Neonatal Leukemia

Neonatal Leukemia

We have discussed numerous common neonatal issues (ex, Analgesia, Umbilical Granuloma, Neonatal Tooth, Hyperbilirubinemia).  Many of us have learned that neonates are challenging and demand respect.  Even the most proficient practitioner will be apprehensive of the sick neonate, given that there are so many conditions to consider with so few clinical clues to help sort through them (ex, ALTE, Omphalitis, PGE1, Neonatal Resuscitation, Hypothermia).

While severe infections, congenital anomalies, and unusual metabolic conditions need to be pondered, it seems completely unfair that you should also have to consider cancer in neonates!!

Neonatal Leukemia – because life is not fair.


Neonatal Leukemia – Basics

  • Neonatal Leukemia is, fortunately, rare!
    •  Estimates of 1-5 per MILLION live births.
      • While rare, it does occur (our group just diagnosed a neonate with a WBC >900,000).
    • <1% of all childhood leukemia is diagnosed during the neonatal period.
  • Neonatal leukemia is not the same as childhood leukemia.
    • Neonatal leukemia is more likely to present with poor prognostic factors.
    • Neonatal ALL has a disease-free survival rate of ~10% compared to >70% in older children.
    • Neonatal leukemia is the leading cause of death in neonate due to neoplastic disease.
  • Trisomy 21 (Down Syndrome) and 11q23 translocation are the most common chromosomal aberrations associated with neonatal leukemia.
  • Timing of Presentation:
    • Some show signs at birth.
    • Some within a few days of birth.
    • Others present between the 3rd and 6th week of life.
      • This group may present in a more vague manner with failure to thrive, pallor, fever, and lethargy.


Neonatal Leukemia – Signs and Symptoms

  • Hyperleukocytosis

    • Present in the majority of ALL cases (85%), but only 49% of AML cases.
    • WBC > 50 x 10^9/L
    • Complications due to Hyperleukocytosis:
      • Leukostasis Syndrome
        • White Cells plug up the micro-circulation.
        • Heart Failure
        • Respiratory Failure (hypoxia, pulmonary infiltrates, tachypnea)
        • Neurologic insults (somnolence, coma, retinal hemorrhage)
  • Hepatosplenomegaly

    • Seen in about 80% of the cases.
    • Liver is more often enlarged than the spleen.
    • Other Lymphadenopathy is seen in only ~25% of cases.
  • Leukemia Cutis

    • Seen in about 60% of cases.
    • Caused by cutaneous leukemic infiltrates.
    • A firm blue, red, or purple nodular eruption.
    • Blueberry muffin baby.” – similar to what is seen with congenital infections.
    • Reported to be the INITIAL presenting sign in about 50% of cases!
      • Keep this on your list of items to look for in the neonate!
      • May precede the other signs by as much as 4 months!
  • Additional Findings

    • Bone Marrow Suppression (due to infiltrative disease)
      • Anemia
      • Thrombocytopenia
      • Neutropenia
    • CNS Infiltration
      • Seizures
      • Cranial Nerve Palsies
      • Bulging Fontanelle
      • Intracranial Hemorrhage
      • Infarction
    • Respiratory
      • Pulmonary Hemorrhage
      • Pneumonia
    • Sepsis


Neonatal Leukemia – on the Differential

  • Leukemoid Reaction
    • Causes elevated WBC counts and Hepatomegaly.
    • May also have BlueBerry Muffin Baby appearance.
    • Seen with Congenital Infections.
      • TOxoplasmosis, Rubella, CMV, HErpes, Syphilis, Listeria.
      • Also with Sepsis.
      • Typically have Intrauterine growth retardation and/or microcephaly.
  • Other Congenital Neoplasms (Neuroblastoma)
  • Hemolytic Disease of the Newborn
  • Congenital HIV Infection


Neonatal Leukemia – Initial Work-up

  • The definitive diagnosis will not be made in the ED, but your suspicion for it should lead you to obtain:
    • CBC with Differential
    • Peripheral Smear
    • Work up for Congenital Infections!
  • During the admission, the child will have Bone Marrow Aspirate performed to help make definitive diagnosis.



Orbach D1, Sarnacki S, Brisse HJ, Gauthier-Villars M, Jarreau PH, Tsatsaris V, Baruchel A, Zerah M, Seigneur E, Peuchmaur M, Doz F. Neonatal cancer. Lancet Oncol. 2013 Dec;14(13):e609-20. PMID: 24275134. [PubMed] [Read by QxMD]

van der Linden MH1, Creemers S, Pieters R. Diagnosis and management of neonatal leukaemia. Semin Fetal Neonatal Med. 2012 Aug;17(4):192-5. PMID: 22510298. [PubMed] [Read by QxMD]

Isaacs H Jr. Fetal and neonatal leukemia. J Pediatr Hematol Oncol. 2003 May;25(5):348-61. PMID: 12759620. [PubMed] [Read by QxMD]

Sande JE1, Arceci RJ, Lampkin BC. Congenital and neonatal leukemia. Semin Perinatol. 1999 Aug;23(4):274-85. PMID: 10475541. [PubMed] [Read by QxMD]


Sean M. Fox
Sean M. Fox
Articles: 583

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