What Is a Liquid Tumor?
HEMATOLOGIC MALIGNANCIES ARE CANCERS OF the blood cells, and they include leukemia and lymphoma, myeloma, and bone marrow failure states. These cancers are so distinct from solid tumors that they deserve their own chapter. If you have any one of these so-called liquid tumors, you will have a different experience in diagnosis, staging, and prognosis than will patients who have solid tumors. Oncologists think very differently about these types of tumors and how to treat them.
The first difference is that hematologic cancers are often detected by routine blood tests. You may have been diagnosed before feeling any symptoms of a disorder, or, in the case of lymphoma, you may have experienced some swelling lymph nodes or night sweats. Subsequent blood tests and DNA tests will reveal whether the circulating abnormal cells are actually cancerous. More important, they can help determine what type of cancer they are.
These types of cancers don’t always fall neatly into a single category, although any of them can ultimately lead to bone marrow failure. While an oncologist can usually classify a cancer as one of the four major types, the variability within each group is enormous. One patient’s large-cell lymphoma is not the same as that of another patient with the same diagnosis.
Every year researchers publish new studies based on molecular pathology, which is the study of the genetic mutations in the cancer cell. This research continues to suggest new classifications and groupings of hematologic malignancies, along with new ways of approaching and treating these cancers. So the pace of change is dizzying. Because of these new developments, it’s getting harder to treat these cancers without the help of a major academic center. If you live in a region with one of these large teaching hospitals, you may want to have your test results reviewed there.
The initial diagnosis and staging of one of these cancers requires special blood tests and bone marrow biopsies. We rely far less on scans for these malignancies, except in the case of lymphoma, where we do rely on scans to see the tumors and how the treatment is working.
Questions to Ask Your Oncologist
When friends contact me to say that a family member of theirs has received this kind of diagnosis, I tell them to ask the following questions of the oncologist:
It may seem odd to have to ask the oncologist whether your cancer is curable, but you may have gone through lots of testing to get at a diagnosis, and patients and doctors alike sometimes skirt this issue. With solid tumors, the staging helps to determine whether a cancer is curable. We know that a stage 4 solid tumor is probably not. Most oncologists who specialize in hematologic cancers believe that many cancers, regardless of the stage, are potentially curable, even if the ultimate chance at a cure is lower than 50 percent. This changes the relationship between doctor and patient. The question you want to ask is how curable it is. In many of these cancers, age is a factor. A patient in her twenties might have an excellent chance for a cure. For example, Neal is a thirty-one-year-old who came to the clinic because of fevers and fatigue. A chest X-ray showed a mass in the middle of his chest, and then a PET-CT (see chapter 6 on the various types of scans and imaging used in cancer treatment) revealed multiple enlarged lymph nodes throughout his body. He now has a diagnosis of stage 4 Hodgkin’s, a lymphoma of the white blood cells. Yet, despite the widespread nature of his cancer, Neal is likely to be cured with chemotherapy.
You also want to know how aggressive the cancer seems to be. If you have an aggressive hematologic malignancy, your doctor will want to start treatment immediately, and you may have already experienced a medical emergency that triggered your diagnosis. You won’t have a lot of time to think about how much treatment and medical intervention you want to have at first. You still want to ask how much chemotherapy you will have to have to get a chance at a cure and whether the oncologist thinks that you might require a bone marrow transplant.
In contrast, if the cancer is indolent, meaning slow growing, you have time to get used to the diagnosis and to consider treatment options. Even if an indolent cancer is treatable but not curable, you will have years—perhaps many years—in which you work with your oncologist to keep the cancer in check, to manage its symptoms and side effects, and to live your life with this diagnosis.
Regardless of whether you are curable or incurable and regardless of your type of cancer, you will want to ask when treatment should begin to give you the best chance at a best-case scenario. Does it need to start immediately, or do you have a few weeks to get used to the diagnosis? And how disruptive is the treatment likely to be? How many weeks or months will it last? As a patient, you want to have an idea of what the future will look like for you. How many hospitalizations, how many side effects are likely if you decide to accept every treatment with the hope for a cure or to live as long as possible.
