Dosing and uses of HemaCord (hematopoietic progenitor cells, cord blood)
Adult dosage forms and strengths
cryopreserved cell suspension
- Contains minimum of 5 x 10^8 total nucleated cells with a minimum of 1.25 x 10^6 viable CD34+ cells per 25 mL
- Suspended in 10% dimethyl sulfoxide (DMSO) and 1% Dextran 40, at the time of cryopreservation
- Exact pre-cryopreservation nucleated cell content provided on container label and accompanying records
Stem Cell Transplantation
Allogeneic cord blood hematopoietic progenitor cell (HPC-C) therapy indicated for unrelated donor hematopoietic progenitor stem cell transplantation procedures in disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment
Use in conjunction with an appropriate preparative regimen for hematopoietic and immunologic reconstitution
The risk benefit assessment for an individual patient depends on the patient characteristics, including disease, stage, risk factors, and specific manifestations of the disease, on characteristics of the graft, and on other available treatments or types of hematopoietic progenitor cells
Dose & HLA matching
- Recommended minimum IV dose: 2.5 x 10^7 nucleated cells/kg at cryopreservation; multiple units may be required to achieve the appropriate dose
- Matching for at least 4 of 6 HLA-A antigens, HLA-B antigens, and HLA-DRB1 alleles is recommended
- HLA typing and nucleated cell content for each individual HPC-C unit are documented on the container label and/or in accompanying records
Renal Impairment
Contains Dextran 40 which is eliminated by the kidneys
Safety of HPC-C has not been established in patients with renal insufficiency or renal failure
Administration
For IV use only
Do not irradiate
Adults: Begin IV infusion at 100 mL/hr and increase the rate as tolerated
Decrease infusion rate if the fluid load is not tolerated
Discontinue the infusion if an allergic reaction occurs, or if moderate-to-severe infusion reaction develops
Monitor for adverse reactions during and for at least 6 hr after administration
Because HPC-C contains lysed red cells that may cause renal failure, careful monitoring of urine output is also recommended
Pediatric dosage forms and strengths
cryopreserved cell suspension
- Contains minimum of 5 x 10^8 total nucleated cells with a minimum of 1.25 x 10^6 viable CD34+ cells per 25 mL
- Suspended in 10% dimethyl sulfoxide (DMSO) and 1% Dextran 40, at the time of cryopreservation
- Exact pre-cryopreservation nucleated cell content provided on container label and accompanying records
Stem Cell Transplantation
Allogeneic cord blood hematopoietic progenitor cell (HPC-C) therapy indicated for unrelated donor hematopoietic progenitor stem cell transplantation procedures in disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment
Use in conjunction with an appropriate preparative regimen for hematopoietic and immunologic reconstitution
The risk benefit assessment for an individual patient depends on the patient characteristics, including disease, stage, risk factors, and specific manifestations of the disease, on characteristics of the graft, and on other available treatments or types of hematopoietic progenitor cells
Dose & HLA matching
- Recommended minimum IV dose: 2.5 x 10^7 nucleated cells/kg at cryopreservation; multiple units may be required to achieve the appropriate dose
- Matching for at least 4 of 6 HLA-A antigens, HLA-B antigens, and HLA-DRB1 alleles is recommended
- HLA typing and nucleated cell content for each individual HPC-C unit are documented on the container label and/or in accompanying records
Renal Impairment
Contains Dextran 40 which is eliminated by the kidneys
Safety of HPC-C has not been established in patients with renal insufficiency or renal failure
Administration
For IV use only
Do not irradiate
Children: Begin IV infusion at 1 mL/kg/hr and increase as tolerated
Decrease infusion rate if the fluid load is not tolerated
Discontinue the infusion if an allergic reaction occurs, or if moderate-to-severe infusion reaction develops
Monitor for adverse reactions during and for at least 6 hr after administration
Because HPC-C contains lysed red cells that may cause renal failure, careful monitoring of urine output is also recommended
