Approach to leukemia: Clinical sciences

Leukemia is a blood malignancy characterized by an abnormal proliferation or differentiation of hematopoietic cells. These malignant cells build up and gradually replace healthy blood cells, causing a decline in normal white and red blood cells, and platelets.

Leukemia can be categorized as either acute or chronic and is further differentiated based on whether it originates from myeloid or lymphoid cells. Thus, there’s four main types: acute myeloid leukemia or AML, acute lymphoblastic leukemia or ALL, chronic myeloid leukemia or CML, and chronic lymphocytic leukemia or CLL.

Here’s your first clinical pearl! The most common types of leukemia in children are ALL and AML, but CML and CLL are rare in this age group.

Now, if your patient presents with a chief concern suggesting leukemia, you should first perform an ABCDE assessment to determine if your patient is unstable or stable. If unstable, stabilize the airway, breathing, and circulation, obtain IV access, and start IV fluids. Next, put your patient on continuous vital sign monitoring, including pulse oximetry, blood pressure, and heart rate. Finally, if needed, don’t forget to provide supplemental oxygen and start broad-spectrum intravenous antibiotics.

Once you stabilize the patient, your next step is to rule out common oncologic emergencies, including tumor lysis syndrome, febrile neutropenia, leukostasis, and disseminated intravascular coagulation or DIC!

Tumor lysis syndrome occurs when a large number of tumor cells break down over a short period of time and release intracellular contents into the bloodstream.

This can occur spontaneously or in the setting of chemotherapy and other interventions.

Patients will report a rapid onset of symptoms, within hours to days; including fever, bone pain, easy bruising or bleeding, or night sweats.

Physical exam will usually reveal tachycardia, low blood pressure, pallor, and generalized weakness.

Other findings may include severe mucosal bleeding and tetany.

Labs will typically reveal hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia.

If left untreated, complications like renal impairment, cardiac arrhythmias, and seizures can occur! Treatment includes volume repletion and hypouricemic agents, like allopurinol or rasburicase.

Next, febrile neutropenia is defined as a single oral temperature of 38.3 degrees Celsius or 101 degrees Fahrenheit; or a temperature greater than or equal to 38 degrees Celsius or 100.4 degrees Fahrenheit lasting an hour or more; in the setting of an absolute neutrophil count or ANC lower than 500 cells per microliter.

This can occur in the setting of chemotherapy, and the management primarily includes antibiotics and sometimes antifungals.

Our next oncologic emergency is leukostasis, which is thought to be due to increased blood viscosity associated with hyperleukocytosis, meaning a white blood cell count exceeding 100 × 10^9/L.

Clumps of these cells can form in the microcirculation, obstructing normal blood flow.

Leukostasis primarily affects the central nervous system, causing neurologic symptoms like headaches, visual changes, and dizziness; as well as the lungs, leading to dyspnea and hypoxia.

Less commonly, other organs can also be impacted, including the heart, kidneys, or gastrointestinal tract, resulting in conditions like myocardial ischemia, renal insufficiency, or bowel infarction.

Management is based on treating the underlying cause, providing supportive care, and cytoreduction or leukapheresis.

Lastly, you should also consider DIC, which occurs when a trigger over-activates the coagulation and fibrinolytic cascades, leading to widespread thrombosis, which can cause organ ischemia.

As DIC progresses, excessive bleeding occurs due to the consumption of platelets and coagulation factors.

Labs will reveal decreased platelets, elevated PT/aPTT, an elevated D-dimer, decreased fibrinogen, and schistocytes on peripheral smear. Management is based on treating the underlying cause, with the addition of anticoagulation and transfusing blood products, as needed.

Okay, now let’s go back to the ABCDE assessment and look at stable patients. Start by obtaining a focused history and physical exam. Next, order labs, including a CBC with differential and a peripheral smear.

Time for another clinical pearl! If you suspect leukemia, you should order additional labs to evaluate for coagulopathy; as well as infections, which can occur from secondary immune dysregulation. Some labs to consider include a blood culture, CMP, ESR, CRP, and coagulation tests.

Your patient will typically report fever, night sweats, fatigue, weight loss, bone pain, and easy bruising and bleeding.

Additionally, physical exam will reveal generalized weakness, pallor, or lymphadenopathy.

You might also notice leukemia cutis, which are skin findings that range from flat reddish patches to raised purple nodules. Other important findings that you might notice include petechiae or purpura, mucosal bleeding, hepatomegaly, and splenomegaly.

Now, here’s a clinical pearl! In adolescent patients, one of the first presenting symptoms of leukemia might be testicular enlargement or swelling. So, don’t forget to do a complete genitourinary exam, and look for enlarged inguinal lymph nodes!

Moving on, labs will usually reveal elevated white blood cell count, possibly with a large number of immature cells called blasts; low hemoglobin; and low platelets.