Palandri Francesca, Castagnetti Fausto, Testoni Nicoletta, Luatti Simona, Marzocchi Giulia, Bassi Simona, Breccia Massimo, Alimena Giuliana, Pungolino Ester, Rege-Cambrin Giovanna, Varaldo Riccardo, Miglino Maurizio, Specchia Giorgina, Zuffa Eliana, Ferrara Felicetto, Bocchia Monica, Saglio Giuseppe, Pane Fabrizio, Alberti Daniele, Martinelli Giovanni, Baccarani Michele, Rosti Gianantonio
Institute of Hematology and Medical Oncology L. and A. Seràgnoli, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Haematologica. 2008 Dec;93(12):1792-6. doi: 10.3324/haematol.13068. Epub 2008 Oct 6.
Imatinib mesylate is the first line treatment for chronic myeloid leukemia. In patients with advanced phase of the disease, the advent of imatinib significantly increased survival. However, few long-term data, based on large, prospective and controlled trials are available on the outcome of these patients.
We conducted a phase II trial of imatinib 600 mg daily in patients with chronic myeloid leukemia in blast crisis. The return to chronic phase was defined as <15% blasts and <30% blasts plus promyelocytes in blood or bone marrow and <20% peripheral basophils. A complete hematologic response required the normalization of platelet and white cell differential counts and absence of extramedullary involvement. Cytogenetic response was assessed by the standard banding technique and rated as usual.
Ninety-two patients were enrolled (20 with lymphoid blast crisis and 72 with myeloid blast crisis). Forty-six patients (50%) returned to chronic phase, and 24 patients (26%) achieved also a complete hematologic response. Sixteen patients (17%) had a cytogenetic response (9 complete, 1 partial, and 6 minor or minimal). The complete cytogenetic response was subsequently lost by all but two patients between 2 and 12 months after first having achieved it: the median duration of complete cytogenetic response was 7 months. All responses were sustained for a minimum of 4 weeks. The median survival of all the patients was 7 months. After a median observation time of 66 months, seven (8%) patients are alive. Three of these patients are on imatinib treatment (1 in complete hematologic remission, 1 in partial cytogenetic response and 1 in complete cytogenetic remission). Three patients are in complete remission after allogeneic stem cell transplantation. One patient is alive in blast crisis, on therapy with a second-generation tyrosine kinase inhibitor.
Imatinib was effective and safe in the short-term treatment of chronic myeloid leukemia in blast crisis, but longer-term outcome was not significantly influenced (ClinicalTrials.gov identifier: NCT00514969).
甲磺酸伊马替尼是慢性髓性白血病的一线治疗药物。在疾病晚期患者中，伊马替尼的出现显著提高了生存率。然而，基于大型前瞻性对照试验的长期数据很少，无法了解这些患者的预后情况。
我们对慢性髓性白血病急变期患者进行了一项每日服用600毫克伊马替尼的II期试验。慢性期的恢复定义为血液或骨髓中原始细胞<15%，原始细胞加早幼粒细胞<30%，外周血嗜碱性粒细胞<20%。完全血液学缓解要求血小板和白细胞分类计数正常且无髓外浸润。细胞遗传学反应通过标准显带技术进行评估并按常规分级。
92例患者入组（20例为淋巴细胞急变期，72例为髓细胞急变期）。46例患者（50%）恢复到慢性期，24例患者（26%）也实现了完全血液学缓解。16例患者（17%）有细胞遗传学反应（9例完全缓解，1例部分缓解，6例微小或极小缓解）。除2例患者外，所有患者在首次达到完全细胞遗传学缓解后的2至12个月内，完全细胞遗传学反应随后均丧失：完全细胞遗传学缓解的中位持续时间为7个月。所有反应至少持续4周。所有患者的中位生存期为7个月。经过66个月的中位观察期后，7例（8%）患者存活。其中3例患者接受伊马替尼治疗（1例处于完全血液学缓解，1例处于部分细胞遗传学反应，1例处于完全细胞遗传学缓解）。3例患者在异基因干细胞移植后完全缓解。1例患者在急变期存活，接受第二代酪氨酸激酶抑制剂治疗。
伊马替尼在慢性髓性白血病急变期的短期治疗中有效且安全，但对长期预后无显著影响（ClinicalTrials.gov标识符：NCT00514969）。