Geriatric dosage forms and strengths
Clinical studies of HPC-C did not include sufficient numbers of patients 65 years or older to determine whether they respond differently than younger subjects
In general, administration patients older than 65 years should be cautious, reflecting their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy
HemaCord (hematopoietic progenitor cells, cord blood) adverse (side) effects
>10%
Hypertension, all grades (48%)
Acute GVHD, grades 2-4 (43%); grades 3-4 (20%)
Day-100 mortality from all causes (25%)
Infusion reaction (18%)
Engraftment syndrome (15%)
Primary graft failure (15%)
Vomiting (14.5%)
Nausea (12.7%)
Sinus bradycardia (10.4%)
1-10%
Allergy (3.4%)
Hypotension (2.5%)
Hemoglobinuria (2.1%)
Hypoxia (2%)
Warnings
Black box warnings
Fatal infusion reactions
- Administration can result in serious, including fatal, infusion reactions
- Monitor patients and discontinue infusion for severe reactions
- Contraindicated with known allergy to dimethyl sulfoxide (DMSO), Dextran 40 or human serum albumin
Graft vs host disease (GVHD)
- GVHD is expected after administration, and may be fatal
- Administration of immunosuppressive therapy may decrease the risk of GVHD
Engraftment syndrome
- Engraftment syndrome may progress to multiorgan failure and death
- Treat promptly with corticosteroids
Graft failure
- Graft failure may be fatal
- Monitor for laboratory evidence of hematopoietic recovery
- Prior to choosing a specific unit of HPC-C, consider testing for HLA antibodies to identify patients who are alloimmunized
Contraindications
Known hypersensitivity to dimethyl sulfoxide (DMSO), Dextran 40 or plasma proteins
Cautions
Acute and chronic GVHD may occur; patients should also receive immunosuppressive drugs to decrease the risk of GVHD (see Black box warnings)
Engraftment syndrome is manifested as unexplained fever and rash in the peri-engraftment period; may also have unexplained weight gain, hypoxemia, and pulmonary infiltrates in the absence of fluid overload or cardiac disease (see Black box warnings)
Primary graft failure, which may be fatal, may occur; defined as failure to achieve an absolute neutrophil count greater than 500/uL blood by Day 42 after transplantation (see Black box warnings)
Allergic reactions may occur and include bronchospasm, wheezing, angioedema, pruritus and hive; serious hypersensitivity reactions, including anaphylaxis, also have been reported and may be due to DMSO, Dextran 40, or a plasma component
Malignancy of donor origin
- Patients who have undergone HPC-C transplantation may develop post-transplant lymphoproliferative disorder (PTLD) manifested as a lymphoma-like disease favoring non-nodal sites
- PTLD is usually fatal if not treated
- PTLD incidence appears to be higher in patients who have received antithymocyte globulin. The etiology is thought to be donor lymphoid cells transformed by Epstein-Barr virus (EBV)
Transmission of serious infection
- May occur because HPC-C is derived from human blood
- Donors are screened for increased risk of infection HIV, human T-cell lymphotropic virus (HTLV), hepatitis B virus (HBV), hepatitis C virus (HCV), T. pallidum, T. cruzi, West Nile Virus (WNV), transmissible spongiform encephalopathy (TSE) agents, and vaccine
- Donors are also screened for clinical evidence of sepsis, and communicable disease risks associated with xenotransplantation
- Maternal blood samples are tested for HIV types 1 and 2, HTLV types I and II, HBV, HCV, T. pallidum, WNV, and T. cruzi
- Testing is also performed for evidence of donor infection due to CMV; however, this is not a donor selection criterion
Transmission of rare genetic diseases
- May transmit rare genetic diseases involving the hematopoietic system for which donor screening and/or testing has not been performed
- Cord blood donors have been screened by family history to exclude inherited disorders of the blood and marrow
- HPC-C has been tested to exclude donors with sickle cell anemia, and anemias due to abnormalities in hemoglobins C, D, and E
- Because of the age of the donor at the time HPC-C collection takes place, the ability to exclude rare genetic diseases is severely limited
Infusion reactions
