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Chapter 50: Complications and Follow-Up After Hematopoietic Cell Transplantation

Michael M. Boyiadzis; Juan C. Gea-Banacloche; Michael R. Bishop

INTRODUCTION

Multifactorial etiology of posttransplant hematopoietic cell transplantation (HCT) complications

  • Chemotherapy and/or radiation therapy used as conditioning regimen

  • Immunodeficiency state following HCT

  • Immunosuppressive therapy and adverse events related to medications

  • Graft-versus-host disease (after allogeneic HCT)

INFECTIOUS COMPLICATIONS FOLLOWING AUTOLOGOUS AND ALLOGENEIC HCT

Infectious Complications Following Autologous and Allogeneic HCT

Freifeld AG et al. Clin Infect Dis 2011;52:e56–e93

Tomblyn M et al. Biol Blood Marrow Transplant 2009;15:1143–1238

Wingard JR. Transpl Infect Dis 1999;1:3–20

Preengraftment Period (Before Neutrophil Recovery)

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Preengraftment Period (Before Neutrophil Recovery)

Autologous and allogeneic transplant recipients are similar with respect to early infectious complications. The risk of infection during this period is related to neutropenia and mucositis resulting from the conditioning regimen
Bacterial Principal causes of sepsis

  • Gram-negative bacilli (eg, Pseudomonas aeruginosa, Enterobacteriaceae)

  • Gram-positive bacteria (eg, viridans group Streptococcus, coagulase-negative staphylococci)

  • Common sources include gastrointestinal tract and intravascular devices
Fungal

Fungal infections become more common with prolonged and profound neutropenia

Candida infections occur early and are often prevented with fluconazole (see table below for doses and duration of prophylaxis)

Aspergillus infections occur later (generally after 10–14 days of neutropenia)

  • There is no proven effective prophylaxis for Aspergillus infections after hematopoietic cell transplantation. The best evidence supports posaconazole; some experts recommend voriconazole, caspofungin, or micafungin
Viral

Herpes simplex virus (HSV) commonly reactivates during this period, and can worsen mucositis

Prophylaxis with acyclovir or valacyclovir reduces HSV reactivation (for dose and duration of prophylaxis see table below)

Early Postengraftment Period (30–100 Days After HCT)

The risk of infection is greater and different for allogeneic recipients than autologous recipients during this period

Autologous HCT

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Autologous HCT

There is some degree of immunodeficiency, but opportunistic infections are the exception rather than the rule
Bacterial Related to an intravascular device
Fungal

Uncommon

Some centers continue prophylaxis against Pneumocystis jirovecii (formerly Pneumocystis carinii) for 6 months after transplantation
Viral VZV reactivation and community respiratory virus infections

Allogeneic HCT

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Allogeneic HCT

The infection risk during this period is related to severely impaired cell-mediated immunity, acute GVHD and its treatment, and CMV reactivation. The latter two increase the risk of viral and fungal infections
Factors That Increase Risks Factors That Lower Risks

  • Haplo-identical stem-cell transplantation

  • Transplants from an HLA-identical sibling

  • Unrelated donor

  

  • Cord blood

  

  • T-cell depletion (CD34 selection)

  
Bacterial

In the absence of acute GVHD and its treatment, the most common pathogens are related to use of an intravascular device and include:

  • Gram-positive organisms (eg, coagulase-negative staphylococci)

  • Nonfermentative Gram-negative bacilli (including Pseudomonas spp., Acinetobacter, and Stenotrophomonas)

    Respiratory infections are also commonly seen, frequently following upper respiratory viral infections

    In the presence of acute GVHD and its treatment, the most common ...

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