EM@3AM: Pediatric Acute Lymphoblastic Leukemia

Authors: Jawad Arshad, MD (EM Resident Physician, Kaiser / San Diego, CA) and Kristy Schwartz, MD/MPH (@kaynani32, EM Attending Physician, UCSD / San Diego, CA) // Reviewed by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

Welcome to EM@3AM, an emDOCs series designed to foster your working knowledge by providing an expedited review of clinical basics. We’ll keep it short, while you keep that EM brain sharp.

Case: A 3-year-old male with no past medical history presents to the emergency department with his parents, who noticed that he looked more pale than normal lately. They also report frequent nosebleeds, as well as bleeding from his gums, for the past week. He is up to date on his vaccinations and is not taking any medications. He had a tactile fever yesterday. The patient’s mother denies recent infections, vomiting, abdominal pain, trauma, or other complaints. He was sent from clinic after his primary care doctor found a hemoglobin of 5 g/dL.

Triage vital signs (VS): BP 100/60, HR 120, T 98.2, RR 16, SpO2 99% on room air. On exam, the patient looks pale and has petechiae across his arms and back. He appears tired but alert. His spleen is palpable. There are no other acute abnormalities on complete physical exam.

Labs reveal WBC 20,900/μL, absolute neutrophil count 10,400/μL, absolute lymphocyte count 1800/μL, hemoglobin 5.9 g/dL, and platelet count 20 × 10³/μL.

What’s the diagnosis?

Answer: Acute Lymphoblastic Leukemia/Lymphoblastic lymphoma (ALL)

Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma are diseases on the same spectrum and, for simplicity, will be referred to as ALL.

Epidemiology:

• Acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL) is the most prevalent cancer among children and adolescents in the United States.
  • Approximately 1/4 of childhood cancers are ALL.¹
• Peak age of onset is 3-7 years.²
• A higher frequency of ALL has been reported in industrialized countries and urban areas.³
• ALL arises from immunologic cells: B lineage (85%), T lineage (10-15%), and NK lineage (<1%).⁴
• ALL rates are higher in males, Hispanics, and Caucasians.^1,3,5
• 10 year survival rates are high with chemotherapy (above 85%).⁶

Pathophysiology:

• ALL is a malignancy of B or T lymphoblasts.
• ALL is characterized by uncontrolled proliferation of immature lymphocytes.
  • This ultimately leads to replacement of other bone marrow elements.⁶

Clinical Presentation:

• ALL often presents with nonspecific symptoms, including fatigue, fevers, pallor, or bruising.²
  • Children may also present with poor appetite, abdominal pain, or episodes of spontaneous bleeding.²
  • Muscular pain or skeletal pain, including issues bearing weight, are also seen.⁷
• Hepatomegaly and splenomegaly are the most common exam findings in ALL patients at 64 and 61%, respectively.⁷
• Half of children with ALL have lymphadenopathy.⁷
• Petechiae are noted in roughly 50% of children with ALL, as well as a relative thrombocytopenia.⁷
• Nausea, emesis, headache, or signs of increased ICP, including papilledema, may be present due to meningeal irritation or CSF obstruction.⁷
• For children presenting with acute onset leukemia or those who recently began chemotherapy, it is important to evaluate for tumor lysis syndrome.⁸

Evaluation:⁸

• CXR (to assess for masses/pneumonia)
• CBC with peripheral smear (to assess for blast crisis, hyperleukocytosis, and relative anemia or thrombocytopenia)
• Chemistry Panel (to assess renal function and for tumor lysis syndrome)
• Ca, Mg, Phosphorus, Uric Acid, UA, LDH (to assess for tumor lysis syndrome)⁹
• LFTs, Coagulation profile, FDP, D-Dimer, Haptoglobin, Fibrinogen (to assess for DIC or other hematologic problems)⁹
• Coagulation studies (to evaluate for underlying cause of bleeding)
• Reticulocyte count
• ESR, CRP
• CT head if altered mentation is present
• Lumbar puncture if concerned for CNS infection

Treatment:^8-14

• Provide IV hydration in patients with hyperleukocytosis.
• For tumor lysis syndrome, consider rasburicase and/or hydroxyurea.⁸
• Potential transfusion of blood products and/or platelets for those with a hemoglobin of less than 7.
• If patient is febrile, cultures should be collected and broad-spectrum antibiotics should be started.⁸
• Long term chemotherapy is the only treatment known to improve survival.^13-14

Disposition:

