Included as part of the PRECAUTIONS section.
Allergic reactions may occur with infusion of HPC, Cord
Blood, including CLEVECORD. 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, hydroxyethyl starch, or a
plasma component of CLEVECORD.
CLEVECORD 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 CLEVECORD administration.
Infusion reactions are expected to occur and may 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 OVERDOSAGE]
Infusion reactions may begin within minutes of the start
of infusion of CLEVECORD, although symptoms may continue to intensify and not
peak for several hours after completion of the infusion. Monitor the patient
closely during this period. When 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 CLEVECORD. Classic acute GVHD is manifested
as fever, rash, elevated bilirubin and liver enzymes, and diarrhea. Patients
transplanted with CLEVECORD 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 multiorgan failure and death. Once engraftment
syndrome is recognized, begin treatment with corticosteroids 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
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
CLEVECORD 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, vaccinia, and Zika virus. 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. CLEVECORD is tested for
sterility. There may be an effect on the reliability of the sterility test
results if the cord blood donor's mother was treated with antibiotics. These
measures do not totally eliminate the risk of transmitting these or other
transmissible infectious diseases and disease agents. Report the occurrence of
a transmitted infection to the Cleveland Cord Blood Center at 1-216-378-3032.
Testing is also performed for evidence of donor infection
due to cytomegalovirus (CMV).
Test results may be found in the accompanying records.
Transmission Of Rare Genetic Diseases
CLEVECORD 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.
CLEVECORD 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 CLEVECORD collection takes place, the ability to exclude
rare genetic diseases is severely limited.
Use In Specific Populations
There are no data with CLEVECORD use in pregnant women to
inform a product-associated risk. Animal reproduction studies have not been
conducted with CLEVECORD. In the U.S. general population, the estimated
background risk of major birth defects and miscarriage in clinically recognized
pregnancies is 2-4% and 15-20%, respectively.
There is no information regarding the presence of
CLEVECORD in human milk, the effects on the breastfed infant, or the effects on
milk production. The developmental and health benefits of breastfeeding should
be considered along with the mother's clinical need for CLEVECORD and any potential
adverse effects on the breastfed infant from CLEVECORD or from the underlying
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 provide sufficient numbers of subjects aged 65 and over to
determine whether they respond differently than younger subjects. In general,
administration of CLEVECORD to patients over age 65 should be cautious, reflecting
their greater frequency of decreased hepatic, renal, or cardiac function, and
of concomitant disease or other drug therapy.
CLEVECORD contains Dextran 40, which is eliminated by the
kidneys. The safety of CLEVECORD has not been established in patients with
renal insufficiency or renal failure.