Stem Cell Infusion

Stem cells are routinely cryopreserved with dimethyl sulfoxide (DMSO). These products are red blood cell (RBC) depleted before cryopreservation and thawed at 37˚C water bath before infusion. They should be infused through standard 170-micron red blood cell filters

The infusion of hematopoietic stem cells may be associated with toxicities that are either specific to hematopoietic products or general to all blood product infusions. The following text provides a minimal guideline to the workup and management of infusion toxicities. Each anticipated toxicity is defined and a plan of action is outlined.

■ Unprocessed marrow contains approximately 20,000 units of heparin, which is infused over 1 to 4 hours. This will result in anticoagulation to a degree sufficient to result in clinical bleeding. Patients at risk are those with a history of recent surgery (e.g., recent line placement or revision), hemorrhagic cystitis, severe thrombocytopenia. However, bleeding can occur in any individual.

■ For a patient with a known hemorrhagic risk, the marrow should be concentrated and washed to remove heparin. If the risk factor is known before a harvest takes place, acid citrate dextrose (ACD) can be used in place of heparin as a cryopreservative, if allowed by protocol. 

■ Infused heparin can be reversed with protamine. One mg of protamine will neutralize approximately 100 units of heparin. Maximum dose is 50 mg and the infusion rate should not exceed 5 mg/minute.

■ Fevers after infusion of stem cell and blood products can be due to bacterial contamination of the product. Often stem cells have a long travel period before infusion, giving skin contaminants an opportunity to grow. Severe fevers, hypotension, or evidence of sepsis needs to be treated aggressively until cultures are either negative or establish an organism.

■ Fevers may be due to contaminated product, cytokines released during collection and processing, or infection coincidental to stem cell infusion.

■ Low-grade fevers can be observed if there is no rigor, hypotension, or systemic symptoms suggestive of infection. The marrow infusion should be completed. The use of antibiotics and/or antipyretics should be up to the treating physician.

■ High fevers ( >100.5) should result in the collection of blood cultures and stem cell product culture. It is generally prudent to start broad-spectrum antibiotics until cultures are known to be negative and the patient has defervesce and is clinically stable.

■ Fluid overload should be treated by slowing the infusion and treating with diuretics as clinically indicated.

■ DMSO toxicity (nausea, vomiting, erythema, headache, pruritis, dizziness, bad-taste in mouth, changes in blood pressure, heart rate) can generally be treated by slowing the rate of infusion. Occasionally, hypotension will require the use of volume expansion. This is typically accomplished with a rapid saline infusion. If severe or not corrected in 20 minutes, consider dopamine. If symptoms are severe the product should have the DMSO removed. 

■ DMSO-preserved product has a distinctive odor (charitably described as “garlic”). It can persist in the patient’s room for 48 to 72 hours. 

■ Mild intravascular hemolysis may occur due to remaining RBCs in marrow collection. Urine tests may be positive for hemoglobin for 24 to 48 hours. This is commonly associated with a rise in serum lactate dehydrogenase (LDH). Maintain hydration and follow creatinine.

■ Arrhythmias such as atrial fibrillation and bradycardia can occur. Hypotension, hypertension, and renal insufficiency can occur. Headache, nausea, vomiting are common. All patients should have cardiac monitoring during stem cell infusion. If arrhythmia is unresponsive to usual treatment measures, it is recommended to involve a cardiologist for management.

■ It is recommended that the amount of DMSO be limited to 40 mL/day regardless of the patient’s weight. If several products are stored, infusions can either be spread out over more than one day or the DMSO can be washed out.

■ A standard blood transfusion reaction investigation should be initiated. 

■ Hydrate the patient to ensure rapid urine flow. If necessary, augment with lasix or mannitol.

■ If DIC is present treat with platelets, fresh frozen plasma (FFP), and transfusions as clinically indicated.

Approximately 10% of the population has a patent foramen ovale (PFO). This is generally not a problem. However, in some patients with increased right-sided pressures there may be R→L blood flow. Infusion of stem cell products, especially, if a filter is not used can result in cerebral emboli because of cell aggregates in the product. We recommend using a standard blood filter for all stem cell products that may have cellular or fibrin aggregates.

For More Information about :  Bone Marrow Transplant Cost in India