Latent Tuberculosis in Hematopoietic Stem Cell Transplantation: Diagnostic and Therapeutic Strategies to Prevent Disease Activation in an Endemic Population

Introduction

Latent tuberculosis infection (LTBI) affects one third of the world population. It is well known that patients with immunodeficiency are at a higher risk of developing active tuberculosis (ATBI). Hematopoietic stem cell transplant (HSCT) recipients have an incidence of ATBI 10 to 40 times greater when compared to the general population, this being related to a higher morbidity and mortality. The aim of this study was to determine the prevalence of LTBI and incidence of ATBI after transplant in recipients and donors of HSCT living in an endemic region.

Methods

Retrospective single-center study that included all HSCT recipients and donors treated and followed at our Institution between February 2000 and June 2018. LTBI and ATBI were categorized according to WHO definitions.

Results

A total of 411 patients were included: 125 allogeneic HSCT (allo-HSCT) recipients, 167 autologous HSCT (auto-HSCT) recipients, and 119 HSCT donors. Median age of the group was 34 years (range 11-70) and 59.9% were male (n=246). Baseline diagnoses that led to HSCT were: acute leukemia in 30.9% (n=127), lymphoma in 17.3% (n=71), and monoclonal gammopathy (MG) in 10.7% (n=44) (Figure 1). Allo-HSCT donors were matched related donors (MRD) in 84.8% (n=106), matched unrelated donors (MUD) in 3.2% (n=4), haploidentical in 10.4% (n=13), and umbilical cord in 1.6% (n=2). The source of HSCT was peripheral blood (PB) in 175 patients (59.9%), bone marrow (BM) in 50 patients (17.1%), primed-BM in 65 patients (22.3%), and umbilical cord in 2 patients (0.7%).

All patients were evaluated pre-HSCT with tuberculin skin test (TST) and thoracic imaging. LTBI was diagnosed in 109 patients (26.5%): 21%, 20%, and 41.2% of patients were auto-HSCT recipients, allo-HSCT recipients, and allo-donors; respectively. One-hundred and seven patients had a positive TST and two patients presented findings suggestive of LTBI on chest X-ray. Seventy-eight percent of LTBI-HSCT recipients were further evaluated with chest CT (n=29), sputum (n=26), gastric fluid (n=15), and/or urine (n=25) cultures to rule out ATBI according to treating physician's criteria. In contrast, only 42.9% (n=21) of donors were further evaluated with chest CT (n=11), sputum (n=15), gastric fluid (n=2) and/or urine (n=12) cultures. All cultures were negative at follow-up.

At LTBI diagnosis 80 patients (73.3%) initiated treatment with isoniazid (INH) 300mg daily for a minimum of 6 months. Treated HSCT recipients represented 91.7% and donors were 51%. Median days of therapy received before HSCT were 76 days (range 0-732) in HSCT recipients and 48 days (range 0-401) in donors.

Distribution of cases according to the patient's state of residency, excluding Mexico City, revealed an increase prevalence of cases in the southern border of the country (Figure 2).

ATBI incidence at 1 year of follow-up in the cohort was 0%. Only one patient developed a pulmonary mycobacterial-related infection; however, the species identified was M. chelonae.

Conclusions

To our knowledge, this is the first study that evaluates the prevalence of LTBI among HSCT recipients in a Latin American country where tuberculosis is endemic. We identified a prevalence of LTBI similar to what the WHO estimates; however, the presence of lower rates in recipients compared to donors in our population suggests a negative impact of depressed humoral immunity over the TST diagnostic yield. Interestingly, we do not report any ATBI cases post-transplant; pre-transplant diagnostic strategies, as well as length of treatment may be influencing factors for these outcomes. Collaborative working groups are required to stablish the best diagnostic and therapeutic approach in order to improve ATBI-attributable morbidity and mortality in this vulnerable HSCT-patient population.

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