Our Facebook Page posts DBA facts written by DBA nurse, Ellen Muir, RN, MSN, CPON. We are pleased to share these facts with our patients and families. Thanks, Ellen!
#2: Iron Content
#5: What You Should Consider Before SCT (stem cell transplantation/bone marrow transplant)
#10: Iron Monitoring
DBA Fact #1: Remission
Approximately 20% of those affected with DBA have a chance of going into spontaneous remission. These can be long lasting. It is possible to go into and out of remission at any point of your life. Remission for DBA is when no treatment (steroids or transfusion) are required for 6 months or more.
DBA Fact #2: Iron Content
One unit of blood contains 200mg of iron, which would be the same amount of iron as eating 69 lean 3oz steaks.
One 3oz steak contains 2.9mg of iron.
Food restrictions of iron are unnecessary in preventing iron overload, however supplemental vitamins should be avoided. (Women’s One a Day vit contains 18mg iron/ Men’s One a Day vit contains 0mg iron)
DBA Fact #3: Red Blood Cell Production and Medication
Red blood cells (RBCs) are produced in the bone marrow. The RBCs carry hemoglobin to all the cells of the body, providing oxygen for function.
Reticulocytes (retics) are immature red blood cells. The % will tell us how hard the bone marrow is working. It is not uncommon in a bone marrow failure syndrome such as DBA to have a retic of less than 1%.
Drugs which have been studied to improve red blood cell production include:
Corticosteroids (prednisone, prelone, prednisolone) Has been the standard drug for treating DBA with a response rate of 80%. Many side effects with long term use, or at high doses, including growth stunting, high blood pressure, cataracts, diabetes, and osteoporosis to name a few. With an initial trial of high doses, there is a risk of infection, especially a serious form of pneumonia. Bactrim can be given to prevent this from happening. If there is a response in hemoglobin and retics, the dose is tapered to a more tolerable lower dose (ideally 0.5 mg/kg every other day)
Cyclosporine A (CSA) and Antithymocyte Globulin (ATG) has been studied in DBA patients with limited success. An NIH-sponsored protocol combining CSA and ATG closed due to poor responses. These drugs are associated with serious side effects, including compromising the immune system and kidney failure.
Epogen (procrit, epo, erythropoietin) Erytropoietin is produced naturally by the kidney to help improve production of RBCs. It can be supplemented by injection for low levels in the system. Patients with DBA have no problem with production, in fact usually have very high levels. Even giving high doses will not increase RBC production in DBA. Proven not to work.
Metoclopramide (Reglan) Has shown to be effective in DBA. A 33% hematologic response rate in a small group of patients with DBA using metoclopramide, an inexpensive, commonly used drug for reflux, induces the release of prolactin from the pituitary gland, thereby increasing prolactin levels. It was proposed that prolactin likely improves erythropoiesis by stimulating cells in the microenvironment of erythroblasts. Unfortunately other studies in the US and Europe did not confirm these responses but showed a 10% response rate.
Leucine (L-leucine) Leucine is a branched chain amino acid (BCAA) used by muscle for energy. Amino acids are the building blocks of protien and commonly found in food. Recently, leucine has been tried in one patient in the literature with DBA. A complete response was associated with its administration (discontinuation of transfusion). In unpublished data 5 more patients have been placed on a leucine trial with partial responses in 4 of the 5 patients (either decreased need for treatment or discontinuation of treatment). Recently we have secured funding, from the Department of Defense (DOD) with the help of the DMAF, to study the safety and possibility of giving leucine to 50 DBA patients on transfusion. This study is soon to open, once the protocol goes through the approval process of the DOD, FDA and hospital review board.
Other drugs undergoing investigation presently or in the near future are: lenalidomide (Revlimid), and drugs used for cancer treatment with a side effect of increased hemoglobin. No results are available yet.
DBA Fact #4: Management of Iron with Transfusion
Criteria for starting chelation:
At transfusion # 10- 20- measure serum ferritin.
