Pre‐emptive plerixafor injection in lymphoma patients mobilized with chemotherapy plus pegfilgrastim followed by apheresis on the same day
Pre‐emptive plerixafor injection in lymphoma patients mobilized with chemotherapy plus pegfilgrastim followed by apheresis on the same day
复制标题
淋巴瘤患者先行注射普乐沙福，化疗加聚乙二醇非格司亭，并于当天进行单采术
DOI：
10.1002/jca.21522
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发表时间：
2017
影响因子：
1.5
通讯作者：
V. Varmavuo
中科院分区：
文献类型：
--
作者：
E. Jantunen;A. Partanen;J. Valtola;M. Pyörälä;P. Mäntymaa;T. Nousiainen;V. Varmavuo
CD 34细胞动员不良是一个常见的临床问题，特别是在淋巴瘤患者打算进行大剂量化疗。无论G-CSF单独使用还是与既往化疗联合使用，约20-30%的患者难以动员。普乐沙福是一种CXCR 4拮抗剂，用于动员骨髓中的CD 34细胞进入循环系统，在随机研究中，与G-CSF单药相比，普乐沙福与G-CSF联合给药的效果更优上级。虽然已经确定了与动员不良相关的几个因素，但在单采前测量的血液CD 34（B-CD 34）细胞计数是目前预测单采产量的最可靠方法。因此，普乐沙福的先发制人或“及时”使用越来越受欢迎。Worel等人最近在杂志上发表的一篇文章评价了这种策略在骨髓瘤和淋巴瘤患者中的应用，在有或没有化疗的情况下，在G-CSF动员4天后血液CD 34细胞计数< 20 3 10/L或在化疗+G-CSF动员患者中WBC计数> 5 3 10/L恢复后的低动员者中具有高成功率（97%实现了最小移植物）。在本研究中，普乐沙福在单采开始前6-11小时给药。在药效学研究中，在接受G-CSF治疗的患者中，在普乐沙福给药后10-14 h测量了CD 34细胞峰值水平。根据标签，plerixafor应在接受G-CSF的患者开始单采前6-11小时皮下给药。传统上，这意味着在晚上9-11点注射。随后评估了各种时间表。在库珀等人的研究中，plerixafor在计划的单采前约15小时给药，48例患者中有47例成功采集血液。另一项研究在单采开始前17小时评价了普乐沙福注射液。特别是在动员能力差的患者中，CD 34细胞动员的动力学可能不同，如Lefrere等人所示。在该研究中，观察到早期动员（3 h），随后在大多数患者中，早在8-12 h，B-CD 34水平就出现早期降低。在许多单采单位中，B-CD 34测量可能仅在白天获得。我们在清晨（5：30）采集B-CD 34样本。并且分析通常在2-3小时内准备好。在许多情况下，第二天早上才能获得采集结果，特别是在第一次单采的情况下。对于B-CD 34计数较低或下降（<10 3 10/L）或既往收集不佳（<1 3 10/kg CD 34细胞）的患者，我们在早晨皮下给予普乐沙福0.24 mg/kg，然后在3-6 h后开始单采。我们的常规操作是使用Spectra Optia（软件7.2，Terumo BCT）在4-5小时内处理2.5倍的估计血量。从开始动员化疗（d1）的中位时间为14天（范围11-16）。我们在6例连续非霍奇金淋巴瘤患者中的经验总结见表1。所有6例患者均接受了高剂量治疗，随后进行了移植物输注。输注的CD 34细胞的中位数（从新鲜样本中采集后测量）为2.7 3 10/kg（范围1.9-4.5 3 10/kg）。中性粒细胞植入时间（>0.5 ~ 3 × 10/L）为10天（9-11天），血小板植入时间（>20 ~ 3 × 10/L）为15天（13-48天）。初步经验表明，这一战略是可行的。我们没有血液成分分离术开始时的B-CD 34计数值，但在除1例采集不良患者外的所有患者中，直到第二天清晨，观察到B-CD 34计数增加了2 - 6倍。（1.9 3 10/kg CD 34细胞，进行三次单采）与我们之前在晚上9-10点预先注射plerixafor，然后在7点开始单采的经验相对应第二天早上八点。值得注意的是，我们所有的患者都接受了化疗以动员CD 34细胞，值得关注的是，最近才与普乐沙福联合使用的培非格司亭。7 -9 4例患者的培非格司亭剂量为6 mg，2例患者的总剂量为12 mg。接受普乐沙福后，我们的患者
To the Editor, Poor mobilization of CD34 cells is a common clinical problem especially in lymphoma patients intended for high-dose chemotherapy. Approximately 20–30% of the patients are hard-to-mobilize independent whether G-CSF is used alone or combined with previous chemotherapy. Plerixafor is a CXCR4 antagonist, used to mobilize CD34 cells from bone marrow to circulation and has been shown to be superior combined with G-CSF compared to G-CSF alone in randomized studies. Although several factors associated with poor mobilization have been identified, blood CD34 (B-CD34) cell counts measured just prior to apheresis are currently the most reliable way to predict apheresis yields. Consequently, pre-emptive or “just in time” use of plerixafor has gained popularity. A recent article in the Journal by Worel et al. evaluated this strategy in myeloma and lymphoma patients mobilized with G-CSF with or without chemotherapy with a high success rate (97% achieved minimal grafts) in poor mobilizers having blood CD34 cell counts< 20 3 10/L after four days of