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Treatment Name: Antithymocyte Globulin (ATG, ATGAM®) + Cyclosporine (Gengraf®, Neoral®)

Antithymocyte Globulin (ATG, ATGAM®) + Cyclosporine (Gengraf®, Neoral®) is an Immunotherapy Regimen for Severe Aplastic Anemia (SAA)

How does cyclosporine + ATG (ATGAM®) work?
In aplastic anemia, it is thought that T-lymphocytes destroy healthy cells within the bone marrow that are required to make white blood cells, red blood cells, and platelets. Both cyclosporine and ATG work by suppressing both the number and function of T-lymphocytes.

Cyclosporine (Gengraf or Neoral) inhibits T-lymphocytes (T-cells) in their ability to grow and divide, and also blocks the release of a chemical from T-lymphocytes, known as interleukin-2 (IL-2), which can further activate T-cells.

ATGAnti-Thymocyte Globulin (ATGAM®) is a medication made up of antibodies derived from a horse that are specifically designed to reduce the number of lymphocytes responsible for causing bone marrow destruction. A horse is exposed to human thymus lymphocytes, and which then makes antibodies against these lymph cells. The antibodies are collected from the horse, purified, and then used to treat humans with overactive lymphocytes thought to cause aplastic anemia.

ATG (ATGAM®) may be used for either moderate or severe aplastic anemia (SAA).

Goals of therapy:
Cyclosporine + ATG is given to increase white blood cells, red blood cells, and platelets. If Cyclosporine + ATG therapy is successful and destruction of healthy bone marrow stops, white blood cells, red blood cells, and platelets grow back. This results in a decrease of symptoms from aplastic anemia such as fatigue, weakness, headaches, shortness of breath, gum bleeding, nose bleeding, bruising, and infection. In addition, red blood cell and platelet transfusions may no longer be required. Although some patients may need to wait longer, the majority of patients have a response within the first 3 months.

In some cases, after therapy with Cyclosporine + ATG, a bone marrow transplant (stem cell transplant) may be performed with the goal of cure.


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  • Antithymocyte globulin (ATG) intravenous (I.V.) infusion over 4 to 24 hours on Days 1, 2, 3, and 4
  • Cyclosporine (typically 2 to 6 oral capsules) by mouth twice daily
    • Your dose may need to be changed several times during therapy to achieve the target blood levels of cyclosporine
    • The dose of cyclosporine is based upon “Ideal Body Weight.” In certain instances, dosing based upon “Actual Body Weight” may lead to too much cyclosporine, which can increase the risk of kidney and liver problems
    • Cyclosporine is available as several different preparations such as: Gengraf, Neoral, or Sandimmune. Importantly, only “modified” forms of cyclosporine should be used. Sandimmune is not modified and should not be used
    • It is generally advisable to take one brand only as switching between preparations may affect blood concentrations and lead to unexpected changes in dosing
    • ATGAM is often infused using a high-flow vein via a “central catheter” to avoid the risk of vein irritation or blood clot

Estimated total infusion time for this treatment:

  • As short as 4 hours, or up to 24 hours for each ATG treatment
  • Infusion times are based on clinical studies, but may vary depending on doctor preference or patient tolerability. Pre-medications and I.V. fluids, such as hydration, may add more time

Only one treatment course (a total of 4 doses) with ATG is usually given. ATG is often given in the hospital, but can be given in an outpatient infusion center (if well-tolerated), allowing the person to go home afterwards. Cyclosporine may be taken in the hospital or at home.

Click here for the common cyclosporine + ATG starting doses.

Note: Individual doses may vary based upon your Doctor's recommendation, or drug availability.

