Meloni G, Diverio D, Vignetti M, Avvisati G, Capria S, Petti M C, Mandelli F, Lo Coco F
Dipartimento di Biotecnologie Cellulari ed Ematologia, University La Sapienza of Rome, Italy.
Blood. 1997 Aug 1;90(3):1321-5.
Reverse-transcription polymerase chain reaction (RT-PCR) of the PML/RAR alpha fusion gene may predict relapse in acute promyelocytic leukemia (APL) patients in hematologic complete remission (CR). We have prospectively studied by RT-PCR 15 PML/RAR alpha+ APL patients undergoing autologous bone marrow transplantation (ABMT) in second CR. The median time of first CR duration was 12 months (range, 6 to 40). All patients were reinduced with all-trans retinoic acid (ATRA), followed in 12 of 15 cases by mitoxantrone and Ara-C as consolidation. Fourteen patients received the BAVC (BCNU, Ara-C, m-AMSA, and VP-16) schedule as conditioning regimen. Unpurged marrows were collected immediately before conditioning treatment, analyzed by RT-PCR, and reinfused at median of 2 months (range, 2 to 7) from the achievement of second CR. Seven patients were PCR+ and eight PCR for PML/RAR alpha in their pretransplant marrows. All seven patients of the former group remained PCR+ during the follow-up and relapsed at a median time of 5 months (range, 2 to 9) from ABMT and 9 months (range, 4 to 14) from second CR. Of the eight PCR- patients, all remained PCR- during the follow-up controls. One patient relapsed at 10 months from ABMT, one died of a secondary (PML/RAR alpha-) leukemia, and six are in hematologic and molecular remission at a median time of 28 months (range, 15 to 60) after ABMT and 32 months (range, 17 to 62) from second CR. Our results indicate that, in APL patients in second CR, ABMT with PML/RAR alpha- marrow cells is likely to result in prolonged clinical and molecular remissions. Conversely, patients who test PCR+ after reinduction necessitate the use of alternative aggressive approaches, including unrelated allogeneic transplant.
急性早幼粒细胞白血病（APL）患者处于血液学完全缓解（CR）时，PML/RARα融合基因的逆转录聚合酶链反应（RT-PCR）可能预测复发情况。我们对15例处于第二次完全缓解期且接受自体骨髓移植（ABMT）的PML/RARα阳性APL患者进行了前瞻性RT-PCR研究。首次CR持续时间的中位数为12个月（范围6至40个月）。所有患者均先用全反式维甲酸（ATRA）进行再诱导，15例中有12例随后使用米托蒽醌和阿糖胞苷进行巩固治疗。14例患者接受BAVC（卡莫司汀、阿糖胞苷、胺苯吖啶和依托泊苷）方案作为预处理方案。在预处理治疗前立即采集未净化的骨髓，通过RT-PCR进行分析，并在达到第二次CR后的中位数2个月（范围2至7个月）进行回输。7例患者移植前骨髓的PML/RARα为PCR阳性，8例为PCR阴性。前一组中的所有7例患者在随访期间仍为PCR阳性，自ABMT起的中位数复发时间为5个月（范围2至9个月），自第二次CR起为9个月（范围4至14个月）。在8例PCR阴性患者中，所有患者在随访对照期间仍为PCR阴性。1例患者在ABMT后10个月复发，1例死于继发性（PML/RARα阴性）白血病，6例在ABMT后的中位数28个月（范围15至60个月）和第二次CR后的32个月（范围17至62个月）处于血液学和分子学缓解状态。我们的结果表明，对于处于第二次CR的APL患者，移植PML/RARα阴性的骨髓细胞进行ABMT可能会带来更长时间的临床和分子学缓解。相反，再诱导后PCR检测呈阳性的患者需要采用其他积极的治疗方法，包括无关供体的异基因移植。
