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Leukemia/Lymphoma

Complications of Autologous Stem Cell Transplantation 
  Submitted By: Jason Waterman, M.D.

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Published online: January 2009

Complications of Autologous Stem Cell Transplantation


Authored by: Jason Waterman, M.D. and Matt Kalaycio, M.D.

Cleveland Clinic Foundation


Autologous stem cell transplantation (ASCT) is now commonly used to treat a variety of illnesses including multiple myeloma, Hodgkin’s lymphoma, and non-Hodgkin’s lymphoma (see “Stem Cell Transplant” by Dr. Matt Kalaycio www.cancernews.com/data/Article/258.asp). The transplant process has multiple steps including preparation prior to transplant, the transplant with post-transplant hospital observation, and long-term observation. Each step in the process has its own complications, and thus requires close monitoring to quickly identify and treat any problems. This article focuses specifically on the identification and management of complications of ASCT.



Prior to autologous transplantation a thorough evaluation will take place by an oncologist including a history and physical examination, lab testing, imaging, bone marrow biopsy, and a social work consultation to determine a patient’s readiness for transplantation. Once a decision to pursue transplantation is made, a sufficient number of the patient’s stem cells are collected in order to have enough stem cells to reestablish the immune system after transplantation.

To make the collection of stem cells easier, the patient is given a medication called granulocyte-colony stimulating factor (G-CSF) for 4-5 days prior to collection to stimulate the bone marrow to produce and release more stem cells into the blood stream. Certain chemotherapy agents may also be used in this process to ensure that the highest possible number of stem cells are collected. The stem cells can be taken from the bone marrow or from the peripheral blood.

Collection of stem cells from the bone marrow proceeds just like a bone marrow biopsy and the extracted liquid marrow then undergoes processing to isolate the stem cells needed for transplantation. The process used to collect the stem cells from the blood is called leukopheresis. Leukopheresis involves taking blood from a patient’s vein and passing it through a machine that will remove the stem cells needed for transplant before returning the blood back to the patient through the vein. Either process takes a few hours and may need to be repeated in order to collect enough stem cells.

Stem cell collection is most often done as an outpatient procedure and generally results in few complications, which are mostly mild and easily reversible. The most common complications of leukopheresis include a drop in blood pressure (hypotension), dizziness, numbness and tingling, nausea, vomiting, and fever. Bone marrow collection can also be complicated by soreness and bleeding at the site of collection, which rarely requires blood transfusion. Treatment for hypotension and dizziness is usually accomplished by giving the patient intravenous fluids to bolster the blood pressure during the collection. Calcium is infused if numbness and tingling occur. Nausea and vomiting are common and multiple medications are available for treatment. Fevers are common, generally mild, and most often short-lived. Fevers associated with stem cell collection frequently respond to acetaminophen, although a small number of patients may need to have their blood evaluated to make sure there is no underlying blood stream infection.



When enough stem cells have been collected and it is time for transplantation, the patient is admitted to the hospital and begins a process called conditioning, or myeloablation. The goal of conditioning is to destroy the cancer cells in the body by administering high doses of chemotherapy with or without radiation therapy. The most dangerous side effect of conditioning is that the patient’s natural immune system is destroyed in the process. This is the portion of the transplant process which is the most important in terms of outcome for the patient, because complications at this stage of transplant are potentially fatal. The next step is then the infusion of stored stem cells back into the patient’s blood stream to regenerate the patient’s natural immune system.



Short-term side effects from the actual transplantation of stem cells include fever, chills, hives, chest tightness, hypotension, and coughing. Usually these are mild, and the transplant is rarely stopped because of these symptoms. Once in the blood stream, the stem cells travel to the bone marrow where they will stay and begin to produce all the body’s different blood cells in a process called engraftment. The process of engraftment can take 2-4 weeks, and full reestablishment of the immune system may take several months. The common complications during engraftment revolve around the lack of appropriate numbers of blood cells from the conditioning process, as well as toxicities from the conditioning agents themselves.

One of the most important and potentially dangerous complications during engraftment is the increased risk of infection with bacteria, fungi, and viruses while the body’s natural immune fighting cells, white blood cells (WBCs), are recovering to normal levels. Antibiotics are often given to prevent some of the more common and dangerous infections like bacterial pneumonia, fungal pneumonia (aspergillus), and viral diseases like herpes zoster or simplex. These are all serious infectious risks that are associated with increased mortality.



In an attempt to minimize the risk of infection, visitors to the patient’s room must wash their hands thoroughly. Patients are not strictly isolated, but at some institutions visitors are asked to wear gowns, shoe covers, gloves, and masks. Treatment with G-CSF stimulates the newly transplanted bone marrow to produce more white blood cells and may shorten the time it takes to reach an acceptable WBC count, thereby decreasing the length of time the patient is at risk for infections. However, prevention by careful avoidance of possible infectious risks by the patient, guests, and the hospital staff is of the utmost importance.

