Targeting Treatments for Chronic Lymphocytic Leukemia
Dr. Joel Silver How do myeloma and chronic lymphocytic leukemia (CLL) develop? What are some risk factors associated with those malignancies? A. We don’t know
Understanding Leukemia Types, Symptoms, Diagnosis, and Treatment Near You at RCCA
Leukemia is one of the most common types of blood cancers. Unlike solid tumors that initially affect just one organ, leukemia circulates throughout the body via the bloodstream. Its potential for rapid progression makes swift, effective treatment imperative. Regional Cancer Care Associates (RCCA) serves patients at more than 20 locations near you throughout New Jersey, Connecticut, Massachusetts, and the Washington, D.C., area, offering accurate diagnoses and the most advanced therapies available, so patients can continue to lead fulfilling lives during and following treatment.
Key Takeaways
- Acute leukemia symptoms include extreme fatigue, easy bruising, recurrent infections, bone pain, enlarged lymph nodes, and unexplained fever.
- Chronic leukemia symptoms include fatigue, an enlarged spleen, enlarged lymph nodes, night sweats, and weight loss. Not all patients with chronic leukemia have symptoms.
- Leukemia is detected with a complete blood count (CBC) test and peripheral blood smear and diagnosed with a bone marrow biopsy and molecular testing.
- Treatment options for leukemia include chemotherapy, targeted therapy, immunotherapy, or stem cell transplantation, depending on the type of leukemia.
What Is Leukemia?
Leukemia is a malignant blood disorder that begins in the bone marrow, where most blood cells are produced. It starts when just a few blood-forming cells mutate. The mutated cells rapidly reproduce and spread throughout the marrow. They also circulate via the bloodstream, spreading the cancer to new parts of the body.
Leukemia vs. Lymphoma vs. Multiple Myeloma
Leukemia is not the only type of blood cancer. There are three main types of blood cancer, distinguished by the cells in which they originate. The other two types are:
- Lymphoma: This form of cancer starts in the lymph nodes and affects white blood cells. The cancer cells collect in the lymph nodes, creating swollen masses.
- Multiple myeloma: This cancer starts in the bone marrow and affects plasma cells, which produce antibodies. The faulty antibodies build up in various organs.
While all three are categorized as blood cancers, they present and behave slightly differently. They also require different approaches to treatment.
How Common Is Leukemia?
Leukemia is the tenth most common cancer overall. About 60,000 to 66,000 new cases are diagnosed annually in the U.S., and more than 475,000 people throughout the country live with or are in remission from leukemia. While most patients with leukemia are adults, leukemia is the most common cancer diagnosis in children, accounting for roughly 25% of all childhood cancer diagnoses.
What Are the Types of Leukemia?
Leukemia cases are categorized based on two factors: where they originate and how quickly they spread. Myeloid leukemias start in myeloid cells, which produce non-specialized white blood cells that support a generalized immune response. Lymphocytic leukemias start in lymphocytes, which produce specialized white blood cells that respond to specific infections or diseases. Acute leukemias spread quickly, while chronic leukemias spread slowly. Taken together, these two points of differentiation result in four major subtypes of leukemia.
Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is a myeloid leukemia that spreads quickly throughout the body. It is one of the most common leukemias in adults, accounting for about one out of three leukemia cases in adults. The cancer spreads rapidly, but many patients who receive prompt treatment achieve total remission.
Why Is AML a Medical Emergency?
AML progresses rapidly. Severe, life-threatening symptoms can develop suddenly, including uncontrolled bleeding, rapid-onset infections, and leukostasis – a condition in which an abnormally high number of white blood cells clog small blood vessels — requiring immediate emergency care.
Acute Lymphoblastic Leukemia (ALL)
Acute lymphoblastic leukemia (ALL) is a lymphocytic leukemia that spreads aggressively. It is a rare type of cancer that occurs more frequently in children and teenagers than in adults. While the cancer spreads quickly, it is also easy to detect with blood tests, making it easier for patients to receive an accurate diagnosis and obtain early treatment.