- Infusion reactions are expected to occur and include nausea, vomiting, fever, rigors or chills, flushing, dyspnea, hypoxemia, chest tightness, hypertension, tachycardia, bradycardia, dysgeusia, hematuria, and mild headache; premedicate with antipyretic, histamine antagonists, and corticosteroids to decrease incidence/intensity of infusion reactions
- Severe reactions may also occur and include respiratory distress, severe bronchospasm, severe bradycardia with heart block or other arrhythmias, cardiac arrest, hypotension, hemolysis, elevated liver enzymes, renal compromise, encephalopathy, loss of consciousness, and seizure
- Many of these reactions are related to the amount of DMSO administered; do not exceed 1 g/kg/day of DMSO; actual amount of DMSO depends on the method of preparation of the product for infusion
- If infusing >1 unit of HPC-C on the same day, do not administer subsequent units until all signs and symptoms of infusion reactions from the prior unit have resolved
- Infusion reactions may begin within minutes of the start of infusion, although symptoms may continue to intensify and not peak for several hours after completion of the infusion; monitor closely during this period
- When a reaction occurs, discontinue the infusion and institute supportive care as needed (see Black box warnings)
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown whether distributed in breast milk; caution advised
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of HemaCord (hematopoietic progenitor cells, cord blood)
Mechanism of action
Following IV infusion, hematopoietic stem/progenitor cells from HPC-C migrate to the bone marrow where they divide and mature; these mature cells are released into the bloodstream, where some circulate and others migrate to tissue sites, partially or fully restoring blood counts and function, including immune function, of blood-borne cells of marrow origin
HPC-C expresses the cell surface marker CD34
In patients with enzymatic abnormalities due to certain severe types of storage disorders, mature leukocytes resulting from HPC-C transplantation may synthesize enzymes that may be able to circulate and improve cellular functions of some native tissues; however, the precise mechanism of action is unknown
Administration
IV Compatibilities
Y-Site: 0.9% NaCL
IV Preparation
Must be prepared in a biological safety cabinet with special equipment including a refrigerated blood bank centrifuge and protective cryogloves (see prescribing information for required equipment, reagent, and supplies)
Prepare the thawing solution with equal volumes of 10% Dextran 40 and 5% albumin (see prescribing information for detailed description of methods for preparation and thawing solution)
Dilute the thawed HPC-C with the prepared thawing solution (see details on how to reconstitute in the prescribing information)
IV Administration
Ensure adequate hydration
Premedicate 30-60 minutes before HPC-C administration; premedications can include any or all of the following: antipyretic, histamine blocker, and corticosteroids
Inspect product for unusual particulates and for breaches of container integrity prior to administration; prior to infusion, discuss all such product irregularities with the laboratory issuing the product for infusion
Administer by IV infusion; do not administer in the same tubing concurrently with products other than 0.9% sodium chloride
May be filtered through a 170-260 micron filter designed to remove clots; do NOT use a filter designed to remove leukocytes
Infusion rate
- Adults: Begin IV infusion at 100 mL/hr and increase the rate as tolerated
- Children: Begin IV infusion at 1 mL/kg/hr and increase as tolerated
- Decrease infusion rate if the fluid load is not tolerated
Storage
Shipped frozen in a steel canister that is contained in an insulating foam sleeve
Store at or below -150°C either inside the container used for shipping (Dry-Shipper) or in a Liquid Nitrogen (LN2)-cooled storage device at the Transplant Center (recommended) until ready for thawing and preparation
Once prepared for infusion, may be stored at 4-25°C for up to 4 hr if DMSO is not removed, and at 4°C for up to 24 hr if DMSO is removed in a washing procedure
