We identified 52 patients with active Mtb infection diagnosed between January 2006 and December 2014, resulting in an average of 6 new cases per year and an overall incidence rate of 0.2 cases per 1000 new cancer diagnoses, Figure 1. Table 1 compares the characteristics and outcomes of active Mtb infection in patients with or without a cancer diagnosis. The two groups were similar except that patients with cancer were significantly older with a median age of 61 years (range: 33–85) as compared to patients without cancer (median age of 53 years [range: 16–78]).
Overall, 36 patients (69%) were male (11 [55%] without cancer and 25 [78%] with cancer). A plurality of patients were Asian (24 [46%]), followed by non-Hispanic white (13 [25%]), Hispanic (10 [(19%]), and black (5 [10%]). A total of 31 patients (60%) were foreign-born, with 29 (56%) originating from countries with a high burden of tuberculosis [14 (70%) without cancer and 15 (47%) with cancer], including the Philippines (9), India (5), China (4), Vietnam (2), Pakistan (2), and Thailand (1). Eighteen patients (35%) had a positive history of Mtb exposure, and 6 patients (11%) had probable exposure.
Additionally, 6 patients (12%) had previously been treated for latent Mtb infection; 3 patients completed an approved regimen, while the other 3 patients’ treatment courses were interrupted. Among the patients who had previously received complete courses of treatment for latent Mtb infection, one patient had acute myeloid leukemia and was receiving ruxolitinib at the time of diagnosis; one patient had been referred for suspicion of malignancy and was not receiving any immunosuppressive medications; and one patient had psoriasis for which she received infliximab and methotrexate 3 months prior to diagnosis. Among the patients who had previously an received incomplete course of therapy for latent Mtb infection, one patient had active breast cancer and Crohn’s disease and was receiving 6-mercaptopurine at the time of diagnosis; one patient had undergone matched unrelated donor HCT 2 years prior for multiple myeloma and was receiving tacrolimus; and one patient who had been referred for suspicion of malignancy was not receiving any immunosuppressive therapy. One additional patient had recurrent active Mtb infection after he had completed an appropriate course of therapy for pulmonary disease approximately 6 months prior. This patient had underlying multiple sclerosis and was on no immunosuppressive therapy at the time of presentation; he had been referred to our institution because of suspicion of malignancy.
A total of 32 patients (62%) had an underlying malignancy, 18 (56%) with solid tumors, 8 (25%) with hematologic malignancies (6 patients with leukemia and 2 with lymphoma), and 6 (19%) had undergone HCT (2 autologous and 4 allogeneic HCT). Sixteen patients with cancer (31%) were in remission at the time of Mtb diagnosis. Seven of 32 patients (22%) had received corticosteroids in the month prior to diagnosis, and 19 out of 32 (59%) had received chemotherapy or other immunomodulating agents in the 6 months prior to diagnosis.
Among the 20 patients (38%) without cancer, the vast majority (17 [85%]) were suspected of having a malignancy but were ultimately diagnosed with active Mtb infection. Three of the patients suspected to have malignancy had received corticosteroids within the month prior to presentation for different indications; 1 patient had multiple sclerosis but was not receiving any immunosuppressive therapy at the time of presentation; and 1 patient had psoriasis and had received infliximab and methotrexate approximately 3 months prior. Of the 3 remaining patients without cancer who were not suspected of having a malignancy, one had underlying HIV infection and presented with pancytopenia; one had psoriasis; and one was a healthy healthcare worker.
The clinical presentation of Mtb infection varied amongst our patients, as shown in Table 1. The majority of patients had pulmonary disease (12 [60%] among non-cancer patients and 20 [63%] among cancer patients); 10 had extrapulmonary disease (5 [25%] among non-cancer patients and 5 [16%] among cancer patients); and 10 patients had disseminated disease (3 [15%] among non-cancer patients and 7 [22%] among cancer patients). Of the 10 patients with disseminated disease, 9 had combined pulmonary and extrapulmonary infection, and 1 had extrapulmonary infection in 2 noncontiguous body sites (abdomen and prostate). The clinical presentation of patients with extrapulmonary Mtb infection included a pelvic mass, osteomyelitis or vertebral lesions, peritoneal disease, and lymphadenitis. With regard to radiographic appearance of disease, chest imaging (most frequently a computed tomographic [CT] scan) showed a variety of findings, including nodules (24 cases), cavitary lesions (11 cases), mass (3 cases), non-nodular infiltrates (7 cases), and pleural disease (5 cases).