If between 10 and 20 transfusions serum ferritin is greater than 1000- 1500 ng/ml, on 2 seperate occasions (a month apart), start chelation. Ferritin levels are elevated with any stress on the body…the flu, a cold, virus, etc…… It is considered ‘an acute phase reactant’. Need to monitor ferritin as a trend, slowly going up or down, not a jump.
If ferritin is high for age or with number of transfusions, you should be tested for the hemochromatosis gene (HFE) which is another disorder which the body retains iron, causing the same problems as transfusions. Combine with transfusion- double trouble.
Before starting chelation, should have hearing and vision testing as well as an echocardiocram and EKG as a baseline and then once a year.
– Dosing of Desferal (Deferoxamine, DFO) 40mg/kg 7 nights a week, then may taper to 5 nights a week.
A Desferal challenge may be done before starting DFO, which is admission to the hospital, collecting urine for 24 hrs to measure iron without DFO and then start DFO, collecting urine for another 24 hrs for iron quantification. If not enough iron is being excreted, may need to hold off starting due to high possiblity of toxicity from DFO.
Desferal only works while it is being infused. Once it is disconnected, the free iron has nothing to bind to in order to be eliminated from the body.
– Some doctors like to use vitamin C with chelation. Must be used with caution. It should not be taken when the DFO is not being infused!!! The vitamin C pulls iron from the tissues into circulation. If there is nothing there to attach to (DFO), it will deposit somewhere else- possibly the heart!!!
– Exjade (deferasirox) dosing is 20 mg/kg and may be escalated to 40 mg/kg maximum dose. Exjade works well to maintain iron balance, does not bring ferritin levels down very quickly. May be used at the same time as DFO ie. DFO 12 hrs over night, then Exjade in the morning.
So as not to make this posting a book, I will continue next week with management of severe iron overload.
Iron Overload is a Serious Health Condition with no symptoms until it is too late. Some complications include:
- cirrhosis or fibrosis of the liver
- cardiac arrythmias, which can be lethal
- reproductive organ failure
- growth stunting
- endocrine failure affecting the thyroid
- as well as others
Please call me with any questions. Iron overload is reversible, even if in trouble with cardiac issues. Diabetes and reproductive failure may not be reversed.
DBA Fact #5: What You Should Consider Before SCT (stem cell transplantation/bone marrow transplant)
Decide what your reasons are for transplant. Is it because you want it? Are you sick and tired of transfusion and chelation or steroid therapies enough that it is affecting your quality of life? Or is it because you need it? Maybe you have developed antibodies, making it impossible to find a compatible blood donor and are resistant to steroids. Maybe you have developed aplastic anemia or myelodysplastic syndrome (MDS) – which are other bone marrow failure syndromes affecting red cells, white cells and platelets. Maybe steroids do not work and you also have the hemochromatosis gene (which makes you load iron even if not transfused).
You should talk with someone who has been through the transplant process and absolutely speak to your hematologist in detail. Please call the DBAR (877-DBA-NURSe), as we have the most experience and information about the outcomes of these types of transplants. Dr. Vlachos has spoken to transplant doctors in other states and has even stopped transplant from taking place, if she felt it was too much of a risk. Complete information regarding transplant can be found at www.marrow.org.
Risks vs. benefits. The benefits must outweigh the risks.
Death may occur due to complications including: GVH, rejection, infection.
Graft vs. Host Disease (GVHD) – the donor cells can actually attack different parts of the recipient’s body, the body’s natural defense tries to fight the donor marrow, as it is seen as “foreign.” Skin – GVH can cause a rash, discoloration, peeling and sloughing. Gastrointestinal – can cause the GI tract (from the mouth to the anus) to slough off causing sores and diarrhea.
Rejection – your own immune system is strong enough to reject the donor cells, this happens sometimes with “mini transplant.”
Infection – may be severe, even life threatening, if you get something as simple as a cold or virus. Even your food needs to be well cooked, no fresh fruits or vegetables, no fast food, until the immune system comes completely back to normal.
Cancer – DBA has a risk of cancer to begin with, even if it is a small risk. The transplant requires chemotherapy, which in itself can actually cause possible cancer in the future.
