Let’s Talk About Chronic Myeloid Leukemia

无论您是否只是been diagnosed with or worry you could have chronic myeloid leukemia, you’re probably nervous, confused, and maybe a little scared. That’s normal, and everyone featured on HealthCentral with a chronic illness felt like you do now. But we—and they—are here for you. Read on to learn about the realities and challenges you’ll face with this condition, as well as the best treatments, helpful lifestyle changes, and all the crucial information to help you not just manage chronic myeloid leukemia—but thrive with it. We’re sure you’ve got a lot of questions … and we’ve got the answers you need.

慢性髓细胞性白血病

我们的专业小组

我们去了美国CML的一些顶级专家，为您带来最新的信息。

Jun H. Choi, M.D.

Hematologist-Oncologist

NYU Langone Perlmutter癌症中心

New York City

格温·尼科尔斯（Gwen Nichols），医学博士

首席医疗官

白血病和淋巴瘤协会

Rye Brook, NY

Jay Yang, M.D.

Hematologist-Oncologist

韦恩州立大学Karmanos癌症研究所

Detroit, MI

白血病有很多类型。我们在这里谈论的那个被称为慢性髓细胞性白血病，也称为慢性粒细胞性白血病或CML，仅20年前的预后较差。今天，如果您的医疗保健提供者说明白血病一词，您想它是CML。发生了什么变化？大约20年前出生的一种奇迹药物将这种致命疾病变成了您可以生活，笑和爱的慢性病。当然，拥有一种癌症的形式总是会令人恐惧，但是您了解CML的越多，您就会对自己或亲人的未来感到越来越欣慰。

But let’s back up for a minute. What isleukemia本身？白血病始于骨髓细胞，涉及您的有效感染的白细胞。当它们正常运作时，白细胞会在您的身体需要时生长和分裂。然而，当某人发展白血病时，骨髓过多产生异常的白细胞，这些血细胞无法按照应有的方式发挥作用。

根据白血病和淋巴瘤协会的数据，估计有61,000人在2021年被诊断出患有白血病，并且有近40万人与白血病生活或缓解。慢性髓样白血病是该疾病的四种主要类型之一，被归类为“急性”（迅速发展）或“慢性”（缓慢生长）。急性形式的白血病会产生无法执行正常功能的不成熟细胞，而患有慢性白血病类型的患者通常具有更多的成熟细胞，至少可以进行一些工作。受影响的白细胞类型（称为淋巴细胞或髓样细胞）也决定了一个人的白血病类型。这是四个主要的：

• 急性淋巴细胞性白血病（全部）：这种类型的白血病在成年人中很少见。它每年影响大约3,000人。但是，在儿童中，一切都更加普遍：它占美国儿童中四分之三的白血病病例。

• Acute Myeloid Leukemia (AML):This form of leukemia develops quickly, as the name implies. It occurs in both children and adults. In adults, AML is the most common acute form of leukemia. It’s diagnosed in about 20,000 people in the U.S. annually.

• 慢性淋巴细胞性白血病（CLL）：这种白血病是影响成年人的慢性白血病的最常见形式。根据最近的统计数据Cll每年在美国大约有20,000人被诊断出。

• 慢性髓细胞性白血病(CML):And here we are back to the core topic at hand. CML is very rarely diagnosed in children and occurs most often in older adults but is still quite uncommon. It’s only diagnosed in about 6,000 people in the U.S. each year.

我们不知道确切为什么some people develop CML, but we do knowhow它发生了。当发育中的骨髓干细胞的DNA（遗传材料）被损坏时，它就开始了，称为获得的突变。骨髓干细胞的工作是形成我们的血细胞（红色，白色和血小板）。然而，该受损细胞开始迅速繁殖，新的突变细胞生长和生存比正常细胞更好，从而挤出了健康的细胞。但这不是全部。当某人患有慢性髓样白血病时，会发生另一个重要的变化：形成了全新的染色体。

If your high school biology is a little fuzzy, let’s get you up to speed. Chromosomes are tightly-wound, thread-like structures consisting of protein and DNA found in a cell’s nucleus that contain the specific instructions to make each of us unique. Normally, humans have 23 pairs of chromosomes that are passed from parents to children. In order for us to grow and function properly, our cells must constantly divide to produce new ones that replace the older worn out cells. Chromosomes play a key role in ensuring that our DNA is accurately copied and distributed evenly during this cell division process. Changes in the number or structure of chromosomes can cause serious problems. One of the better known examples of this is Down Syndrome, when a child is born with three copies of chromosome 21 instead of the normal two (one from each parent).

