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慢性髓性白血病淋巴细胞性母细胞危象患者接受化疗、达沙替尼和干扰素α治疗后达到深度分子缓解。

Deep Molecular Response Achieved with Chemotherapy, Dasatinib and Interferon α in Patients with Lymphoid Blast Crisis of Chronic Myeloid Leukaemia.

机构信息

Department of Haemato-Oncology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacký University, 779 00 Olomouc, Czech Republic.

Department of Biology, Faculty of Medicine and Dentistry, Palacký University, 779 00 Olomouc, Czech Republic.

出版信息

Int J Mol Sci. 2023 Jan 20;24(3):2050. doi: 10.3390/ijms24032050.

Abstract

The treatment outcome in patients with chronic myeloid leukaemia (CML) in blast crisis (BC) is unsatisfactory despite the use of allogeneic stem cell transplantation (ASCT). Moreover, in some patients ASCT is contraindicated, with limited treatment options. We report the case series of two patients with lymphoid BC CML in whom ASCT was not approachable. The first patient developed BC two months after diagnosis in association with dic(7;9)(p11.2;p11.2) and T315I mutation. Blast crisis with central nervous system leukemic involvement and K611N mutation of the SETD2 gene developed abruptly in the second patient five years after ceasing treatment with nilotinib in major molecular response (MMR) at the patient's request. Both underwent one course of chemotherapy in combination with rituximab and imatinib, followed by dasatinib and interferon α (INFα) treatment in the first and dasatinib alone in the second case. Deep molecular response (DMR; MR 4.0) was achieved within a short time in both cases. It is probable that DMR was caused by a specific immune response to CML cells, described in both agents. The challenging medical condition that prompted these case series, and the subsequent results, suggest a re-visit to the use of a combination of well-known drugs as an area for further investigation.

摘要

尽管采用了异基因造血干细胞移植(allo-SCT),但慢性髓系白血病(CML)急变期(BC)患者的治疗结局仍不理想。此外,在一些患者中 allo-SCT 存在禁忌证,治疗选择有限。我们报告了两例 CML 淋巴母细胞性 BC 患者的病例系列,他们无法进行 allo-SCT。第一例患者在诊断后两个月出现与 dic(7;9)(p11.2;p11.2)和 T315I 突变相关的 BC。第二位患者在停止达沙替尼治疗五年后,因患者要求以主要分子学缓解(MMR)停止治疗,突然出现伴有中枢神经系统白血病累及和 SETD2 基因 K611N 突变的 BC。两位患者均接受了一个疗程的联合化疗,联合利妥昔单抗和伊马替尼治疗,随后在第一例患者中接受达沙替尼和干扰素 α(INFα)治疗,在第二例患者中仅接受达沙替尼治疗。在短时间内,两例患者均达到深度分子缓解(DMR;MR4.0)。很可能是由于这两种药物都能引起针对 CML 细胞的特异性免疫反应,从而导致 DMR。促使进行这些病例系列研究的具有挑战性的医疗状况以及随后的结果表明,需要重新考虑联合使用这些知名药物作为进一步研究的领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56b0/9916434/7415e0df3d8d/ijms-24-02050-g001.jpg

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