Infertility – Chemotherapy can cause the inability of the reproductive organs to work correctly.
Return of DBA -This can happen with a related donor who has “silent” DBA. That is, they have the same gene as the patient, but never knew because they never had anemia or congenital anomalies which sometimes go along with DBA. This is why the donor needs to be carefully screened.
A successful transplant eliminates the need for transfusion and steroids for treatment of anemia in the future. It does not eliminate the 50% possibility of passing it on to your children or the other risks associated with DBA. DBA is in all your genes. Transplant “fixes” the bone marrow production of red blood cells, but does NOT “cure” all aspects of DBA.
DBA Fact #6: Recommended Labs For Chronically Transfused Patients
We have been working closely with an adult endocrinologist, Dr. Irwin Klein, at the Feinstein Institute for Medical Research, who has done a lot of research studying heart disease in relation to thyroid dysfunction. Being that DBA patients who are chronically transfused have thyroid issues due to iron overload, he has taken an interest in working with us to prevent thyroid disease as well as cardiac failure due to thyroid dysfunction. As we know, other endocrine organs are also affected – pancreas, gonads, pituitary, as well as linear height.
Here is a list of recommended labs to monitor and prevent the devastating effects of iron overload in the thyroid, heart, and the effects of diabetes:
- total T3
- total T4
- T3 uptake (instead of free T4)
- IGF-1(monitors acute fluctuations in insulin action and determines inadequate insulin treatment or poor control of dietary intake)
- NT-proBNP (aids in diagnosis of left ventricular dysfunction in heart failure)
- Antithyroid Abs (Antithyroglobulin and AntiThyroperoxidase)
- Fructosamine (useful in situations where the A1C cannot be reliably measured – as with transfused persons)
- Vitamin D
Any questions, please feel free to e-mail me firstname.lastname@example.org or call 1-877-DBA-NURSe (322-6877).
DBA Fact #7: The Bone Marrow Examination – What Is It and Why Should It Be Done
The bone marrow is the “factory” where hematopoiesis takes place (that is a fancy word for the production of the cells in the blood – red blood cells, white blood cells and platelets). A bone marrow examination is a test that looks at the cells in the bone marrow, to see how many there are and what they look like. The bone marrow is found in the center of the bones and is made up of both spongy bone and liquid marrow.
Most of the time, the information from the bone marrow exam can be useful in diagnosing DBA and rule out other disorders which may cause a change in the marrow (such as leukemia, aplastic anemia or myelodysplastic syndrome [MDS]). A bone marrow examination is usually done to make the initial diagnosis of DBA. If this hasn’t been done, it is recommended to be done before starting steroids as the medicine can change the appearance of the cells. Aplastic anemia, acute leukemia and MDS have been reported in DBA. For this reason, we perform a bone marrow evaluation if there is a change in blood counts seen on the complete blood counts (CBC), such as a steady decrease in white blood cell count or platelet count. We do not perform routine yearly bone marrow exams in patients whose blood counts are stable and have not changed.
A Bone Marrow Aspirate is usually done from the posterior (back) hip (iliac) bone. Rarely it can be done from the anterior (front) hip bone or the chest bone (sternum). The area to be used is numbed with a topical anesthetic, usually lidocaine. The area is then sterilely cleaned and a needle is placed into the bone. Liquid marrow is removed with a syringe and sent for the following tests:
Morphology of the bone marrow is usually done by the hematologist or the pathologist or both. This is where the bone marrow is spread on a slide and stained with special stains that will “color” the blood cells, making them easier to identify under the microscope. The cells are counted and viewed for their appearance. Abnormalities in the number of cells can give information about potential Aplastic anemia (too few cells of all three cell lines) and abnormalities in their shapes or sizes can be important to diagnose myelodysplastic syndrome or leukemia.
