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Treatment Name: HyperCVAD (Part B)

HyperCVAD (Part B) is a Chemotherapy Regimen for Acute Lymphoid Leukemia (ALL)

Hyper - Hyperfractionated 
C - Cyclophosphamide 
V - Vincristine 
A - Adriamycin (doxorubicin) 
D - Dexamethasone

Alternative names: hypercvad, hyper-cvad, hyper cvad

How does HyperCVAD (Part B) work?
Each of the medications in HyperCVAD (Part B) (methotrexate + cytarabine) are designed to kill cancer cells in the blood stream and bone marrow.

Goals of therapy:
To eliminate leukemia cells from the body and to decrease symptoms from ALL, such as bleeding, bruising, and recurrent infections. HyperCVAD chemotherapy is commonly given with the goal of cure.


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  • Methotrexate intravenous (I.V.) infusion, usually given over 24 hours on Day 1
  • Cytarabine I.V infusion, usually given over two hours, every 12 hours on Days 2 and 3 (four doses per Cycle)
  • Leucovorin I.V. infusion or 15 mg to 50 mg oral tablet, starts 12 hours after the end of methotrexate infusion and continues every six hours until the level of methotrexate in the blood decreases to a safe level
  • Prednisolone eye drops. 2 drops in each eye every six hours, started before the first dose of cytarabine

Click here for common starting doses.

Part B of HyperCVAD usually requires a 4 - 5 day stay in a hospital (or sometimes longer). Levels of methotrexate are monitored in the blood to ensure that it is being eliminated from your body. Patients usually go home once the level of methotrexate reaches a very low level in the blood. Sometimes a short course of leucovorin tablets may be taken at home after leaving the hospital.

HyperCVAD Part B is alternated with HyperCVAD Part A every 21 days. This sometimes takes longer if waiting for normal blood counts recover after the previous cycle. When both Part A and Part B are completed, this is known as one Cycle.

  • Each cycle may be repeated up to four times, depending upon the stage of the disease.
  • Duration of therapy may last up to 8 months, depending upon response, tolerability, and number of cycles prescribed.
  • On occasion, your doctor may choose to start with Part B, instead of Part A.

In some cases of ALL, two pieces of two chromosomes trade small sections of their DNA forming what is known as the “Philadelphia Chromosome."


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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 with HyperCVAD (Part B) are shown here:

  • Infection (23%),
  • Fever (23%),
  • Neurotoxicity (5%),
  • Mouth sores (5%),
  • Rash (4 - 5%),
  • Blisters and rash on palms of hands and soles of feet (3%),
  • Liver toxicity (2%),
  • Kidney toxicity (2%),
  • Diarrhea (1%),
  • Nausea and vomiting (percentage not listed).

Side effect videos Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaNeutropenic FeverNeutropenic FeverPainPainAnemiaAnemiaFatigue Fatigue BleedingBleeding


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How often monitoring needed?
Labs (blood tests) will be checked before treatment, daily while in the hospital, then periodically in clinic. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), blood methotrexate concentrations, also known as "methotrexate levels", plus any others your doctor may order.

How often is imaging needed?

Imaging may be checked before treatment or during therapy if there is concern for a blood clot or infection. Imaging may include: X-rays or computerized tomography (CT) scans.

How might blood test results/imaging affect treatment? Depending upon the results, your doctor may advise to continue chemotherapy as planned, or delay or switch therapy.


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ChemoExperts Tips

  • The pH of your urine will need to be higher than normal to help eliminate methotrexate from the body. To raise the pH, a continuous intravenous sodium bicarbonate solution is given. Other methods that may also be used are sodium bicarbonate tablets, or a drug called acetazolamide. The pH of your urine will be checked multiple times per day until methotrexate is eliminated from the body
  • Short-term difficulty with writing, walking, or talking may occur but is rare and usually reversible. To prevent these problems, various neurological tests are done prior to each dose of cytarabine, to look for early signs of toxicity. Examples of these tests include: follow an object with your eyes, repeat various phrases, sign your name, or walk a straight line
  • Typically, filgrastim (Neupogen®) or pegfilgrastim (Neulasta®) is given after chemotherapy to stimulate production of white blood cells and avoid periods of neutropenia
  • Antibiotics, antifungal agents, and antiviral medications are commonly used to prevent infection. Be sure to tell your doctor if you experience discomfort anywhere as this may be a symptom of an infection
  • A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
  • Clinical trials may exist for ALL. 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 HyperCVAD (Part B), 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 HyperCVAD (Part B). Depending upon your income, they may be able to help cover the cost of:

  • Methotrexate
  • Cytarabine
  • Leucovorin

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 HyperCVAD (Part B) 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 HyperCVAD (Part B)

Individual Drug Label Information

Methotrexate (Trexall®)

  • Methotrexate is an intravenous infusion and is bright yellow in color 
  • Methotrexate has the following FDA Black-Box Warnings. The risk of experiencing these side effects is much higher if methotrexate is not cleared from the body appropriately:  
    1. Low red blood cells, white blood cells, and platelets
    2. Kidney injury
    3. Liver injury
    4. Severe diarrhea
    5. Mouth ulcers
    6. Stomach ulcers
  • Dosage adjustments may be required for poor kidney function or poor liver function 
  • May cause severe skin reactions a few days after administration 
  • Is harmful to the fetus during pregnancy. If you are of childbearing age, use multiple forms of birth control 
  • May interact with non-steroidal inflammatory drugs (NSAIDs), aspirin, proton-pump inhibitors, phenytoin, and sulfa or penicillin antibiotics. These drugs should NOT be used the day before or the day of therapy with methotrexate. 
  • Ask your doctor or pharmacist to review your medications prior to receiving methotrexate 
  • Click on the methotrexate package insert below for reported side effects and possible drug interactions

Side Effect Videos
Nausea and VomitingNausea and VomitingDiarrheaDiarrheaHair LossHair LossFatigue Fatigue PainPainAnemiaAnemiaNeutropenic FeverNeutropenic Fever

See DailyMed package insert.

Cytarabine (Ara-C)

  • Cytarabine is most commonly given as an intravenous infusion but may be given subcutaneously
  • FDA Black-Box Warnings for low white blood cells, low platelets, low red blood cells, nausea, vomiting, diarrhea, mouth sores, liver damage, and abdominal pain
  • Dosage adjustments may be required renal or liver function
  • May cause a series of symptoms known as Cytarabine (Ara-C) Syndrome within 6 to 12 hours after administration. Symptoms may include fever, rash, chest pain, muscle aches, bone pain, tiredness, and inflammation and redness of the eye
General Cytarabine (Ara-C) Side Effects
  • Low red blood cells, white blood cells, or platelets
  • Nausea or vomiting
  • Liver dysfunction
  • Click on the cytarabine (Ara-C) package insert below for reported side effects and possible drug interactions

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

See DailyMed package insert.

Leucovorin (Folinic acid)

  • Leucovorin is an intravenous (I.V.) drug that is a derivative of folic acid, also known as vitamin B9
  • Is clear to slightly yellow in color 
General Leucovorin (Folinic Acid) Side Effects 
  • Seizures and fainting have been rarely reported 
  • Click on the leucovorin (Folinic Acid) package insert below for reported side effects and possible drug interactions
See DailyMed package insert.

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1. Kantarjian HM, O’Brian S, Smith TL, et al. Results of Treatment With Hyper-CVAD, a Dose-Intensive Regimen, in Adult Acute Lymphocytic Leukemia. J Clin Oncol. 2000;18:547-651.

2. Kantarjian HM, Thomas D, O’Brian S, et al. Long-Term Follow-Up Results of Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone (Hyper-CVAD), a Dose-Intensive Regimen, in Adult Acute Lymphocytic Leukemia. Cancer. 2004;101:2788-2801.

3. Thomas DA, Faderl S, O’Brian S, et al. Chemoimmunotherapy with Hyper-CVAD plus Rituximab for the Treatment of Adult Burkitt and Burkitt-Type Lymphoma or Acute Lymphoblastic Leukemia. Cancer. 2006;106:1569-1580.

Created: August 29, 2015 Updated: February 22, 2017

What is Acute Lymphoid Leukemia (ALL)?