When someone develops CML, an error called a “translocation” occurs, in which a piece of one chromosome breaks off and attaches to another chromosome, creating an abnormal “fusion gene.” All cases of CML are caused by the BCR-ABL1 fusion gene, which is not found in normal blood cells. It’s formed by a translocation between parts of chromosomes 9 and 22. As a result of the translocation, chromosome 9 is longer than normal and chromosome 22 is shorter than normal. The abnormal chromosome 22 is known the Philadelphia chromosome, so named because it was discovered in Philly. More than 95% of chronic myeloid leukemia patients have the Philadelphia chromosome and are referred to as “Ph positive” (Ph+). A small number of patients will have the BCR-ABL1 fusion gene, but will be Ph negative (Ph-).

谁最有可能发展这个流氓基因和染色体？有关此的信息令人惊讶地稀薄。尽管对导致CML的原因有相当有力的了解，但科学家仍在努力理解什么使某些人比其他人更有可能体验这种染色体突变。一些已知的风险因素包括：

年龄

No one is born with chronic myeloid leukemia. It occurs when there is an injury to the DNA of a single bone marrow cell, and the older you are the greater your chance of developing it. The average age of diagnosis is 64, but for reasons that aren’t yet clear, it is being seen more often in younger adults as well.

性别

尽管男人和女人都可以发展CML，但男性中的慢性髓细胞性白血病比男性更为普遍。研究人员尚不确定为什么是这种情况。

Radiation Exposure

在少数病例中，慢性髓样白血病可能是由于暴露于高剂量的辐射（例如核反应堆事故）或已用于治疗其他形式癌症的辐射疗法引起的。尽管如此，大多数患有CML的人尚未暴露于高剂量的辐射，并且大多数接受放射治疗的人都不会患上慢性骨髓性白血病。

Just as there are few known risk factors for CML, there are few symptoms for this disease in the early stages. Many patients are diagnosed when they’ve gone to the doctor for a routine physical or some other ailment, and blood work reveals:

• an increased, often very high, white blood cell count

• 红细胞计数减少

• an increase or decrease in the number of platelets, depending on how severe the CML has become

In chronic forms of leukemia, there are still some healthy mature cells able to do their job, which is why it can take longer for symptoms to develop—even if someone isn’t feeling 100%, they very often feel well enough to not warrant a doctor’s visit. Still, left untreated, chronic myeloid leukemia will eventually crowd out healthy blood cells, causing these symptoms:

• Weakness, fatigue, and shortness of breath during basic activities due to anemia (a lack of red blood cells)

• Pain or a feeling of fullness below the ribs on the left due to an enlarged spleen (CML cells often set up house in the spleen)

• Fever

• 骨痛

• Unexplained weight loss

• 夜汗

That’s a tricky question—why would you go to the doctor if you don’t know you have a health issue? Like all cancers, you want to catch it early, and the best way to ensure that happens is to have a physical and a complete blood count annually. And if you do develop any of the above symptoms, see your primary care physician as soon as you can. If he or she suspects CML (or any form of leukemia), you’ll need to see a medical specialist who treats cancers of the blood known as a hematologist-oncologist for full diagnosis and treatment.

无论出于何种原因，您都会带您去医生，这些都是在CML诊断过程中期望的测试。习惯他们 - 许多人也将用于跟踪您对治疗的反应。

Complete Blood Count (CBC) With Differential

This routine blood test to measure the number of red blood cells, white blood cells, and platelets is usually the first clue that something is amiss. It also reveals how much hemoglobin—a protein that carries oxygen—is in your red blood cells, as well as the percentage of red blood cells in the sample. “With differential” means that the types of white blood cells in the sample are also measured—that’s important because there are different types of white blood cells and CML affects some more than others. Red flags your healthcare provider will be on the lookout for include an increased, often very high, white blood cell count; a decreased red blood cell count; and a platelet count that’s high or low, depending on the severity of your illness.

外周血涂片

在此测试中，您的血细胞被染色，然后在显微镜下检查以确定数量，大小，形状和类型。白细胞的特定模式；与成熟的健康细胞的比例相比，爆炸细胞的比例（未成熟）。健康的人通常没有血液中的任何爆炸细胞。

Bone Marrow Aspiration and Biopsy

这两个测试通常同时进行，以寻找骨髓细胞中的异常。首先，您将获得药物来使皮肤麻木，然后，在骨髓抽吸期间，使用空心针头去除液体样品。然后使用较宽的针头去除一小块骨头，该骨头含有骨髓进行活检。使用显微镜，然后检查两个样品。

Cytogenetic Analysis

This is the process of analyzing bone marrow cells under a microscope for chromosomal abnormalities, including the telltale Philadelphia chromosome present in 95% of people with chronic myeloid leukemia. The term “cytogenetics” refers to the study of chromosomes.

Fluorescence In Situ Hybridization (FISH)

FISH is a more sensitive laboratory test than the standard cytogenetic tests for the Philadelphia chromosome and the BCR-ABL1 gene. Color probes that bind to DNA are used to locate the gene and the pieces of chromosomes 9 and 22 that were relocated.

