Infections in Recipients of Haploidentical Bone Marrow Transplant: A Modified Prospective Cohort Study
Allogeneic hematopoietic stem cell transplantation (HSCT) from HLA-matched donors cures people with hematological malignancies, but suitable HLA-matched donors are available for a minority. More options are provided with related, haploidentical HSCT (haplo) donors. Our center has pioneered haplo HSCT, especially with use of reduced-intensity (RI) conditioning before bone marrow infusion, and high-dose cyclophosphamide as GVHD prophylaxis. Although low rates of non-relapse mortality (NRM) have been reported, no studies have assessed the epidemiology and outcomes of infections in this unique population.
A modified prospective cohort study that employed active consent and 3-month windows for data capture (by record review and patient contact) was performed to assess event-driven infectious complications for one year after HSCT. We report details of infections developing in 53 of 162 HSCT recipients enrolled who received haplo HSCT after RI in 2012.
Median age was 60 (range 20-75), with most male (77%) and Caucasian (89%). Non-Hodgkin`s lymphoma was the most common underlying disease, followed by AML, with 34% having relapsed or active disease at HSCT. Mortality at 1-year was 30%. 186 infectious events were identified. Per-patient incidence for CMV, bacterial, Clostridium difficile, viral respiratory, BK virus, and invasive fungal infections were 43%, 42%, 30%, 26%, 26%, 13%, respectively. Timing and type of infectious events are shown in the Figure. Bacteremia was present in 55% of bacterial infections, mostly with gram-negatives and coagulase-negative Staphylococci. Lower respiratory tract infections were the second most common (26%), followed by GU (13%). While CMV reactivation was common, disease was rare (n=3). Most common non-microbiologically documented infections were respiratory (61%), and skin (34%).
Despite low (NRM), infections are relatively common, with frequencies highest during the first 3-months. Capture of event data emphasizes the missing microbial cause of many treated respiratory and skin infections. More knowledge of risks will enable development of more tailored screening and prevention algorithms.
S. O. Alp,
Merck: Grant Investigator, Grant recipient and Research support
Pfizer: Investigator, Research support
Cubist: Investigator, Research support
Viropharma: Investigator, Research support
N. Lu, None
D. Ostrander, None
R. Avery, Viropharma/Shire: Investigator, Research support
Astellas: Investigator, Research support
Chimerix: Investigator, Research support
Merck: Investigator, Research support
K. A. Marr, Astellas: Consultant and Scientific Advisor, Consulting fee
Merck: Consultant, Consulting fee
Pfizer: Consultant, Consulting fee