Cytogenetics is the study of the structure of DNA within the cell nucleus. This is done in two parts: Karyotype gives information about the number of chromosomes. A normal person has 23 pairs of chromosomes; one of those pairs is XX (female) or XY (male). An extra chromosome (trisomy) or a missing chromosome (monosomy) will indicate a disease process (for example, an extra chromosome 21 is associated with Down Syndrome). Fluorescence in situ hybridization (FISH) provides researchers with a way to see and map the genetic material in an individual’s cells, including specific chromosomes or portions of chromosomes.
A Bone Marrow Biopsy can be done at the same time as the bone marrow aspirate. A piece of the spongy bone is removed, usually using the same needle and puncture area. The biopsy specimen is removed and sent to pathology for:
Cellularity – This is the percentage of cells in the specimen. Bone marrow contains hematopoietic stem cells and fat cells. If a sample is hypocellular, it has fewer than the expected number of hematopoietic cells (cells that mature into red blood cells, white blood cells and platelets). If a sample is hypercellular, it has more than the expected number of hematopoietic cells. Cellularity is age dependent – in newborns, all marrow is hematopoietic (shows 100% cellularity). With age, hematopoiesis (the number of cells) decreases, and the amount of fat increases. Normal cellularity of an adult bone marrow ranges between 30-70% and changes under pathological conditions- a marrow is reported as hypercellular (over 70%), normocellular (30-70%) or hypocellular (under 30%).
If you have any questions, please don’t hesitate to contact me or speak to your doctor. Ellen Muir, RN, MSN, CNS “DBA Nurse” 1-877-DBA-NURSe/ 1-877-322-6877, email@example.com
DBA Fact #8: Some Things to Consider When Having a Port Placed
Always weigh the risks and the benefits of any medical intervention.
A port is a small medical device placed under the skin and is used to infuse fluids for medical treatment into the blood stream and to also withdraw blood from a large vein. It is accessed with a special needle, in usually one stick. Its parts include a reservoir with a septum (area where the needle is inserted), and catheter. The special needle used to access it is called a ‘huber’ needle. It has a 90 degree bend so it is comfortable when in use and is ‘non coring,’ which means it won’t leave a hole when the needle is removed.
A port may sometimes be referred to as a port-a-cath, mediport, or passport. Depending on the manufacturer, the name varies. Just as the name varies, so does the size and materials it is made of. Most port reservoirs are made of stainless steel, titanium or plastic. For anyone who may need to have a cardiac MRI to look for iron overload, we recommend a plastic port so it does not interfere with the results. If it cannot be plastic, placement outside the scanning field is recommended (such as right side of chest). If your hospital does not use plastic ports, they can be special ordered.
The reservoir has a silicone septum which allows it to be punctured with a special needle, hundreds of times. It is self sealing so it does not leak when the needle is taken out. The catheter, which attaches to the reservoir, is made of a soft, bendable silicone or polyurethane. The surgeon must make a pocket for the reservoir under the skin, usually in the chest area. Speak to your surgeon to decide on what area is best for you. Your options for placement are upper chest, over the ribs (under the breast), or sometimes in the forearm. The catheter is then threaded through a major vein and ends at the superior vena cava of the heart.
Poor IV access when receiving monthly blood transfusion is one reason for placing any type of central venous access device (CVAD). Other reasons may include for delivery of chemotherapy, IV nutrition, antibiotics and for dialysis. A Broviac (Hickman, Groshong) is another type of CVAD, where the access point is outside of the body. This type of ‘tunneled catheter’ is what is used during stem cell transplantation. A peripherally inserted central catheter (PICC) is another type of external catheter that is used for temporary IV access.
IV’s can be started quickly and relatively easily without repeated needle sticks. You can continue to bathe and even swim with a port once the surgical incision has healed. A numbing cream can be placed to the port site 30 minutes before accessing it so you don’t feel the pinch.
Some homecare agencies will not provide 24/7 Deferral therapy with an IV that is not a central line. A port is a good option.
Infection – a severe bacterial infection can compromise the device, require its surgical removal, and seriously jeopardize the health. To prevent infection, these ports are accessed using sterile technique, the needle should be changed once a week. If you experience fever, you need to seek medical attention immediately, so blood cultures can be taken (sometimes from the port and from a vein in the arm). Antibiotics need to be given through the port right away to prevent sepsis, a serious life threatening blood infection.