Table 2 shows the differences in diagnostic testing between non-cancer and cancer patients. Overall, a smear for acid-fast bacilli (AFB) was positive in 7/51 patients (4/20 [25%] without cancer and 3/31 [10%] with cancer). Types of samples included 3 sputum specimens, 2 lung tissue specimens, 1 bronchoalveolar lavage (BAL) fluid specimen, and 1 fine needle aspirate (FNA) from a lymph node. Among the 3 tissue specimens on which molecular testing was performed, 2 samples were positive and 1 negative. Mycobacterial cultures were done on tissue specimens in 19 cases (37%), BAL fluid in 14 cases (27%), other body fluid or FNA in 10 cases (19%), and sputum in 7 cases (13%); 2 positive cultures were obtained simultaneously from BAL fluid and FNA in the same patient.
Twenty-four patients were tested with an interferon-gamma release assay (IGRA) at the time of diagnosis, 22 with Quantiferon TB-Gold® (QFT.TB, Qiagen) and 2 with T-Spot.TB® (T-spot.TB, Oxford Immunotec, Inc, Memphis, TN). Sixteen IGRA tests (67%) showed positive results; 4 (17%) were negative; and 4 (17%) were inconclusive (either indeterminate or invalid).
Drug susceptibility testing was performed on all clinical isolates. The majority of isolates, 73%, were susceptible to all first-line antituberculous agents, while 14 isolates (27%) were resistant to at least one agent (3 [15%] from patients without cancer and 11 [34%] from patients with cancer). Seven of these 14 isolates (50%) were resistant to pyrazinamide, 3 (22%) to streptomycin, 2 (14%) to isoniazid, and 2 (14%) to both isoniazid and streptomycin. No multidrug resistant (MDR) Mtb isolates, defined as resistance at least to isoniazid and rifampin, were identified in this cohort.
Management and outcomes
A total of 49 patients received therapy for active Mtb infection. The remaining 3 patients were non-cancer patients who presented with a lung mass (2 patients) or pancytopenia (1 patient); these patients ultimately received medical care elsewhere. There was no difference between non-cancer and cancer patients with regard to treatment characteristics. The median time from obtaining a positive mycobacterial culture to start of therapy was 21 days (range: 5–72 days). The median treatment duration of the 32 patients with complete data available was 6 months.
Ten of 43 patients (23%) for whom data were available developed significant side effects from therapy; 9 of these 10 had cancer. However, all patients were able to restart their medications or change regimens in order to complete a full treatment course. Overall, twenty-eight of 33 patients (85%) for whom complete data were available completed their therapy. Among the 5 patients who were not able to complete a full course of therapy, 4 had treatment interruption because of death, and one patient received only 4 months of therapy for extrapulmonary tuberculosis because of concern about drug-drug interactions between chemotherapy and antituberculous medications. Chemotherapy was delayed in 9 out of 17 patients (53%) who required such treatment. Forty out of 42 patients (95%) for whom data were available had documented initial clinical and/or radiographic improvement with treatment.
Overall mortality in this cohort was 21%, with 11 deaths out of 52 patients; all 11 deaths were in patients with cancer. A total of 4 deaths occurred while on antituberculous therapy; 2 of these 4 patients died within 12 days of initiation of therapy. Death was attributed to active Mtb infection in 3 patients (6%). Two patients had advanced solid tumors (esophageal cancer and neuroendocrine tumor) and were receiving palliative care; they died with disseminated Mtb infection. The third patient had relapsed multiple myeloma after autologous HCT 6 years prior to diagnosis of pulmonary tuberculosis. Of note, 2 of the 3 patients with death attributable to active Mtb infection had isolates that were resistant to at least 1 first-line agent (1 to pyrazinamide and 1 to both isoniazid and streptomycin).