Wassmann Barbara, Pfeifer Heike, Goekbuget Nicola, Beelen Dietrich W, Beck Joachim, Stelljes Matthias, Bornhäuser Martin, Reichle Albrecht, Perz Jolanta, Haas Rainer, Ganser Arnold, Schmid Mathias, Kanz Lothar, Lenz Georg, Kaufmann Martin, Binckebanck Anja, Brück Patrick, Reutzel Regina, Gschaidmeier Harald, Schwartz Stefan, Hoelzer Dieter, Ottmann Oliver G
Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
Blood. 2006 Sep 1;108(5):1469-77. doi: 10.1182/blood-2005-11-4386. Epub 2006 Apr 25.
The best strategy for incorporating imatinib in front-line treatment of Ph+ acute lymphoblastic leukemia (ALL) has not been established. We enrolled 92 patients with newly diagnosed Ph+ ALL in a prospective, multicenter study to investigate sequentially 2 treatment schedules with imatinib administered concurrent to or alternating with a uniform induction and consolidation regimen. Coadministration of imatinib and induction cycle 2 (INDII) resulted in a complete remission (CR) rate of 95% and polymerase chain reaction (PCR) negativity for BCR-ABL in 52% of patients, compared with 19% in patients in the alternating treatment cohort (P = .01). Remarkably, patients with and without a CR after induction cycle 1 (INDI) had similar hematologic and molecular responses after concurrent imatinib and INDII. In the concurrent cohort, grades III and IV cytopenias and transient hepatotoxicity necessitated interruption of induction in 87% and 53% of patients, respectively; however, duration of induction was not prolonged when compared with patients receiving chemotherapy alone. No imatinib-related severe hematologic or nonhematologic toxicities were noted with the alternating schedule. In each cohort, 77% of patients underwent allogeneic stem cell transplantation (SCT) in first CR (CR1). Both schedules of imatinib have acceptable toxicity and facilitate SCT in CR1 in the majority of patients, but concurrent administration of imatinib and chemotherapy has greater antileukemic efficacy.
在费城染色体阳性（Ph+）急性淋巴细胞白血病（ALL）的一线治疗中，纳入伊马替尼的最佳策略尚未确立。我们开展了一项前瞻性、多中心研究，纳入92例新诊断的Ph+ ALL患者，以序贯研究伊马替尼的两种治疗方案，即伊马替尼与统一的诱导和巩固方案同时给药或交替给药。伊马替尼与诱导周期2（INDII）同时给药的完全缓解（CR）率为95%，52%的患者BCR-ABL聚合酶链反应（PCR）呈阴性，而交替治疗组患者的这一比例为19%（P = 0.01）。值得注意的是，诱导周期1（INDI）后达到CR和未达到CR的患者在伊马替尼与INDII同时给药后，血液学和分子反应相似。在同时给药组中，分别有87%和53%的患者因III级和IV级血细胞减少以及短暂性肝毒性而需要中断诱导治疗；然而，与单纯接受化疗的患者相比，诱导治疗时间并未延长。交替给药方案未观察到与伊马替尼相关的严重血液学或非血液学毒性。在每个队列中，77%的患者在首次完全缓解（CR1）时接受了异基因干细胞移植（SCT）。伊马替尼的两种给药方案毒性均可接受，且大多数患者在CR1时便于进行SCT，但伊马替尼与化疗同时给药具有更强的抗白血病疗效。