Side Effects

In a multi-drug regimen, each medication has unique side effects. When these medicines are given together, drug-related side effects reported in clinical studies give the best estimate of what to expect. In clinical studies, the most commonly reported side effects of cyclosporine + ATG (ATGAM) are shown here:

A note about side effect percentages

  • Neutropenic fever (40%)
  • Sinus infection (8%)
  • Sore throat (3%)
  • Swelling in extremities [edema] (2%)
  • Serum sickness (2%)
  • Diarrhea and infection of the colon with clostridium difficile (2%)
  • Heavy menstrual bleeding (2%)
  • Chest pain (1%)
  • Nose bleed (1%)
  • Blood in sputum (1%)
  • Pneumonia (1%)
  • Eye infection (1%)
  • Ear infection (2%)

*A low platelet count may be from having aplastic anemia, however, ATGAM has also been associated with a low platelet count (thrombocytopenia). Platelet transfusions may be needed after receiving ATGAM in order to increase the platelet count and reduce the risk of bleeding.

Serum sickness from ATGAM, when it occurs, is reported to happen within 6 to 18 days of receiving the first dose.

Importantly, not all people who experience a side effect from ATGAM (horse) + Cyclosporine (Gengraf® or Neoral®) will experience it in the same way. It may be mild in some or severe in others, depending upon the individual. Everybody is different. Additionally, side effects may vary over time. For some, side effects may be a reason to delay or switch treatment, reduce the dose, or avoid future treatment with a certain medication altogether.

Side effects may be treatable when they occur or preventable by taking certain medications before they happen. When medications are taken to prevent a problem, this is known as prophylaxis, or "prophy" for short.

After starting treatment with ATGAM (horse) + Cyclosporine (Gengraf® or Neoral®), be sure to come back and watch all of the side effect videos shown below. Each of these videos contain valuable information about side effect management that will hopefully help you to both feel better and stay out of the hospital.

Side effect videos Side Effect Videos
Neutropenic FeverNeutropenic FeverPainPainBleedingBleedingFatigue Fatigue DiarrheaDiarrheaAnemiaAnemia


How often is monitoring needed?
Labs (blood tests) may be checked before ATGAM treatment and periodically during ATGAM treatment. Labs often include: a bone marrow biopsy, Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), magnesium, cyclosporine blood levels, folic acid, vitamin B12, reticulocyte count, plus any others your doctor may order.

How often is imaging needed?
Imaging may be checked if there are concerns for infection or bleeding. Imaging may include: X-rays, computerized tomography (CT) scans, or magnetic resonance imaging (MRI).

How might blood test results/imaging affect treatment?
Depending upon the results, your doctor may advise to continue cyclosporine + ATG as planned, increase the dose of cyclosporine, reduce the dose of cyclosporine, temporarily stop treatment until the side effect goes away, or switch to an alternative therapy.

Cyclosporine trough blood levels are measured periodically (such as weekly for the first month, then every other week) to maintain the cyclosporine level between 200 – 400 ng/mL for the first six months. Afterwards, the dose is typically reduced by 25% every three months over the subsequent 18 months, then discontinued.

ATGAM prescribing information recommends monitoring for cytomegalovirus (CMV) infection as some studies suggested an increase in the incidence of CMV infection after patients received ATGAM

