What is the workup for post-transplant neutropenia (absolute neutrophil count decrease) in a transplant recipient?

From the Guidelines

The workup for post-transplant neutropenia should begin with a complete blood count with differential to confirm the neutropenia and assess other cell lines, and management typically includes granulocyte colony-stimulating factor (G-CSF) at 5-10 μg/kg/day subcutaneously if neutropenia is severe (absolute neutrophil count <500 cells/μL) or associated with infection, as recommended by the American Society of Clinical Oncology 1.

Key Considerations

• Neutropenia after transplantation is commonly caused by immunosuppressive medications, particularly mycophenolate mofetil, azathioprine, and sirolimus, so medication review and potential dose adjustment or temporary discontinuation may be necessary.
• Infectious causes should be evaluated with blood cultures, viral studies (particularly for cytomegalovirus, Epstein-Barr virus, and parvovirus B19), and consideration of opportunistic infections.
• Bone marrow aspiration and biopsy may be indicated if the cause remains unclear or if there are concerns about graft failure or malignancy.
• Antimicrobial prophylaxis should be considered for severe neutropenia, including trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia and fluconazole for fungal infections, as recommended by the Infectious Diseases Society of America and the American Society of Clinical Oncology 1.

Phases of Infection Risk

• Phase I, preengraftment: characterized by prolonged neutropenia and breaks in the mucocutaneous barrier, with prevalent pathogens including Candida species and Aspergillus species.
• Phase II, postengraftment: dominated by impaired cell-mediated immunity, with critical pathogens including CMV, Pneumocystis carinii, and Aspergillus species.
• Phase III, late phase: characterized by recovery of immune system function, but with ongoing risk of infections such as CMV, varicella-zoster virus, and encapsulated bacteria, particularly in patients with chronic GVHD or receiving alternate donor allogeneic transplants 1.

From the FDA Drug Label

If neutropenia develops (ANC < 1.3 x 10^3/μL), dosing with mycophenolate mofetil should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately [see Dosage and Administration (2.5)]. Patients receiving mycophenolate mofetil should be monitored for neutropenia. Consider monitoring with complete blood counts weekly for the first month, twice monthly for the second and third months, and monthly for the remainder of the first year

The workup for post-transplant neutropenia in patients receiving mycophenolate mofetil includes:

• Interrupting or reducing the dose of mycophenolate mofetil if neutropenia develops (ANC < 1.3 x 10^3/μL)
• Performing appropriate diagnostic tests
• Managing the patient appropriately
• Monitoring patients for neutropenia with complete blood counts:
  • Weekly for the first month
  • Twice monthly for the second and third months
  • Monthly for the remainder of the first year 2 2

From the Research

Workup for Post-Transplant Neutropenia

• The workup for post-transplant neutropenia involves a comprehensive evaluation, including a history, physical examination, and laboratory tests, such as complete blood cell counts (CBCs) with differentials and bone marrow examination with cytogenetics 3.
• Neutrophil antibody testing may be useful in the context of clinical and bone marrow findings 3.
• The discovery of genes responsible for congenital neutropenias now permits genetic diagnosis in many cases 3.
• In patients with febrile neutropenia, treatment with antibiotics is recommended, and the risk of febrile neutropenia should be assessed systematically 4, 5.
• The use of granulocyte colony-stimulating factor (G-CSF) is recommended for the treatment of severe chronic neutropenia 3, 6.

Risk Factors and Outcomes

• High-risk CMV status and valganciclovir (VGCV) use are significant predictors of neutropenia in kidney transplant recipients, while only VGCV use is a predictor in liver transplant recipients 7.
• Neutropenia is associated with worse survival in kidney transplant recipients, but not in liver transplant recipients 7.
• Neutropenia is also associated with an increased risk of acute rejection episodes in both kidney and liver transplant recipients 7.

Laboratory Evaluation

• Laboratory evaluation generally includes repeat complete blood cell counts (CBCs) with differentials and bone marrow examination with cytogenetics 3.
• The absolute neutrophil count (ANC) is used to define neutropenia, with an ANC of less than 1,500/mcL indicating neutropenia 3, 5.
• The duration of leukopenia and the clinical status of the patient should also be considered in the assessment of patients with neutropenia 5.