Late infections following allogeneic bone marrow transplantation: Suggested strategies for prophylaxis

Abstract

Bone marrow transplant recipients remain at risk for infections for a variable period of time even after adequate hematologic reconstitution. Late infections are a significant cause of morbidity and can be fatal in 4–15% of these patients. Patients with chronic graft versus host disease (GVHD) and unrelated-donor transplant recipients, even without GVHD, are at particular risk. Most late infections occur in the first post-transplant year, the majority are caused by bacteria, particularly encapsulated organisms, or herpes group viruses (CMV and VZV) and present with cutaneous, sino-pulmonary or systemic involvement. Effective chemoprophylaxis is available only for the encapsulated bacteria (penicillin or erythromycin) and Pneumocystis carinii (trimethoprim-sulfamethoxazole). Routine use of long-term IV immunoglobulin supplementation has not been shown to be effective and may be harmful as it may delay reconstitution of humoral immunity. Active immunization (pneumococcal vaccine, influenza vaccine and HiB) can be effective in patients more than 6–12 months from transplant who do not have GVHD. In this review we present our experience, a summary of published literature on the subject of late infections in bone marrow transplant patients and offer guidelines for preventative strategies.

Allogeneic bone marrow transplant recipients undergo complete ablation of hematopoietic and immune function. After transplant, hematologic recovery is usually complete by 4–6 weeks. Immune reconstitution takes longer and some aspects of immune function may take 1–2 years for complete recovery. Immune reconstitution is further delayed in patients with GVHD. BMT recipients, therefore, remain at risk for infections for a long period even after adequate engraftment. Patients with chronic GVHD and recipients of URD transplants even without GVHD are particularly at risk. The infections are more frequent in the first post-transplant year and infections occurring early more often result in severe morbidity or mortality. Bacteria, particularly encapsulated gram positive organisms, cause the majority of late post-transplant infections followed by Herpes group viruses (CMV and VZV). Infections caused by gram negative bacteria, fungi or pneumocystis are less frequent, but often carry a high mortality.

Effective preventative measures are not available against most of the infections seen in post-transplant patients. With the exception of penicillin and TMP-sulfa for prophylaxis against pneumococcus and Pneumocystis carinii respectively, routine long-term chemo-prophylaxis against other infectious agents is not routinely recommended. Routine passive immunization with long-term IVIg supplementation has been not been shown to be an effective prophylactic strategy and may delay recovery of humoral immunity. Active immunization is not likely to elicit an adequate immune response in patients with GVHD or less than a year post-transplant, the very patients who need prophylaxis the most. Later immunization in the absence of GVHD can result in protective antibody response in a significant proportion of patients. An awareness of patient groups at particular risk and an individualized approach of aggressive surveillance, early diagnosis and prompt treatment is most likely to reduce the morbidity and mortality from late post-transplant infections.

Key Words:

• Bone marrow transplant
• infections
• prophylaxis
• immunization
• immune defects
• immunoglobulin therapy