集均在标准剂量化疗动员后进行，随后每日皮下注射300微克粒细胞集落刺激因子（G-CSF）。研究了造血重建与相关患者特征、移植物大小（以单个核细胞（MNC）总数、粒细胞/巨噬细胞集落形成单位（CFU-GM）数量和CD34+细胞数量衡量）以及干细胞回输后G-CSF的使用情况之间的关系。
回输的CFU-GM和CD34+细胞数量与粒细胞和血小板恢复相关，但MNC数量与二者无关。回输至少5×10⁶个CD34+细胞/千克体重的患者在回输后第12天（范围：第7 - 37天）实现了血小板输注独立，显著早于接受较少细胞的患者（p = 0.001）。30例回输后接受G-CSF（每日皮下注射300微克）的患者在第9天（范围：第8 - 12天）实现了粒细胞恢复（≥500×10⁶/升），而10例连续未接受G-CSF的患者粒细胞恢复的中位时间为15天（范围：第10 - 28天）（p = 0.0003）。1例接受1.4×10⁶个CD34+细胞/千克的患者在移植后3个月出现继发性骨髓衰竭。回输冷冻保存的自体骨髓后迅速恢复。
经中剂量化疗和G-CSF动员的外周干细胞，在大剂量化疗后，当回输至少3 - 5×10⁶个CD34+细胞/千克时，可实现快速且持久的植入。细胞数量较低时也可能令人满意，但与粒细胞和血小板恢复较慢相关。回输后使用中等剂量的G-CSF可显著加速粒细胞恢复，且不影响血小板恢复。