By asking this series of questions, you will get an excellent idea of the prognosis (the likely course and outcome of your disease) and treatment. You will also be able to come to terms with what is required for the best chance at the best-case scenario and how much treatment is right for you.
How Curable Is Leukemia?
These cancers are malignancies among the bone marrow cells, generally immature white blood cells. When these cells are overproduced, they crowd out functioning bone marrow cells and lead to anemia and other problems. You may have been told that you have one of the two types of leukemia, chronic or acute.
The chronic leukemias consist of chronic myelogenous leukemia (CML) and chronic lymphocytic leukemia (CLL). Chronic leukemias tend to be very treatable even if they aren’t curable. Twenty years ago when I first started in oncology, CML was fatal unless you received a bone marrow transplant. And even then the cure rate was barely above 50 percent. But now CML is a chronic illness controlled for years on end by a pill. It’s a dramatic success story. The survival rate for people with CML is almost as good as the survival rate for people without CML. CLL, however, can be an indolent disease until it starts to cause problems, and then patients require multiple chemotherapy regimens to keep it under control.
The acute leukemias are completely different. Acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL) are medical emergencies when diagnosed. Patients are often admitted to the hospital right away and started on aggressive chemotherapy. Many patients with AML and ALL will require a bone marrow transplant to have the best chance at being cured. The road with AML and ALL can be a long one with multiple stays in the hospital.
I treated Josephine five years ago when she had a localized colon cancer. Thankfully, it was stage 1, and she didn’t need any chemotherapy or radiation after her surgery. I continued to follow her for the next five years to make sure that the cancer didn’t return, a period of care we call surveillance. At the end of that time, Josephine called me to say that she was extremely tired and she worried that the cancer had come back. She came in the next day and had blood drawn. During our clinical visit, her blood work popped up on my computer screen to show a white blood cell count of 115,000, a level ten times the normal range, and it was almost all blasts, or immature white blood cells. I knew immediately that she had AML. Josephine was admitted directly to the hospital to prepare for a regimen of chemotherapy to eliminate these AML blast cells, and she remained in the hospital for most of the next month. Unfortunately, the genetics of her AML showed that she had an extremely aggressive form and would need a bone marrow transplant if she wanted to be cured. The next two years are going to be hard for Josephine, as she will be in and out of the hospital for treatment.
As you can imagine, age and general health are both key factors in how aggressively your doctor can treat acute leukemias. The underlying genetics of leukemia also makes a huge difference in prognosis and treatment. Some mutations in the DNA carry a very poor prognosis, and patients with these mutations will require a bone marrow transplant for any reasonable chance at cure. Other mutations carry a very good prognosis with chemotherapy alone. Additionally, patients over the age of sixty can struggle to manage the side effects of aggressive chemotherapy. In general, patients over the age of seventy aren’t offered bone marrow transplants, which are considered too dangerous at this age. The curability of acute leukemia declines as you get older.
How Curable Is Lymphoma?
Lymphomas are collections of cancerous blood cells growing in the lymph system. Indolent lymphomas are rarely curable, but patients can do extremely well with treatment because the cells aren’t reproducing quickly and because they often respond well to treatment. Sometimes you can have a lymphoma and not need any treatment right away. If your lymphoma is indolent, you can expect to have a close relationship with your oncologist for years as you both monitor the disease and the intermittent treatment required.
The aggressive lymphomas are often more curable, but the treatments are aggressive and can involve a bone marrow transplant. If you’re diagnosed with an aggressive lymphoma, you won’t have weeks to decide what you want to do. Often your doctor will want to know your preferences that week because you’re either very sick at that point or you will be shortly. If you have an aggressive lymphoma and it’s potentially curable, as they often are, then you’ll need to decide quickly whether you want to go down the path to cure.
How Curable Is Myeloma?
Unfortunately, myeloma is very rarely curable. Nevertheless, new treatments in the past ten years have made the prognosis for patients with myeloma much better. Patients with myeloma can often live productive lives for five years or more before they get sick from their cancer. Myeloma is different from the other hematologic malignancies in that the tumors secrete proteins called immunoglobulins that we can measure and follow during the course of treatment. These proteins can also cause damage to other organs, particularly the kidneys. Dealing with the side effects of these proteins and kidney damage can be a major focus of both the treatment and the supportive care that patients receive.