G-CSF or after recovery in WBC count> 5 3 10/L in patients mobilized with chemotherapy plus G-CSF. In this study plerixafor was given 6–11 h before start of apheresis. In pharmacodynamic studies, peak CD34 cell levels have been measured 10–14 h after plerixafor administration in patients receiving G-CSF. According to the label, plerixafor should be given subcutaneously 6–11 h before the start of apheresis in patients receiving G-CSF. Traditionally this has meant injection in the late evening at 9–11 p.m. Various time schedules have been evaluated subsequently. In the study by Cooper et al., plerixafor was given about 15 h before the planned apheresis and successful collections were obtained in 47/48 patients. Another study evaluated plerixafor injection 17 h before start of apheresis. Especially in poor mobilizers, the kinetics of CD34 cell mobilization may be different as illustrated by Lefrere et al. In that study an early mobilization (3 h) was observed followed by an early decrease in B-CD34 levels as early as 8–12 h in the majority of the patients. In many apheresis units, B-CD34 measurements may be obtained only during the day time. We take B-CD34 samples in the early morning (at 5.30 a.m.) and the analysis is usually ready in 2–3 h. In many cases, the results of collections are obtained only next morning especially in the case of the first apheresis. In patients with low or decreasing B-CD34 counts (<10 3 10/L) or in those with a poor previous collection (<1 3 10/kg CD34 cells), we have given plerixafor 0.24 mg/kg subcutaneously in the morning followed by start of apheresis 3–6 h later. Our routine is to process 2.5 times of the estimated blood volume in 4–5 h with the Spectra Optia (Software 7.2, Terumo BCT). The median time from the start of mobilizing chemotherapy (d1) was 14 days (range 11–16). Our experiences in six consecutive nonHodgkin lymphoma patients are summarized in Table 1. All six patients proceeded to high-dose therapy followed by the graft infusion. The median number of infused CD34 cells (measured after collection from fresh samples) was 2.7 3 10/kg (range 1.9–4.5 3 10/kg). The time to the neutrophil engraftment (>0.5 3 10/L) was 10 days (9–11 days) and to the platelet engraftment (>20 3 10/L) 15 days (13–48 days), respectively. This preliminary experience suggests that the strategy is feasible. We do not have values from B-CD34 counts at the time of start of apheresis but an increase of 2to 6-fold was observed until early next morning in all but one patient with a poor collection (1.9 3 10/kg CD34 cells with three aphereses) corresponding to our previous experience in a pre-emptive plerixafor injection given at 9–10 p.m. followed by start of apheresis at 7–8 a.m. on the next day. It is noteworthy that all our patients had received chemotherapy to mobilize CD34 cells and, of interest, pegfilgrastim, which has only recently been combined with plerixafor.7–9 The dose of pegfilgrastim was 6 mg in four patients and two patients received a total dose of 12 mg. After receiving plerixafor our patients had so