Palumbo A, Pileri A, Triolo S, Omedè P, Bruno B, Ciravegna G, Galliano M, Frieri R, Boccadoro M
Dipartimento di Medicina ed Oncologia Sperimentale, Az Ospedaliera S Giovanni Battista, Torino, Italy.
Bone Marrow Transplant. 1997 Jan;19(1):23-9. doi: 10.1038/sj.bmt.1700599.
Attempts to increase dose intensity have been hampered by hematologic toxicity. To address this issue, we designed a study to determine whether the reinfusion of PBPC significantly reduces the toxicity of multicyclic dose-intensive chemotherapy. Thirty refractory patients, median age 63, received CY 3 g/m2 plus melphalan 60 mg/m2 followed by PBPC and G-CSF (CM regimen). CY (at day 0) and G-CSF were used to mobilize PBPC harvested by a single leukapheresis at day 10. Melphalan was infused at day 11. PBPC were kept unprocessed at 4 degrees C for 48 h and reinfused at day 12. This regimen was repeated three times every 6 months. Outcomes were compared with those of 30 similar patients treated with melphalan 30 mg/m2 followed by G-CSF only, and repeated every 2 months for a total of six cycles. In patients receiving CY plus melphalan followed by PBPC reinfusion, the median duration of neutropenia (ANC < 500/microliters) and thrombocytopenia (platelets < 2500 microliters) was only 5 and 2 days respectively, and did not increase after the subsequent courses. Hematologic toxicity was quite similar to that observed after melphalan 30 mg/m2 plus G-CSF. The CM regimen was followed by 30% complete remission and 86% response > 50%, melphalan 30 mg/m2 by no complete remissions and 38% response > 50%. Patients receiving CM regimen showed a longer progression-free survival (22 vs 10 months, P < 0.01). The dose intensity of melphalan can be doubled by reinfusing PBPC without increasing toxicity. The combination of CY and melphalan followed by PBPC improves response rate and outcome when compared to low-dose melphalan.
提高剂量强度的尝试因血液学毒性而受到阻碍。为解决这一问题，我们设计了一项研究，以确定外周血祖细胞（PBPC）的回输是否能显著降低多周期剂量密集化疗的毒性。30例难治性患者，中位年龄63岁，接受环磷酰胺（CY）3 g/m²加美法仑60 mg/m²，随后进行PBPC和粒细胞集落刺激因子（G-CSF）治疗（CM方案）。CY（第0天）和G-CSF用于动员在第10天通过单次白细胞分离术采集的PBPC。美法仑在第11天输注。PBPC在4℃下未处理保存48小时，并在第12天回输。该方案每6个月重复3次。将结果与30例仅接受30 mg/m²美法仑加G-CSF治疗、每2个月重复一次、共六个周期的类似患者的结果进行比较。在接受CY加美法仑随后PBPC回输的患者中，中性粒细胞减少（中性粒细胞绝对值<500/微升）和血小板减少（血小板<2500/微升）的中位持续时间分别仅为5天和2天，且在后续疗程后未增加。血液学毒性与30 mg/m²美法仑加G-CSF后观察到的毒性相当相似。CM方案后30%完全缓解，86%缓解率>50%，30 mg/m²美法仑无一例完全缓解，38%缓解率>50%。接受CM方案的患者无进展生存期更长（22个月对10个月，P<0.01）。通过回输PBPC可使美法仑的剂量强度加倍而不增加毒性。与低剂量美法仑相比，CY和美法仑联合PBPC可提高缓解率和治疗效果。