ALL Prognoses in Children vs. Adults
Although ALL is more common in children and teenagers, most deaths from ALL occur in adults. This is partly because childhood ALL frequently is marked by favorable genetics and is responsive to chemotherapy, while adult ALL is more aggressive and treatment-resistant. It is also because children often tolerate aggressive treatment better than adults. As a result, about 80% of children with ALL enter remission, while less than 50% of adults achieve long-term survival.
Chronic Myeloid Leukemia (CML)
Chronic myeloid leukemia (CML) is a slow-growing myeloid leukemia. It is relatively uncommon, accounting for only 15% of all new leukemia cases, and primarily affects older adults. Although CML usually spreads slowly, it sometimes changes and starts acting like an acute leukemia.
CML Phases
CML cases are categorized as being in one of three phases:
- Chronic phase: There are fewer than 10% blasts (abnormal blood cells) in the blood. Patients experience few to no symptoms.
- Accelerated phase: The blood has a higher percentage of blasts, basophils, promyelocytes, or the platelet count is low, or there are new chromosomal changes. Patients experience more noticeable symptoms.
- Blast crisis phase: At least 20% of blood cells are blasts, or the blasts have spread beyond the blood and bone marrow, or the leukemia cells have formed a tumor. Patients experience severe symptoms.
The prognosis for CML worsens as it progresses to more aggressive phases, although modern treatments have greatly improved survival rates for even blast-crisis CML.
CML and the Philadelphia Chromosome
Up to 95% of CML cases have a BCR::ABL1 gene abnormality called the Philadelphia chromosome. Targeting this gene has revolutionized the treatment of CML, transforming it into a manageable disease with a 10-year survival rate of 80%-85%. Imatinib, the therapy that targets the Philadelphia chromosome, is one of the first major successes for targeted therapy.
Chronic Lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia (CLL) is a lymphocytic leukemia that progresses extremely slowly. It is often detected incidentally on routine blood tests, and most patients experience no symptoms for several years. Even so, the cells continue to build up and may eventually cause complications in the lymph nodes, liver, and spleen.
Richter’s Transformation
Although CLL is usually slow-growing, on rare occasions it undergoes a change called Richter’s transformation. The leukemia abruptly turns into a fast-growing, aggressive lymphoma. Richter’s transformation is difficult to treat and has a worse outlook than standard CLL, with a median overall survival of 8 to 14 months.
What Are Leukemia Symptoms by Type?
Symptoms vary depending on the type of leukemia. Acute and chronic leukemias behave differently, producing different symptom types and onsets. Recognizing the signs of disease requires understanding how each type of leukemia presents.
Acute Leukemia Symptoms
In patients with acute leukemia, symptoms appear suddenly. The disease can very quickly progress to a crisis state where severe symptoms require emergency care. Patients may experience:
Anemia
In acute leukemia, blasts (abnormal cells) quickly outnumber healthy blood cells. Without enough healthy cells to transport oxygen, the organs become starved. Patients develop severe anemia with symptoms that include fatigue, shortness of breath, dizziness, and pale skin.
Easy Bruising
Acute leukemia causes thrombocytopenia, or a low platelet count. Platelets are a component of blood that play an important role in blood clotting. Without enough platelets, the body cannot stop minor bleeding. The patient bruises easily and more severely than usual.
Recurrent Infections
Because leukemia prevents white blood cells from maturing, the body lacks the tools it needs to fight disease effectively. The patient experiences severe infections more frequently than normal. People may also be slower to recover after getting sick.
Bone Pain
When leukemia cells reproduce quickly, the cancerous cells start to crowd the bone marrow. The bone’s outer shell is hard and cannot expand to accommodate the new growth. This creates intense pressure inside the bone, leading to dull or stabbing bone pain.
Enlarged Lymph Nodes
The lymph nodes are tiny glands that collect and destroy disease pathogens such as bacteria and viruses. Defective lymphocytes can get trapped in the lymph nodes, where they continue to multiply. The accumulation of defective white blood cells creates a lump that feels firm but rubbery and may be tender.
