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Lung Transplant Rejection


Detecting Rejection  |   Acute Rejection  |  Antibody Mediated-Rejection    Chronic Rejection


“Rejection” is a word that someone who has had a lung transplant never wants to hear. It sounds scary — and it can be — because you want your body to accept your new lung(s) completely. When you hear the word “rejection,” you know that your body is having a problem accepting your new lung(s) as its own. Gaining an understanding of acute and chronic rejection will allow you to have an informed discussion with your doctor about treatment options.


DETECTING REJECTION

As a lung transplant recipient, you will have scheduled bronchoscopies following your transplant. A bronchoscopy is a procedure in which, while you are typically under sedation, a tube is passed down your throat into your lungs. A small piece of your lung is snipped and biopsied to determine whether acute rejection is present. A lavage (rinsing) of your lungs is also done to determine if there is any infection in the transplanted lung(s). Per your transplant center’s protocol, you could have bronchoscopies daily (while in the hospital), weekly, or monthly during the first year post-transplant. After the first year, you may have a routine bronchoscopy at every annual visit. Or you may have a bronchoscopy only if rejection or infection is suspected (or if other problems are present, such as stenosis).


ACUTE REJECTION (T-Lymphocyte Rejection)

Around 60 percent of lung transplant recipients will experience an episode of acute rejection within the first year. Acute rejection is diagnosed by bronchoscopy results, a chest x-ray, and a drop in your Fev1 of greater than 10 percent.  Your transplant team will tell you symptoms to look for that may indicate acute rejection. Treatment for acute rejection includes a high dose of corticosteroids. Usually this consists of three daily doses of intravenous Solu-Medrol, which may be done in a hospital setting or at home, depending on how you feel and your doctor’s preference. It is usually followed by a prednisone taper over the next few weeks until you are back down to your baseline dose. Follow-up bronchoscopies may be done to determine whether the rejection is gone. Unfortunately for some, treatment with corticosteroids may not rid your lungs of acute rejection. Other therapies that can be used if steroids do not help are cytolytic therapy such as rabbit anti-thymocyte globulin (RATG) or horse anti-thymocyte globulin. These are aggressive therapies designed to deplete your T-lymphocytes (which are the cause of most acute rejection episodes) and interfere with their normal function. If you need this therapy, you will be monitored in the hospital for the duration of the therapy (5-7 days). There may be some uncomfortable side effects from this treatment. Your doctor will discuss these with you and will also determine what prophylactic medications you may need to prevent infection following the treatment. Because depleting your T-lymphocytes weakens your immune system even further than your maintenance anti-rejection therapy, you will be at increased risk of infection for weeks to months following treatment. You will need to take the necessary precautions to avoid exposing yourself to infection. If you are still experiencing acute rejection following steroid treatment and anti-thymocyte globulin therapy, you may receive a drug called Campath (alemtuzumab). Campath is an extremely potent medication that can only be given in a hospital setting. It is given as a one-time dose, and can cause many side effects. Prophylactic medications must be given for several months to years after the dose is given, and your immune system will be severely compromised for a long time. You must use extreme infection control following Campath. Your doctor will discuss with you the medications you will be taking, how to avoid infections, and how to identify side effects and symptoms of infection.


ANTIBODY MEDIATED-REJECTION

Antibody-mediated rejection is another form of rejection. It is treated differently than T-Lymphocyte rejection. This form of rejection is caused by anti-HLA antibodies that target your transplanted lung(s). These antibodies can be present before transplant (especially if you have had a previous pregnancy, transplant, or blood transfusion) or can develop after transplant. Treatments for antibody-mediated rejection are different than those used for T-Lymphocyte rejection. Treatments can include plasmapheresis, intravenous immunoglobulin (IVIG), Rituxan (rituximab), and Velcade (bortezomib).


CHRONIC REJECTION

(Bronchiolitis Obliterans Syndrome) The lungs have the highest rate of rejection compared to all other transplanted solid organs. Therefore, life expectancy is shorter for those who’ve had lung transplants than for those who’ve had other solid organ transplants. The number one reason for this is chronic rejection, or BOS (Bronchiolitis Obliterans Syndrome). BOS is present in approximately 48 percent of recipients within five years of the transplant and in 76 percent of recipients within 10 years. This disease course varies among each and every transplant recipient, and there are some patients who will never develop BOS post-transplant. Diagnosis of BOS is tricky. It can only be detected 30 percent of the time via biopsy taken during a bronchoscopy. Therefore, diagnosis must usually rely upon the absence of any other cause for a declining fev1 and a decrease in your forced expiratory flow (FEF 25-75).  Since BOS is characterized by dense fibrous scar tissue in the small airways of the lungs, air may become trapped in the small airways. A chest CT scan may be ordered to determine if air trapping is present. Risk factors for BOS include, but are not limited to:

  • gastro-esophageal reflux disease (GERD).
  • numerous acute rejection episodes.
  • poor compliance with anti-rejection treatment.
  • primary lung graft dysfunction (PGD).
  • fungal, bacterial, and viral infections.

BOS can also occur without any risk factors present. Treatments that may be tried if BOS is suspected are:

  • changing the dose of your anti-rejection medications.
  • adding additional medications to your immunosuppressant regimen, such as Cellcept, Everolimus, Serolimus, or Azithromycin.
  •  RATG (three to five IV doses).
  • Campath (single IV dose).
  • photopheresis treatments.
  •  a surgical procedure called a Nissen fundoplication (stomach wrap) if GERD is present.

Unfortunately, there are no proven treatments for BOS. The Lung Transplant Foundation’s mission is to fund research into this life-shortening syndrome. Multi-center clinical trials are needed to adequately study the onset, progression and treatment options for BOS. As a patient, you can do your part by taking the best care of yourself, being compliant with all medications, and reporting any symptoms to your transplant team.

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