A case review on blast crisis…

Case:

A patient in his 60s presented to the emergency department with symptoms of abdominal pain, vomiting, and shortness of breath. The patient mentioned he was seen about week ago with gingival bleeding and was diagnosed with gingivitis and sent home with antibiotics. He felt okay up until 3-4 days later when he started developing stomach pain. Since that time he has had multiple episodes of NBNB emesis and was unable to tolerate any oral intake. He has been trying to stay hydrated but noticed dark urine with possible blood clots. He denies fevers, urinary frequency or urgency, or dysuria. In the ED, work up is significant for a CBC with WBC of 259 and blasts of 76%

Background:

Leukemia is a cancer in the blood. It is important to understand if the leukemia is chronic or acute. Acute leukemia is neoplastic proliferation of undifferentiated (blast) cells, defined as an accumulation of greater than 20% in the bone marrow or peripheral blood. Chronic leukemia is neoplastic proliferation of differentiated (mature) cells. Acute leukemia can be further differentiated into AML or ALL (myelogenous or lymphoid) depending on phenotype of the proliferated cell. This blog entry will focus on acute leukemia, specifically AML. As there is an increased in the proliferation of blasts, this “crowds out” the bone marrow and normal hematopoiesis. The result is thrombocytopenia, anemia, and neutropenia leading to bleeding, fatigue, and infections. 

AML, while the second most common type of leukemia in adults, is relatively rare; it comprises approximately 1% adult cancer in the US. Median age of diagnosis is 68 years old. The underlying causes of AML are multifactorial including environmental factors, chemicals, radiation, viral, or pre-existing dysplasia (MDS, myeloproliferative dysplasia).

Clinical presentation:

The constellation of symptoms from acute leukemia are likely related to bone infiltration by blasts and extramedullary sites (lymph nodes, spleen, skin). For some patients, diagnosis is incidental.

• Pallor
• Bleeding, bruising, petechiae (particularly recurrent or unexplained mucosal bleeding)
• Infections
• Bone pain
• Hepatomegaly, splenomegaly, lymphadenopathy

Diagnosis:

AML should be suspected in a patient with the above clinical findings, or in the event of incidental circulating blasts or unexplained medical complications such as DIC or tumor lysis syndrome.

• Initial testing usually includes CBC, peripheral smear, coagulation studies, chemistry panel, uric acid, LDH
• White blood cell count is increased in approx. 5-20% of patients; however, despite this elevation many are neutropenic
• If fever or concern for infection is present, obtain urine and blood cultures
• CXR may show evidence of pneumonia, mediastinal mass, infiltrates, or cardiomegaly 

• The definitive diagnosis of AML requires a bone marrow biopsy or peripheral smear
  • Greater than 20% blasts of myeloid lineage
  • Specific chromosomal or molecular abnormalities
  • Subclassification is based on multiple factors including cytogenetics, lineage of immature myeloid cells, surface markers

In AML myeloblast have positive cytoplasmic staining for myeloperoxidase (MPO) and crystal aggregates of MPO can been seen as Auer Rods.

Source

source

Treatment:

The goal of any treatment is to induce remission and minimize treatment toxicity (effects of radiation, chemo, drugs). Most of the management will be completed by oncology but in the ED we have to identify critical patients, and understanding this disease process can help resuscitation efforts.

Approach to critical patient care:

• Provide fluids (may help with leukostasis and help treat TLS)
• Correct electrolyte abnormalities (in AML there is high cell turnover or tumor lyse syndrome which can lead hyperuricemia, hyperphosphatemia, hypocalcemia, hyperkalemia)
• Evaluate for evidence of bleeding due to thrombocytopenia or DIC
• Avoid RBC transfusion unless absolutely necessary (can cause worsening of hyperviscosity syndrome)
• Maintain low threshold for infections workup and empiric antibiotics given non-functional blast cells
• Obtain early oncology consult
• Consider leukapheresis in patients with evidence of leukostasis

Complications:

There are a variety of complication associated with AML. Abrupt treatment is needed for electrolyte abnormalities, cytopenia, infections, and hyperviscosity.

• Anemia is common due to crowding out of the bone marrow, impaired hematopoiesis, hemolysis, blood loss (due to thrombocytopenia), IDA. Treatment depends on symptoms and blood counts. Remember that transfusion should be avoided to prevent worsening hyperviscosity syndrome.
• Leukocytosis is considered a poor prognostic factor

• Hyperleukocytosis is a WBC of >100,000. 
• Leukocytosis can cause leukostasis, TLS, and DIC
• Leukostasis is clinical diagnosis of intravascular aggregation of leukocytes inevitably leading to damage of organs (particularly CNS and lungs). Urgent leukapheresis may be considered.
• Thrombocytopenia

• Platelets should be administered if levels are less than 20,000; platelet transfusion does not appear to increase risk of leukostasis (unlike RBC transfusions)
• Risk of spontaneous intracranial hemorrhage is extremely low until the platelets drop <5,000
• Infection risk is increased due to non-functioning myeloid cells or bone marrow suppression
  • Patients may not present with typical SIRS criteria because they do not mount a robust immune response
  • Maintain a low threshold for sepsis work up and antibiotic coverage

• DIC may require platelets, coag factors, cryoprecipitate, FFP, fibrinogen
• TLS should be managed with supportive care including fluids and electrolyte correction

Summary and Conclusions:

Patients in the Emergency room can have a variety of symptoms, often vague, that may indicate a concern for underlying leukemia. Our job as Emergency Physicians is to identify lab abnormalities and life threatening complications related to this condition such as blast crisis or leukostasis. Generally unexplained bleeding, recurrent infections, fatigue, pallor, or pain should lead to a suspicion of leukemia. Understanding the pathophysiology of the disease helps with recognition and management of the sequelae of AML; clonal expansion of the myeloid lineage can cause leukostasis and hyperviscosity, while bone marrow crowding can lead to anemia, thrombocytopenia, and infection. While much of the definitive treatment will be provided by the oncology team, critically ill or unstable patients with AML may require prompt management started in the ED.

Written By: Matthew Alfarano, MD

Peer Reviewed and Edited by: Dr. Koshy

Sources: 

1. UptoDate
2. Tintinalli, Judith E., and O. John Ma. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. McGraw-Hill, 2020.
3. Cover Image: https://www.ready.gov/nuclear-explosion