Umbilical cord blood cell infusion for stroke treatment
Overview
Intravenous infusion of umbilical blood cells is a therapeutic procedure used in patients recovering from stroke.
Umbilical cord blood is collected from placenta via the umbilical cord vein.
To achieve an optimum therapeutic effect, a dose of 50 million cells per kg is required, and each infusion includes cord blood collected from 4 to 8 donors.
The entire course of infusions is scheduled over two to three days, and after each infusion, the patient is monitored for several hours for any potential adverse reactions.
In the majority of patients, cord blood infusions have resulted in mild improvement of cognitive and motor functions. These functional gains become noticeable within the first few weeks after the infusion and continue for the next 3 to 6 months.
Adverse reactions to cord blood cell infusions are rare and generally mild.
The treatment effect
Cord blood infusion is not intended to be a replacement for standard therapy in the management of stroke, it is additional therapeutic approach that may gain additional improvement of cognitive and motor functions.
In patients undergoing cord blood therapy, there no need to temporarily discontinue other types of pharmaceutical or physical therapy.
Intravenous cord blood cell infusions enhance the regenerative activity of brain cells in stroke patients.
Clinical studies suggest that cord blood therapy is more effective when administrated soon after stroke occurs.
Patients begin to notice improvements within a few weeks after the infusion. The cord blood cells are eliminated from the patient’s body within 6 to 8 weeks; however, patients experience functional gains over the next 3 to 6 months, with sustained functional improvement. Achieved improvement is permanent, patients do not experience worsening of the achieved improvement.
Patients with severe functional impairment may experience little or no improvement, and patients with mild or minimal impairment experience moderate improvement.
Clinical studies have shown that the most important factor influencing the therapeutic effect of cord blood infusion is cell dosage. In a recent clinical trial at Duke University on pediatric cerebral palsy patients (mostly induced by stroke), only patients who received more than 25 million cells per kg showed significant therapeutic effect (Kurtzberg et al; Blood 2015). In each of our cord blood infusions, the patient receives a standard of more than 50 million cells per kg.
Another study suggests that repeated cord blood infusions may lead to further functional improvements.
The treatment procedure
The cord blood infusion procedure involves the intravenous infusion of donated cord blood cells. The procedure differs from standard blood transfusions with regard to the source of blood cells.
Umbilical cord blood is the blood that remains in the placenta after the newborn’s umbilical cord has been clamped and cut. Collection of cord blood from the placenta is harmless and painless for child and mother. The residual placenta and umbilical blood or “cord blood” is collected via the umbilical vein. When cord blood is not collected, it is discarded with the placenta.
Each single donor cord blood collection is designated as a Cord Blood Unit (CBU). Cord blood units are stored in liquid nitrogen at approximately -200°C (-320°F).
In order to maximize therapeutic effect, a dose of greater than 50 million cord blood cells per kg from 4 to 8 donors is infused in each procedure, and the cord blood infusions are generally administered over the course of 2 to 3 days.
Before the procedure
Consultations
In the initial phone or video consultation, our physicians collect a comprehensive medical history, provide detailed information about the procedure and address any unanswered questions.
Based on the initial evaluation, the consulting physician will determine if you are eligible for the procedure and if any additional diagnostic procedures and tests will be necessary prior to treatment. Based on your weight and blood group, cord blood units will be preselected and reserved for your treatment.
Examination
On the first day in the clinic, a number of preliminary tests need to be completed. Blood group determination must be completed if previously unknown. Standard biochemical tests will be performed for assessment of kidney function and an echocardiogram (EKG/ECG) will be performed to assess cardiac function. If results will show abnormalities, additional diagnostics may be done.
After the preliminary interview, examination, and baseline testing, the treating physician will propose a final treatment plan.
During the procedure
Every Cord Blood Unit (CBU) is double-checked to ensure patient compatibility.
Each patient’s treatment plan is different. After the nurse establishes intravenous access, and infusions may last from 20 minutes to 2 hours, depending on how many units are infused.
During and after each infusion, patients are attended by doctors and medical staff to monitor for any potential adverse reactions.
After a final examination by the treating physician, you will be released from the clinic. One side effect of treatment is a somewhat fishy odor on your breath for the next 24 hours. The fishy odor is caused by small amounts of dimethyl sulfoxide, a cytoprotective agent used in cryopreservation, diffusing into the lungs from the blood.
On a next day, you will return to clinic for additional infusions according to scheduled treatment plan.
After the procedure
Following the last infusion, there will be one final check-up with the treating physician. After completion of therapy, your doctor will be in contact over the next 6 months to monitor treatment effectiveness and any potential adverse effects.
Risks
Blood transfusion risks are rare well known and mostly easily manageable.
Allergic reactions
The most common adverse reactions reported are allergic reactions including hives, itching, and fever. Mostly, these reactions are mild and can be easily managed with medications. In the event of adverse reactions, transfusions are stopped immediately.
Bloodborne infections
Transmission of infectious agents such as HIV or Hepatitis B virus are extremely rare events in cord blood transfusions. Donated placental cord blood and maternal blood are screened by sensitive nucleoid acid tests to ensure safety of the blood.
AB0 mismatch reactions
Cord blood units are carefully screened and matched with each patient in order to ensure ABO blood group compatibility and prevent adverse transfusion reactions. In case of mismatch adverse reaction will occur, donor’s red cells are attacked by patient’s immune system.
To compare to standard blood transfusion cord blood cells infusions is safer for three reasons:
- CBUs selection is not done in urgency it can be done carefully and with several controlling steps.
- Cord blood infusions are administered in small volumes over the course of multiple days.
- From cord blood units most of the red cells are removed.
Mismatched cord blood transfusion is extremely improbable. If it will happen the reaction will be minimal due to small volume and minimal amount of transfused red blood cells.
If an acute mismatch adverse reaction will occur the transfusion will be immediately stopped and it will be managed by medication if needed.
Transfusion related graft versus host disease (TA GvHD)
In such a case transfused white cells may begin to attack patient‘s bone marrow cells. It occurs mostly in patients undergoing chemotherapeutic treatment of hematological malignancy like lymphoma or leukemia. Severe immunodeficiency caused by disease and worsen by chemotherapy disables patient’s immune system to remove donated cells as it is normal several weeks after every transfusion. If TA GvHD occurs it often leads to death of a patient due to an infection.
Incidence is extremely rare therefore precise rate of this adverse event is unknown. According to our estimation based on published data the TA GvHD occurs in less than one case of 7 000 000 transfusions.
The mechanism of therapeutic effect
The mechanism of the cord blood cells therapeutic effect is unknown. The cord blood immune cells probably modulate immune and regenerative activity of patients cells. However other cord blood cells including thrombocytes may play role in complex signaling.
Clinical research
Further clinical studying is needed to achieve higher certainty in cord blood therapeutic effect. In US the cord blood cell infusion for stroke clinical trials phase 3. needs to be done to achieve FDA approval. This could be expected by 2023 or later. A multicenter clinical trial phase 2. is led by prof. Kurtzberg at DUKE University investigating cord blood infusion to a patient up to 10 days after stroke. Preliminary published results showed improvement in all patients.