Acute Lymphoid Leukemia (ALL), also known as acute lymphoblastic leukemia, is a disease of the lymphoid cells found in the bone marrow. Lymphoid cells are responsible for developing into cells of the immune system called B-cells, T-cells, or Natural Killer cells. In ALL, immature lymphoid cells know as "blasts" replicate at a very fast rate. Sometimes blasts crowd out the normal cells in the bone marrow so that red blood cells or platelets are unable to develop.

Common symptoms of ALL include fatigue, infection, and bruising or bleeding. ALL is the most common cancer diagnosed in children, but is rare in adults. Most cases of ALL are considered "de novo" meaning that the cause is unknown; however, some cases can be linked to certain genetic syndromes. There is no staging system for ALL. Chromosomes are often analyzed to determine which mutations in the chromosomes exist. The effectiveness of the treatment may depend upon the specific chromosome mutations that are present.

NOTE: Treatment Options listed below are not all-inclusive. Other treatments may be available. ChemoExperts provides drug information and does not recommend any one treatment over another. Only your Doctor can choose your therapy.

What is Leucovorin?

Leucovorin is not a chemotherapy agent. It is a special form of folic acid that helps decrease side effects from methotrexate. Doses may be increased during therapy depending on the amount of methotrexate in the blood. Folic acid should NOT be confused with leucovorin (folinic acid) as it does not work the same way.

What is the Philadelphia Chromosome (Ph+)?

If this is present, another medication such as imatinib (Gleevec®), nilotinib (Tasigna®), dasatinib (Sprycel®), will also be given. These medications are commonly used to treat another form of leukemia called Chronic Myeloid Leukemia (CML). The side effects are similar to those seen when used to treat ALL. These medications can either be taken continuously throughout therapy or intermittently during the first cycle of HyperCVAD.

Clinical Trial Results

If you are interested in reading the clinical trial results, please click on the references below:

1. Kantarjian HM, O'Brien S, Smith TL, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult lymphocytic leukemia. J Clin Oncol. 2000;18:547-561.

2. Kantarjian H, Thomas D, O'Brien S, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004;101:2788-2801.

3. Thomas DA, Faderl S, O'Brien S, et al. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006;106:1569-1580.

What is Tumor Lysis Syndrome?

Tumor lysis syndrome occurs when many cancer cells die quickly and release their contents into the bloodstream. Many times the body has the ability to flush these substances out through the kidneys or metabolize them via the liver. However, sometimes the body needs medicines to help eliminate these substances and to prevent organ damage.

Prednisolone eye drops

Steroid eye drops, such as Prednisolone, decrease inflammation. They are often started before the first dose of cytarabine to prevent eye lid irritation known as conjunctivitis. Eye drops may be continued at home for up to 72 hours after the last dose of cytarabine

Common Starting Doses

  • Methotrexate 1000 mg/m2 intravenous (I.V.) infusion, usually given over 24 hours on Day 1
  • Cytarabine 3000 mg/m2 I.V. infusion, usually given over two hours, every 12 hours on Days 2 and 3 (four doses per Cycle)
  • Leucovorin I.V. infusion or 15 mg to 50 mg oral tablet, starts 12 hours after the end of methotrexate infusion and continues every 6 hours until the level of methotrexate in the blood decreases to a safe level
  • Prednisolone eye drops. 2 drops in each eye every six hours, started before the first dose of cytarabine and finishing 72 hours after completing the last dose

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

What is neutropenia?

This occurs when there is an abnormally low amount of a certain type of white blood cells, called neutrophils, in the blood. These neutrophils help the body body fight infections caused by bacteria and viruses. Many chemotherapy drugs temporarily damage bone marrow where white blood cells are created, resulting in neutropenia. Please watch our video on neutropenia to learn more.

What does it mean to "hyperfractionate" chemo?

This is a strategy used to split up one large daily dose of chemotherapy into multiple smaller doses. This is done to expose more cancer cells to chemotherapy over a longer period of time with the hopes of killing a greater percentage of them. Not all chemotherapy medicines can be hyperfractionated because the side effects may too severe to tolerate.

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, doctors use 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.