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Treatment Name: R-DHAP (Rituximab + Dexamethasone + Cytarabine + Cisplatin)

R-DHAP (Rituximab + Dexamethasone + Cytarabine + Cisplatin) is a Chemotherapy Regimen for Lymphoma, Mantle Cell

How does R-DHAP work?

Rituximab is an antibody that is designed to target and bind to a protein on the surface of cancerous b-cells. When rituximab binds to this protein, it helps your immune system destroy the cancer cell. Dexamethasone, cytarabine, and cisplatin are designed to kill rapidly dividing cells such as cancerous lymphocyte cells.

RRituximab (Rituxan®)
DDexamethasone (Decadron®)
HAHigh-dose Ara-C (Cytarabine)
P - CisPlatin

Goals of therapy:

R-DHAP is given to shrink lymph nodes and decrease symptoms from lymphoma such as enlarged lymph nodes and spleen. It is commonly given with the goal of cure, but may require a bone marrow transplant.

Schedule

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How is R-DHAP therapy for mantle cell lymphoma given?

  • Rituximab intravenous (I.V.) infusion on Day 1. The time of infusion varies depending on tolerability
  • Dexamethasone 40 mg (ten 4 mg oral tablets) by mouth once daily on Days 1, 2, 3, and 4
  • Cytarabine I.V. infusion over 2 hours every 12 hours for 2 total doses on Day 2
  • Cisplatin I.V. infusion over 24 hours on Day 1

Click here for the common R-DHAP starting doses.

R-DHAP usually requires a 2 to 3 day stay in a hospital. In some cases, rituximab may be given in an outpatient infusion center prior to hospital admission while cytarabine, dexamethasone, and cisplatin are given in the hospital. Dexamethasone may be taken at home on Days 3 and 4 if you are no longer admitted to the hospital.

R-DHAP is repeated every 21 days. This is known as one Cycle. Each cycle may be repeated up to six times, depending upon the stage of the disease. Duration of therapy may last up to 5 months, depending upon response, tolerability, and number of cycles prescribed.

Side Effects

What are the most common side effects from R-DHAP for mantle cell lymphoma?

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 R-DHAP are shown here.

  • Low white blood cells [neutropenia] (53%)
  • Low platelets [thrombocytopenia] (39%)
  • Infection (31%)
  • Kidney damage (20%)
  • Gastrointestinal upset [nausea, vomiting, diarrhea, etc.] (20%)
  • Lung injury (6%)
  • Tumor lysis syndrome (5%)
  • Neurologic toxicity (5%)

Importantly, not all people who experience a side effect from R-DHAP 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 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 R-DHAP, 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.

Watch videos on common R-DHAP therapy side effects below

Side effect videos Side Effect Videos
BleedingBleedingNeutropenic FeverNeutropenic FeverDiarrheaDiarrheaNausea and VomitingNausea and Vomiting

Monitoring

How often is monitoring needed?

Labs (blood tests) may be checked before each treatment and in between treatments at the discretion of your doctor. Labs often include: Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), uric acid, plus any others your doctor may order. Prior to getting rituximab, you may be checked for hepatitis B and HIV.

How often is imaging needed?

Imaging may be checked before treatment, at the completion of treatment to assess response, or if there are any concerns for certain side effects. Imaging may include: X-rays, magnetic resonance imaging (MRI), computerized tomography (CT) scans, or positron emission tomography (PET) scans.

How might blood test results/imaging affect treatment?

Depending upon the results, your doctor may advise to continue R-DHAP as planned, reduce the dose of future treatments, delay the next dose until the side effect goes away, or switch therapy.

Questions to Ask Your...

A better understanding of your treatments will allow you to ask more questions of your healthcare team. We then hope that with the answers, you will get better results and have greater satisfaction with your care. Because we know it's not always easy to know what questions to ask, we've tried to make it easy for you!

Choose any healthcare provider below to see common questions that you may want to ask of this person. Then, either print each list to bring to your clinic visits, or copy the questions and send them as a message to your healthcare team through your electronic medical record.

