Bone Marrow Transplant Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China.
Int J Hematol. 2011 Aug;94(2):156-162. doi: 10.1007/s12185-011-0887-7. Epub 2011 Jul 5.
During imatinib therapy, many patients with chronic myeloid leukemia (CML) develop severe neutropenia, leading to treatment interruptions, and potentially compromising response to imatinib. Berbamine (a bisbenzylisoquinoline alkaloid) has been widely used in Asian countries for managing leukopenia associated with chemotherapy. To investigate whether berbamine shows clinical benefit in reversing imatinib-associated neutropenia, we analyzed 63 chronic-phase CML patients who had developed grade ≥2 neutropenia and were treated with (n = 34, berbamine group) or without (n = 29, control group) berbamine. Among those patients with grade 2 neutropenia, five of 13 (38.5%) progressed to grade 3 neutropenia without berbamine support, while in the berbamine group, the rate decreased to 3/20 (15%) (p = 0.213). Although the rate of recovery from grade ≥3 neutropenia was similar in the two groups (94.1 vs. 90.5%, p = 0.559), berbamine markedly shortened the recovery time (median, 11 vs. 24 days, p = 0.006), and prevented recurrence of grade ≥3 neutropenia (18.8 vs. 52.6%, p = 0.039). Moreover, with berbamine support, the time to achieve complete cytogenetic response was significantly shorter (median, 6.5 vs. 10 months, p = 0.007). There were no severe adverse events associated with berbamine treatment. In conclusion, the present study reveals the potential clinical value of berbamine in the treatment of CML with imatinib-induced neutropenia. The use of berbamine may improve response to imatinib by stimulating normal hematopoiesis and faster neutropenia recovery.
在伊马替尼治疗期间，许多慢性髓性白血病（CML）患者会出现严重的中性粒细胞减少症，导致治疗中断，并可能影响对伊马替尼的反应。小檗胺（一种双苄基异喹啉生物碱）已在亚洲国家广泛用于治疗与化疗相关的白细胞减少症。为了研究小檗胺在逆转伊马替尼相关中性粒细胞减少症方面是否具有临床益处，我们分析了 63 例慢性期 CML 患者，这些患者发生了≥2 级中性粒细胞减少症，并接受了（n=34，小檗胺组）或未接受（n=29，对照组）小檗胺治疗。在那些发生 2 级中性粒细胞减少症的患者中，有 13 例（38.5%）未经小檗胺支持的情况下进展为 3 级中性粒细胞减少症，而在小檗胺组中，这一比例降至 3/20（15%）（p=0.213）。尽管两组从≥3 级中性粒细胞减少症恢复的比例相似（94.1%对 90.5%，p=0.559），但小檗胺明显缩短了恢复时间（中位数，11 对 24 天，p=0.006），并防止了≥3 级中性粒细胞减少症的复发（18.8%对 52.6%，p=0.039）。此外，在小檗胺支持下，达到完全细胞遗传学缓解的时间明显缩短（中位数，6.5 对 10 个月，p=0.007）。小檗胺治疗没有严重的不良反应。总之，本研究揭示了小檗胺在治疗伊马替尼诱导的中性粒细胞减少症的潜在临床价值。小檗胺的使用可能通过刺激正常造血和更快地恢复中性粒细胞减少症来改善对伊马替尼的反应。