Fever
Cancer cells release increased numbers of cytokines, which are proteins that regulate immune responses such as inflammation. The abundance of cytokines tells the body to increase its temperature as if it were fighting infection, resulting in an unexplained fever.
Chronic Leukemia Symptoms
In contrast to acute leukemia, chronic leukemia develops slowly. Many patients have no symptoms at all at the time of their diagnosis. When symptoms appear, they may be subtle and easy to dismiss:
Fatigue
Cancer cells require large amounts of energy to fuel their rapid growth. To obtain this energy, they draw from the body’s own supply. Patients may notice declining energy levels and persistent feelings of tiredness that do not improve with rest.
Unexplained Weight Loss
Cancer’s energy demands also lead to weight loss. Fat stores are used to feed the cancer without being replenished, resulting in sudden weight loss that cannot be explained by exercise, dieting, stress, or other lifestyle factors.
Night Sweats
In acute leukemia, cancer cells produce enough cytokines to trigger a severe fever. In chronic leukemia, the cancer still produces cytokines, but in lower quantities. The slightly raised body temperature results in nighttime overheating and drenching sweats.
Enlarged Spleen
The spleen is an organ that filters the blood to remove debris and invaders. Abnormal white blood cells get caught in the spleen, where they continue to multiply. As blast cells build up, the spleen increases in size, creating a feeling of fullness on the left side of the abdomen.
Enlarged Lymph Nodes
Abnormal white blood cells also become trapped in the lymph nodes, causing them to swell in the same way they do with acute leukemia. The enlarged lymph nodes may feel hard or rubbery to the touch, and they may be painful or tender.
How Is Leukemia Diagnosed?
Diagnosing leukemia involves a combination of blood tests, biopsies, and genetic evaluations. Each phase of evaluation provides oncologists with more information about the cancer, helping them pinpoint the condition and determine which treatments are likely to be effective.
Complete Blood Count
A complete blood count (CBC) test often provides the first clue indicating possible leukemia. A CBC test analyzes a sample of blood to determine how many white blood cells, red blood cells, and platelets are present. Unusually high or low white blood cell counts, low red blood cell counts, and low platelet levels may point toward leukemia – among other possible causes — prompting doctors to conduct further testing.
Peripheral Blood Smear
A peripheral blood smear involves spreading a drop of blood very thinly across a glass slide. The blood is stained and then examined under a microscope. This test enables pathologists or hematologists to examine white blood cells, red blood cells, and platelets directly. Physicians can spot abnormal or immature blast cells in the bloodstream, indicating that the patient has blood cancer.
Bone Marrow Biopsy
When the CBC and peripheral blood smear indicate that a patient has blood cancer, the hematologist will order a bone marrow biopsy. This procedure uses a specialized hollow needle to extract a small amount of the liquid portion of the bone marrow. The sample is examined under a microscope to look for blasts, abnormal marrow cells, and other cancer indicators. The biopsy provides a conclusive cancer diagnosis.
Cytogenetic and Molecular Testing
The bone marrow sample is also used to conduct cytogenetic and molecular testing. Pathologists use advanced technologies to identify specific mutations, abnormalities, and molecular features that can be used to guide treatment. Methods used in molecular testing include:
- Next-Generation Sequencing: NGS rapidly scans large groups of genes simultaneously, helping pathologists find specific gene mutations that respond well to targeted treatments.
- Fluorescence In Situ Hybridization: FISH uses fluorescent labels to increase DNA visibility under a microscope, helping pathologists map specific DNA sequences or chromosomes.
- Karyotype analysis: Cells are stimulated to divide, then treated with chemicals to stop division when chromosomes are most visible for examination under a microscope.
Lumbar Puncture
A lumbar puncture is sometimes required for assessing acute lymphocytic leukemia (ALL). ALL has the potential to cross the blood-brain barrier and infiltrate the cerebrospinal fluid (CSF). Chemotherapy drugs cannot easily cross the blood-brain barrier, so ALL that is present in the central nervous system requires a different treatment approach. A lumbar puncture takes a sample of CSF from the lumbar spine to determine whether cancer cells are present.
