Infections Caused by Mycobacterium tuberculosis in Recipients of Hematopoietic Stem Cell Transplantation

Abstract

Mycobacterium tuberculosis (M. tuberculosis) infections are uncommon in recipients of hematopoietic stem cell transplantation. These infections are 10–40 times commoner in recipients of stem cell transplantation than in the general population but they are 10 times less in stem cell transplantation recipients compared to solid organ transplant recipients. The incidence of M. tuberculosis infections in recipients of allogeneic stem cell transplantation ranges between <1 and 16% and varies considerably according to the type of transplant and the geographical location. Approximately 80% of M. tuberculosis infections in stem cell transplant recipients have been reported in patients receiving allografts. Several risk factors predispose to M. tuberculosis infections in recipients of hematopoietic stem cell transplantation and these are related to the underlying medical condition and its treatment, the pre-transplant conditioning therapies in addition to the transplant procedure and its own complications. These infections can develop as early as day 11 and as late as day 3337 post-transplant. The course may become rapidly progressive and the patient may develop life-threatening complications. The diagnosis of M. tuberculosis infections in stem cell transplant recipients is usually made on clinical grounds, cultures obtained from clinical specimens, tissues biopsies in addition to serology and molecular tests. Unfortunately, a definitive diagnosis of M. tuberculosis infections in these patients may occasionally be difficult to be established. However, M. tuberculosis infections in transplant recipients usually respond well to treatment with anti-tuberculosis agents provided the diagnosis is made early. A high index of suspicion should be maintained in recipients of stem cell transplantation living in endemic areas and presenting with compatible clinical and radiological manifestations. High mortality rates are associated with infections caused by multidrug-resistant strains, miliary or disseminated infections, and delayed initiation of therapy. In recipients of hematopoietic stem cell transplantation, isoniazid prophylaxis has specific indications and bacillus Calmette-Guerin vaccination is contraindicated as it may lead to disseminated infection. The finding that M. tuberculosis may maintain long-term intracellular viability in human bone marrow-derived mesenchymal stem cells complicates the development of effective vaccines and strategies to eliminate tuberculosis. However, the introduction of linezolid, cellular immunotherapy, and immunomodulation in addition to autologous mesenchymal stem cell transplantation will ultimately have a positive impact on the overall management of infections caused by M. tuberculosis.

The demanding attention of tuberculosis in allogeneic hematopoietic stem cell transplantation recipients: High incidence compared with general population

“…Several risk factors for the development of TB after HSCT have been reported, including AML, CML, MDS, the use of busulfan, cyclophosphamide, TBI, corticosteroid therapy, mismatched allografts, GVHD, or history of previous TB infection [2]. Our study shows that extensive chronic GVHD is associated with the development of TB.…”

Autologous Hematopoietic Stem Cell Transplantation—10 Years of Data From a Developing Country

“…Debilitating fungal infection was observed in 1 patient only at our center and required surgical removal. Mycobacterium tuberculosis infection has been reported occasionally in both autologous and allogeneic transplant recipients, possibly due to reactivation after the myelosuppression caused by conditioning therapy [24]. Only 1 patient developed M. tuberculosis in our series.…”

Miliary tuberculosis after initiation of ibrutinib in chronic lymphocytic leukemia

“…Additionally and despite normal T cell counts, the T cell compartment in CLL is often profoundly impaired [6]. Due to the impaired cell-mediated immunity after SCT, TB is seen in recipients of allogeneic grafts mainly in endemic areas mostly within the first 90 days of SCT [7]. It is unlikely that SCT crucially contributed to the occurrence of TB because of the long interval between SCT and ibrutinib, the absence of immunosuppression, and normal T cells.…”