Joffe J K, Bell J B, Denham S, Adshead F, Millar J L, Millar B C
Section of Medicine, Institute of Cancer Research, Sutton, Surrey, UK.
Exp Hematol. 1995 Apr;23(4):376-82.
Colony-stimulating activity (CSA) was measured by the production of granulocyte-macrophage colony-forming units (GM-CFU) from normal donor bone marrow in the plasma of 29 patients with multiple myeloma (MM) after intensive treatment with high-dose melphalan (HDM) with or without autologous bone marrow rescue (ABMR). Although patients who received ABMR had an earlier recovery of circulating neutrophils compared with those who received HDM alone, the time at which CSA reached a maximum was similar in both groups (10 to 11 days) after therapy. The decline in CSA correlated with the recovery of the neutrophil count. In plasma from patients who received recombinant human granulocyte colony-stimulating factor (rhG-CSF), in addition to an autograft, CSA reached a maximum earlier (7 days). Furthermore, neutrophil recovery was earlier in these patients. Platelet recovery was not increased by rhG-CSF. The time at which CSA was maximum in four patients who were undergoing intensive therapy for the second time occurred 9 days after treatment with HDM. Although the period without neutrophils was longer in three (of four) patients who survived long term, one patient who received rhG-CSF had a shorter period of neutropenia than the two who had not had the cytokine. G-CSF was detected in plasma from seven of seven patients but not at all times after treatment. In plasma samples that contained G-CSF, colony numbers were increased by recombinant interleukin-4 (rIL-4) in vitro. Neither IL-3 nor GM-CSF was detected in plasma; however, antibody to GM-CSF reduced CSA in all samples after intensive therapy. The data suggest that CSA is a consistent physiologic response to intensive therapy, even in previously treated patients, but that hematologic recovery is dependent on the availability of viable progenitor cells.
通过在29例接受大剂量美法仑（HDM）强化治疗（有或无自体骨髓挽救[ABMR]）的多发性骨髓瘤（MM）患者血浆中，检测正常供体骨髓来源的粒细胞 - 巨噬细胞集落形成单位（GM - CFU）的产生，来测定集落刺激活性（CSA）。尽管接受ABMR的患者与仅接受HDM的患者相比，循环中性粒细胞恢复得更早，但两组在治疗后CSA达到最大值的时间相似（10至11天）。CSA的下降与中性粒细胞计数的恢复相关。在接受重组人粒细胞集落刺激因子（rhG - CSF）以及自体移植的患者血浆中，CSA更早达到最大值（7天）。此外，这些患者的中性粒细胞恢复也更早。rhG - CSF并未增加血小板的恢复。4例接受第二次强化治疗的患者，其CSA达到最大值的时间在HDM治疗后9天。尽管4例长期存活患者中有3例无中性粒细胞的时间更长，但1例接受rhG - CSF的患者中性粒细胞减少期比另外2例未接受该细胞因子的患者短。7例患者中有7例血浆中检测到G - CSF，但并非在治疗后的所有时间都能检测到。在含有G - CSF的血浆样本中，体外重组白细胞介素 - 4（rIL - 4）可增加集落数量。血浆中未检测到IL - 3和GM - CSF；然而，GM - CSF抗体在强化治疗后的所有样本中均降低了CSA。数据表明，即使在既往接受过治疗的患者中，CSA也是对强化治疗的一种持续生理反应，但血液学恢复取决于存活祖细胞的可用性。
