How is leukocytosis (elevated white blood cell count) managed in pregnancy?

Management of Leukocytosis in Pregnancy

Leukocytosis in pregnancy is most commonly physiologic and requires no intervention, but when pathologic causes are suspected—particularly hematologic malignancies—treatment must begin immediately without delay, as any postponement compromises maternal survival. 1, 2

Understanding Physiologic vs. Pathologic Leukocytosis

Normal Pregnancy-Related Changes

• The upper reference limit for total WBC increases by 36% during pregnancy, with neutrophils increasing by 55% 1
• Physiologic leukocytosis occurs frequently, especially in the third trimester, and resolves spontaneously after delivery 3
• Non-pathologic leukocytosis with WBC counts above 20 × 10⁹/L can persist throughout pregnancy and typically normalizes within 1 day postpartum 3

When to Suspect Pathologic Causes

• Constitutional symptoms (fever, weight loss, bruising, fatigue) suggest hematologic malignancy and require urgent hematology referral 4
• Abnormal peripheral blood smear findings (immature cells, blasts, atypical lymphocytes) indicate need for malignancy evaluation 5, 4
• First trimester leukocytosis (WBC > 13.8 × 10⁹/L) is associated with increased risk of preterm delivery, small for gestational age infants, and hypertensive disorders 6

Initial Evaluation Algorithm

For Suspected Infection

• If urinary symptoms present with moderate leukocytes on urinalysis: obtain urine culture before initiating antibiotics using clean-catch midstream or catheterized specimen 1
• Pyuria plus bacteriuria plus symptoms indicates true UTI requiring treatment 1
• Initiate empirical antibiotics while awaiting culture results if symptomatic, to prevent maternal and fetal complications 1
• Critical pitfall: Negative nitrites do not rule out UTI, as nitrite testing has only 53% sensitivity 1

For Suspected Malignancy

• Obtain peripheral blood smear immediately to assess for blasts, immature cells, and cell morphology 5, 4
• Urgent hematology/oncology referral is mandatory if malignancy cannot be excluded 4
• Do not delay diagnostic workup or treatment initiation 1, 2

Management of Hematologic Malignancies in Pregnancy

Acute Myeloid Leukemia (AML) and Acute Lymphocytic Leukemia (ALL)

Treatment must begin immediately without delay regardless of trimester—maternal mortality increases with any postponement. 7, 1, 2

First Trimester Management

• Discuss therapeutic termination once patient is hemodynamically stable, as this allows immediate standard therapy 7, 1, 2
• If pregnancy continuation desired: use daunorubicin monotherapy only 7, 1, 2
• Idarubicin is absolutely contraindicated due to higher lipophilicity causing increased placental transfer and greater fetal toxicity 7, 1, 2
• Never delay treatment to reach a "safer" gestational age 1, 2

Second Trimester Management

• Induction therapy with doxorubicin and cytarabine is the standard approach 7, 1
• Standard 3+7 regimen: daunorubicin 60 mg/m² days 1-3 plus cytarabine 100-200 mg/m² days 1-7 7, 1, 2
• Chemotherapy appears reasonably safe during second trimester, though risks include premature delivery, low birth weight, and intrauterine growth restriction 7, 2

Third Trimester Management

• Consider inducing labor and initiating therapy after delivery 7, 1
• If immediate treatment required, use doxorubicin and cytarabine regimen 7
• Avoid delivery while patient and fetus are cytopenic 7

Acute Promyelocytic Leukemia (APL)

First Trimester

• Discuss pregnancy termination as ATRA is highly teratogenic 7, 1, 2
• If pregnancy continuation desired: daunorubicin monotherapy only 7, 1, 2
• ATRA is contraindicated in first trimester due to high teratogenicity 7, 1, 2
• Arsenic trioxide is contraindicated at any stage of pregnancy due to severe embryotoxicity 7, 1, 2

Second and Third Trimesters

• Doxorubicin plus ATRA can be used starting in second trimester 7, 1
• ATRA can be safely added to chemotherapy from second trimester onward 7, 1, 2
• In third trimester, consider inducing labor and initiating therapy after delivery 7, 1

Chronic Myeloid Leukemia (CML)

• First trimester: interferon-alpha is safe and preferred 7, 1
• Second and third trimesters: interferon-alpha OR imatinib can be used 7, 1
• More than 200 pregnant women with CML have been reported with favorable outcomes using this approach 7

Lymphomas

Non-Hodgkin Lymphoma (NHL)

• CHOP chemotherapy starting in second trimester shows favorable pregnancy outcomes 7, 1
• If chemotherapy needs to be urgently started during first trimester, discuss pregnancy termination 7
• Rituximab may cause B-cell depletion in newborn but spontaneous recovery occurs; can be used if postponement would significantly compromise maternal prognosis 7

Hodgkin Lymphoma

• ABVD chemotherapy starting in second trimester without significant fetal impairment 7, 1

Critical Multidisciplinary Considerations

Team Involvement

• Mandatory involvement from diagnosis: hematologist, obstetrician, and neonatologist must collaborate 7, 1, 2
• Joint decision-making with patient regarding pregnancy continuation versus termination 7

Delivery Planning

• Avoid delivery while patient and fetus are cytopenic 7
• Consider induction of labor between cycles of chemotherapy 7
• For deliveries before 36 weeks: administer antenatal corticosteroids to reduce respiratory distress syndrome risk 1

Postpartum Considerations

• Breastfeeding is contraindicated if chemotherapy or arsenic trioxide continues after delivery 1
• Monitor newborn for B-cell depletion if rituximab was administered during pregnancy 7

Common Pitfalls to Avoid

• Never use idarubicin—always choose daunorubicin due to increased placental transfer and fetal toxicity 7, 1, 2
• Never delay treatment to reach a "safer" gestational age—maternal mortality increases with delays 1, 2
• Never use arsenic trioxide at any trimester due to severe embryotoxicity 7, 1, 2
• Never use ATRA in first trimester due to high teratogenicity 7, 1, 2
• Avoid unnecessary antibiotic treatment for asymptomatic physiologic leukocytosis, as this may cause more harm than benefit 1
• Do not rely on negative nitrites to rule out UTI in symptomatic patients 1
• Avoid excessive red blood cell transfusions in hyperleukocytosis, as this increases blood viscosity 7

Supportive Care for Malignant Leukocytosis

Hyperleukocytosis Management

• Hydroxyurea at dosages up to 50-60 mg/kg per day until WBC < 10-20 × 10⁹/L 7
• Prevent tumor lysis syndrome with hydration, allopurinol or rasburicase, and urine pH control 7
• Avoid excessive red blood cell transfusions until WBC reduced 7