How Curable Is Myelodysplastic Syndrome?
This is a group of bone marrow disorders that cause bone marrow failure. The disorder is exactly what it seems to be. Your bone marrow can’t make enough red cells, white cells, and platelets to keep you alive. Unfortunately, myelodysplastic syndrome (MDS) isn’t curable without a bone marrow transplant. Even with a transplant, MDS is not often cured. It usually occurs in older adults who are not candidates for bone marrow transplant. In this case, your doctor will work with you to relieve your symptoms and slow down the failure of the bone marrow, if possible.
Staging
Hematologic malignancies are staged differently than solid tumors are, and the traditional TNM stage of cancer is less predictive of your chance at a cure; indeed, it may be irrelevant. You may know someone with a solid tumor, and if so, you know that staging relies on the size of the tumor in the organ where it started along with how far it has spread in the body. If a solid tumor has spread to the lymph nodes or to another organ, you know that the cancer is at an advanced stage. In solid tumors, oncologists use biopsies, scans, and other tests to determine staging.
In hematologic malignancies, doctors use blood tests as a starting point to identify abnormal cells. But, once there is a suspicion of cancer, your doctor knows that he or she has to look at the source of those abnormal cells, meaning the bone marrow, to see how many abnormal cells there are and how aggressive they are.
Bone marrow is the spongy center of your largest bones, and it contains the stem cells that create all the blood cells in your body. These cells are created in the bone marrow and then mature over the course of a few days. In your bone marrow at any one time, there are red blood cells and white blood cells and platelets in various stages of maturation. In the case of leukemia, the bone marrow will contain an unusual number of cells that are stuck at an immature phase of development and yet are multiplying. In the case of acute leukemia, such as AML or ALL, these cells are stuck at the earliest stage of development, called a blast, and have filled up the bone marrow and have even spilled out into the bloodstream. Chronic leukemias, such as CML or CLL, will show more mature cells that look more like normal white blood cells. But there will simply be too many of them. Over several years, they will squeeze out production of other types of blood cells and cause problems.
None of this information about what’s going on inside the bone marrow is available through simple blood tests. So your doctor will probably order a bone marrow biopsy. It sounds intimidating, but the procedure is actually completely routine.
The Bone Marrow Biopsy
Most of your bone marrow is located in three areas: the sternum, vertebrae, and pelvis. The easiest and safest way to get a sample of bone marrow is with a needle biopsy into the pelvis.
For a bone marrow biopsy, you will be asked to change into a hospital gown and then lie on your stomach on an exam table. The usual spot for a biopsy of this kind is an area on your back called the iliac crest. If you feel the top of your hip bone on your side and then follow the top of that bone to your back just below the area of your kidneys, you’ll find the spot where the needle will go in. Don’t worry about that part yet. First the area will be cleaned with iodine. Then the doctor or nurse will inject lidocaine, a pain medication, to numb both the skin and the bone marrow. If you are especially nervous, you can take pain medication or antianxiety medication as well about fifteen minutes before the procedure.
By the time the needle biopsy itself has started, you will feel pressure as the needle enters the iliac crest. The doctor will take two samples of bone marrow. First, he or she will draw back on the syringe and remove some of the liquid bone marrow. This is often the most painful part of the biopsy. The sudden draw of the syringe can cause a brief, sharp pain in the hip. The second part of the biopsy is a core biopsy, in which the doctor will take about a one-centimeter piece of bone marrow. This will feel like someone is pushing down hard on your hip. It shouldn’t hurt, but you will feel the pressure. And then you’re done. You will be able to get up and go home. After the lidocaine wears off, you will be sore for a couple of days. You may have a bruise, but there is often no visible sign that you’ve had a procedure at all, except for the Band-Aid that was put over the site.
In the lab, both the liquid and solid components are prepared so that we can look at them under the microscope. We can often tell by how the cells look (i.e., its morphology) what type of cancer you have and how extensive it is. But we almost never rely on morphology today. The DNA tests on the bone marrow often tell the story of exactly what type of cancer you have and what the treatment and prognosis are. These tests will take several days to even a few weeks to come back.
