- Prednisone to Boost Platelets Before Lymphoma Chemo
- Treatment Name: Prednisone
- Deciding on a treatment for ITP is in a way like buying, owning, and driving a car. Think about the following similarities to help you understand which treatment is right for you:
- Faster platelet recovery by high‐dose dexamethasone compared with standard‐dose prednisolone in adult immune thrombocytopenia: a prospective randomized trial
Prednisone to Boost Platelets Before Lymphoma Chemo
Q1. My dad has been diagnosed with high-grade malignant B-cell lymphoma. They have done test after test, and they are saying he has a massive tumor in his stomach, about 56 cm. He was supposed to start chemo this week, but the doctor called at the last minute saying they can’t because his platelets are too low. While in the hospital a month ago, his platelets were at 77,000, and now they are at 55,000. The doctor is starting him on prednisone. How can this increase his platelets?
First, it is important to know why his platelets are low. One possibility is that the lymphoma has invaded his bone marrow. Another possibility is that he has a condition often associated with lymphoma called ITP (immune thrombocytopenic purpura). With ITP, the body’s immune system mistakenly destroys platelets.
Corticosteroids like prednisone can help raise the platelet count in the blood by suppressing the immune system, which is why they’re used to treat ITP. Recent studies have shown that some patients with ITP and an infection called H. pylori (linked to ulcers and a slow-growing type of lymphoma involving the stomach) may respond to treatment of the infection with antibiotics.
If bone marrow involvement is causing low platelets, prednisone may help somewhat (as it is one of the components of the chemotherapy regimen), but combination chemotherapy is likely to be more helpful.
Q2. My mother has had non-Hodgkin’s lymphoma and ITP since 2001. Many times her platelet counts fall to zero. What can we do to get those up, especially prior to chemo so her treatment is not delayed? Her chemo right now is CVP (cyclophosphamide, vincristine/Oncovin and prednisone) and she’s on the fourth treatment, which is the furthest she’s gotten in a six-cycle regimen ever. Is there anything we can do to keep them up so she doesn’t fall to zero?
Unfortunately, there is no easy way to increase the platelets in terms of diet or supplements. As you know, ITP (immune thrombocytopenic purpura) is a disorder in which the body’s immune system mistakenly destroys platelets. There are a number of different approaches to ITP, including steroids, gamma globulin, rituximab (Rituxan) and surgical removal of the spleen. There are also platelet growth factors being studied in clinical trials for ITP. It may be worthwhile for your mother to see a hematologist with expertise in ITP for a second opinion.
Q3. I’ve been diagnosed with large B-cell lymphoma stage Ie. In the beginning, it was confirmed that it did not spread through the body (bone marrow, blood work, etc.), and that it was localized. After the third treatment, a CAT scan revealed that only scar tissue remains. What is the typical number of chemotherapy treatments given? Four, six, eight? And what are the dangers of the different numbers of treatments?
For localized large cell lymphoma, one option is abbreviated chemotherapy (typically three or four cycles) plus radiation to the initial site of disease. The other option is chemotherapy only, for six to eight cycles.
A recent study done in Germany looked at the benefit of RCHOP (rituximab, cyclophosphamide, doxorubicin/hydroxydoxorubicin, vincristine/Oncovin and prednisone) given every two weeks as opposed to every three, which is routinely done in this country. The evidence showed no benefit to eight cycles over six. Given that your CT after three cycles is negative, I think six cycles would be reasonable if you were to receive chemotherapy only.
Q4. I’ve just completed my CHOP+R chemo, having had it three weeks apart. I got along remarkably well till after the third session, at which time I experienced fatigue, frequent urination, being thirsty and diarrhea. I was told the prednisone had driven me into diabetes. My blood sugar prior was always around 96. I was ingesting 155 grams or more of sugar in grape juice, Ensure and canned fruit, etc. I’ve since cut all this out! Do you think my sugar can now get back to normal? A friend tells me he has stayed diabetic.
Unfortunately, it is difficult to predict whether your blood sugars will return to normal after completing chemotherapy. Other factors — such as whether you may have had slightly abnormal blood sugars pre-chemotherapy and whether you gained weight during chemo — may contribute to whether you will remain diabetic. This should be followed closely after you finish treatment.
(Editor’s note: CHOP+R stands for cyclophosphamide, doxorubicin/hydroxydoxorubicin, vincristine/Oncovin and prednisone, plus rituximab/Rituxan. Read more about this treatment in our Life with Lymphoma blog.)