The bone marrow produces cells called platelets which aid in the process of blood clotting. Thrombocytopenia is the term for low platelets, and it usually lasts about 3 weeks post-transplant. Bruising, nosebleeds, and bleeding gums are common with thrombocytopenia. Platelet transfusions may be needed if the platelet count falls below a certain level or if bleeding is significant. The bone marrow is also responsible for the production of oxygen carrying red blood cells (RBCs). Transplant patients can have low RBC counts requiring blood transfusions because of either decreased production of RBCs or increased loss of RBCs due to bleeding. RBC transfusions and the use of erythropoietin, a medication to increase the production of RBCs from the newly transplanted bone marrow, are common post-transplant.

Because of the exposure to high-dose chemotherapy prior to transplant there is a high rate of nausea, vomiting, fluid/electrolyte imbalances, and damage to the mucous membranes lining the lips, mouth, and the gastrointestinal system, called mucositis. Many transplant centers have created management protocols for nausea and vomiting that minimize patient discomfort. However, mucositis can be extremely painful and continue to make eating difficult. Patients with mucositis may suffer from malnutrition requiring nutritional supplementation, and in severe cases where oral feeding is not tolerated, nutrition may be given intravenously through a process called total parenteral nutrition (TPN). Fluid and blood chemical (electrolyte) imbalances are also common in these patients because of changes in intake and exposure to medications which affect the kidneys’ ability to regulate fluids and electrolytes. Keeping accurate estimates of fluids taken in and put out during the day is vital to maintaining an appropriate balance. Supplemental fluids or electrolytes may be necessary and their use should be guided by the recorded intake/output and laboratory values. Hemodialysis is rarely used for severe imbalances of either fluids or electrolytes.

Lung conditions can develop after the transplant due to pre-transplant chemotherapy, radiation therapy, or viral infections. Lung problems are heralded by breathing changes, cough, or shortness of breath. One such condition is diffuse alveolar hemorrhage (DAH) which is caused by widespread damage to the lining of the airspaces in the lung. DAH usually presents within the first 30 days of the transplant and may require a doctor to look down into the lungs (a procedure called bronchoscopy) to make a diagnosis. The treatment for DAH includes high-dose anti-inflammatory steroids for 3-5 days followed by a steroid taper over the next 2-4 weeks. Another lung complication, called interstitial pneumonitis, causes damage to the spaces between the cells that make up lung tissue. The treatment for interstitial pneumonitis also includes anti-inflammatory steroids.

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstructive syndrome, is a potentially life-threatening condition affecting the liver which is caused by high-dose chemotherapy given in preparation for the transplant. VOD can develop within the first 1-3 weeks post-transplant and patients usually complain of right upper abdomen pain with increased fluid retention, weight gain, and abdominal fullness. Treatment of VOD includes aggressive management of fluids to avoid excessive swelling and other supportive interventions, but there is no known treatment to reverse the damage to the liver. However, there is ongoing research looking at the use of blood thinning agents as a treatment option.

After the transplant is completed and the engraftment process replaces the body’s immune system to acceptable levels the patient can be discharged home. This latter phase of the transplant has its own complications. There is certainly still a chance that the patient may require blood or blood-product transfusions in the post-transplant period after leaving the hospital. Infections are still a concern, even with acceptable numbers of infection fighting cells in the blood stream. However, there are several other unique post-transplant complications which are rare, but carry with them a high risk of complications or death.

The most feared complications include a return of the original cancer or development of a second malignancy, such as acute leukemia or myelodysplastic syndrome (MDS), a disease causing poor function of the bone marrow. Chemotherapy or radiation therapy prior to the transplant may increase the risk of developing leukemia or MDS. Decreasing the incidence of these conditions is important because both acute leukemia and MDS are associated with a very poor prognosis. Therefore, the risks and benefits of chemotherapy for each patient must be carefully weighed, and decisions on treatment should be made after discussions between the patient and the oncologist.

A condition known as hemorrhagic cystitis that can be caused by certain viral infections or pre-transplant chemotherapy, develops late in the course of some transplant recipients. Hemorrhagic cystitis can cause and increased urge to urinate, a need to urinate multiple times per day, pain with urination, abdominal discomfort, and/or blood in the urine, called hematuria, which can be life-threatening if not treated appropriately. Prevention measures include administration of a medication called mesna, which protects the kidneys and bladder and diuretics, which increase urine production and flush out the toxins. Management can be limited to observation if there is little bleeding and the patient is making a good amount of urine. Insertion of a special bladder catheter which allows passage of blood clots and continuous irrigation of the bladder may be required if bleeding and clots become a significant problem. There are medications which can be instilled into the bladder if bleeding persists.

ASCT is now commonly used in the treatment of Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, and multiple myeloma, with excellent results including cure for many patients. The process does have its own set of complications, as noted above. However, it is important to note that many of these complications can be prevented and most of them can be treated. Prevention begins with diligent monitoring and patient education about possible complications and their warning signs. The complications are well known and transplant centers have numerous prevention and treatment protocols in place to minimize the risks to patients. Research is also on-going at many centers to make the transplant process as safe as possible 


 


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