Activity and safety of combination chemotherapy with methotrexate, ifosfamide, l‐asparaginase and dexamethasone (MILD) for refractory lymphoid malignancies: a pilot study
Activity and safety of combination chemotherapy with methotrexate, ifosfamide, l‐asparaginase and dexamethasone (MILD) for refractory lymphoid malignancies: a pilot study
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甲氨蝶呤、异环磷酰胺、L-天冬酰胺酶和地塞米松 (MILD) 联合化疗治疗难治性淋巴恶性肿瘤的活性和安全性：一项初步研究
DOI：
10.1111/j.1600-0609.2009.01395.x
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发表时间：
2010
影响因子：
3.1
通讯作者：
K. Sugimoto
中科院分区：
文献类型：
--
作者：
Yutaka Tsukune;Y. Isobe;H. Yasuda;S. Shimizu;Yuna Katsuoka;M. Hosone;K. Oshimi;N. Komatsu;K. Sugimoto
对于传统的环磷酰胺、阿霉素、长春新碱和泼尼松疗法难以治疗的淋巴恶性肿瘤，尚未建立最佳的挽救化疗。为了探索有效的治疗方案，我们进行了甲氨蝶呤、异环磷酰胺、L-天冬酰胺酶和地塞米松 (MILD) 联合化疗的 I 期试点研究，这些药物不受 MDR1 编码的 P-糖蛋白的影响。 2 年期间共有 18 名致命性淋巴恶性肿瘤患者入组。中位年龄为 63 岁。 11 名患者患有 T/NK 细胞恶性肿瘤，6 名患者患有 B 细胞恶性肿瘤，1 名患者被诊断患有母细胞性浆细胞样树突状细胞肿瘤。年龄≥60岁和<60岁的患者计划接受一组起始剂量的甲氨蝶呤和异环磷酰胺，这应该会引起骨髓抑制。 11 名患者完成了两个疗程的 MILD 治疗。在一名患者中观察到因系统性毛霉菌病而导致的治疗相关死亡。主要的治疗相关不良事件是3级或以上的血液学毒性，其中包括与剂量限制性毒性相对应的淋巴细胞减少。最常见的 3 级非血液学毒性是发热性中性粒细胞减少症。在接受评估的 14 名患者中，三名患者获得完全缓解，四名患者出现部分缓解。总体回应率为57%。非常有趣的是，七名应答者都患有 T/NK 细胞恶性肿瘤。 MILD 疗法对于难治性或致死性淋巴恶性肿瘤患者来说是可行的，并且具有可接受的毒性。应进一步评估 T/NK 细胞恶性肿瘤的疗效。
Optimal salvage chemotherapy has not been established for lymphoid malignancy, which is refractory to the conventional cyclophosphamide, doxorubicin, vincristine, and prednisone regimen. To explore an effective regimen, we conducted a phase I pilot study of combination chemotherapy with methotrexate, ifosfamide, l‐asparaginase and dexamethasone (MILD), which are unaffected by MDR1‐encoded P‐glycoprotein. A total of 18 patients with lethal lymphoid malignancy were enrolled over a 2‐yr period. The median age was 63 yr. Eleven patients had T/NK‐cell malignancies, six had B‐cell malignancies, and one was diagnosed with a blastic plasmacytoid dendritic cell neoplasm. Patients aged ≥60 and <60 yr were planned to receive a set of starting doses of methotrexate and ifosfamide, which should induce myelosuppression. Eleven patients completed two courses of MILD therapy. Treatment‐related death because of systemic mucormycosis was observed in one patient. Major treatment‐related adverse events were grade 3 or more hematologic toxicities, which included lymphopenia corresponding to dose‐limiting toxicity. The most common grade 3 non‐hematologic toxicity was febrile neutropenia. Of the 14 evaluated patients, three achieved a complete response, and four showed a partial response. The overall response rate was 57%. It was very interesting that all of seven responders had T/NK‐cell malignancies. MILD therapy was feasible and presented acceptable toxicity in patients with refractory or lethal lymphoid malignancies. The efficacy for T/NK‐cell malignancies should be further evaluated.