Q5. Last year, my husband was diagnosed with T-cell lymphoma. So far the only thing the oncologist is doing is keeping watch via CT scan. At first, my husband had to go every three months. Now he goes every six months. From time to time his energy level gets really depleted. We’ve tried vitamin B12 shots, but it doesn’t even begin to touch his fatigue level. Although he is very tired, he continues going and going. What can we expect from T-cell lymphoma, and what can we do about his energy level?
There are many types of T-cell lymphomas, some of which grow rapidly. Others, like T-cell large granular lymphocyte leukemia, can progress very slowly over years without need for treatment. These types of lymphomas can be very difficult to categorize, so it is important that a pathologist specializing in lymphoma agrees with the diagnosis in your husband’s case.
It’s difficult to say how his disease may progress without knowing the specific sub-type of T-cell lymphoma he has. Fatigue can occur for many reasons and may or may not be directly related to the lymphoma. If it is related to the lymphoma, that may be a reason to stop watching and waiting, and consider treatment.
Q6. I was diagnosed with B-cell lymphoproliferative disease with a T-cell component in December 2007. I had been on methotrexate for rheumatoid arthritis for 14 years and Humira (adalimumab) for four years up until my diagnosis. My oncologist put me on four rounds of rituximab, waited four weeks and did a new PET scan . My lymph nodes by my pancreas had decreased from 4 cm to 2.5 cm. An epicardio lymph node did not reduce in size, and he is not sure that this node is from lymphoma. My doctor wants to wait eight weeks and do a new PET and then put me on rituximab maintenance, one infusion every two months. He feels CHOP (cyclophosphamide, hydroxydoxorubicin/Adriamycin, Oncovin/vincristine and prednisone) could be harmful, and he said his first job is to do no harm. I don’t understand why we are not doing chemo as a first-line treatment so I would have a chance of remission. Is it still possible that the rituximab could put me in remission? At this time we are not sure if my lymphoproliferative disease is indolent or aggressive. I was diagnosed with breast cancer in 1992 and treated with chemo and radiation. I am 60 years old.
Lymphoproliferative disease refers to several medical conditions in which white blood cells are overproduced. Lymphoma, for example, is a type of lymphoproliferative disease.
I agree that determining whether your lymphoproliferative disease is indolent or aggressive is an important point. Some cases will get better with withdrawal of methotrexate or other drugs that suppress the immune system, but with the cases that look like large B-cell lymphoma, more aggressive therapy may be necessary.
I suspect your doctor is concerned about your prior chemotherapy for breast cancer, which often uses Adriamycin, a drug that may be toxic to the heart in large doses. Adriamycin is also part of standard treatment for aggressive lymphoma.
However, I think your concerns are valid, and you may want to discuss getting another opinion at a medical center that handles a high volume of lymphoma patients, as the specifics of your case are complicated. An expert hematopathologist, a pathologist who specializes in the study of cells involved in the formation of blood, may be helpful in further evaluating the original biopsy.
Q7. My husband was diagnosed four years ago with follicular lymphoma, stage IV, grade II. He received six treatments of CHOP (cyclophosphamide, doxorubicin/hydroxydoxorubicin, vincristine/Oncovin and prednisone) plus Rituxan. He obtained a partial remission and was advised to do a stem cell transplant. He chose instead to do Rituxan treatments every six months, which is keeping him stable, and he is enjoying a good quality of life. He is 59 years old. Should we continue these treatments or opt for a more aggressive approach?
Since he is already receiving Rituxan (rituximab) maintenance and does not have evidence of progressive disease, I think it is reasonable to continue with this approach.
Stem cell transplants are routinely performed in otherwise healthy patients up to the age of 70, so he would potentially be eligible for a stem cell transplant at the time his disease progresses, as long as his disease is effectively treated with second-line chemotherapy before the transplant.
Learn more in the Everyday Health Lymphoma Center.
Treatment Name: Prednisone
What is Immune Thrombocytopenic Purpura (ITP)?
A disorder where platelets decrease in number due to decreased production in the bone marrow and increased destruction in the blood. This can lead to an increased risk of spontaneous bruising or bleeding (without injury), especially when the platelet count drops below 30,000 cells per microliter of blood.
I = Immune, ITP is caused by a disturbance in the immune system
T = Thrombocytopenic, a medical term meaning low platelet count
P = Purpura, a type of bleeding in the skin
ITP is NOT a cancer, but it is commonly managed by hematologists (blood doctors) who often treat blood cancers as well. ITP is an uncommon condition and may be caused by auto-immune disorders, infections, certain medications, or pregnancy. However, in many cases, a cause cannot be identified which gives rise to its other name-idiopathic (meaning “cause unknown”) thrombocytopenic purpura. Although ITP may spontaneously resolve, for some patients lifelong therapy may be needed.