If receiving 24/7 IV therapy, the dressing must stay dry and needle be changed weekly to prevent any bacteria from growing.
Thrombosis – formation of a blood clot in the catheter may clog the port. To prevent clotting, the port is flushed with saline and heparin, usually by a nurse or other medical professional, or someone properly trained that is a family member or the patient, at least once every four weeks, if not being used and after it is used for treatment or blood draw.
If a thrombin sheath forms at the tip of the catheter (forms a kind of flap) blood is not able to be withdrawn. The catheter can still infuse as it the flap is pushed away with pressure of the fluid. In the future, this may become a complete blockage or be a source of infection.
Mechanical failure – sometimes when withdrawing blood the tip of the catheter is pulled against the wall of the vein and no blood is able to be withdrawn, due to too much suction. The catheter can still infuse as it is pushed away from the vein wall with the pressure of the fluid.
Infiltration – if the needle is not placed through the port septum, fluid can leak and cause pain, swelling and sometimes redness.
Age – If the device is put into a child, the child’s growth means that the catheter becomes relatively shorter and will move further away from the superiorvena cava – it may be necessary to remove or replace it.
Complications can occur during surgery, speak to your surgeon and anesthesiologist.
If you are trying to decide which port is right for your needs, you can contact me and I can help guide you on a more personal level.
Ellen Muir, RN, MSN, CNS
DBA Fact #9: Monitoring Transfusional Iron Overload
As part of a large hematology team at Cohen Children’s Medical Center of New York, we see hematology as well as oncology patients, as many centers do. Several clinicians (doctors, nurses, nurse practitioners and physician assistants) see and make treatment decisions for a variety of patients with very different diagnoses. For this reason we found it important to develop a consistent plan of care and treatment for those who are at risk for transfusional iron overload see attached document. Please feel free to print and share with your treating clinicians. Use it to formulate questions and have a discussion with your clinician to develop a plan that meets your needs.
Methods of determining degree of iron overload:
Serum ferritin Ferritin is a protein found inside cells that stores iron so your body can use it to make red blood cells. Since DBA individuals do not make their own red blood cells, ferritin is not used and builds up with each transfusion. A ferritin test indirectly measures the amount of iron in your blood and can be used as a ‘marker’. Ferritin is not always accurate as it is affected by factors other than iron loading such inflammation. Ferritin is useful over time to monitor a trend, up or down, to see if chelation is helping to reduce iron burden. This may be misleading as it does not reveal how much iron is stored in the organs and tissue. Chelators will pull the iron from the tissue into circulation and the ferritin level will go up.
FerriScan/ T2*/ R2 are all magnetic resonance imaging (MRI) based technologies for the non-invasive measurement of iron concentration. The difference between them is the method used to calculate the amount of iron stored. FerriScan is just the brand name for R2 (like Xerox is for photocopy machines). Not all MRI machines are equipped with the software to do this type of testing. I would advise you to call your radiology department directly and ask to speak to the radiologist to see if they can do a T2* (* = star) for liver and heart iron quantification. Disadvantages include possible increased reading if there is any metal in the field of study, such as metal clips if your spleen was removed. Most ‘hardware’ is now MRI compatible, which means it won’t be attracted to the magnet. You may feel a warm sensation if you have a port or a joint replacement.
Liver biopsy is an invasive procedure, requiring anesthesia and a biopsy needle to obtain small pieces of liver. Disadvantages include risk of bleeding, risk of infection and the possibility of obtaining a piece of liver that does not have as much iron as another area of the liver. There is no way of knowing which area of the liver to take a sample, as it does not store iron evenly, so 3 or 4 different areas are usually biopsied. This procedure is usually done by a gastroenterologist or interventional radiologist and requires you to lie still for 4- 6 hours after the test, without eating, just in case there is bleeding and you need to go to the operating room to stop the bleed. Advantages over other methods of testing include the ability to actually see the condition of the liver and look for cirrhosis and fibrosis.