Ultimately, the bone marrow biopsy is giving your medical team a more complete picture of your hematologic malignancy. Sometimes, the blood tests can tell your doctor most of what’s needed to confirm the diagnosis. In this case, the bone marrow biopsy is a final confirmation of both the stage and type of cancer cells that are causing the problem. In other cases, such as leukemia and bone marrow failure, the biopsy gives critical information about the state of your bone marrow and what the cancer cells in it are up to.
Scans in Lymphoma
The third major staging need for hematologic cancers is imaging, which is primarily done for lymphomas to see whether the lymph nodes throughout the body are involved and whether the cancer is invading the organs.
Even in solid tumors, the lymph nodes are a significant part of staging. Your lymph system runs throughout your body and follows the venous system. Lymph is milky liquid that circulates through your body and contains white blood cells, specifically the B and T cells that fight both infection and cancer. The lymph nodes are larger pockets containing these cells. When you are fighting an illness, they tend to become swollen as they work to isolate and destroy invading bacteria. They also swell when they are invaded by cancer cells. A normal lymph node is less than one centimeter in size, and usually less than five millimeters. A lymph node that has swollen to a size larger than one centimeter may contain cancer cells. Your doctor may order a PET scan as a way to look at the lymph nodes and see what’s going on. In fact, a PET scan is so valuable in seeing cancer cells in the lymph system that patients will often have several of these scans over time to see how the lymphoma is responding to treatment.
Looking at the Brain
The last step of staging is to look at the brain. Hematologic cancers can often hide out in the brain, where standard chemotherapies can’t reach them. There is a blood-brain barrier that separates the circulating blood from the cerebrospinal fluid in the nervous system. Your doctor will want to look at the cerebrospinal fluid, located in the brain or spinal cord, to see whether any of these white or red blood cells are circulating in it. If so, the cancer may have migrated to this fluid.
Your doctor may order a magnetic resonance imaging (MRI) of the brain and then order a spinal tap to sample the spinal fluid to check it for these red or white blood cells. Again, this may sound like a difficult procedure, but is fairly simple.
The Spinal Tap
In this procedure, you will lie on your side while the doctor inserts a small needle in the space between two vertebrae in your lower back. If you’ve had an epidural while giving birth, this will feel exactly the same. The doctor will numb the area beforehand and then use a needle to remove a few milliliters of cerebrospinal fluid. The procedure should be relatively painless. Afterward, you may have a headache, called a spinal headache, because of the changes to the levels of spinal fluid circulating in your central nervous system. You can take acetaminophen and fluids to treat it, but it should last just a day or two. In rare instances, the needle can cause a small tear in the compartment that holds the spinal fluid in place, and in that case you might require a blood patch. For this, a doctor will inject a small amount of your blood directly into the area of the first injection so that it can repair the tear. Thankfully, this is an unusual complication.
Parameters of Staging
After we have the peripheral blood, the bone marrow, the scans (CT, PET, and MRI), and the brain evaluated, we have completed the staging of your hematologic cancer. At this point, it’s important to ask whether there is any confusion in the diagnosis. For most hematologic malignancies, there is little confusion. The leukemias and myelomas are usually straightforward diagnoses. One source of confusion in the diagnosis of leukemias may be that the genetics are inconclusive. The genetics of leukemias often determine the likelihood of success and cure with a particular treatment. Sometimes the genetics of a particular leukemia aren’t straightforward, and there may be disagreement among experts on the best way to approach treatment.
While most lymphomas are straightforward pathologic diagnoses, different subtypes of lymphomas are being recognized all the time, and these distinctions can have a profound impact on treatment. A pathologic diagnosis of lymphoma can be very difficult, and if you are at a community hospital or cancer center, it may be beneficial to ask that the pathology slides be read by a lymphoma expert in pathology at the closest academic medical center.
The staging of hematologic cancers does give us an idea of the curability of a certain cancer. So your oncologist should tell you which stage of cancer you have. And, as is the case with solid tumors, the stages are classed with the numbers 1 through 4. Still, your stage 4 lymphoma is not like your aunt’s stage 4 breast cancer. Stage 4 large-cell lymphoma is often quite curable while stage 4 solid tumors are rarely curable. Most hematologic cancers have prognostic scoring systems associated with them, and you should ask your oncologist how your tumor scored on these systems.
