A 5-year-old boy presents to his primary care physician for recurrent colds, fatigue, and fussiness. Over the past several weeks, the child has been more fatigued and his parents state that “he always seems to be sick.” They state that sometimes he complains about his bones hurting and they note that he is less playful. He is up to date on his vaccinations. His temperature is 102°F (38.9°C), blood pressure is 92/60 mmHg, pulse is 115/min, respirations are 23/min, and oxygen saturation is 99% on room air. Physical exam is notable for diffuse non-tender lymphadenopathy. Abdominal exam reveals hepatosplenomegaly. Laboratory studies are ordered as seen below.

Hemoglobin: 8.0 g/dL
Hematocrit: 23%
Leukocyte count: 27,500/mm^3 with 35% lymphoblasts
Platelet count: 49,000/mm^3

Serum:
Na+: 139 mEq/L
Cl-: 101 mEq/L
K+: 4.0 Eq/L
HCO3-: 24 mEq/L
BUN: 16 mg/dL
Glucose: 100 mg/dL
Creatinine: 0.7 mg/dL

Which of the following is the most likely diagnosis?
Parvovirus B19 infection
Acute lymphoblastic leukemia
Chronic myelogenous leukemia
Acute myelogenous leukemia
Acute lymphoblastic leukemia
This pediatric patient is presenting with recurrent colds, fatigue, non-tender lymphadenopathy, hepatosplenomegaly, and leukocytosis with increased lymphoblasts, which are concerning for acute lymphoblastic leukemia (ALL).

ALL is the most common hematologic cancer in pediatric patients. It initially presents with a vague constellation of symptoms including fatigue, fevers, easy bleeding/bruising, bone pain, lymphadenopathy, hepatosplenomegaly, and possibly testicular enlargement. The diagnosis is supported when the white blood cell count (which can be low, normal, or high) demonstrates increased lymphoblasts. Further confirmatory testing may include testing for the 12:21 translocation, which is more common with a better prognosis, or the 9:22 translocation (the Philadelphia chromosome), which is less common and denotes a poor prognosis.

Onciu reviews ALL. He notes that ALL has a high cure rate with intensive chemotherapeutic regimens and that new research is improving outcomes in this very common condition. He recommends early treatment with these regimens for an improved prognosis.

Incorrect Answers:
Answer B: Acute myelogenous leukemia is a malignancy of myeloblasts and is more common in the elderly. Patients will present with systemic symptoms, weight loss, anorexia, leukocytosis, anemia (causing fatigue), thrombocytopenia (causing bleeding including gingival bleeding and bleeding from the gastrointestinal tract), and neutropenia (predisposing patients to life-threatening infection). Myeloblasts produce increased amounts of myeloperoxidase which can lead to the formation of Auer rods that can be seen on peripheral smear.

Answer C: Chronic myelogenous leukemia is a neoplastic proliferation of myeloid stem cells and presents with a leukocyte count > 50,000/mm3. There are different presentations for this condition. Most patients present in the chronic phase with minimal symptoms (and a low blast count); however, they can also present with an accelerated phase and a blast phase which can lead to a hematologic emergency termed a blast crisis which may cause a hyperviscosity syndrome.

Answer D: Leukemoid reaction is an overly robust immune reaction (often to infection) that resembles chronic myelogenous leukemia. However, the leukocyte alkaline phosphatase level is elevated. This elevated level indicates it is a robust immune response rather than increased cell levels from malignancy.

Answer E: Parvovirus B19 infection presents with erythema infectiosum (fifth disease) which may include "slapped cheek" rash, fever, malaise, and possibly respiratory symptoms. In healthy patients, symptoms are usually minimal and self-limited. However, in patients with hemoglobinopathies (such as sickle cell disease), the transient halt in erythropoiesis that occurs in addition to hemolysis may lead to significant anemia requiring transfusion.

Bullet Summary:
Acute lymphoblastic leukemia presents in pediatric patients with pancytopenia, fatigue, repeat infections, easy bleeding, bone pain, lymphadenopathy, hepatosplenomegaly, and increased blast cells on peripheral smear.