Gene testing for hereditary hemochromatosis provides information on likelihood but not level of iron loading. The presence of this gene will cause transfused individuals to load iron even more quickly than those not affected by the gene. If the test is positive for even one copy of the gene, DBA patients may need to come off transfusions and try steroids or have a stem cell transplant as maintaining iron balance will be a very difficult battle. Disadvantages are that there are a number of hemochromatosis genes, but only one, HFE, can be easily identified.
DBA Fact #10: Iron Monitoring
Please use this information to have a conversation with your hematologist. Together you can work to prevent the effects of transfusional iron overload.
Iron is naturally absorbed from food through the intestines and transported throughout the body by transferrin, a protein produced by the liver. Iron contained in blood transfusions, bypasses the intestines and goes straight into the body’s circulation. About 70% of the iron transported is incorporated into the hemoglobin inside red blood cells. The remainder is stored in the tissues as ferritin or hemosiderin, and small amounts of it are used to produce other proteins such as myoglobin, and some enzymes. Since DBA patients cannot make their own red blood cells (which is why they are transfused in the first place!), all of the iron is stored in the body’s tissue and organs causing them to work harder and possibly cause organ failure.
In some patients, ferritin may not necessarily reflect the amount of iron that needs to be unloaded from transfusions. Ideally, to assess the level of excess iron, patients should have a MRI (T2*) or a liver biopsy. If these are unavailable, or you cannot get them frequently enough, these following common lab tests may help to determine if you are being chelated adequately:
Transferrin is the main protein in the blood that binds to iron and transports it throughout the body. The amount of transferrin that is available to bind to and transport iron is reflected in measurements of the total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC) or transferrin saturation (% sat).
Ferritin is an iron-containing protein that is the primary form of iron stored inside of cells. The small quantity of ferritin that is released into the blood is a reflection of the amount of total iron stored in the body.
- Serum iron – measures the level of iron in the blood.
- TIBC (total iron-binding capacity) – measures all of the proteins in the blood that are available to bind with iron, including transferrin. Since transferrin is the primary iron-binding protein, the TIBC test is a good indirect measurement of transferrin. The body produces transferrin in relationship to the need for iron. When iron stores are low, transferrin levels increase and vice versa. In healthy people, about one-third of the binding sites on transferrin are used to transport iron.
- UIBC (unsaturated iron-binding capacity) – measures the reserve capacity of transferrin, the portion of transferrin that has not yet been saturated. UIBC also reflects transferrin levels.
- Transferrin saturation – This is a calculation that is done with the iron test result and TIBC or UIBC. It represents the percentage of the transferrin that is saturated with iron. This number should be less than 50%. If this is higher than 50%, it mean that there is not much more room to transport out any more iron.
- Serum ferritin – reflects the amount of stored iron in your body; ferritin is the main storage protein for iron inside of cells. Since this level is elevated with any stress on the body, it is not accurate as a single measurement. You need to monitor a trend. Steady upward trend is showing a buildup of iron. One high level is showing an ‘acute phase reactant’, where there is stress on the body, such as illness. Start chelation when 1000- 1500 ng/ml on more than one occasion, when feeling well.
Just a reminder, the starting dose of chelating agents are:
Exjade 20 mg/kg/day every day. Every dose missed is a day that iron is causing damage. The dose can be increased up to 40 mg/kg/day. If you experience side effects – nausea, diarrhea, rash, elevated liver function tests, you can go back to your last dose tolerated and go up slowly to maximum dose.
Desferal (DFO) 40 mg/kg/day either subcutaneously (SQ, SC) or intravenously (IV). Maximum dose is 60 mg/kg/day. It is believed that high doses of DFO can cause delayed growth. So can iron overload!! DFO doesn’t work when it is not being infused. The longer you can tolerate it, the better job it will do. If you can handle 12 hours as opposed to 8 hours at the same dose – Great!
Deferiprone (L1) it is true that this drug may cause irreversible agranulocytosis- your counts can drop and never recover, this doesn’t mean that there are not situations which may be beneficial to use this drug. With careful monitoring of blood counts, this drug is very effective in unloading iron in desperate situations such as heart failure.