ChemoExperts Tips

  • Premedications such as diphenhydramine (Benadryl®), acetaminophen (Tylenol®), and hydrocortisone (Solu-Cortef®) may be given before rituximab to help avoid infusion related reactions.
  • The first dose of rituximab is often the hardest. It may lead to fever, shaking, and chills even if medications are given beforehand to help prevent these side effects. Side effects generally go away when the rituximab is stopped. It may then be restarted at a slower rate. Most patients are able to receive the entire dose, although it may take longer. In most cases, after the first dose is well tolerated, rituximab can be given over 90 minutes.
  • Because severe neutropenia and neutropenic fever may occur after R-DHAP, growth factor therapy known as G-CSF (examples: filgrastim or pegfilgrastim) is recommended. G-CSF helps keep the good white blood cells, known as neutrophils, from dropping too low. This in turn, helps to prevent serious infections that could result in hospitalization or even death.
  • Intravenous (I.V.) fluids may be given while receiving cisplatin to maintain good hydration and protect against kidney damage. These fluids may contain electrolytes such as potassium and magnesium.
  • Corticosteroid eye drops, such as prednisolone, are often started before the first dose of cytarabine to prevent eye irritation known as conjunctivitis. Eye drops may be continued at home for up to 72 hours after the last dose of cytarabine.
  • Short term difficulty with writing, walking, or talking may occur but is rare and usually reversible. To prevent these problems, various neurological exercises are done prior to each dose of cytarabine, to test 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.
  • A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately.
  • Clinical trials may exist for mantle cell lymphoma. Ask your doctor if any studies are currently enrolling in your area. If not, go to clinicaltrials.gov 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 R-DHAP (Rituximab + Dexamethasone + Cytarabine + Cisplatin), 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 R-DHAP (Rituximab + Dexamethasone + Cytarabine + Cisplatin). Depending upon your income, they may be able to help cover the cost of:

  • Rituximab
  • Dexamethasone
  • Cytarabine
  • Cisplatin

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 R-DHAP (Rituximab + Dexamethasone + Cytarabine + Cisplatin) 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 R-DHAP (Rituximab + Dexamethasone + Cytarabine + Cisplatin)

Individual Drug Label Information

Rituximab (Rituxan®, Truxima®, Ruxience®)

  • Rituximab is an intravenous infusion
  • Acetaminophen (Tylenol®) and antihistamines (e.g. diphenhydramine = Benadryl®) should be given prior to each dose
  • Patients should be screened for hepatitis B as rituximab can cause a re-activation of this infection
  • May cause vaccines to work less well for 6 - 12 months after the last dose of rituximab. It is advised that vaccines be given two to four weeks prior to rituximab if possible
General Rituximab Side Effects
  • May cause an infusion reaction, which could include skin reaction, shaking, chills, fever, or shortness of breath. These reactions may be severe, but are very rarely life-threatening Infusion reactions does not usually happen after the first dose, but are possible
  • May increase the risk of infection. Your doctor may prescribe antibiotics to prevent certain infections associated with rituximab use
  • Click on the rituximab package insert below for reported side effects and potential drug Interactions

Side Effect Videos
Fatigue Fatigue

See DailyMed package insert.

Dexamethasone (Decadron®)

  • Dexamethasone is supplied as an oral tablet or oral liquid
  • Dexamethasone may increase the risk of infection. Depending upon how much dexamethasone is taken, antibiotics may be prescribed to help prevent infection
  • Should be taken with food and with a large glass of water to avoid stomach irritation or ulcers
  • Should be taken before 6 p.m. when possible, to avoid trouble falling asleep
  • May decrease the response to vaccines; vaccines may need to be repeated at a later date to obtain maximal response
  • If taken daily for several days or weeks, the dose of dexamethasone may need to be gradually decreased (tapered) to avoid withdrawal symptoms
  • If you miss a dose, take the next dose as soon as possible
  • Should be stored at room temperature
General Dexamethasone (Decadron) Side Effects
  • May cause high blood sugar, weight gain, irritability, high blood pressure, difficulty sleeping, stomach ulcers, bone loss, muscle weakness
  • Click on the dexamethasone (Decadron) package insert below for reported side effects and potential drug Interactions
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.