The effectiveness of medications may depend upon the causes of ITP and the ability to remove these causes, or whether a splenectomy (removal of the spleen) has been performed, or is able to be performed.
Deciding on a treatment for ITP is in a way like buying, owning, and driving a car. Think about the following similarities to help you understand which treatment is right for you:
BUYING: “0 – 50 time” (0 to 50 k/µL platelets, instead of 0 – 60 m.p.h) is an important performance feature
Once the platelet count exceeds 50 k/µL, bleeding episodes are rare. Therefore, the time it takes to go from very few platelets to a platelet count over 50 k/µL matters. In general, steroids such as prednisone and dexamethasone have the fastest “0 – 50” time.
- Although exceptions, the thrombopoeitin receptor agonists romiplostim and eltrombopag usually have a 0 – 50 k/µL platelet time of 1 – 2 weeks
- Although exceptions, one-half of rituximab recipients have a 0 – 50 k/µL platelet time below 5.5 weeks, and the other half over 5.5 weeks. The response to rituximab is often unpredictable
OWNING: Warranty offered?
A 5-year bumper-to-bumper warranty helps us worry less about something breaking or going wrong with our vehicle after we buy it. Likewise, not all medications used for ITP have a long-lasting effect in keeping the platelet count above 50 k/µL.
- When it works, rituximab can work for 1 – 2 years, but lasting responses beyond two years are rarer. The 5 year rituximab response rate is estimated at 20 – 25%. When the rituximab “warranty” runs out and platelets fall, patients with ITP that had a long lasting response to rituximab may respond to another course of therapy. Certain insurances require the platelet count to be less than 30 k/µL before it will be covered.
- When they work, the thrombopoeitin receptor agonists romiplostim and eltrombopag generally have lasting effect beyond that of rituximab. The “warranty” period where the platelet count remains above 50 k/µL often lasts 2 years or longer
DRIVING: Cruise control optional?
The ability for a treatment to maintain the platelet count within the goal range is similar to setting the cruise control on a car.
- Steroids are given in a pulse (example: dexamethasone daily for 4 consecutive days) or given daily for several weeks (example: prednisone), then decreased over several weeks and eventually discontinued a few months after it is started. As a result, when steroids are no longer taken there is a chance for ITP to relapse
- Because eltrombopag and romiplostim are administered continuously, these medications have the highest likelihood of keeping the platelet count in the goal range for the long haul
- Rituximab is typically given once weekly for 4 doses, and usually takes several weeks to determine if it is working (see above), therefore it is difficult to predict who will have a lasting response to this therapy
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.
Faster platelet recovery by high‐dose dexamethasone compared with standard‐dose prednisolone in adult immune thrombocytopenia: a prospective randomized trial
Oral prednisolone is the conventional initial treatment for immune thrombocytopenia (ITP) . It is able to increase platelet counts to 50 × 109 L−1 in two‐thirds of patients within 1 week . However, in a non‐randomized trial, pulse methylprednisolone not only resulted in a higher response, but also faster recovery . Furthermore, in a single‐arm study, pulse dexamethasone showed 85% response rate with platelets above 100 × 109 L−1 after 1 week . Subsequent reports employed repeated pulse treatments and confirmed these excellent responses . Comparing these two high‐dose steroids, dexamethasone is cheaper, available in oral forms and does not require electrocardiogram monitoring. However, the efficacy of steroids must be weighed against the multiple toxicities that can arise through long‐term use because adult ITP usually shows a chronic course. A single dexamethasone pulse that yields a durable response in 50% of patients would possibly allow more rapid steroid reduction. Despite promising data, randomized controlled trials have been lacking.
This is a prospective randomized open‐labelled trial. The inclusion criteria were adult primary ITP in Chulalongkorn Hospital with platelet counts below 20 × 109 L−1, or below 30 x 109 L−1 with clinical bleeding (hemorrhagic score ≥ 2 ). The exclusion criteria were secondary ITP, life‐threatening bleeding (hemorrhagic score 5), steroid contraindications or steroid refractoriness. The subjects were assigned using shuffled concealed envelopes. The first arm received 10 mg dexamethasone every 6 h (orally or intravenously) for 4 days, followed by oral prednisolone 30 mg day−1. The second arm was given oral prednisolone 60 mg day−1. If severe thrombocytopenia persisted beyond 5 days, prednisolone patients could be transferred to dexamethasone treatment. Intravenous immunoglobulin was used in the event of life‐threatening bleeding. Both regimens were continued for 14 days before tapering dosages. Prednisolone was decreased by 10 mg day−1 every 2 weeks until the dosage reached 30 mg day−1, and thereafter by 5 mg day−1 per month if platelet counts were above 50 × 109/L. Patients’ data were recorded after day 5, day 15 and 1 month of therapy and then monthly for 6 months.