Under chelation — missed doses, partial doses, not high enough doses, can cause the medicine to pull iron from one area of the body, but not have enough there to escort it out of the body, thus, it will redeposit it somewhere else. So your liver may look good but now the iron is in your pancreas or heart.
Depending on degree of iron overload, these drugs can be used in combination.
Remember to have your vision and hearing checked yearly. High doses of chelators can cause changes. This is mostly due to toxicity (not enough iron to be removed).
Please be aware that iron overload is preventable and reversible!! Do not give up. The war on iron is on. So grab your chelators and with knowledge, support, courage and patience, you can win!
DBA Fact #11: What is a “mini-transplant?”
- Autologous transplant – bone marrow or stem cells are taken from the patient and given back (transplanted) to themselves after chemotherapy and/or radiation therapy is given
- Allogeneic transplant – bone marrow, stem cells or cord blood are taken from another person (donor) and transplanted after chemotherapy and/or radiation therapy is given to the patient (recipient)
- Preparative chemotherapy and/or radiation therapy – the regimen given to destroy the recipient’s bone marrow prior to the transplant thus making way for the new cells of the donor. There are different types of regimens to prepare the patient for the transplant:
- Myeloablative – these regimens contains high doses of chemotherapy and/or radiation that will destroy the bone marrow of the patient and allow new donor stem cells to grow in the bone marrow
- Reduced Intensity or Non-myeloablative – these regimens use lower doses of chemotherapy and/or radiation and use increased doses of transplant anti-rejection drugs (immunosuppressive) medications
Q: What is a “mini-transplant”?
A: “Mini-transplant” refers to the type of preparative regimen a patient receives before he/she undergoes a stem cell/bone marrow transplant. A “mini-transplant” is also called a non-myeloablative or reduced-intensity transplant and is a type of allogeneic transplant.
A “mini-transplant” uses lower, less toxic doses of chemotherapy and/or radiation to prepare the patient for an allogeneic transplant. The use of lower doses of chemotherapy and radiation eliminates some, but not all, of the patient’s bone marrow. It also suppresses the patient’s immune system to prevent rejection of the transplant.
Unlike traditional myeloablative transplant, cells from both the patient and the donor may exist in the patient’s body for some time after a “mini-transplant.” Once the cells from the donor begin to engraft, they may destroy the remaining patient cells that were not eliminated by the chemotherapy and/or radiation.
Using lower doses of chemotherapy and/or radiation has allowed older patients, and patients with other health problems to have a transplant. “Mini-transplants” tend to have lower occurrences of early transplant-related complications and death. However no transplant is without risk. This type of transplant can be associated with long-term effects of graft-versus-host disease (GVHD), side effects of the treatment, resulting in other complications and serious infections.
This approach does allow the application of a potentially curative procedure to elderly or medically infirm patients who would not otherwise tolerate high-dose preparative regimens.
In patients with leukemias and lymphomas, transplantation consists of treatments with conventional preparative regimens included high doses of chemotherapy with or without total body irradiation (TBI). However, because of toxicities from the intensive preparative regimens to non-marrow organs such as gut, liver, lung, and heart, conventional high-dose transplants have been restricted to patients younger than 50-55 years of age who are in good medical condition. “Mini-transplants” reduce the intensity of preparation to minimize regimen-related toxicities.
The risks of “mini-transplants” include longer time to having a good immune system and rejection. Graft rejection is much higher in “mini-transplants” than in myeloablative ones. In fact, non-engraftment, i.e. having the transplant not take and be accepted in the patient’s body, is one of the major complications with this type of transplant.
In Diamond Blackfan anemia, this type of transplant is preferred in many adult patients because of their other health issues. In children, the standard of care is still transplantation with myeloablative regimens. As our transplant regimens improve, there may come a time in the future that “mini-transplants” are used routinely in children to decrease the toxicities associated with myeloablative regimens. Non-myeloablative regimens have been used with some success in young patients already who had other co-existing medical issues.
