Effect of CD34(+) selection and various schedules of stem cell reinfusion and granulocyte colony-stimulating factor priming on hematopoietic recovery after high-dose chemotherapy for breast cancer
Effect of CD34(+) selection and various schedules of stem cell reinfusion and granulocyte colony-stimulating factor priming on hematopoietic recovery after high-dose chemotherapy for breast cancer
复制标题
DOI：
10.1182/blood.v89.5.1521.1521_1521_1528
复制
发表时间：
1997-03-01
期刊：
影响因子：
20.3
通讯作者：
Doroshow, JH
中科院分区：
文献类型：
--
作者：
Somlo, G;Sniecinski, I;Doroshow, JH
我们评估了88例接受大剂量化疗（包括顺铂250 mg/m2、依托泊苷60 mg/kg和环磷酰胺100 mg/kg）的晚期乳腺癌患者外周血干细胞（PBSC）回输、粒细胞集落刺激因子（G-CSF）预充和CD 34（+）富集的不同方案对造血恢复的影响。在用G-CSF预充后收集PBSC（大于或等于7.5 x 10（8）个有核细胞/kg），并立即冷冻保存（48例患者;队列A和B）或首先处理用于CD 34（+）富集（40例患者;队列C和D）。组群A和C中的患者在第0天接受PBSC;组群B和D中的患者在第-2天接受25%的有核细胞，在第0天接受75%的有核细胞（分流再输注）。组群A、B和C中的患者用G-CSF 10 μ g/kg皮下（SC）致敏，每天一次;组群D中的患者用5 μ g/kg G-CSF SC致敏，每天两次（bid）。每日2次给予G-CSF产生的PBSC产品中CD 34（+）细胞数量比每天1次给予相同总剂量高2.3至4.7倍（P=.002）。在第-2天再输注25%的APPBSC（中位数，2.26 x 10（8）/kg有核细胞[范围，1.7至3.3 x 10（8）/kg]）;当与第0天所有干细胞的再输注相比时，第0天再输注的剩余细胞导致更早的粒细胞恢复到大于或等于500/μ L（B组，中位数8天[范围，7 - 11] vs A组，10天[范围，8 - 11]，P=.0003）;在达到血小板非依赖性方面未观察到时间依赖性差异（B组，11.5天[范围，5 - 21]; A组，12天[范围，8 - 24]，P=不显著）。CD 34（+）选择性PBSC的分次方案回输未加速粒细胞恢复。在D组和C组中，粒细胞恢复的中位天数分别为12天（范围，8 - 22）和11.5天（范围，9 - 13）;患者分别在第15天（范围，6 - 22）和14天（范围，12 - 23）开始不依赖血小板。CD 34（+）选择性PBSC补救治疗与CD 34（+）选择性PBSC再输注相比，可降低再输注后恶心、呕吐和氧饱和度下降的发生率（P均小于或等于0.005）。早期回输约2.26 × 108/kg有核细胞可加速造血恢复。较早的恢复可能是由CD 34（+）细胞群中包括的祖细胞以外的组分触发的。CD 34（+）-选择性外周血干细胞也可以实现持续的造血恢复。按照bid方案给药G-CSF可提高白细胞去除产物中的CD 34（+）细胞产量。在早期“牺牲性"回输约2 × 10（8）/kg有核细胞同时给予大剂量化疗是否能进一步缩短绝对粒细胞减少的持续时间，同时启动持续的长期造血恢复，还需要进一步研究。(C)1997年，美国血液学会。
We evaluated the effects of various schedules of peripheral blood stem cell (PBSC) reinfusion, granulocyte colony-stimulating factor (G-CSF) priming, and CD34(+) enrichment on hematopoietic recovery in 88 patients with advanced breast cancer treated with high-dose chemotherapy, consisting of ; cisplatin 250 mg/m(2), etoposide 60 mg/kg, and cyclophosphamide 100 mg/kg. PBSC (greater than or equal to 7.5 x 10(8) nucleated cells/kg) were collected following priming with G-CSF and were either immediately cryopreserved (48 patients; cohorts A and B) or were first processed for CD34(+) enrichment (40 patients; cohorts C and D). Patients in cohorts A and C received PBSC on day 0; patients in cohorts B and D received 25% of their nucleated cells on day -2 and 75% on day 0 (split reinfusion). Patients in cohorts A, B, and C were primed with G-CSF 10 mu g/kg, subcutaneously (SC), once a day; patients in cohort D were primed with 5 mu g/kg G-CSF, SC, twice daily (bid). Bid administration of G-CSF yielded 2.3 to 4.7 x higher numbers of CD34(+) cells in the PBSC product than the same total dose given once a day (P=.002). Reinfusion of 25% of unselected PBSC on day -2 (median, 2.26 x 10(8)/kg nucleated cells [range, 1.7 to 3.3 x 10(8)/kg]) with the; remaining cells reinfused on day 0 resulted in earlier granulocyte recovery to greater than or equal to 500/mu L when compared with reinfusion of all stem cells on day 0 (group B, median of 8 days [range, 7 to 11] v group A, 10 days [range, 8 to 11], P=.0003); no schedule-dependent difference was noted in reaching platelet independence (group B, 11.5 days [range, 5 to 21]; group A, 12 days [range, 8 to 24], P=not significant). Split schedule reinfusion of CD34(+)-selected PBSC did not accelerate granulocyte recovery. In groups D and C, the median number of days to granulocyte recovery was 12 (range, 8 to 22) and 11.5 (range, 9 to 13); patients became platelet independent by day 15 (range, 6 to 22) and 14 (range, 12 to 23), respectively. CD34(+)-selected PBSC rescue decreased the incidence of postreinfusion nausea, emesis, and oxygen desaturation in comparison to unselected PBSC reinfusion (P less than or equal to.005 for each). Hematopoietic recovery may be accelerated by earlier reinfusion of approximate to 2.26 x10(8)/kg unselected nucleated cells. Earlier recovery may be triggered by components other than the progenitors included in the CD34(+) cell population. Sustained hematopoietic recovery can also be achieved with CD34(+)-selected PBSC alone. Dosing of G-CSF on a bid schedule generates higher CD34(+) cell yield in the leukapheresis product. Whether even earlier ''sacrificial'' reinfusion of approximately 2 x 10(8)/kg unselected nucleated cells concomitant with the administration of high-dose chemotherapy would reduce the duration of absolute granulocytopenia further while initiating sustained long-term hematopoietic recovery will require further investigation. (C) 1997 by The American Society of Hematology.