T-Cell Disorders Treatment & Management

Updated: Oct 14, 2021
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Harumi Jyonouchi, MD  more...
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Treatment

Approach Considerations

Exploration of mutations and analysis of cellular changes related to lymphocyte defects and immune dysregulation has fueled the development of novel treatment options for some primary T-cell disorders that might otherwise by fatal. [20]  It is important to integrate clinical, histopathological, immunohistochemical, and molecular findings in patients with T-cell lymphoid proliferations. [21]

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Medical Care

The FDA approved the first therapy to reconstitute immunity in children with congenital athymia in October 2021. Allogeneic processed thymus tissue (Rethymic) is implanted surgically in the quadriceps muscle of the recipient. 

Approval of allogeneic processed thymus tissue was based on 10 prospective single-arm, open-label studies that included 105 patients from 1993 to 2020. Survival rates were analyzed with the longest follow-up period of 25.5 years. In the EAS, Kaplan-Meier estimated survival rates (95% CI) were 77% (0.670–0.841) at 1 year and 76% (0.658–0.832) at 2 years. For patients who were alive at 1 year post implantation, the estimated long-term survival rate was 94% at a median follow-up time of 10.7 years. For the patients in the clinical trials, naïve T-cell levels were measured using flow cytometry at 6, 12, and 24 months after implantation. Patients in the clinical trials started out with very few naïve T cells, but naïve CD4 and CD8 T cells began to reconstitute over the first year, with a durable increase through the second year. Reductions in the number of infections over time during the first 2 years after treatment were statistically significant (p < 0.001). [22]

Sinopulmonary infections with common viral and bacterial agents are characteristic of partial T-cell disorders. Conventional therapy appropriate for the immunologically healthy host is administered, although patients with T-cell defects characteristically have more prolonged and severe clinical courses. Prophylaxis against infection by respiratory syncytial virus (RSV) using RSV-polyclonal immunoglobulin or the humanized monoclonal antibody, palivizumab, is specifically indicated in patients with T-cell disorders. Mucocutaneous candidiasis is more frequent but is conventionally treated in patients, and the disease uncommonly disseminates.

Bone marrow transplantation must be offered early in infancy to patients with Wiskott-Aldrich syndrome (WAS) to ensure better outcome. In addition, transplantation is the only effective treatment in most patients with Chediak-Higashi syndrome (CHS) and is indicated prior to development of the accelerated phase. Patients with DiGeorge syndrome (DGS) rarely have complete absence of T-cell function; these few patients require stem cell reconstitution, usually via bone marrow transplantation.

Routine childhood immunizations are usually indicated because patients with partial T-cell defects, even those with abnormalities in immunoglobulin levels, often respond with adequate specific antibody titers, although the levels may be lower than normal. However, administration of the oral live-attenuated poliovirus vaccine is contraindicated and should be replaced with the inactivated poliovirus vaccine. As a result of the frequency of bacterial sinopulmonary infections, administration of the conjugated pneumococcal vaccine (Prevnar) is particularly important.

Usually, treatment in persons with autoimmune disorders mirrors that for hosts who are immunocompetent. However, infectious complications pose a greater risk in patients with T-cell disorders who receive systemic steroids and other immunosuppressive drugs.

Overproduction of cytokines by T cells and other effector cells of the immune system can be controlled through use of anticytokine monoclonal antibodies, such as anti–tumor necrosis factor (TNF)–α (infliximab), for inflammatory bowel disease.

Insulin-dependent diabetes mellitus (IDDM), hypoadrenalism, hypothyroidism, glomerulonephritis, and autoimmune enteropathy present in patients at unusually young ages, typically in patients younger than 1 year who have immune dysregulation/autoimmunity disorders.

Patients with WAS and older patients who have chromosomal breakage syndromes (CBSs) have a high risk of malignancy. Chemotherapy in patients with ataxia telangiectasia (AT) and Nijmegen breakage syndrome (NBS) is not usually tolerated at conventional doses because of DNA instability. Thus, lower doses and longer intervals between doses are usually used.

Gene therapy is being studied as a possible alternative to allogeneic hematopoietic stem cell transplantation for the treatment of severe combined immunodeficiency (SCID), [23] as well as a treatment for WAS. [24, 25, 26]

Several drugs that block the lymphocyte voltage-gated potassium channel, kv1.3, as well as biologic therapies, are being explored as autoimmune disease treatments. [27, 28]

Graft versus host disease (GVHD) has been prevented successfully in mice through ex vivo selection and expansion of CD4(+)CD25(+) immunoregulatory T cells, specific for recipient alloantigens. [29]

Mesenchymal stem cells have shown some promise in enhancing engraftment and both preventing and treating GVHD in bone marrow transplant recipients. [30]

Antithymocyte globulin has been shown to reduce acute and chronic GVHD in randomized trials. [31]

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Surgical Care

With the exception of cardiac procedures in patients with DGS, surgery is not usually required for patients with partial T-cell disorders.

Splenectomy has been used to control autoimmune hemolytic anemia and thrombocytopenia in patients with WAS and immune dysregulation/autoimmunity syndromes. In patients with WAS and Fas and Fas ligand deficiencies, overwhelming postsplenectomy sepsis has occurred despite immunization and antibiotic prophylaxis directed against Streptococcus pneumoniae.

Tumor-stage vulvar mycosis fungoides responded to local low-dose radiotherapy (Bakar et al, 2014).

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Consultations

Clinical immunologists and geneticists are integral to the evaluation and treatment in patients with partial T-cell disorders.

Intervention performed by neurologists is important in patients with CBSs and CHS.

Physical therapists and rehabilitation specialists are critical to achieving optimal functioning in patients with CBSs and CHS.

Autoimmune disorders are best controlled with the help of collaboration by hematologists, endocrinologists, and gastroenterologists.

The malignancies in CBSs may require alteration of chemotherapeutic regimens because of the increased DNA instability of host cells.

When a T-cell disorder is suspected, the Immune Deficiency Foundation offers a consultation service for physicians. Laboratories in Seattle (the University of Washington), Boston (Children's Hospital Boston), and New York City (The Jeffrey Modell Foundation) are funded to provide molecular analysis or can assist in contacting other research facilities.

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Diet

As with other primary immunodeficiencies, supplemental nutrition can be an essential component of care for the patient with chronic enteropathy or chronic infection.

Unfortunately, many patients remain thin with short stature or become wasted.

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Activity

The goal of care is to optimize daily functioning. Care to minimize exposure to certain viruses (eg, RSV, varicella) is important, but complete isolation is not recommended for patients with partial T-cell disorders.

Patients with WAS and CHS who have increased bleeding tendencies must be educated to avoid trauma and, especially, to wear helmets during certain activities.

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