Hematologic malignancy experts look at staging and these scoring systems as a way to tell us how much tumor burden someone has, meaning roughly how many cancer cells are being produced. The higher the tumor burden, the less curable the cancer and the more side effects someone is likely to suffer from treatment. The lower the tumor burden, the more curable the cancer and the less likely someone is to suffer side effects.
Choosing Treatment Options
With hematologic malignancies there is often a chance of curing people who have advanced cancer by using very aggressive therapy. In solid tumors, we know quickly after staging whether someone has a chance at a cure or not. As a result, oncologists who specialize in these liquid tumors are always looking for a way to try to cure you, even if that means using extremely aggressive chemotherapy that will require a bone marrow transplant. Of course, as you get older, there is a greater likelihood that these aggressive treatments can be difficult, and you may have to consider how your body will tolerate them.
In the beginning, you may be convinced that you will endure anything to have a chance at a cure, and that’s great, but over the course of treatment, your feelings may change, and you want to be able to communicate these feelings to your medical team. You want to work with an oncologist who understands you and your goals for treatment, someone who is a good communicator and a good listener.
Bone Marrow Transplant
Many hematologic malignancies can be cured—even if they are widespread—by a bone marrow transplant. This is the process of replacing damaged stem cells in the bone marrow with healthy cells. These healthy cells can come from your own body or from a donor (see chapter 14). These new stem cells can then create a new generation of white blood cells that can attack the cancer cells in your bone marrow and blood stream. When it is effective, this is called the graft versus leukemia (or lymphoma) effect.
As miraculous as a successful bone marrow transplant can be, it also carries serious risks. If the grafted stem cells were taken from your own body, they will likely take hold without many complications. But if they come from a donor, which is called an allogeneic transplant, they can cause problems. The new white blood cells that come from a donor may be incompatible at first with your system. In this case, these new white cells can view your normal cells as foreign and attack them. This is called graft versus host disease. Allogeneic bone marrow transplants were extremely dangerous when they were first introduced in 1958. At that time, the mortality from the procedure was roughly 30 percent, which means that nearly one-third of all people who had them died of complications from the procedure. Another 30 percent of people were completely cured of their cancer. These numbers have improved over the years, but you should definitely talk to your doctor about the risks of developing life-threatening complications from a transplant. It is also critical that you get your physical symptoms aggressively treated while you are going through a bone marrow transplant. New data from our institution shows that patients who are undergoing this procedure who have a palliative care consultation during transplant have a much better quality of life and lower rates of depression and anxiety.
Your oncologist should be able to tell you whether your cancer is indolent or aggressive. An indolent cancer has probably been in your system for many months or years prior to your diagnosis. You have time to digest the diagnosis and make a decision about when to start treatment. This is again different from solid tumors, in which doctors usually want to start treatment right away to have the best chance at a best-case scenario.
If your cancer is aggressive, your doctor will warn you that you can get sick very quickly. In fact, you may have been admitted to the hospital at the time of diagnosis because of a medical emergency related to the cancer. In that case, you will have to make decisions within the first few days about starting treatment. This can feel overwhelming. If you have a chance at a cure, this will influence your decision. But if you have no chance at a cure, or if you are elderly, you may want to think about how much medical intervention you want and how difficult it will be to endure before you make a decision. It’s important not to be isolated while thinking about these things. Spouses and immediate family members can help you think about what you value and what you really want from your medical team. If you have no spouse or immediate family, a trusted friend can help you navigate these decisions.
Also, give your doctor permission to talk about what he or she would do in your situation and why. If your doctor is younger than you are, ask what she would do if you were her mom or dad. If your doctor is much older, ask what he would do if you were his child. This is your first time in this situation, but your oncologist has talked to and helped hundreds of people in this situation and is probably expecting these questions from you.
Unfortunately, some doctors are uncomfortable with these questions and refuse to answer them. I welcome these questions because they allow me to talk to patients about their goals and values.