Leukocyte Adhesion Deficiency: Treatment, Cost and Side Effects

Leukocyte Adhesion Deficiency is a rare autosomal recessive disorder characterized by immunodeficiency which causes frequent infections. Immunodeficiency is described as a state wherein the immune system of a body's usual work, which is to fight infectious diseases and cancer is either compromised or completely absent. Immunodeficiency can be of two types, primary, and secondary. Primary immunodeficiency is also known as congenital recessive immunodeficiency and is very rare. They are usually hereditary and autosomal recessive( one of the ways a trait, disorder, or disease can be passed down through families, a disease in this case. The abnormal gene must be present in two copies in order for the disease to develop). The treatment of these usually involves antibody infusions, long-term antibiotics and even stem cell transplantation in some cases. The exact treatment used depends mostly on the nature of the defect. Secondary immunodeficiency is also known as acquired immunodeficiency. Secondary immunodeficiency can result from immunosuppressive(Reduction of the activation of efficacy of the immune system.) agents, such as aging, malnutrition, some medications like chemotherapy and immunosuppressive drugs used after organ transplants and glucocorticoids(Steroid hormones that are a part of the feedback mechanism of the immune system. It reduces certain aspects of immune function), along with environmental toxins such as mercury, pesticides, and petrochemicals like ethylphenol and xylene. A person who has immunodeficiency of any kind is known to be immunocompromised and could be potentially vulnerable to infections and cancer. Leukocyte adhesion deficiency is a form of immunodeficiency. It is congenital recessive immunodeficiency, also known as primary immunodeficiency. Leukocyte adhesion deficiency is divided into three subtypes

1. leukocyte adhesion deficiency 1,
2. leukocyte adhesion deficiency 2 and
3. leukocyte adhesion deficiency 3.

Leukocyte adhesion deficiency was first identified in the 19070s and causes recurrent bacterial infections, defects in neutrophil adhesion, and a delay in umbilical cord sloughing.

The treatment of LAD syndromes are usually directed toward the specific symptoms that are apparent in each individual. Antibiotic therapy is the main aspect of treatment to treat the repeated, characteristic infections associated with the leukocyte adhesion deficiency syndrome disorders. During acute infectious episodes, prompt antibiotic therapy is extremely crucial. Moderate or mild forms of leukocyte adhesion deficiency usually respond to conservative therapy and prompt treatment for acute episodes. For patients with leukocyte adhesion deficiency 2, using fucose supplementation to correct the underlying defect must be attempted. Treating life-threatening infectious complications during some situations in leukocyte adhesion deficiency may require white blood cell transfusions. These transfusions are done rarely, and only in cases where all other options have been rendered useless, due to the possibility of adverse side effects during the transfusion itself. Stem cells found in bone marrow that produce various types of blood cells are termed as hematopoietic stem cells. The only therapy for individuals with LAD syndromes that actually cures it is a bone marrow transplant, which involves the donation of stem cells from another person, who is usually a closely matched family member. This is extremely risky, as stem cell transplants can cause severe, even life-threatening complications, and they are usually reserved for those who have no other viable treatment options. The survival rate of those who have had a bone marrow transplant to attempt to cure LAD 1 is seventy-five percent, which is encouraging. Researchers are studying the use of implanting healthy copies of the ITGB2 gene into the hematopoietic, or bone marrow stem cells of individuals who have LAD 1, as it is a promising concept which could potentially cure it. However, these forms of treatment will not be seen used widely for a long time.

Many of the types of treatment that have been described above are not used on all individuals who have LAD. For example, stem cell transplants are the only curative therapy for individuals with LAD syndromes, and even this is only used in individuals with severe complications or individuals who have no other viable treatment options, as stem cell transplants can cause complications, such as fatigue and weakness for months after the transplant itself, bleeding and anemia, infections, liver damage and disease, and dry and damaged lungs esophagus, moth, and other organs. Moreover, if you are using a donors stem cells, which is what is usually done in the treatment of LAD, there are complications such as graft versus host disease which develops when blood cells formed from the donor's stem cells think your cells are foreign and attack them. This can be mild, or even life-threatening, and affects a large number of those who use donor stem cells for transplants, like LAD patients, who use the stem cells of closely matched family members. Many other potential treatments are still in the experimental phase, and will still take a long time to get into normal practice.

Many people who are suffering from LAD will not even be considered for some of the treatments for this disease, as these treatments are still very experimental, and some have very adverse risks, that can potentially even be fatal. For example, treating life-threatening complications during some situations in leukocyte adhesion deficiency may require white blood cell transfusions, which have adverse effects such as delayed hemolytic reaction, anaphylactic reactions, which happen within minutes of starting a transfusion and may be life-threatening, due to swelling of the face and the throat, shortness of breath, and low blood pressure.

There is still no definite treatment for LAD other than hematopoietic stem cell transplantation, which, as has been discussed above, is far from safe. Complications include failure to engraft, rejection(graft vs host disease), and acute graft vs host disease. Less than five percent of patients who undergo this treatment experience failure to engraft and rejection, which causes an irreversible decline in blood counts, which can be treated using corticosteroids for several weeks. Acute graft vs host disease occurs in between forty to eighty percent of those who undergo this treatment and can cause fever, rash, hepatitis with hyperbilirubinemia, vomiting, diarrhea, abdominal pain and weight loss. Diagnosis of acute GVHD is obvious based on history, physical examination, and liver function test results, and is treated by using 2 mg/kg of methylprednisolone once a day. Later complications can include chronic GCHD and disease relapse.

If you have taken a stem cell transplant, and are feeling a fever, you should alert your doctor or nurse immediately. You will need to regularly return to the hospital to monitor your progress if you experience a persistent headache, a rash or itching, a sudden decline in your health, any unusual bruises and bleeds e.g. blood in your bowel movements, urine, bleeding gums or nose bleeds, or any such symptoms. You will be monitored very closely in the days following your transplant, and they will take your blood regularly to ensure your body has accepted the new stem cells, and the new ones are doing their job in your bone marrow.

Recovery from a stem cell transplant will take some time. This recovery time varies from person to person and is dependent on your disease, which in this case is LAD. It also depends on any other treatments you received or any complications you may have experienced, like some of the ones mentioned above. For an autologous transplant, recovery usually takes about three to six months, while if you have had an allogeneic transplant, recovery can take as much as twelve to eighteen months. Regular visits to the hospital to monitor the progress of your treatment will be necessary.

The transfusion of the white blood cells alone cost about sixteen thousand rupees in India. However, the cost of stem cell transplants cost a lot of money, as they are still considered experimental by many leading experts. If a matching donor is found in your factory, a stem cell transplantation costs about nineteen lakh rupees in Inida, and if a matching donor is not found, the price increases by about twelve lakh, which makes the total price abot thirty one lakh rupees.

Most of the forms of treatment for LAD are just to curb some of the symptoms, and the only permanent fix is a stem cell transplantation, which is risky, experimental and costly.

Currently, stem cell transplantation is the only permanent fix. However, some alternatives may come up later, as some treatments show promising results, like gene therapy which can be considered as an alternative to the treatment.