Peculiarities of the immune status of patients with multidrug­resistant pulmonary tuberculosis after application of treatment regimens with bedaquiline and linezolid

Objective — to investigate immuno-metabolic homeostasis in patients with new and recurrent cases of destructive forms of multidrug-resistant pulmonary tuberculosis (MDR-PTB) after treatment with bedaquiline and linezolid. Materials and methods. A clinical and laboratory examination of 175 people with MDR-PTB (89 patients with new cases and 86 patients with recurrent cases of destructive forms of MDR-PTB). The study was performed before and after treatment with bedaquiline and linezolid. The total leukocytes count (L), the leukocyte differential count (leukocyte formula), was determined in all subjects, The content of populations and subpopulations of lymphocytes were calculated using monoclonal antibodies to CD3+, CD4+, CD8+, CD19+, CD23+, CD56+ lymphocytes antigen in the reaction of indirect immunofluorescence. Quantitative determination of serum immunoglobulins was performed by Manchini radial immunodif­fusion in a gel. The level of circulating immune complexes (CIC) was determined by the spectrophoto­metric method by precipitation in polyethylene glycol. Results and discussion. In patients with new cases of destructive forms of MDR-PTB to treatment revealed hypersensitivity reactions of the first and the fourth type. Expressed activation of humoral and killer parts of immunity detected. In patients with recurrent cases of destructive forms of MDR-PTB before treatment, there are pronounced hypersensitivity reactions of the fourth type and activation of the humoral and killer parts of the immune system.Patients with new cases of destructive forms of MDR-PTB after application of treatment regimens with bedaquiline and linezolid have hypersensitivity reactions of the first and fourth types. Activation of humo­ral and killer parts of immunity detected. In patients with recurrent cases of destructive forms of MDR-PTB after the application of treatment regimens with bedaquiline and linezolid revealed a pronounced hypersensitivity reaction of the first type and activation of the killer and humoral parts of the immune system. Conclusions. In patients with new cases of destructive forms of MDR-PTB before treatment revealed T-cell immunodeficiency, which is expressed by a decrease in the level of T-lymphocytes (1.7 times relative to normal) and T-helpers (twice below normal). In patients with recurrent cases of destructive forms of MDR-PTB before treatment revealed T-cell immunodeficiency with a marked decrease in the level of T-lymphocytes (1.8 times normal) and T-helpers (1.8 times below normal). In patients with new cases of destructive forms of MDR-PTB after the application of treatment regimens with bedaquiline and linezolid revealed activation of the T-cell immune system due to increased levels of T-suppressors. In patients with recurrent cases of destructive forms of MDR-PTB after the application of treatment regimens with bedaquiline and linezolid revealed T-cell immunodeficiency due to the reduced content of T-lymphocytes (1.5 times below normal), namely T-helpers (1.9 times lower than normal).

Activity of blinatumomab in lymphoblastic leukemia with impaired T-cell immunity due to congenital immunodeficiency

Blinatumomab, a single-chain, bispecific, T-cell–engaging antibody targeting CD19, is effective in B-precursor acute lymphoblastic leukemia (BCP-ALL), even in the context of chemotherapy-related partial T-cell immunodeficiency. We report 2 patients with BCP-ALL and congenital T-cell immunodeficiency, who obtained an excellent response to blinatumomab. The first, a 6-year-old girl with Schimke immuno-osseous dysplasia (SIOD) and combined immunodeficiency disorder (CID) obtained a minimum residual disease–negative (MRD−) remission of high hyperdiploid BCP-ALL with blinatumomab. At last follow-up, the remission had been sustained for 14 months from diagnosis. The second was a 9-year-old boy with Omenn syndrome and CID who received a mismatched bone marrow transplant from his mother at the age of 4 months and was diagnosed with t(3;11)+ (KMT2A-LARS2) BCP-ALL 9 years after his transplant. He received a 4-drug induction followed by blinatumomab for persistent MRD as a chemotherapy-sparing bridge to transplant and achieved an MRD− remission. T-lymphopenia, whether congenital or acquired, does not compromise the efficacy of blinatumomab.

Facts and Challenges in Immunotherapy for T-Cell Acute Lymphoblastic Leukemia

T-cell acute lymphoblastic leukemia (T-ALL), a T-cell malignant disease that mainly affects children, is still a medical challenge, especially for refractory patients for whom therapeutic options are scarce. Recent advances in immunotherapy for B-cell malignancies based on increasingly efficacious monoclonal antibodies (mAbs) and chimeric antigen receptors (CARs) have been encouraging for non-responding or relapsing patients suffering from other aggressive cancers like T-ALL. However, secondary life-threatening T-cell immunodeficiency due to shared expression of targeted antigens by healthy and malignant T cells is a main drawback of mAb—or CAR-based immunotherapies for T-ALL and other T-cell malignancies. This review provides a comprehensive update on the different immunotherapeutic strategies that are being currently applied to T-ALL. We highlight recent progress on the identification of new potential targets showing promising preclinical results and discuss current challenges and opportunities for developing novel safe and efficacious immunotherapies for T-ALL.

A First Case Report of DiGeorge Syndrome from Ethiopia Highlights Challenges in Identifying and Treating Children with Primary T-Cell Deficiencies in Low Resource Settings

Background. Cellular primary immunodeficiencies are rarely reported from Africa. DiGeorge syndrome is a commonly recognized form of a congenital T-cell deficiency. The disorder is characterized by hypoplastic or aplastic thymus, hypocalcemia, recurrent infections, and other associated congenital defects. Case Report. We report an eleven-month-old infant presenting with recurrent chest and diarrheal infections, failure to thrive, lymphopenia, hypocalcemia, and hypoplastic thymus on imaging. A diagnosis of DiGeorge syndrome was confirmed after determining very low CD3 and CD4 levels. Conclusions. We describe the first case report of an Ethiopian child with a congenital T-cell immunodeficiency. We have outlined essentials for diagnosis and management of cellular primary immunodeficiency disorders in low resource settings.