Chronic Lymphocytic Leukemia

Signs & symptoms

许多患者在诊断时没有任何症状, 除了白细胞计数升高. 有些病人会感到疲劳, 肿大由于脾脏肿大而引起的淋巴结肿大或腹部肿大.

When CLL becomes more advanced and begins to replace normal bone marrow, low blood counts can cause:

• 贫血，由于红细胞水平低
• 感染，由于白细胞水平低，称为中性粒细胞
• 血小板水平过低导致出血

CLL also increases a person's risk of infection because of low production of antibodies (gamma globulins) that help fight bacteria.

在5%到10%的病例中, CLL causes the destruction of the patient's own red blood cells and/or platelets through an "autoimmune" process. 血小板破坏被称为免疫性血小板减少性紫癜(ITP)。, 红细胞的破坏称为自身免疫性溶血性贫血(AHA).

Diagnosis

Chronic lymphocytic leukemia is diagnosed through the detection of a high white blood cell count composed primarily of small lymphocytes. 通过“免疫表型”(流式细胞术)确诊。, 是什么决定了白血病细胞上的蛋白质类型. CLL classically expresses CD19 (a B-lymphocyte protein) and CD 5 (a T-cell lymphocyte protein) simultaneously.

CLL是一种有正式分期系统的白血病:

• RAI阶段0到I. 在疾病的早期阶段, 淋巴细胞计数升高(0)，淋巴结肿大(1)。.
• 第II阶段. 在中间阶段，脾脏变大.
• RAI第三至第四阶段. 在疾病的晚期, bone marrow function is disturbed and there is a significant decrease in red blood cell (III) or platelet counts (IV).

RAI分期预测生存率:

• 阶段0或I. 10年以上
• 第II阶段. Six years
• raiii或IV. 一到两年

新的生物标记，包括染色体异常，也可以帮助预后. 染色体正常, 额外的12号染色体, or a missing part of chromosome 13 are favorable; a missing part of either chromosome 11 or 17 is unfavorable.

在5%到10%的病例中，CLL可以转变为侵袭性 lymphoma. 这被称为里希特氏综合征，需要淋巴瘤治疗.

Treatments

Most patients with early-stage chronic lymphocytic leukemia do not need any treatment when the disease is first diagnosed. These patients will live 10 to 15 years on average, and early treatment offers no advantage.

Treatment should start when the patient either has an advanced form of the disease or has an intermediate stage with significant symptoms, very enlarged lymph nodes or a rapid increase in the lymphocyte count (doubling in less than 12 months).

化疗

CLL最常见的治疗方法是化疗药物氟达拉滨. This is given intravenously (through an IV) five days a week once a month, for four to six months. 虽然氟达拉滨的时间表相当不方便, 它只会产生轻微的副作用, 比如疲劳. Most patients will have a good response to this treatment and remain in remission without further treatment for two to three years.

The remission rate and length of remission are increased by adding a monoclonal antibody, 利妥昔单抗(也用于治疗淋巴瘤)优于氟达拉滨. 最具侵略性的养生法, 氟达拉滨+环磷酰胺+美罗华(FCR), 具有最高的响应率(接近100%), 但代价是感染风险很高. 一种新的化疗药物, bendamustine, was recently approved for CLL; the patient receives two doses intravenously every month. 另一个代理, lenalidomide (Revlimid的), which is FDA-approved for the treatment of multiple myeloma and certain types of myelodysplastic syndrome, 在CLL中有活性并且是口服药物.

苯丁酸氮芥, 口服化疗药物, 可以代替氟达拉滨使用吗, 特别是对老年人或体弱病人.

干细胞移植

异体干细胞移植, also called bone and marrow transplantation (BMT), can be used to potentially cure CLL. However, 这种疗法仅用于治疗偶尔患有侵袭性CLL的年轻患者, since most patients with CLL live so long that the risk of transplant can seldom be justified.

临床实验的治疗

UCSF is dedicated to improving outcomes for CLL patients through the use of investigational therapies and clinical research trials. Clinical trials currently available to UCSF patients include Flavopiridol for CLL cases that don't respond to standard treatment. 黄匹吡醇能迅速杀死CLL，导致血盐和酸碱异常, 可能导致肾衰竭. The first cycle of Flavopiridol is given in the intensive care unit with kidney hemodialysis immediately available. 也有加入生物制剂的国家试验, 比如来那度胺, 标准接受的CLL疗法.

了解更多关于 临床试验及其工作原理.