Cisplatin (Platinol®)

  • Cisplatin is an intravenous (I.V.) infusion that is typically given over one to two hours
  • Cumulative toxicity to kidneys from cisplatin can be severe 
  • Other toxicities from multiple doses are:  low blood counts, nausea, vomiting, and hearing loss
  • Dosage adjustments may be required for poor kidney function or bone marrow toxicity (low blood counts) 
  • Cisplatin is hazardous to a human fetus; women should avoid pregnancy while on this drug 
  • Women should not breast-feed while on cisplatin; it has been reported to be in human milk 
  • Patients on anticonvulsant drugs may have decreased levels while on cisplatin 
General Cisplatin (Platinol) Side Effects 
  • Kidney problems (nephrotoxicity), especially in elderly patients. 
  • Nausea and vomiting, both acute (within first 24 hours) and delayed (two to five days after infusion) 
  • Diarrhea 
  • Low blood cell counts (myelotoxicity, acute leukemia)
  • Hearing problems- ringing ears.  All patients should have a baseline hearing test done.  All children should have hearing test done before each dose and for several years after therapy is complete 
  • Low blood electrolytes:  magnesium, potassium, calcium, sodium, and phosphate
  • Nerve pain 
  • Vision problems; improvement and/or complete recovery usually occurs after stopping therapy 
  • Liver toxicity; recovery usually occurs after stopping therapy 
  • Click on the cisplatin (Platinol) package insert below for reported side effects and possible drug interactions

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

See DailyMed package insert.

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References

1) Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood 1988 Jan;71(1):117-22.

Created: May 17, 2021 Updated: May 17, 2021

What is Lymphoma, Mantle Cell?

Mantle Cell lymphoma (MCL) is one of about 30 sub-types of Non-Hodgkin Lymphoma. MCL represents up to 8% of all diagnosed lymphomas. It is a cancer of the B-lymphocyte. Most patients who have MCL are 60 years old or greater and more commonly male than female. Many patients are diagnosed with swollen lymph nodes in the neck, armpit, or groin, or an enlarged spleen, which may cause fullness under the left rib cage or abdominal pain.

The cause(s) of MCL are unknown. The stage of MCL can vary at diagnosis and throughout treatment. Stages of MCL include stage I, II, III, or IV. Although therapies are usually given with curative intent, many times the lymphoma returns within 1 – 2 years. Stem cell transplant and combined, multi-drug therapies are usually more effective than single medications.

Medications for MCL may include intravenous infusions, oral tablets or capsules, or a combination of IV and oral medications. Patients may be diagnosed with MCL without having any symptoms. Others may go to their doctor with symptoms of swollen lymph nodes, a large spleen, or decreased appetite. The effectiveness of the treatment may depend upon the stage at diagnosis.

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 which therapy is appropriate for you.

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.

Common Starting Doses

  • Rituximab 375 mg/m2 I.V. infusion on Day 1. The time of infusion varies depending on tolerability
  • Dexamethasone 40 mg by mouth daily on Days 1, 2, 3, and 4
  • Cytarabine 2000 mg/m2 I.V. infusion over 2 hours every 12 hours for 2 total doses on Day 2
  • Cisplatin 100 mg/m2 I.V. infusion over 24 hours on Day 1

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

What is an Antibody?

An antibody is a small protein shaped like a “Y” that can attach to specific things in the blood, such as a cancer cell.
  • Once an antibody binds to something, your immune system may attempt to get rid of it.
  • Antibodies may also work by binding to the cancer cell surface and prevent other things from binding to the cancer cell that help it survive. Without the ability to bind growth factors, cancer cells may be forced to die"

What is Tumor Lysis Syndrome (TLS)?

Tumor lysis syndrome, or TLS, 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.

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

Calcium:
14) Serum calcium