• Stabilize the patient with aforementioned interventions.
• Consult Pediatric Hematology-Oncology to admit patient and facilitate treatments.
  • Admission to children’s hospital or appropriate facility capable of treating pediatric oncologic cases is essential.
• Break the news of the cancer diagnosis to the family.¹⁵
  • Be clear and use non-medical terminology.
  • It is OK to say you do not know.
  • Allow time for questions.
  • Can stress the treatability of ALL with 10-year survival rates above 85%.¹¹

Pearls:

• ALL is the most common pediatric cancer.
• Presenting symptoms may be subtle or nonspecific, including pallor, fever, fatigue, bruising, or bleeding.
• The most common physical exam findings are hepatomegaly and splenomegaly in the context of new onset bleeding.
• A full work-up is merited to assess for other diagnoses as well as potential complications from ALL including tumor lysis syndrome, CNS involvement, or DIC.

Further Reading:

FOAM:

1. http://www.emdocs.net/leukemia-clues/
2. https://emergency.unboundmedicine.com/emergency/view/5-Minute_Emergency_Consult/307370/all/Leukemia
3. http://www.emdocs.net/9077-2/

References:

1. Ward E, Desantis C, Robbins A, Kohler B, Jemal A. Childhood and adolescent cancer statistics, 2014. CA: A Cancer Journal for Clinicians. 2014;64(2):83-103. doi:10.3322/caac.21219
2. Bickle I. Acute lymphoblastic leukemia: Radiology Case: Radiopaedia.org. Radiopaedia Blog RSS. https://prod-assets-static.radiopaedia.org/cases/acute-lymphoblastic-leukaemia?lang=us. Accessed February 2, 2021.
3. Larson RA, Anastasi J. Acute Lymphoblastic Leukemia: Clinical Presentation, Diagnosis, and Classification. Acute Leukemias Hematologic Malignancies.:109-118. doi:10.1007/978-3-540-72304-2_7
4. Mueller EL, Sabbatini A, Gebremariam A, Mody R, Sung L, Macy ML. Why pediatric patients with cancer visit the emergency department: United States, 2006-2010. Pediatric Blood & Cancer. 2014;62(3):490-495. doi:10.1002/pbc.25288
5. Cancer Incidence and Survival among Children and Adolescents: United States SEER Program 1975-1995. PsycEXTRA Dataset. 1999. doi:10.1037/e407432005-001
6. Roganovic J. Acute Lymphoblastic Leukemia in Children. Leukemia. 2013. doi:10.5772/55655
7. Clarke RT, Bruel AVD, Bankhead C, Mitchell CD, Phillips B, Thompson MJ. Clinical presentation of childhood leukaemia: a systematic review and meta-analysis. Archives of Disease in Childhood. 2016;101(10):894-901. doi:10.1136/archdischild-2016-311251
8. Wynn RF. Acute Lymphoblastic Leukemia. Pediatric Hematology and Oncology. 2010:75-94. doi:10.1002/9781444315134.ch7
9. Coiffier B, Altman A, Pui CH, et al. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 2008; 26:2767.
10. Buffler PA, Kwan ML, Reynolds P, Urayama KY. Environmental and Genetic Risk Factors for Childhood Leukemia: Appraising the Evidence. Cancer Investigation. 2005;23(1):60-75. doi:10.1081/cnv-46402
11. Price RA. The Pathology of Central Nervous System Leukemia. Central Nervous System Leukemia. 1983:1-9. doi:10.1007/978-94-009-6708-3_1
12. Pediatric Oncologic Emergencies – PEMCincinnati. http://www.pemcincinnati.com/blog/wp-content/uploads/2015/09/Ped-Onc-Emergenices.pdf. Accessed February 2, 2021.
13. Paolucci G, Vecchi V, Favre C, et al. Treatment of childhood acute lymphoblastic leukemia. Long-term results of the AIEOP-ALL 87 study. Haematologica. https://www.ncbi.nlm.nih.gov/pubmed/11410410. Published May 2001. Accessed January 26, 2021.
14. Ma, H., Sun, H. & Sun, X. Survival improvement by decade of patients aged 0–14 years with acute lymphoblastic leukemia: a SEER analysis. Sci Rep 4, 4227 (2014). https://doi.org/10.1038/srep04227
15. Brouwer MA, Maeckelberghe EL, van der Heide A, Hein IM, Verhagen EA. Breaking bad news: what parents would like you to know. Archives of Disease in Childhood. 2020. doi:10.1136/archdischild-2019-318398