ChemoExperts Tips

  • ATG may cause serious allergic reactions such as anaphylaxis. Acetaminophen (Tylenol®) and diphenhydramine (Benadryl®) are given before each ATG infusion to help prevent reactions. Patients are monitored for signs and symptoms of an allergic reaction throughout the infusion. If an infusion reaction occurs, the infusion is stopped until symptoms subside, then restarted at a slower infusion rate
  • In some cases, before the ATG infusion a very small dose of ATG is injected under the skin and the area is watched for raised skin and redness around the injection site (known as a wheal). If a skin reaction does not occur after ten minutes, the I.V. dose of ATG is then given. If a skin reaction occurs, the infusion of ATG is typically given over a longer period of time or a desensitization to ATG may be performed
  • ATG can potentially cause a condition known as serum sickness. A corticosteroid such as prednisone is typically given during the first 10 days of treatment to help prevent serum sickness. After 10 days, the dose is decreased over 7 days (tapered) and stopped. If serum sickness occurs, a longer prednisone taper schedule may be required
  • Additional medications that may be prescribed include inhaled pentamidine once monthly for 6 months, or Bactrim® (Sulfamethoxazole/Trimethoprim; unless you have a sulfa allergy) to prevent Pneumocystis jirovecii Pneumonia and acyclovir (Zovirax®), valacyclovir (Valtrex®) or famciclovir (Famvir®) for at least 2 months to prevent viral infections such as reactivation of herpes simplex virus (HSV) or varicella zoster virus (VZV)
  • Cyclosporine blood levels are best drawn in the morning right before you take cyclosporine. This is known as a “trough” concentration. On days when a cyclosporine level is drawn in the clinic, it is important to bring your morning dose with you to your appointment so you can take the dose immediately after the cyclosporine blood level is taken
  • Lemons, limes, and other types of oranges are okay to eat and do not interact with cyclosporine. Try to avoid grapefruit and grapefruit juice, pomegranate, starfruit, and seville oranges (found in marmalade) as they may increase the concentration of cyclosporine in your blood
  • Certain medications (example: diltiazem or fluconazole) may increase or decrease blood levels of cyclosporine. A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately. It is important to remember to adjust the dose of cyclosporine when a new interacting medications is added, but also when it is taken away as this too will affect the level of cyclosporine in the bloodstream
  • Immunizations should not be given without the approval of the hematologist (blood doctor) treating aplastic anemia. Certain immunizations, such as live vaccines, may lead to the infection that they are meant to prevent due to the immunosuppressant effects of ATGAM
  • Clinical trials may exist for aplastic anemia. Ask your doctor if any studies are currently enrolling in your area. If not, go to to search for other centers offering study medications

Patient Assistance & Co-payment Coverage

Patients under the age of 65 years, or those with private insurance plans:
If you have insurance and are looking for patient assistance or copay assistance for Antithymocyte Globulin (ATG, ATGAM®) + Cyclosporine (Gengraf®, Neoral®), we have provided links that may help.

Visit our Patient Assistance page and click the links to various patient assistance programs for help paying for Antithymocyte Globulin (ATG, ATGAM®) + Cyclosporine (Gengraf®, Neoral®). Depending upon your income, they may be able to help cover the cost of:

  • Cyclosporine
  • ATG (Anti-Thymocyte Globulin)

For Branded medications (may be available for generic medications too), check with the manufacturer to determine if a co-pay card is offered and if it could reduce your monthly copay.

  • If you are uninsured, check with the manufacturer to determine if you are eligible to receive medication at no cost.

Medicare and Medicaid patients (Patients 65 years or older):
The clinic providing treatment will likely pre-authorize medications and immune therapies such as Antithymocyte Globulin (ATG, ATGAM®) + Cyclosporine (Gengraf®, Neoral®) and are the best source to help you understand drug cost.

  • Ask to speak with a patient assistance technician or financial counselor at the clinic or hospital administering this therapy.

Emotional Wellness

What is Emotional Wellness?
Emotional wellness is having a positive outlook balanced with a realistic understanding of current life events. This requires both an awareness and acceptance of your emotions. It is with this knowledge that you can develop a plan to take the necessary actions to positively impact your life.

Emotional wellness uses an ongoing process to continually reflect on the stressors of life in a constructive manner to move forward and create happiness.

Because emotional wellness is deeply connected with physical, social, and spiritual wellness, pursuing it often becomes particularly difficult in times of major illness. Despite this difficulty, working toward emotional wellness has been connected to improved treatment outcomes and a higher likelihood of achieving goals of therapy.

Learn more about pursuing emotional wellness while receiving treatment with Antithymocyte Globulin (ATG, ATGAM®) + Cyclosporine (Gengraf®, Neoral®)

Individual Drug Label Information

Cyclosporine (Gengraf® Neoral®)

