How I prevent viral reactivation in high-risk patients

Abstract

Preventing viral infections at an early stage is a key strategy for successfully improving transplant outcomes. Preemptive therapy and prophylaxis with antiviral agents have been successfully used to prevent clinically significant viral infections in hematopoietic cell transplant recipients. Major progress has been made over the past decades in preventing viral infections through a better understanding of the biology and risk factors, as well as the introduction of novel antiviral agents and advances in immunotherapy. High-quality evidence exists for the effective prevention of herpes simplex virus, varicella-zoster virus, and cytomegalovirus infection and disease. Few data are available on the effective prevention of human herpesvirus 6, Epstein-Barr virus, adenovirus, and BK virus infections. To highlight the spectrum of clinical practice, here we review high-risk situations that we handle with a high degree of uniformity and cases that feature differences in approaches, reflecting distinct hematopoietic cell transplant practices, such as ex vivo T-cell depletion.

Graphical abstract

Figure 1.

CMV prevention strategies in HCT, including potential combined approaches. Red circles indicate weekly monitoring for CMV viremia; open circles indicate test time points that yielded viral loads below the threshold for the initiation of PET antiviral therapy; filled shapes indicate test time points with values above this threshold. Black arrows indicate the administration of antiviral PET. Black bars indicate administration of antivirals as prophylaxis. Blue triangles indicate administration of vaccine dose. All the strategies include clinical surveillance. ^aVaccination of transplant donor and/or recipient; ^bvarious vaccination schedules used; ^cvarious experimental vaccines currently being studied. D⁺R⁻, donor positive, recipient negative; Exp, experimental; IM, immune monitoring; PET, preemptive therapy; R⁺, recipient positive; RCT, randomizwd controlled trial; Tx, therapy. Reproduced with permission from Limaye et al.

Figure 2.

Case 1: viral kinetics, antiviral prophylaxis, treatment, and relevant clinical data of a 55-year-old woman with anaplastic large cell lymphoma (ALCL) undergoing matched-related reduced intensity peripheral blood stem cell transplantation with CMV reactivation. HLA, human leukocyte antigens; PBC, peripheral blood cell; TBI, total body irradiation; VZV, varicella-zoster virus; y/o, years old.

Figure 3.

Venn diagram showing the most common mutations conferring resistance to CMV antivirals. Drugs for treatment of CMV are labeled in each oval, with the abbreviations listed in parentheses. The proteins (bold and underlined) and specific amino acid mutations commonly found to confer drug resistance are shown below the drug names. Mutations associated with resistance to more than 1 drug are shown in the overlap between multiple ovals. Figure adapted from Chou.

Figure 4.

Case 2: antiviral prophylaxis, treatment, and other relevant clinical data of a 33-year-old man with AML undergoing cord blood transplantation for disseminated VZV infection. AML, acute myeloid leukemia; CSP, cerebrospinal; Cy, cyclophosphamide; Flu, fludarabine.

Figure 5.

Case 4: viral kinetics, antiviral treatment, and relevant clinical data of a 25-year-old man with ALL undergoing double cord blood transplantation with adenovirus infection. ALL, acute lymphocytic leukemia.

Figure 6.

Case 5: viral load, clinical symptoms, and other relevant clinical data of a 19-year-old man with ALL undergoing PBSC transplant and BK virus associated hemorrhagic cystitis. ALL, acute lymphocytic leukemia; CBI, continuous bladder irrigation; IV, intravenous; PBSC, peripheral blood stem cell; RBC, red blood cells; Tacro, tacrolimus; UA, urine analysis.