The Role of Tuberculin Skin Test As a Guide to Preventive Chemotherapy for Latent Tuberculosis Infection in Haematopoietic Stem Cell Transplantation in a Region with Intermediate Prevalence and Routine BCG Vaccination: A Preliminary Report from Turkey

Turkey is a country with intermediate tuberculosis (TB) prevalence (24 cases per 100000 population) where BCG vaccination is mandatory. Immunocompromised patients are at risk for TB infection. However, tuberculin skin test (TST) has limitations in immunocompromised patients while diagnosing latent TB infection (LTBI) and commencing isoniazid (INH) chemoprophylaxis. After 2000 consensus statements recommended INH prophylaxis in higher risk patients with a cut-off TST value of 5 mm. This retrospective study was conducted to determine the frequency of TB in HSCT recipients and the role of chemoprophylaxis with different cut-off values of TST (<5 mm, 5 to 10 mm, 10 to 20 mm, and ≥ 20 mm) in a region with intermediate TB prevalence.  Patients and Methods: Five hundred and ninety two patients [320 (54 %) autologous and 272 (46 %) allogeneic] transplanted at our center between September 2003 and July 2014 and survived for ≥ 100 days post-transplantation were included. The median age was 51 years-old (range 16- 71) in autologous and 29 years-old (range 15- 64) in allogeneic HSCT recipients. The decision to initiate INH prophylaxis was usually based on universal guidelines however modifications were also made at the discretion of the pulmonologist responsible for the pre-transplantation consultation or the new released guidelines. Anergy was defined as any reaction size of 0 to 2 mm in diameter. Results: BCG scar data was available in 148 of 320 autologous (46,3 %) and 133 of 272 (48,9 %) allogeneic HSCT recipients. Distribution of positive BCG scar and INH prophylaxis with respect to TST values are given in table. Anergy was detected in 141 (44,1 %) of autologous and 124 (45,7 %) of allogeneic HSCT recipients. Positive BCG vaccination scar data was available in 47% of anergic patients.  Ninety- two (28,8 %) of autologous and 64 (23,5 %) of allogeneic HSCT recipients received INH prophylaxis. None of the allogeneic HSCT recipients and 1 in 320 (0,3 %) patients in autologous HSCT developed TB. This patient was TST anergic prior to transplantation and was not on chemoprophylaxis. Conclusion: Our data showed low frequency of TB after HSCT despite variable chemoprophylaxis practices. Recent guidelines recommended reduction of TST threshold to 5 mm in higher risk patients. However our results suggest that these general guidelines do not apply to all patients and all regions.

Table Distribution of BCG scar positivity and presence of INH prophylaxis with respect to TST values

	Autologous HSCT	Allogeneic HSCT
	N=320	N=272
TST value	Positive BCG scar/INH prophylaxis/total # of patients	Positive BCG scar/INH prophylaxis/total # of patients
0-4,9 mm 5- 9,9 mm 10- 19,9 mm ≥ 20 mm data not available	68/13 /153 21/14/ 37 53/56/ 87 5/9/ 17 26	70/10/ 137 24/16/ 33 31/29/ 57 7/7/ 8 37