Quantitative Polymerase Chain Reaction (qPCR)

这是用于检测和测量血液和骨髓样品中BCR-ABL1基因的最敏感测试。它能够在100,000至100万个正常细胞中检测到一个慢性髓样白血病细胞，即使找不到费城染色体。

诊断后，癌症通常根据肿瘤的大小以及癌症是否扩散到淋巴结和人体其他部位。您的医疗保健提供者将根据您的舞台确定治疗计划。然而，使用CML，没有肿瘤可以测量，恶性细胞已经通过血液流过体体。取而代之的是，基于您的血液和骨髓中您有多少未成熟的白细胞（称为“爆炸”），CML分为严重的三个阶段。

The Chronic Phase

This is when most people are diagnosed and the least serious. However, left untreated, chronic myeloid leukemia will eventually progress to the two more advanced phases. People in the chronic phase:

• Have an increased number of white blood cells.

• May not have any symptoms yet, although some do.

• Usually respond well to treatment, meaning that symptoms go away, an enlarged spleen is reduced in size, and white blood cell counts return to normal

The Accelerated Phase

当患者达到这一阶段时，未成熟的爆炸细胞的数量已经增加，并且正在迅速增长。处于加速阶段的人可能有：

• Additional chromosome abnormalities in the CML cells.

• 脾脏大小增加。

• 低血小板计数与治疗无关。

• More then 15%, but less than 30%, blasts in the blood and bone marrow.

• 在血液中，超过20％的白细胞被称为嗜碱性粒细胞（通常占嗜碱性粒细胞不到循环白细胞的1％）。

• Worsening anemia due to low levels of red blood cells.

The Blast Phase

This most serious phase is very similar to the acute form of myeloid leukemia (AML) and has the following characteristics:

• Abdominal pain

• 贫血

• A platelet count that’s very high or very low

• A very high white blood cell count

• Blast cells have topped 30% in the blood and bone marrow and have spread to other tissues and organs

• 流血的

• 骨痛

• 具有新染色体异常的CML细胞

• 脾脏扩大

• Fatigue

• Fever

• Infections

• Poor appetite and weight loss

• Shortness of breath

除了钉住您所处的阶段外，您的血液学家 - 综合医生还将使用其他一些因素来确定您的预后（可能的病程）和治疗。诊断时的这些“预后因素”与不利的结果相关：

• A high number of blasts in the blood

• 嗜碱性粒细胞增加

• Being age 60 or older

• Having an enlarged spleen

• 非常高或非常低的血小板计数

Next, your hematologist-oncologist will take your phase and prognostic factors and plug them into one of three scoring systems to determine if you are low risk, intermediate risk, or high risk. The lower risk you are, the more likely you are to have a better response to treatment.

现在，有了一些积极，令人振奋的新闻：在过去的二十年中，慢性髓细胞性白血病治疗发生了革命性，这要归功于一种称为酪氨酸激酶抑制剂（TKIS）的药物。在2001年批准之前，供体的干细胞移植是CML的唯一治疗方法，生存率仅为三到五年。随着TKIS的出现，五年的生存率已提高了三倍，超过71％，而参加临床试验的患者也更高。

TKI疗法

So what is a tyrosine kinase inhibitor? When the abnormal BCR-ABL1 fusion gene is formed, it produces a protein known as “tyrosine kinase” that sends signals causing uncontrolled CML cell growth. TKIs work by identifying and switching off (inhibiting) the tyrosine kinase made by the BCR-ABL1 gene. In turn, the bone marrow stops cranking out abnormal white blood cells. Bonus: TKIs are what’s known as a targeted therapy. That means, unlike traditional cancer treatments such as chemotherapy, they cause less damage to normal, healthy cells. Even better: TKIs come in pill form that you take orally once or twice a day—no needles, no infusions, no time-consuming visits to clinics.

大多数在慢性阶段被诊断出的人（绝大多数CML患者）将对TKI治疗有良好的反应。但是，有些人没有，有些人最终会产生对他们正在服用的药物的抵抗力。幸运的是，现在有几代TKIS，因此，如果一个人不起作用，则通常还有更有效的选择可以进步。您的血液学家 - 检查医生也可能会根据您的健康病史和潜在的副作用选择其他。这是TKI治疗阶梯：

• gleevec（伊马替尼梅赛）：This highly effective drug is usually well-tolerated and brings about stable remission in most people who have chronic phase CML. It was the first treatment of this type approved by the FDA in 2001, so it’s known as a第一代TKI。It’s a good option for people who are lower risk and don’t need an aggressive treatment, as well as those who are older or have other health issues.