Medical Imaging
Medical imaging cannot be used to diagnose leukemia, which does not typically form solid tumors. It may, however, be used during leukemia management. X-rays, computed tomography (CT) scans, positron emission tomography (PET) scans, and bone scans can check for chest infections, enlarged organs, and other complications of leukemia.
How Is Leukemia Treated?
No two cases of leukemia are alike. Effective treatment requires a personalized plan that accounts for the leukemia type, its subtype or phase, and the patient’s age and overall health. RCCA offers a range of advanced treatments to help patients achieve remission and long-term survival, including:
Watchful Waiting
Watchful waiting is sometimes recommended for chronic leukemia that does not cause any symptoms. Instead of treating the leukemia, hematologists monitor it with frequent blood tests to make sure that the disease has not accelerated. Active treatment can begin if and when the leukemia begins to behave more aggressively.
Chemotherapy
Most leukemia cases are treated with chemotherapy. This treatment uses strong drugs that circulate via the bloodstream, making them effective at destroying abnormal cells throughout the body.
Induction Chemotherapy
Induction is the first, most-aggressive phase of chemotherapy. The goal is to kill leukemia cells, halt their spread, and achieve normal blood counts. Induction chemotherapy also lowers healthy blood cell counts, making patients more vulnerable to infections and other problems. Patients receiving induction chemotherapy may require weeks of hospitalization.
Consolidation Chemotherapy
Successful induction is followed by consolidation. During this phase, the goal is to prevent relapse by destroying any cancer cells that were left behind following induction. The drugs administered are less intense, and most patients only need brief periods of hospitalization during this phase of treatment.
Intrathecal Chemotherapy
If acute lymphocytic leukemia (ALL) has moved into the central nervous system, intrathecal chemotherapy is required. The treatment involves injecting chemotherapy drugs directly into the cerebrospinal fluid to reach the brain and spinal cord.
Targeted Therapy
Targeted therapy is the latest advance in leukemia care. A type of personalized medicine, targeted therapy uses drugs that attack cells with specific mutations. By blocking the proteins that drive out-of-control proliferation, targeted therapy effectively stops or slows the spread of leukemia.
BCR-ABL Inhibitors
BCR-ABL inhibitors, such as imatinib, block the BCR-ABL1 protein. They are used to treat chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphocytic leukemia (ALL).
FLT3 Inhibitors
FLT3 inhibitors, including midostaurin and gilteritinib, block the mutant FLT3 protein. Mutations in this gene are found in about 25% of acute myeloid leukemia (AML) cases.
IDH Inhibitors
IDH inhibitors include enasidenib and ivosidenib. These drugs block mutated IDH1 and IDH2 enzymes, which are sometimes found in acute myeloid leukemia (AML) cells.
BTK Inhibitors
BTK inhibitors block Bruton’s tyrosine kinase (BTK). This protein is sometimes found in chronic lymphocytic leukemia (CLL) as well as some types of lymphoma.
Venetoclax
Venetoclax blocks the BCL-2 protein. It is a versatile drug that can be used for some types of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML).
Immunotherapy
Immunotherapy is another type of personalized medicine that has transformed the landscape for leukemia care. It works by giving the patient’s own immune system the tools to fight cancer, often providing favorable long-term results where other treatments fail. Like targeted therapy, immunotherapy is personalized for each patient’s unique case.
Monoclonal Antibodies
Monoclonal antibodies are laboratory-produced antibodies. They fasten onto specific proteins on the surface of leukemia cells, telling the immune system where to attack.
Blinatumomab
Blinatumomab is a bispecific T-cell engager (BiTE) that binds T-cells, or specialized white blood cells, to cancer cells. The bridge prompts the T-cell to attack and destroy the cancer.
Checkpoint Inhibitors
Some leukemia cells produce proteins that mask their presence from the immune system. Checkpoint inhibitors block these proteins, helping the immune system locate and attack the cancer cell.
CAR-T Cell Therapy
CAR-T Cell therapy modifies the patient’s own white blood cells with instructions to destroy leukemia cells. It is an emerging therapy that is primarily used for ALL and CLL when other treatments fail.
