Department of Hematology of the Hospitals Institut Català d'Oncologia-Hospital Germans Trias i Pujol, Badalona, Spain.
Haematologica. 2010 Jan;95(1):87-95. doi: 10.3324/haematol.2009.011221. Epub 2009 Oct 1.
Imatinib, given concurrently or alternating with chemotherapy, has improved the response and survival of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) but relapses are still frequent. The aim of this study was to evaluate the feasibility and results of giving imatinib concurrently with intensive chemotherapy, stem cell transplantation and post-transplant imatinib maintenance therapy in patients with newly diagnosed Ph(+) ALL.
This was a phase II study of patients with newly diagnosed Ph(+) ALL given standard chemotherapy, together with imatinib (400 mg/day) until stem cell transplantation, followed by imatinib maintenance therapy for all patients regardless of the molecular status of the disease.
Of the 30 patients included, 27 (90%) achieved complete remission, one was resistant to treatment and two died during induction therapy. The percentages of major and complete molecular responses were 86% and 21% after induction, and 81% and 65% after consolidation, respectively. Similar results were observed assessing minimal residual disease by flow cytometry. Of the 27 patients who achieved complete remission, 21 underwent stem cell transplantation (16 allogeneic, 5 autologous). Imatinib (400 mg/day) could be administered after transplantation for a median of 3.9 months in 12 patients, although it was interrupted in 10 patients (in 2 cases because of side effects of the drug). Nine patients relapsed, four before and five after stem cell transplantation and eight patients died of transplant-related causes. With a median follow-up of 4.1 years, the probabilities (95% CI) of disease-free and overall survival were 30% (15% to 45%) and 30% (16% to 45%), respectively.
These results confirm that imatinib is an effective first-line treatment for adult Ph(+) ALL when given concurrently with chemotherapy, making stem cell transplantation feasible in a high proportion of patients. However, post-transplantation imatinib administration was limited, mainly because of transplantation-derived complications rather than drug-specific toxicity.
伊马替尼与化疗同时或交替使用可提高费城染色体阳性急性淋巴细胞白血病（Ph(+) ALL）患者的反应和生存，但复发仍很常见。本研究旨在评估伊马替尼与强化化疗、干细胞移植和移植后伊马替尼维持治疗联合用于新诊断的 Ph(+) ALL 患者的可行性和结果。
这是一项新诊断的 Ph(+) ALL 患者接受标准化疗联合伊马替尼（400 mg/天）治疗直至干细胞移植的 II 期研究，然后所有患者无论疾病分子状态如何均接受伊马替尼维持治疗。
30 例患者中，27 例（90%）达到完全缓解，1 例对治疗耐药，2 例在诱导治疗期间死亡。诱导后主要和完全分子反应率分别为 86%和 21%，巩固后分别为 81%和 65%。通过流式细胞术评估微小残留病也观察到类似的结果。27 例完全缓解的患者中，21 例行干细胞移植（16 例异基因，5 例自体）。12 例患者可在移植后中位 3.9 个月时给予伊马替尼（400 mg/天），但 10 例患者中断（2 例因药物副作用）。9 例患者复发，4 例在移植前，5 例在移植后，8 例患者因移植相关原因死亡。中位随访 4.1 年后，无病生存和总生存的概率（95%CI）分别为 30%（15%至 45%）和 30%（16%至 45%）。
这些结果证实，伊马替尼与化疗同时使用是成人 Ph(+) ALL 的有效一线治疗方法，可使大多数患者可行干细胞移植。然而，移植后伊马替尼给药受到限制，主要是由于移植相关并发症而不是药物特异性毒性。
