Millar B C, Millar J L, Bell J B, Raje N, Milan S, Mehta J, Singhal S, Middleton G W, Sheperd V, Catovsky D, Powles R L
Section of Academic Haematology, McElwain Laboratories, Sutton, Surrey, UK.
Bone Marrow Transplant. 1996 Nov;18(5):871-8.
During the period December 1992 to June 1995, 95 patients were treated with high-dose melphalan (HDM) with peripheral blood stem cell rescue (PBSCR). Sixty-five had received previous treatment and 28 had relapsed. Among patients who had relapsed 21/28 had received HDM previously including one who received HDM twice during the course of the study. Seventy-five patients were given HDM/PBSCR for the first time. Comparisons have been made between engraftment times for platelets and neutrophils among patients who received less than or greater than 2 x 10(6) CD34+ cells at rescue. Analyses have also been done to evaluate the effect of previous HDM on recovery. Mobilization of progenitor cells was done with granulocyte colony-stimulating factor (G-CSF). Patients received only PBSCR. No growth factors were given to the PBSCR recipients during the recovery period. The percentage of patients from whom the number of CD34+ cells mobilized was > 2 x 10(6)/kg was similar in patients who received HDM for the first time (23%) compared with those who had had it previously (19%). The yield of CD34+ cells correlated with the number of granulocyte-macrophage colony forming units (CFU-GM). Although the number of CD34+ cells infused was < 2 x 10(6)/kg in 77% of patients, all engrafted for neutrophils to > 0.5 x 10(9)/l. This was delayed in patients who had had previous HDM (P < 0.02). Platelet recovery to > 25, 50 and 100 x 10(9)/l was delayed in all patients who received < 2 x 10(6) CD34+ cells/kg infused (P < 0.02). In patients who had had previous HDM both neutrophil (P < 0.05) and platelet recovery (P < 0.007) were delayed compared with recovery in patients who had not had HDM. In patients who had had previous HDM and received < 2 x 10(6) CD34+ cells/kg infused only 3/17 regained platelets to > 100 x 10(9)/l compared with 3/4 who had > 2 x 10(6) CD34+ cells/kg infused (P < 0.05 Fisher's exact test). There was no evidence that low numbers of CD34+ cells in the PBSCR were associated with early death. The data show that previous treatment with HDM had adverse effects on the subsequent engraftment of platelets among patients given HDM/PBSCR. The data suggest that additional measures are needed to achieve platelet reconstitution in these heavily pre-treated patients.
在1992年12月至1995年6月期间,95例患者接受了大剂量美法仑(HDM)联合外周血干细胞救援(PBSCR)治疗。65例患者曾接受过先前治疗,28例复发。在复发患者中,21/28例先前接受过HDM治疗,其中1例在研究过程中接受了两次HDM治疗。75例患者首次接受HDM/PBSCR治疗。对救援时接受少于或多于2×10⁶个CD34⁺细胞的患者的血小板和中性粒细胞植入时间进行了比较。还进行了分析以评估先前HDM对恢复的影响。祖细胞动员采用粒细胞集落刺激因子(G-CSF)。患者仅接受PBSCR。在恢复期未向PBSCR接受者给予生长因子。首次接受HDM治疗的患者中动员出的CD34⁺细胞数>2×10⁶/kg的患者百分比(23%)与先前接受过HDM治疗的患者(19%)相似。CD34⁺细胞产量与粒细胞-巨噬细胞集落形成单位(CFU-GM)数量相关。尽管77%的患者输注的CD34⁺细胞数<2×10⁶/kg,但所有患者的中性粒细胞均植入至>0.5×10⁹/L。先前接受过HDM治疗的患者植入延迟(P<0.02)。所有接受输注的CD34⁺细胞数<2×10⁶/kg的患者血小板恢复至>25、50和100×10⁹/L均延迟(P<0.02)。与未接受HDM治疗的患者相比,先前接受过HDM治疗的患者中性粒细胞(P<0.05)和血小板恢复(P<0.007)均延迟。在先前接受过HDM治疗且接受输注的CD34⁺细胞数<2×10⁶/kg的患者中,只有3/17的患者血小板恢复至>100×10⁹/L,而接受输注的CD34⁺细胞数>2×10⁶/kg的患者中有3/4(P<0.05,Fisher精确检验)。没有证据表明PBSCR中CD34⁺细胞数量少与早期死亡有关。数据表明,先前HDM治疗对接受HDM/PBSCR治疗的患者随后的血小板植入有不利影响。数据表明,需要采取额外措施来实现这些经过大量预处理患者的血小板重建。