  • Is an oral capsule available in 25 mg, 50 mg and 100 mg
  • Modified cyclosporine (Gengraf®, Neoral®) and Non-modified cyclosporine (Sandimmune®) are not equivalent and should not be used interchangeably
  • Each dose of cyclosporine can be taken with or without food
  • If you miss a dose, take the dose as soon as possible unless the next scheduled dose is supposed to be taken in a few hours
  • Cyclosporine should be stored room temperature (68°to 77°F)
  • Dosage adjustments may be required for blood levels of cyclosporine that are too high or too low, liver dysfunction, or drug interactions
  • Cyclosporine may interact with certain antifungal and seizure medications. Ask your doctor or pharmacist to review your medications for any possible interactions
  • Cyclosporine may also interact with grapefruit and grapefruit juice, pomegranate, star fruit, or seville oranges (in marmalade) causing increased blood levels of cyclosporine
  • Avoid eating or drinking these foods during treatment Avoid therapy with St. Johns Wort, carbamazepine, or phenytoin as they will decrease blood levels of cyclosporine
  • Use during pregnancy may cause fetal harm. Cyclosporin should not be used during pregnancy unless the potential benefit to the mother justifies the potential risk to the fetus
General side effects from cyclosporine (Gengraf®, Neoral®)
  • Kidney injury
  • High blood pressure
  • Decreased blood magnesium
  • Thickening of the gums
  • Joint or muscle pain
  • Muscle tremors
  • Liver injury, increased bilirubin in blood
  • Excessive body hair growth
  • Nausea
  • Diarrhea
  • Click on the cyclosporine (Gengraf®, Neoral®) package insert below for reported side effects, possible drug interactions, and other cyclosporine prescribing information

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrhea

See DailyMed package insert.

ATG (Anti-Thymocyte Globulin) (ATGAM®)

  • ATG, also known as ATGAM®, is an intravenous infusion
  • ATGAM may cause serious allergic reactions. A skin test may be done prior to receiving the full dose to see if an allergic reaction develops
  • Although no cases have been reported, transmission of viruses and Creutzfeldt-Jakob disease (CJD) agent is possible after receiving ATG
  • It is not known if ATG is safe in pregnancy and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
General side effects from ATG (ATGAM®)
  • Fever
  • Chills
  • Skin rash
  • Low platelets [thrombocytopenia]
  • Joint pain
  • Hives
  • Headache
  • Itching
  • Nausea
  • Diarrhea
  • Sore throat
  • Serum sickness
  • Increased infection risk
  • Kidney or liver injury
  • High or low blood pressure
  • Click on the ATG (ATGAM®) package insert below for reported side effects, possible drug interactions, and other ATG prescribing information

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaFatigue Fatigue BleedingBleedingPainPainAnemiaAnemiaNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

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Scheinberg P, Nunez O, Weinstein B, et al. Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med. 2011;365:430-438.

Created: March 7, 2018 Updated: January 15, 2020

What is Severe Aplastic Anemia (SAA)?

Severe aplastic anemia (SAA) is a rare blood disorder that can be life-threatening if left untreated. SAA is thought to result from certain cells of the immune system inappropriately attacking healthy cells within the bone marrow. This leads to:

  • A low white blood cell count, which increases the risk of infection
  • A low red blood cell count, which decreases the ability to deliver oxygen and may cause fatigue, weakness, and shortness of breath
  • A low platelet count, which increases the risk of bruising and bleeding

The treatment of aplastic anemia may include immunosuppressant agents (shown below) or a stem cell transplant if a stem cell donor can be identified. A matched sibling donor is often thought to be be the best option, if one is available. The goals of these treatments are to restore the healthy bone marrow cells, prevent infection and bleeding, and to stop the need for blood or platelet transfusions.

What does Cure mean?

The word “cure” means there are no cancer cells left in the body and cancer will never come back. Depending on the cancer type and stage, this may be the true goal of therapy. However, it is very difficult to prove all cancer cells are gone. Even though images, like X-rays and MRI’s, and blood tests may not show any signs of cancer, there can be a small amount of cancer cells still left in the body. Because of this, the word “remission” is used more often. This means there are no signs or symptoms of cancer. Patients in remission are followed closely for any signs of cancer returning. Sometimes, more chemotherapy may be given while in remission to prevent the cancer from coming back.

Doctors usually do not consider a patient “cured” until the chance of cancer returning is extremely low. If cancer does return, it usually happens within 5 years of having a remission. Because of this, doctors do not consider a patient cured unless the cancer has not come back within 5 years of remission. The five-year cutoff does not apply to all cancers.

What is Ideal Body Weight (IBW)?

