Included as part of the "PRECAUTIONS" Section
Allergic reactions may occur with infusion of HPC, Cord Blood, including ALLOCORD. Reactions
include bronchospasm, wheezing, angioedema, pruritus and hives [see ADVERSE REACTIONS]. Serious
hypersensitivity reactions, including anaphylaxis, also have been reported. These reactions may be due
to dimethyl sulfoxide (DMSO), Dextran 40, or a plasma component of ALLOCORD.
ALLOCORD may contain residual antibiotics if the cord blood donor was exposed to antibiotics in
utero. Patients with a history of allergic reactions to antibiotics should be monitored for allergic
reactions following ALLOCORD administration.
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. Premedication with antipyretics, histamine antagonists, and corticosteroids may reduce
the incidence and intensity of infusion reactions.
Severe reactions, including 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 also may occur. Many of these
reactions are related to the amount of DMSO administered. Minimizing the amount of DMSO
administered may reduce the risk of such reactions, although idiosyncratic responses may occur even at
DMSO doses thought to be tolerated. The actual amount of DMSO depends on the method of
preparation of the product for infusion. Limiting the amount of DMSO infused to no more than 1 gram
per kilogram per day is recommended [see OVERDOSE].
Infusion reactions may begin within minutes of the start of infusion of ALLOCORD, although symptoms
may continue to intensify and not peak for several hours after completion of the infusion. Monitor the
patient closely during this period. If a reaction occurs, discontinue the infusion and institute supportive
care as needed.
If infusing more than one unit of HPC, Cord Blood, on the same day, do not administer subsequent units
until all signs and symptoms of infusion reactions from the prior unit have resolved.
Graft-Versus -Host Disease
Acute and chronic graft-versus-host disease (GVHD) may occur in patients who have received
ALLOCORD. Classic acute GVHD is manifested as fever, rash, elevated bilirubin and liver enzymes,
and diarrhea. Patients transplanted with ALLOCORD also should receive immunosuppressive drugs to
decrease the risk of GVHD [see ADVERSE REACTIONS].
Engraftment syndrome is manifested as unexplained fever and rash in the peri-engraftment period.
Patients with engraftment syndrome also may have unexplained weight gain, hypoxemia, and pulmonary
infiltrates in the absence of fluid overload or cardiac disease. If untreated, engraftment syndrome may
progress to multi-organ failure and death. Begin treatment with corticosteroids once engraftment
syndrome is recognized in order to ameliorate the symptoms [see ADVERSE REACTIONS].
Primary graft failure, which may be fatal, is defined as failure to achieve an absolute neutrophil count
greater than 500 per microliter blood by Day 42 after transplantation. Immunologic rejection is the
primary cause of graft failure. Patients should be monitored for laboratory evidence of hematopoietic
recovery. Consider testing for HLA antibodies in order to identify patients who are alloimmunized
prior to transplantation and to assist with choosing a unit with a suitable HLA type for the individual
patient [see ADVERSE REACTIONS].
Malignancies Of Donor Origin
Patients who have undergone HPC, Cord Blood, 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.
The incidence of PTLD 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). Serial
monitoring of blood for EBV DNA may be warranted in high-risk groups.
Leukemia of donor origin also has been reported in HPC, Cord Blood recipients. The natural history is
presumed to be the same as that for de novo leukemia.
Transmission Of Serious Infections
Transmission of infectious disease may occur because ALLOCORD is derived from human blood.
Disease may be caused by known or unknown infectious agents. Donors are screened for increased risk
of infection with human immunodeficiency virus (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 vaccinia. 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. ALLOCORD is tested for sterility. These measures do not totally eliminate the risk
of transmitting these or other transmissible infectious diseases and disease agents. Report the
occurrence of a suspected transmitted infection to the St. Louis Cord Blood Bank of the SMM Cardinal
Glennon Children's Medical Center at 1-888-253-CORD (1-888-253-2673).
Testing is also performed for evidence of donor infection due to cytomegalovirus (CMV). The result
may be found in accompanying records.
Transmission Of Rare Genetic Diseases
ALLOCORD may transmit rare genetic diseases involving the hematopoietic system for which donor
screening and/or testing has not been performed [see ADVERSE REACTIONS]. Cord blood donors have
been screened by family history to exclude inherited disorders of the blood and marrow. ALLOCORD
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 ALLOCORD collection takes
place, the ability to exclude rare genetic diseases is severely limited.
Use In Specific Populations
Pregnancy Category C
Animal reproduction studies have not been conducted with ALLOCORD. It is
also not known whether ALLOCORD can cause fetal harm when administered to a pregnant woman or
can affect reproduction capacity. There are no adequate and well-controlled studies in pregnant women.
ALLOCORD should be used during pregnancy only if the potential benefit justifies the potential risk to
HPC, Cord Blood, has been used in pediatric patients with disorders affecting the hematopoietic system
that are inherited, acquired, or resulted from myeloablative treatment [see DOSAGE AND ADMINISTRATION, ADVERSE REACTIONS, and Clinical Studies].
Clinical studies of HPC, Cord Blood, (from multiple cord blood banks) did not include sufficient
numbers of subjects aged 65 years and over to determine whether they respond differently than younger
subjects. In general, administration of ALLOCORD to patients over age 65 years should be cautious,
reflecting their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant
disease or other drug therapy.
ALLOCORD contains Dextran 40 which is eliminated by the kidneys. The safety of ALLOCORD has
not been established in patients with renal insufficiency or renal failure.