Belani Rajesh, Saven Alan
Division of Hematology/Oncology, M/S 217, Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA.
Hematol Oncol Clin North Am. 2006 Oct;20(5):1109-23. doi: 10.1016/j.hoc.2006.06.008.
Cladribine results in prolonged complete remissions in most patients wo have HCL. Several studies have indicated that patients who are in complete remission have survivals that are comparable to those of normal age-matched controls. HCL-related mortality is distinctly uncommon. Nevertheless, it is unlikely that cladribine treatment of HCL is curative because MRD is common in the bone marrows of complete responders. Response criteria for HCL include clinical, hematologic, and morphologic criteria, but do not include flow cytometry, immunohistochemical analysis, or molecular studies. More sensitive techniques have been used by Filleul and colleagues to detect MRD. The used clonoegenic probes from the hypervariable regions of the immunoglobulin heavy-chain gene and performed polymerase chain reactions (PCRs) on bone marrow biopsy specimens, All seven patients who were in morphologic complete remission after a single cladribine infusion were PCR positive. These data indicate that cladribine induces protracted remissions but is not necessarily curative. MRD can be detected in most patients when sensitive techniques are used. Persistence of immunohistochemical MRD may predict detected MRD remains to be studied in a large number of patients. Investigators from the University of Pisa in Italy have used a combination of cladribine and rituximab to eradicate MRD in patients who have HCL. Ten patients received treatment with a standard infusion of cladribine. Two patients achieved a complete remission, 6 patients achieved a partial remission, and 2 patients failed to respond. All were PCR positive for the immunoglobulin heavy-chain (IgH) gene product at the completion of cladribine treatment. All 10 patients had achieved a complete hematologic response 2 months after the completion of ritximab therapy. The curative nature of this treatment will require long-term follow-up. Cladribine represents a major therapeutic advance in the treatment of HCL. The prognosis of patients who have HCL has improved greatly with cladribine therapy. Future strategies should address combination therapy with purine analogs and monclonal antibodies. These strategies should address eradication of MRD in an attempt to develop a potentially curative combination treatment program.
克拉屈滨可使大多数毛细胞白血病(HCL)患者获得长期完全缓解。多项研究表明,处于完全缓解状态的患者生存率与年龄匹配的正常对照相当。HCL相关死亡率明显罕见。然而,克拉屈滨治疗HCL不太可能治愈,因为微小残留病(MRD)在完全缓解者的骨髓中很常见。HCL的缓解标准包括临床、血液学和形态学标准,但不包括流式细胞术、免疫组化分析或分子研究。Filleul及其同事使用了更敏感的技术来检测MRD。他们使用来自免疫球蛋白重链基因高变区的克隆ogenic探针,并对骨髓活检标本进行聚合酶链反应(PCR),单次输注克拉屈滨后形态学完全缓解的所有7例患者PCR均为阳性。这些数据表明,克拉屈滨可诱导持久缓解,但不一定能治愈。使用敏感技术时,大多数患者可检测到MRD。免疫组化MRD的持续存在是否可预测检测到的MRD仍有待在大量患者中进行研究。意大利比萨大学的研究人员使用克拉屈滨和利妥昔单抗联合治疗来根除HCL患者的MRD。10例患者接受标准剂量克拉屈滨输注治疗。2例患者实现完全缓解,6例患者部分缓解,2例患者无反应。克拉屈滨治疗结束时,所有患者免疫球蛋白重链(IgH)基因产物的PCR均为阳性。利妥昔单抗治疗结束2个月后,所有10例患者均实现了完全血液学缓解。这种治疗的治愈性质需要长期随访。克拉屈滨是HCL治疗的一项重大治疗进展。克拉屈滨治疗使HCL患者的预后有了很大改善。未来的策略应涉及嘌呤类似物和单克隆抗体的联合治疗。这些策略应致力于根除MRD,以试图制定一个潜在的治愈性联合治疗方案。