Approach to leukemia: Clinical sciences

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Introduction0:00–1:11

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 a ll 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 A LL and A ML 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 ABCD E 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.

Unstable Patient1:11–6:28

Next. Put your patient on continuous vital sign monitoring, including pulse, oximetry, BP and heart rate.
Finally, if needed, don't forget to provide supplemental oxygen and start broad spectrum intravenous antibiotics. Here's a big clinical pearl to keep in mind.
Once you stabilize your patient, your next step is to rule out common oncologic emergencies including tumor lysis syndrome, febrile, neutropenia, leukostasis, and disseminated intravascular coagulation or D IC 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 typically reveal tachycardia, low BP, 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 °C or 101 °F or a temperature greater than or equal to 38 °C or 100.4 °F lasting an hour or more in the setting of an absolute neutrophil count or a NC lower than 500 cells per microliter.
This can occur in the setting of chemotherapy and the management primarily includes antibiotics and sometimes anti fungals.
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 times 10 to the ninth power per liter, 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 D IC which occurs when a trigger over activates the coagulation and fibrinolytic cascades leading to widespread thrombosis which can cause organ ischemia.
As D IC progresses, excessive bleeding occurs due to the consumption of platelets and coagulation factors. Labs will reveal decreased platelets, elevated PTA PTT, 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.
Ok. Now, let's go to the ABCD E 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.

Stable Patient6:28–8:46

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, pe S RCR P 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 petechia 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.
Here's a high yield fact, patients with leukemia typically have elevated white blood cells but they're dysfunctional. So these patients are actually immunosuppressed and not able to properly fight off infections.
Thus, assessment of a patient with leukemia includes ruling out infections secondary to immunosuppression. With these findings, you should consider leukemia.
So your next step is to assess the findings on peripheral blood smear. If the peripheral smear reveals small, mature and uniform lymphocytes with or without smudge cells which reflect the fragility of malignant cells when smeared.

Chronic Lymphocytic Leukemia8:46–9:29

Consider chronic lymphocytic leukemia to confirm the diagnosis order immunophenotyping with flow cytometry. If this diagnostic method reveals cells positive for CD five CD 19 CD 20 CD 23 extracellular markers.
You can diagnose chronic lymphocytic leukemia. Ok.
Let's return to the peripheral smear if the smear reveals lymphoblasts, which are immature blast cells consider acute lymphoblastic leukemia.

Acute Lymphoblastic Leukemia9:29–11:18

Your next step is to obtain a bone marrow biopsy. In this case, you can expect a hypercellular marrow with more than 20% of lymphoblasts.
Next, obtain immunophenotyping with flow cytometry to determine the type of acute lymphoblastic leukemia. If immunophenotyping is positive for CD 19 and CD 22 you can diagnose B cell acute lymphoblastic leukemia or ba ll.
On the other hand, if immunophenotyping is positive for CD seven C D3 and CD one A, you can diagnose T cell acute lymphoblastic leukemia or Ta ll.
Here's a clinical pearl to remember certain genetic conditions such as Trisomy. 21 put patients at higher risk for developing acute lymphoblastic leukemia.
So you should keep a higher index of suspicion for leukemia in these patients. Ok.
Now that we've discussed lymphoid leukemias, let's go back and focus on myeloid leukemias. If peripheral blood smear reveals myeloblasts, which are precursors for neutrophils as well as our rods which are cytoplasmic inclusion bodies that can be seen in myeloblasts consider acute myeloid leukemia.
Next order a bone marrow biopsy, you can expect a hypercellular marrow with more than 20% myeloblasts and our rods then obtain genetic testing to distinguish between subtypes of acute myeloid leukemia.

Acute Myeloid Leukemia11:18–12:58

Ok. If genetic testing reveals no translocation of chromosomes 15 and 17 and no promyelocytic leukemia, retinoic acid receptor alpha or PML ra ra fusion gene.
You can diagnose acute myeloid leukemia or AML. On the other hand, if genetic testing does reveal a translocation of chromosomes 15 and 17 and identifies the PML ra ra fusion gene, you can diagnose a subtype of a ML called acute promyelocytic leukemia or APL L.
For short, here's a clinical pearl. The PML ra ra fusion gene results in an abnormal retinoic acid receptor on the malignant cell.
Because of this, the management of APL includes a form of Vitamin A called all trans retinoic acid. Finally, let's go over our last leukemia.
If the peripheral blood smear here reveals myeloid cells at all stages of differentiation. Consider chronic myeloid leukemia.
Next order a bone marrow biopsy which in chronic myeloid leukemia reveals a hypercellular marrow with myeloid hyperplasia and less than 5% myeloblasts lastly obtained genetic testing to confirm the diagnosis if genetic testing reveals a translocation involving chromosomes nine and 22 widely known as the Philadelphia chromosome and identifies the BCR ABL fusion gene.

Chronic Myeloid Leukemia12:58–15:02

You can diagnose chronic myeloid leukemia. One last high yield fact, the breakpoint cluster region Abelson or just BCR ABL fusion gene leads to an overactive tyrosine kinase enzyme.
Because of this treatment of CML is typically with a tyrosine kinase inhibitor like imatinib and one last clinical pearl.
If you diagnose a patient with leukemia, you'll need to perform further testing as part of your pre treatment evaluation.
This may include checking for other organ involvement. For example, with imaging and testing for latent viral infection like hepatitis B and CMV, which may reactivate during chemotherapy.
All right. As a quick recap leukemia is a blood malignancy characterized by abnormal proliferation or differentiation of hematopoietic cells.
If your patient is unstable, first stabilize them, then rule out common oncologic emergencies including tumor lysis syndrome, febrile, neutropenia, leukostasis and disseminated intravascular coagulation.
If your patient is stable, check their peripheral blood smear. First check for mature lymphocytes and smudge cells if present, perform immunophenotyping to diagnose cll.
But if the peripheral smear shows lymphoblasts, perform bone marrow biopsy and immunophenotyping to diagnose A ll. On the other hand, if the smear reveals myeloblasts and our rods order a bone marrow biopsy and genetic testing to diagnose A L lastly, if there are cells at all stages of myeloid differentiation, order a bone marrow biopsy and genetic testing to diagnose CML.

Review15:02–15:20