The success of any transplant relies on the general health of the patient, in particular their iron overload status and in the match of the donor to the patient.
DBA Fact #12: Immunizations in the DBA patient
It is generally safe to vaccinate DBA patients. Most DBA patients have normal immune systems. Therefore, they should undergo a standard regimen of childhood immunizations. For DBA patients who present with anemia before 6 months of age, the most recommended practice is to treat anemia with monthly transfusions. Steroid therapy is usually delayed until 1 year of age, if possible. Children can therefore safely receive all the early immunizations without any interruption. When the patient is initially diagnosed with DBA, it is generally recommended that the patient is on transfusion therapy. It is advised to give the 12-month live vaccines (Varicella [chicken pox] and MMR [Measles, Mumps and Rubella]) and then proceed to start the steroid trial at least 2 weeks after these vaccines are administered. It is also recommended that DBA patients receive the yearly Influenza (flu) vaccine.
For patients who start corticosteroid therapy (usually Prednisone or Prednisolone) before 12 month of age, it is generally safe to give the “killed” vaccinations. The only downfall is that the patients may not get the full “effect” of the vaccine because the steroids can dampen the immune response to the vaccine.
The Red Book 2012 (The Infectious Disease Guidelines of the American Society of Pediatrics) states the following:
“Children who receive systemic corticosteroid therapy can become immunocompromised. The minimal amount of systemic corticosteroids and duration of administration sufficient to cause immunosuppression in an otherwise healthy child are not well defined. A dosage equivalent to ≥2 mg/kg per day of prednisone or equivalent to a total of ≥20 mg/day for children who weigh more than 10 kg, particularly when given for more than 14 days, is considered sufficient to raise concern about the safety of immunization with attenuated live-virus vaccines.
Accordingly, guidelines for administration of attenuated live-virus vaccines to recipients of corticosteroids are as follows:
- Physiologic maintenance doses of corticosteroids: Children who are receiving only maintenance physiologic doses of corticosteroids can receive attenuated live-virus vaccines.
- Low or moderate doses of systemic corticosteroids given daily or on alternate days: Children receiving <2 mg/kg per day of prednisone or its equivalent, or <20 mg/day if they weigh more than 10 kg, can receive attenuated live-virus vaccines during corticosteroid treatment.
- High doses of systemic corticosteroids given daily or on alternate days for fewer than 14 days: Children receiving ≥2 mg/kg per day of prednisone or its equivalent, or ≥20 mg/day if they weigh more than 10 kg, can receive attenuated live-virus vaccines immediately after discontinuation of treatment. Some experts, however, would delay immunization with attenuated live-virus vaccines until 2 weeks after corticosteroid therapy has been discontinued.
- High doses of systemic corticosteroids given daily or on alternate days for 14 days or more: Children receiving ≥2 mg/kg per day of prednisone or its equivalent, or ≥20 mg/day if they weigh more than 10 kg for 14 days or more, should not receive attenuated live-virus vaccines until corticosteroid therapy has been discontinued for at least 1 month.
These guidelines are based on concerns about vaccine safety in recipients of high doses of corticosteroids. When deciding whether to administer attenuated live-virus vaccines, the potential benefits and risks of immunization for an individual patient and the specific circumstances should be considered.”
If possible, the patient can continue with transfusion therapy until the 12-month live vaccines are given. Ideally, the steroid trial can begin about 2-3 weeks later. If the patient is unable to be on a transfusion regimen until 12 months of age (due to venous access issues or blood availability) then the patient can start the steroid trial earlier. Practically, live vaccines can be held until the patient is on weaning doses of Prednisone, that is less than 2 mg/kg, or less than 20 mg for those patients over 10kg.
Rarely DBA patients are noted to have an immune component to their disease and get frequent infections. These patients should have an immunologic evaluation and may require immunoglobulin therapy. It is still safe for these patients to receive all immunizations prior to the 12-month live vaccines as the early vaccines contain no live viral particles. The live vaccines should be given in coordination with the immunologist to be given safely and to ensure that the response to the vaccines is adequate.