Balduzzi A, Perseghin P, Dassi M, Bonanomi S, Rovelli A, Gaipa G, Biondi A, Uderzo C
Clinica Pediatrica, Università degli Studi di Milano Bicocca, Monza, Italy.
Bone Marrow Transplant. 2002 Oct;30(7):413-6. doi: 10.1038/sj.bmt.1703685.
Few experiences of peripheral blood (PB) hematopoietic stem cell mobilization for autologous transplantation have been reported to date in children with acute leukemia (AL). The five-drug-chemotherapy 'DIAVE' (dexamethazone, idarubicine, cytosine-arabinoside, vincristine, etoposide), followed by G-CSF, previously reported as consolidation, was adopted as a mobilization regimen in 29 children (median age: 8 years, range: 3-21; median weight: 34 kg, range: 15-73) with ALL in second remission (CR2: 21), in CR3 (2) or ANLL in CR1 (6). A median peak of 94 x 10(6) CD34(+)cells/l (range: 10-604) was reached at a median time of 12 days (range: 10-18) after the beginning of the mobilizing regimen, which was well tolerated. A median of 10.9 x 10(6) CD34(+)cells/kg (range: 2.4-56.6) were collected in 25 patients (86%), approaching 40 x 10(6)/l CD34(+) cells in the PB (ALL in CR2: 20/21, in CR3: 0/2; ANLL: 5/6) by means of one (20) or two (5) leukaphereses; a median of 2.5 blood volumes was processed. Patients with ANLL mobilized more cells than patients with ALL; moreover, the shorter the interval between remission and mobilizing therapy, the higher was the yield. The products collected underwent purification, aiming at achieving complete removal of possibly contaminating leukemic cells, in 21 cases; also, unmanipulated aliquots were stored as rescues for all but one patient. All the 23 patients undergoing transplantation engrafted (ANC >0.5 x 10(9)/l) at a median of 12 days. In conclusion, the DIAVE regimen compares favorably with conventional mobilizing regimens, usually containing cyclophosphamide, in terms of low toxicity, collection time predictability, and efficacy, as shown by the high proportion of patients mobilizing, the large amounts of stem cell collected by means of one or two leukaphereses only, and the prompt engraftment after infusion.
迄今为止，关于急性白血病（AL）患儿外周血（PB）造血干细胞动员用于自体移植的经验报道较少。29例儿童（中位年龄：8岁，范围：3 - 21岁；中位体重：34kg，范围：15 - 73kg）采用了五药联合化疗方案“DIAVE”（地塞米松、伊达比星、阿糖胞苷、长春新碱、依托泊苷），随后使用G - CSF，该方案之前报道用于巩固治疗，此次作为动员方案用于处于第二次缓解期（CR2：21例）、第三次缓解期（2例）或首次缓解期的急性非淋巴细胞白血病（ANLL，6例）的急性淋巴细胞白血病（ALL）患儿。动员方案开始后中位12天（范围：10 - 18天）达到中位峰值94×10⁶个CD34⁺细胞/升（范围：10 - 604），耐受性良好。25例患者（86%）采集到的CD34⁺细胞中位值为10.9×10⁶个/kg（范围：2.4 - 56.6），通过一次（20例）或两次（5例）白细胞分离术，外周血中CD34⁺细胞接近40×10⁶/升（处于第二次缓解期的ALL：20/21例，第三次缓解期的ALL：0/2例；ANLL：5/6例）；处理的血容量中位值为2.5倍。ANLL患者动员的细胞比ALL患者多；此外，缓解期与动员治疗之间的间隔越短，产量越高。采集的产物中有21例进行了纯化，旨在完全去除可能污染的白血病细胞；另外，除1例患者外，未处理的等分样本均作为备用保存。所有23例接受移植的患者均在中位12天实现植入（中性粒细胞绝对值>0.5×10⁹/升）。总之，“DIAVE”方案在毒性低、采集时间可预测性和疗效方面优于通常含有环磷酰胺的传统动员方案，这体现在动员患者的比例高、仅通过一次或两次白细胞分离术就能采集到大量干细胞以及输注后迅速植入等方面。
