What is the appropriate workup and management for a patient with uterine leiomyosarcoma (stage 3b) on gemcitabine (Gemzar) with docetaxel (Taxotere) who develops severe leukocytosis after recent uterine resection with positive margins?

From the Guidelines

For a patient with stage 3b uterine leiomyosarcoma on gemcitabine/docetaxel who develops severe leukocytosis after uterine resection with positive margins, immediate management should focus on determining the cause of leukocytosis while optimizing oncologic treatment. First, obtain a complete blood count with differential, blood cultures, and comprehensive metabolic panel to distinguish between infection, paraneoplastic leukemoid reaction, or chemotherapy effect, as suggested by the guidelines for diagnosis and treatment of soft tissue and visceral sarcomas 1. Imaging studies including CT chest/abdomen/pelvis should be performed to evaluate for disease progression or abscess formation at the surgical site. If infection is suspected, broad-spectrum antibiotics (such as piperacillin-tazobactam 4.5g IV every 6 hours or meropenem 1g IV every 8 hours) should be initiated while awaiting culture results. For paraneoplastic leukocytosis, hydroxyurea at 500-1000mg twice daily may be used for cytoreduction if WBC count exceeds 50,000/μL. Regarding oncologic management, the positive margins require multidisciplinary discussion about additional surgery versus radiation therapy. Radiation to the tumor bed (typically 45-50 Gy in 1.8-2 Gy fractions) should be considered, as part of the standard approach for managing uterine leiomyosarcoma with positive margins 1. The current gemcitabine/docetaxel regimen (typically gemcitabine 900mg/m² on days 1 and 8 with docetaxel 75-100mg/m² on day 8, every 21 days) should be continued if the patient is tolerating it well, as this is standard first-line therapy for uterine leiomyosarcoma, according to the ESMO-EURACAN-GENTURIS clinical practice guidelines for diagnosis, treatment, and follow-up of soft tissue and visceral sarcomas 1. However, if disease progression is evident, second-line options include doxorubicin (60-75mg/m² every 3 weeks), trabectedin (1.5mg/m² every 3 weeks), or pazopanib (800mg daily), as these agents have shown activity in leiomyosarcoma and are recommended in the guidelines for the treatment of advanced uterine leiomyosarcoma 1. Close monitoring of blood counts is essential during this period, with growth factor support (filgrastim 5μg/kg daily) if neutropenia develops during continued chemotherapy. Key considerations in the management of this patient include:

• Determining the cause of leukocytosis and managing it appropriately
• Optimizing oncologic treatment, including consideration of additional surgery or radiation therapy for positive margins
• Continuing or adjusting chemotherapy based on disease progression and patient tolerance
• Providing supportive care, including growth factor support as needed, to minimize the risk of complications and improve quality of life.

From the Research

Patient Presentation

The patient presents with uterine leiomyosarcoma stage 3b, currently on gemcitabine with docetaxel, and has recently undergone resection of the uterus with positive margins. The patient has developed severe leukocytosis, with a white blood cell (WBC) count of 48 yesterday and 59.7 today.

Differential Diagnosis

The differential diagnosis for leukocytosis is broad and includes:

• Infections or inflammatory processes 2, 3
• Primary bone marrow disorders, such as acute or chronic leukemias, or myeloproliferative neoplasms 2, 4
• Physiologic responses to stress, including physical or emotional stress 2, 3
• Medication-induced leukocytosis, such as with corticosteroids, lithium, or beta agonists 2
• Persistent inflammation-immunosuppression and catabolism syndrome (PICS) 5

Workup

The workup for this patient should include:

• Repeat complete blood count (CBC) with peripheral smear to evaluate for types and maturity of white blood cells, uniformity of white blood cells, and toxic granulations 3
• Leukocyte differential to evaluate for eosinophilia, lymphocytosis, or other abnormalities 3
• Careful review of the patient's medical history, including recent surgeries, infections, or medication changes 4
• Physical examination to evaluate for signs of infection, inflammation, or other underlying conditions 4
• Consideration of bone marrow aspiration and biopsy, imaging studies, and specialized molecular tests if a primary hematologic disorder is suspected 4

Management

Management of the patient's leukocytosis will depend on the underlying cause. If an infection is suspected, antimicrobial therapy should be initiated promptly. If a primary hematologic disorder is suspected, referral to a hematologist/oncologist is indicated. Supportive measures, such as careful monitoring of fluid balance, control of uric acid production, and control of urine pH, may be necessary to prevent complications such as tumor lysis syndrome or leukostasis 6.