An individual's Ideal Body Weight (IBW) can be calculated using the following equations:

  • Men: IBW = 50 kg + 2.3 kg for each inch over 5 feet
  • Women: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet

Common cyclosporine + ATG starting doses

  • ATG 40 mg/kg intravenous (I.V.) infusion over 4 to 24 hours once daily on Days 1, 2, 3, and 4
  • Usual cyclosporine starting dose: 5 mg/kg by mouth twice daily (Important note: Ideal Body Weight is recommended for dosing cyclosporine)

What is a CBC?

A Complete Blood Count (CBC) is a frequently ordered blood test that tells clinicians the status of your: 1) White blood cell count, 2) Hemoglobin, and 3) Platelet count at the time the test was taken.

Common uses:
1) White blood cell count (WBC): is used to determine infection risk, or response to chemotherapy. Certain chemotherapy agents may harm our good infection-fighting cells. Sometimes chemotherapy may need to be delayed to allow these cells to recover.

2) Hemoglobin: is used to determine if someone is anemic. Anytime the hemoglobin is below 12 g/dL, the person is said to be anemic. Red blood cell transfusions, and sometimes iron can be given to restore the hemoglobin level, but anemia treatment should always aim at treating the underlying cause or condition.

3) Platelet count: is used to determine if the risk of bleeding is increased or if a platelet transfusion is required to prevent bleeding. Certain medications that increase bleeding risk, such as: aspirin, certain chemotherapy agents, and blood thinners, may need to be stopped temporarily until the platelet count is within a safe range.

What is a CMP?

A Comprehensive Metabolic Panel (CMP) is a frequently ordered blood test that tells clinicians the status of your: 1) Electrolytes & Acid/Base status2) Kidney function, 3) Liver function, 4) Blood sugar, and 5) Calcium at the time the test was taken. It is commonly used to monitor liver and kidney function when beginning new medications such as chemotherapy. A total of 14 tests are run simultaneously and are shown below.

Electrolytes & Acid/Base status:
1) Sodium, 2) Potassium, 3) Carbon dioxide, 4) Chloride

Kidney Function:
5) BUN (blood urea nitrogen), 6) Serum creatinine (Scr)

Liver Function:
7) AST, 8) ALT, 9) Total bilirubin, 10) Alk Phos, 11) Albumin, 12) Total protein

Blood sugar:
13) Serum glucose

14) Serum calcium

Cyclosporine Trough Concentration

Cyclosporine blood levels are best drawn in the morning right before you take cyclosporine. This is known as a “trough” concentration.

On days when a cyclosporine level is drawn in the clinic, it is important to bring your morning dose with you to your appointment so you can take the dose immediately after the cyclosporine blood level is taken

What is a Desensitization?

Desensitization is a process that helps the body adjust to a medication to lower the risk of experiencing serious allergic reactions. Typically, the process is done slowly over several hours in a hospital setting. Very small doses of the medication are initially given and the doses are increased over time until the total amount of the medication is received.

What is Serum Sickness?

Serum sickness occurs when the body recognizes medications like ATG as “foreign” proteins and uses the immune system to attack the foreign protein to eliminate it. Symptoms typically start a few days after treatment and can include skin rash, hives, itching, joint pain, fevers, and weakness. In severe cases it can cause low blood pressure, and rarely organ damage.

What is Pneumocystis Jirovecii Pneumonia (PJP)?

PJP is a rare form of lung infection that typically affects only those with a weakened immune system (also called “immunocompromised”). A yeast-like fungus causes pneumocystis pneumonia. PJP is sometimes referred to using its former name, pneumocystis carinii pneumonia, or PCP.

Medications are commonly used to prevent PJP during periods when the immune system is weakened. Commonly used medications include: Inhaled pentamidine, oral Bactrim (trimethoprim/sulfamethoxazole), dapsone, or atovaquone. Your doctor will choose the best medication for you.

A note about side effect percentages

The number you see next to the percent sign (%) means how many people out of 100 are likely to experience this side effect.

For example, if the side effect is reported to occur in 8% of patients, this means that roughly 8 out of 100 people receiving this treatment will experience this side effect.