• Sprycel (dasatinib):该药物于2006年获得批准，被称为second-generation TKI。Some studies have shown it is more potent and induces a faster and deeper molecular response than Gleevec, but it has not yet been shown to increase survival compared to Gleevec. It may not be prescribed if you have lung (pulmonary) disease or breathing issues.

• tasigna（尼洛替尼）：Thissecond-generation TKI在2007年获得批准，与Sprycel一样，尽管没有增加生存率，但已被证明会引起更好的反应。对于那些有或有患心血管问题风险的人来说，这可能不是最佳选择。（与您的医生交谈，确定。）

• 波索利夫（博索替尼）：Approved in 2012, this is anothersecond-generation TKIthat can be used for those newly diagnosed or who are no longer benefitting from another treatment. It may not be recommended for someone who has liver, stomach, or gastrointestinal issues.

• Iclusig (ponatinib):Thisthird-generation TKIwas approved in 2012. It is recommended for certain patients who have a genetic mutation in BCR-ABL1 that makes them resistant to the four other TKIs, but it has more significant side effects so it may not be a good option for some.

化学疗法

Chemo is a drug treatment that uses powerful chemicals to kill off fast-growing cancer cells. This mainstay of treatment for many—if not most—cancers is only used to treat the most serious cases of chronic myeloid leukemia. That includes patients in the blast phase to help return them to the chronic phase. Or it may be used prior to a stem cell transplant as a “conditioning therapy” to destroy as many cancer cells as possible and weaken the immune system so the body is less likely to reject the donated cells.

Immunotherapy

This type of drug therapy stimulates the immune system and has shown promising results for other types of cancer but is not used as much in treating CML. Prior to TKIs, one type, interferon, was considered a first-line treatment for people who could not receive a stem cell transplant. Now, interferon may be an option for people who can’t tolerate TKI side effects or who are pregnant.

干细胞移植

在TKI出现之前，同种异体干细胞移植是唯一的实际治疗选择。同种异体意思是“从同一物种的不同个体中获取”。在这种情况下，干细胞从健康的人（捐赠者）转移到患者的身体。成功后，健康的供体细胞取代了骨髓中现有的患病细胞并创建新的免疫系统。

Make no mistake: This is a big deal and a long process. You can expect to be in the hospital for about four weeks because you’ll need a germ-free environment until your new immune system starts working again. Even after you’re home, it may be several months before you can resume a regular schedule. You’ll need all new vaccines and—this is a biggie—if you’re young, your fertility is likely to be affected. Fortunately, there are options like egg freezing and sperm banking available if you must go the transplant route, but for most people of childbearing age, TKI therapy will be an equally effective long-term solution. People considered eligible for stem cell transplantation are those who have resistance to at least two types of TKI, those who are intolerant to all TKIs, and those who are in the accelerated or blast phase of CML.

If you’re diagnosed in the chronic phase of CML, once you get past the shock of having cancer and begin treatment, you will likely find your life returns to pretty close to normal. You’ll need your meds daily, and you’ll have to visit your doctor regularly, but there’s very little you won’t be able to do, as long as you stick to your medication regime (missing doses or not taking the right doses can lead to worse outcomes). You may experience some side effects from the TKI you are taking—mostly fatigue but sometimes nausea or diarrhea—but many people find them manageable and treatable. And while there’s no direct evidence that exercising and eating a healthy diet will impact CML, these good-for-you habits can go a long way toward improving your overall physical and mental health (bring on those mood-enhancing endorphins!).

所有这些快乐新闻的一个警告是有一个家庭。尽管TKI不影响男性的精子数，但它们被认为是致病性的，这意味着它们会导致胎儿流产和异常。接受TKI疗法的妇女也可能应处于节育措施，如果希望生育孩子，则需要与血液学家综合医生紧密合作。那些在很长一段时间内实现了足够深的缓解的人可能能够在受孕之前和怀孕期间停止使用TKI，但需要在分娩和避免母乳喂养后立即恢复治疗。

也不要忘记您的心理健康。癌症 - 不管有多可治疗的是一种压力很大的经历，而在CML的情况下，您将不得不处理余生。与家人和朋友分享您的感受，并寻求医疗建议，如果您感到难过，沮丧或不知所措，持续了两个星期或更长时间。治疗患有慢性健康状况的治疗师可能会有很大的帮助，在线或本地支持小组也是如此。癌症或慢性生活并不容易，但是凭借砂砾，优雅和决心，您的生活仍然可以成为您想要必威体育 西汉姆联的。

Meet Our Writer

Stephanie Wood

斯蒂芬妮·伍德（Stephanie Wood）是屡获殊荣的自由作家和前杂志编辑，专门研究健康，营养，健康和育儿。

接下来要阅读什么

Let’s Talk About Chronic Myeloid Leukemia Symptoms and Causes

让我们谈谈慢性髓细胞性白血病诊断和治疗