Chapter 28: Transplantation
During which phase of HSCT is the patient at most risk for encapsulated bacterial and varicella-zoster virus infections?
C. Late engraftment phase
C. Late engraftment phase
Hematopoietic cell transplantation is the transfer of stem cells from the same individual (autologous) or another (allogenic) with the goal of lifelong engraftment of the administered cells, leading to cure or improved outcomes for hematologic malignancies, bone marrow failure, and immunodeficiencies. The preparative myeloablative regimen for HSCT causes a prolonged recovery of the immune system (Fig. 28-1). Neutrophil recovery is dependent on the graft type and can take 2 to 4 weeks. Lymphocyte recovery takes months (with natural killer T cells followed by B cells and CD8 T cells and then CD4 T cells).
Figure 28-1. Immune cell counts peri and post myeloablative regimen of hematopoietic cell transplantation. (From Storek J (2008). Immunological reconstitution after hematopoietic cell transplantation-its relation to the contents of the graft, Expert Opinion on Biological Therapy, 8:5, 583-597. Reprinted by permission of the publisher (Taylor & Francis Ltd.) NK = natural killer.
Due to this sequence of immune recovery, the risk of infections of HSCT is divided into 3 sections: pre-engraftment phase, or phase I (< 15–45 days after HSCT), during which infection results from profound neutropenia and mucocutaneous breakdown; postengraftment phase, or phase II (30–100 days after HSCT), during which infection results from impaired cell-mediated immunity; and late phase, or phase III (> 100 days after HSCT), during which chronic GVHD plays a role (Fig. 28-2).
Figure 28-2. Phases of opportunistic infections. (Reprinted with permission from Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143-1238.)
EBV = Epstein-Barr virus; HHV = human herpesvirus; PTLD = post-transplant lymphoproliferative disorder.
In the pre-engraftment phase, infections result from Gram-negative bacilli, Gram-positive organisms, gastrointestinal streptococcal species, Aspergillus species, and Candida species (choice A).
In the postengraftment phase, infections from Pneumocystis jirovecii, CMV, and EBV-associated PTLD appear (choice B). In the late engraftment phase, infections from encapsulated bacteria and varicella-zoster virus appear (choice C). Infections from Aspergillus, HSV reactivation, and community-acquired respiratory viruses are possible in all 3 phases (choice D). Timing from transplant and presence of graft-versus-host disease are the 2 main risk factors for infection. Other risk factors include HLA match, disease status, donor type, graft type, type and duration of pre- and post-immunosuppression, conditioning intensity, and neutrophil engraftment.
Which of the following can be seen 3 months post HSCT?