Stem Cell Transplantation
Stem cell transplantation plays an essential role in leukemia treatment. After the leukemia cells are destroyed with chemotherapy or targeted therapy, they are replaced with healthy stem cells from a genetically matched donor. The healthy cells help to replenish healthy blood while also hunting down any remaining cancer cells in what is called the graft-versus-leukemia (GVL) effect.
Find Expert Leukemia Care Near You in NJ, CT, MA, and the Washington, D.C., Area
Patients can access cutting-edge leukemia care at Regional Cancer Care Associates. We offer treatment at more than 20 locations near you across New Jersey, Connecticut, Massachusetts, and the Washington, D.C., area, enabling you to receive care close to home. Contact RCCA today to learn more or to schedule your leukemia consultation.
Frequently Asked Questions About Leukemia
What is leukemia?
Leukemia is a type of cancer that develops from blood-forming cells in the bone marrow. It can be acute (fast-developing) or chronic (slow-developing).
What are the symptoms of leukemia?
Symptoms vary between types of leukemia. Acute leukemias may cause extreme fatigue, pallor, easy bruising, recurrent infections, bone pain, enlarged lymph nodes, and fever. Chronic leukemias may cause fatigue, an enlarged spleen, enlarged lymph nodes, night sweats, and weight loss.
What is the difference between acute and chronic leukemia?
Acute leukemia develops and spreads quickly, while chronic leukemia spreads gradually. Some chronic leukemias can turn into acute leukemia.
Is leukemia curable?
Some forms of leukemia can be treated into remission, while others can often be managed successfully over many years. Outcomes depend on the leukemia type and individual patient factors.
What is the treatment for AML?
AML (acute myeloid leukemia) has multiple treatment options, including chemotherapy, targeted therapy, and stem cell transplantation.
What is the treatment for CML?
CML (chronic myeloid leukemia) can be treated with chemotherapy or targeted therapy depending on the genetic mutations involved in its development. Alternatively, for CML cases that do not cause symptoms, watchful waiting may be an option.
Does a bone marrow biopsy hurt?
The site selected for a bone marrow biopsy is treated with local anesthetics to prevent pain. Patients may experience mild pain, pressure, or a pinching sensation during the procedure and soreness afterward.
Can leukemia be detected in a routine blood test?
Yes, leukemia can be detected in a routine blood test, although further testing is needed to confirm the diagnosis. Many cases of chronic leukemia are found through routine testing before the patient develops any symptoms.
What is the survival rate for leukemia?
The overall 5-year survival rate for leukemia is about 68%. This number varies significantly based on the type of leukemia. Advances in medical therapy are constantly improving outcomes, driving better survival rates and a higher quality of life for people with leukemia.
What is Richter’s transformation in CLL?
Richter’s transformation is a rare phenomenon in which chronic lymphocytic leukemia (CLL) turns into an aggressive type of lymphoma.
Fight Leukemia with Regional Cancer Care Associates
All Regional Cancer Care Associates locations across New Jersey and Connecticut are equipped with state-of-the-art technology to provide the latest, most comprehensive treatments available. To learn more or to schedule an appointment, contact us today.
Physicians SPECIALIZED IN Leukemia
RELATED ARTICLES
What Is Immunotherapy – and Is It Right for You?
If you or a loved one has been diagnosed with cancer, doctors can choose from many treatments to provide the best care possible for each
CAR T-Cell Therapy: New Hope for Remission in Leukemia
Gurpreet S. Lamba, MD What are the main types of leukemia? How do they differ in terms of their effects, how they present and how
View All Cancer Trials
When standard cancer treatments aren’t providing the results you want, clinical trials may offer hope. Our physicians use clinical trials to study new treatments, helping transform cancer care for the better. You can enroll in a clinical trial to try groundbreaking treatment plans at zero cost to you.
Regional Cancer Care Associates is one of fewer than 200 medical practices in the country selected to participate in the Oncology Care Model (OCM); a recent Medicare initiative aimed at improving care coordination and access to and quality of care for Medicare beneficiaries undergoing chemotherapy treatment.