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多发性骨髓瘤患者外周血祖细胞动员的比较:大剂量环磷酰胺加粒细胞巨噬细胞集落刺激因子与单独使用粒细胞集落刺激因子的对比

Comparison of peripheral blood progenitor cell mobilization in patients with multiple myeloma: high-dose cyclophosphamide plus GM-CSF vs G-CSF alone.

作者信息

Alegre A, Tomás J F, Martínez-Chamorro C, Gil-Fernández J J, Fernández-Villalta M J, Arranz R, Díaz M A, Granda A, Bernardo M R, Escudero A, López-Lorenzo J L, Fernández-Rañada J M

机构信息

Hematology Department, Hospital Universitario de la Princesa, Madrid, Spain.

出版信息

Bone Marrow Transplant. 1997 Aug;20(3):211-7. doi: 10.1038/sj.bmt.1700867.

Abstract

The best method for peripheral blood progenitor cell (PBPC) mobilization in patients with multiple myeloma (MM) remains controversial. We report the results of two different methods of PBPC collection for autologous transplantation in 40 patients with stage II or III MM. In group I (n = 18), HD-CY, 4 g/m2 i.v., was administered followed by GM-CSF, 8 microg/kg/day s.c., until the end of collection, starting the leukaphereses after hematological recovery (>1 x 10(9)/l WBC). In group II (n = 22), G-CSF, 10 microg/kg/day s.c., was used alone until the last day of collection, starting consecutive aphereses on the 5th day. A minimum of two aphereses were performed to collect at least 2 x 10(6)/kg CD34+ cells. Both patient groups were comparable for age, sex and clinical prognostic features as well as previous therapies. In group I, the median yields per pheresis were: MNC 1.47 (1.38-2.32) x 10(8)/kg, CFU-GM 0.82 (0.18-13.2) x 10(4)/kg and CD34+ cells 1.98 (0.96-6.96) x 10(6)/kg. In group II these results were: MNC 2.44 (2.06-3.6 x 10(8)/kg) (P = 0.03), CFU-GM 0.75 (0.16-7.8) x 10(4)/kg and CD34+ 1.05 (0.32-3.4) x 10(6)/kg (P = 0.02). The median number of aphereses performed in each group was 5 (4-12) with a median of 5.24 +/- 2.51 in group I and 3 (2-6) with a median of 3.1 (+/- 0.91) in group II (P = NS). Hospitalization for PBPC mobilization was required in all patients in group I and the treatment-related toxicity was greater in this group: 12 patients (66%) developed fever requiring antibiotics during the neutropenic period after HD-CY and six (33%) patients required transfusion support. After receiving busulfan 12 mg/kg p.o. and melphalan 140 mg/m2 i.v., as the conditioning regimen, the median periods to reach granulocytes (>0.5 x 10(9)/l) and platelet (>20 x 10(9)/l) engraftment were 12 and 11 days respectively (ranges 8-20 and 10-16) in group I (HD-CY plus GM-CSF group), and 11 and 13 days respectively (ranges 7-42 and 10-38) in group II (G-CSF group) (P = NS). In conclusion, these data suggest that although HD-CY plus GM-CSF is superior to G-CSF alone based on mean CD34+ cell yield per pheresis, adequate CD34+ cell collections can be achieved with G-CSF alone in most MM patients with less toxicity and with simplification of the procedure.

摘要

多发性骨髓瘤(MM)患者外周血祖细胞(PBPC)动员的最佳方法仍存在争议。我们报告了40例II期或III期MM患者采用两种不同方法进行PBPC采集用于自体移植的结果。在第一组(n = 18)中,静脉注射4 g/m²的大剂量环磷酰胺(HD - CY),随后皮下注射8 μg/kg/天的粒细胞巨噬细胞集落刺激因子(GM - CSF),直至采集结束,在血液学恢复(白细胞计数>1×10⁹/L)后开始进行白细胞单采。在第二组(n = 22)中,仅皮下注射10 μg/kg/天的粒细胞集落刺激因子(G - CSF)直至采集的最后一天,在第5天开始连续进行单采。至少进行两次单采以采集至少2×10⁶/kg的CD34⁺细胞。两组患者在年龄、性别、临床预后特征以及既往治疗方面具有可比性。在第一组中,每次单采的中位数产量为:单个核细胞(MNC)1.47(1.38 - 2.32)×10⁸/kg,粒 - 巨噬细胞集落形成单位(CFU - GM)0.82(0.18 - 13.2)×10⁴/kg,CD34⁺细胞1.98(0.96 - 6.96)×10⁶/kg。在第二组中,这些结果分别为:MNC 2.44(2.06 - 3.6×10⁸/kg)(P = 0.03),CFU - GM 0.75(0.16 - 7.8)×10⁴/kg,CD34⁺细胞1.05(0.32 - 3.4)×10⁶/kg(P = 0.02)。每组进行单采的中位数次数为5次(4 - 12次),第一组的中位数为5.24±2.51次,第二组为3次(2 - 6次),中位数为3.1(±0.91)次(P = 无显著差异)。第一组所有患者进行PBPC动员均需要住院,且该组与治疗相关的毒性更大:12例患者(66%)在HD - CY后的中性粒细胞减少期出现发热需要使用抗生素,6例(33%)患者需要输血支持。在接受口服12 mg/kg白消安和静脉注射140 mg/m²美法仑作为预处理方案后,第一组(HD - CY加GM - CSF组)达到粒细胞植入(>0.5×10⁹/L)和血小板植入(>20×10⁹/L)的中位时间分别为12天和11天(范围8 - 20天和10 - 16天),第二组(G - CSF组)分别为11天和13天(范围7 - 42天和10 - 38天)(P = 无显著差异)。总之,这些数据表明,虽然基于每次单采的平均CD34⁺细胞产量,HD - CY加GM - CSF优于单独使用G - CSF,但在大多数MM患者中,单独使用G - CSF可以在毒性较小且操作简化的情况下获得足够的CD34⁺细胞采集量。

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