1, Epidemiology of tuberculosis infection
Between 2014 and 2019, a total of 1347 patients were diagnosed with MDS in our center, including 113 patients were MDS with single lineage dysplasia (MDS-SLD), 9 patients were 5q- syndrome, 209 patients were MDS with multi lineage dysplasia (MDS-MLD), 94 patients were MDS-unspecified (MDS-U), 416 patients were MDS with excess blasts 1 (MDS-EB1), and the rest 407 patients were MDS with excess blasts 2 (MDS-EB2). Among them, thirty-four patients were diagnosed with TBI. The overall incidence of TBI in patients with MDS during the study period was 2.5 %, and the numbers of TB cases among each WHO subtype of MDS were as follows: SLD, n = 2 (1.77%); MLD, n = 5 (2.39%); MDS-U, n = 2 (2.13%); MDS-EB1, n = 12 (2.88%); MDS-EB2, n = 13 (3.19%); Patients with MDS-EB seemed more likely to develop TBI than patients with other sub-type (3.04% vs. 2.1%, p = 0.334; odds ratio, 1.45; 95% confidence interval, 1.39- 4.41),but the difference was not significant.
2, Clinical and laboratory characteristics of patients with tuberculosis infection
Among 34 patients diagnosed with MDS and TBI during the period of study, male to female was 24:10,median age was 61 years old, 18 had intermediate-1, 13 had intermediated-2, and 3 had high risk according to IPSS risk. When classified through IPSS-R, 2 patients had low, 10 had intermediate, and 15 had high risk, while the rest 5 had very high risk. Moreover, fifteen patients were synchronously diagnosed with TBI and MDS and the rest 19 patients were developed TB after MDS more than 3 months (non-synchronous).
Persistent fever appeared in almost all patients and most were high fever without regular type, other clinical features were not predicative, all patients had no response to general spectrum antibacterial drugs. In synchronous group, only one patient had previous TBI, while in the non-synchronous group, 12 patients had a previous history of TBI. Further analysis showed that patients diagnosed synchronously with TBI were more likely to have higher risk classification (14/15 vs. 8/19, P=0.002 ), more frequent persistent high fever (11/15 vs. 7/12, P=0.03 ) and higher tendency to transform to AML (8/15 vs. 4/19, P=0.04 ). The median time to AML was significantly shorter in the synchronous group (7.68 months) than those in non-synchronous group (23.83 months, P<0.01). However, other clinical characteristics, such as gender, age, blood cell count, and organs involved in TBI, were not significantly different between the two groups. The baseline characteristics of the patients were given and compared in Table 1.
3, Diagnosis of TBI
Only 4 patients (11.76%) had both positive acid-fast bacilli staining of samples including sputum and lymphoid tissue and culture for TB in our study, and 22 patients had just positive tissue staining without culture results. The remaining 8 patients were clinical-radiological TBI. Besides, the interferon-γ release test of all patients in our study was positive. The organ most common involved with TBI was lung, followed by lymph nodes, which were seen in 70.5% (24/34) and 41.18% of patients respectively. TBI occurred only in lung and lymph node in 13 and 9 patients respectively, and 13 (38.24%) patients had pulmonary involvement also had concomitant extra-pulmonary tuberculosis (lymph nodes, 5; Pleural cavity, 4 ), two patients had lumbar tuberculosis, one patient had TBI of the skin,there was no significant difference in organs involved between the two groups.
4, The treatment and outcome of patients with TBI and MDS
Most patients received supportive care for MDS (22/34, 64.71%), eleven patients received decitabine therapy, and only 1 patient received hematopoietic stem cell transplantation (HSCT). For 22 patients received support care,10 have transformed to AML, but in those received decitabine therapy, only 2 patients proceeded to AML. In synchronous group, 10 patients received supportive care and 5 patients received decitabine therapy, while in non-synchronous group, 12 patients received support care and 7 received active therapy, and there were no significant difference between the two groups.
Thirty-three patients received ATT, among which 26 received standard ATT (isoniazide, rifampin, ethambutol, and pyrazinamide) and 7 (21.2%) patients received fluoroquinolone based ATT. Twenty-four patients had response to ATT, and 9 patients had no response,manifesting as lasting fever, six patients were in synchronous group and 3 in non-synchronous group. Two patients died of TBI without control, and 16 patients died due to MDS progression, among which 9 patients had transformed into AML, and 4 patients died of complication related to treatment. For patients were still alive, 7 have progressed disease, and 3 patients have transformed into AML, 5 patients are still on ATT.
The median OS of all patients was 25.63(95% CI 12.50-38.76)months (Fig 1A). In synchronous group, it was just 14.17 (95% CI 13.17-15.18) moths, while in non-synchronous group, OS was relatively longer, 34.07 (95% CI 13.61-54.53) moths ( P = 0.01)(Fig 1B). While OS were compared between patients received different treatments, it was 25.63(95% CI 10.85-40.41) months in support care group, and 29.53(95%CI 0-59.51) months in patients received decatabine and HSCT (P=0.32).(Fig 1C).