The primary outcome was satisfactory response, defined as platelet count over 50 × 109 L−1 without clinical bleeding after day 5 of treatment. The secondary outcome was the average monthly doses of steroid during 6 months of follow‐ups. For this, dexamethasone dose was converted to a prednisolone equivalence by dividing by 0.15. There was no intention to look at the long‐term outcome of the patients.
During 2006–2007, 45 patients were screened. Nine patients were excluded due to refusal (3), prior treatments (2), HIV (2), systemic lupus erythematosus (1) or refractoriness (1). Eighteen patients were randomized to each arm. Baseline characteristics were similar between these two arms (Table 1). The mean age was 42 years. All new cases were symptomatic for less than 1 month and had not previously been treated. All relapsed patients had received only steroids with current doses of 5 mg day−1 prednisolone or lower, and none had been splenectomized. In the dexamethasone and prednisolone groups, five and six patients, respectively, displayed mild transaminase elevation.
- All numerical data are expressed as means ± standard deviations. *The sample size (36) was calculated using α error = 0.05, power = 0.7, P0 = 40% and P1 = 80%. †Chi square and Student’s t‐tests were used for the comparisons of categorical and numerical data, respectively. ‡Primary outcome. §Monthly prednisolone equivalent doses. ¶Secondary outcome.
Satisfactory responses were significantly higher in the dexamethasone arm (Table 1). Of the five relapsed cases, four responded (two from each arm). The mean platelet count on day 5 was significantly higher in dexamethasone‐treated patients when compared with those receiving prednisolone. Despite this, the bleeding scores decreased similarly . Four cases showed fresh hemorrhage (scores > 0) and platelet counts below 10 × 109 L−1. The three patients in the prednisolone arm were changed to pulse dexamethasone on day 6 followed by 30 mg day−1 of prednisolone. All three of these subsequently responded to the second‐line treatment. The non‐responding patient in the dexamethasone arm suffered from severe mucosal bleeding and intravenous immunoglobulin was given to raise the platelet count while waiting for the effects of steroid treatment. Despite these alterations, the mean platelet counts were still significantly higher in the dexamethasone arm on day 15 according to the intention‐to‐treat analysis.
From day 15, no patients from either arm exhibited any clinical bleeding (score 0). Mean platelet counts after the second week, and up to 6 months, rose similarly in both arms. One patient in the dexamethasone group had a relapse during steroid dose tapering. A colchicine and dapsone combination was added and gave a good response. Two other cases responded slowly and as a consequence colchicine was given. One case in the prednisolone arm subsequently became pregnant and had a recurrence. Two monthly pulses of dexamethasone were administered, resulting in partial and non‐sustained responses. All three patients that were switched from prednisolone to dexamethasone had steroid reduction according to the planned schedule.
The total administered steroids in both arms were the same in the first month. However, the doses were appreciably different at later time points (Table 1). No patient discontinued treatment due to steroid toxicity. One patient in the dexamethasone group developed hyperglycemia. Seven of the patients (19%) (three on dexamethasone) complained of dyspepsia. Six patients (17%) (four on dexamethasone) had acne.
Our data demonstrate the superior effect of high‐dose dexamethasone on platelet counts over standard dose prednisolone in the acute management of patients with severe thrombocytopenia. The primary outcome (i.e. platelet counts above 50 × 109 L−1 on day 5) was set a priori because the margin of safety over the threshold of 30 × 109 L−1 permits patients to be discharged early. In addition, alternative analyses also found that the platelet counts were significantly higher after dexamethasone on days 5 and 15. Therefore, pulse dexamethasone is the drug‐of‐choice for severe ITP. The second‐line therapy and the small sample size preclude the analysis for the difference in clinical bleeding.
Furthermore, this study illustrated that initial high‐dose dexamethasone made possible the more rapid reduction of prednisolone, without influencing the long‐term effect on platelet counts. Nevertheless, this marked difference does not result in fewer steroid side‐effects, probably due to the inadequate power of this study. Despite this, the adverse reactions that arose in both arms were manageable. We found occasional patients, outside this study, who had to stop high‐dose dexamethasone due to severe dizziness, agitation and insomnia. More data are now needed to assess the incidence of uncommon adverse events from pulse dexamethasone. In conclusion, the study suggests that pulse dexamethasone followed by half‐dose prednisolone is the preferred primary treatment of ITP.