tandardized. The most common infusion reactions were hypertension, vomiting, nausea and bradycardia. Hypertension and any grades 3-4 infusion related reactions occurred more frequently in patients receiving HPC-C in volumes greater than 150 milliliters and in pediatric patients. The rate of serious adverse cardiopulmonary reactions was 0.8%.
Table 1. Incidence of Infusion-Related Adverse Reactions Occurring in ≥1% of Infusions (The COBLT Study) Any grade Grade 3-4
Any reaction 65.4% 27.6%
Hypertension 48.0% 21.3%
Vomiting 14.5% 0.2%
Nausea 12.7% 5.7%
Sinus bradycardia 10.4% 0
Fever 5.2% 0.2%
Sinus tachycardia 4.5% 0.2%
Allergy 3.4% 0.2%
Hypotension 2.5% 0
Hemogloburia 2.1% 0
Hypoxia 2.0% 2.0%
For patients who received HEMACORD, information on infusion reactions was from voluntary reports for 244 patients. The population included 56% males and 44% females of median age 25 years (range 0.2-73 years). Preparative regimens and graft-vs-host disease prophylaxis were not standardized. The reactions were not graded. Eighteen percent of patients had an infusion reaction. The most common infusion reactions were hypertension (14%), nausea (5%), vomiting (4%), hypoxemia (3%), dyspnea (1%), tachycardia (1%), and cough (1%). The rate of serious adverse cardiopulmonary reactions was 0.1%.
Other Adverse Reactions
For other adverse reactions, the raw clinical data from the docket was pooled for 120 adult and 1179 pediatric patients transplanted with an HPC-C total nucleated cell dose ≥2.5 x 107/kg. Sixty-six percent (n=862) of the 1299 patients in the docket and public data underwent transplantation as treatment for hematologic malignancy. The preparative regimens and graft-vs-host disease prophylaxis varied. The median total nucleated cell dose was 6.4 (range, 2.5-73.8) x 107/kg. For these patients, Day-100 mortality from all causes was 25%. Primary graft failure occurred in 16%; 42% developed grades 2-4 acute graft-vs-host disease; and 19% developed grades 3-4 acute graft-vs-host disease.
Data on other adverse reactions were available for 155 patients treated with HEMACORD at a total nucleated cell dose ≥2.5 x 107/kg from voluntary reports. For these patients, Day-100 mortality from all causes was 25%. Primary graft failure occurred in 15%; 43% developed grades 2-4 acute graft-vs-host disease; and 20% developed grades 3-4 acute graft-vs-host disease.
Data from published literature and from observational registries, institutional databases, and cord blood bank reviews reported to the docket for HPC-C revealed nine cases of donor cell leukemia, one case of transmission of infection, and one report of transplantation from a donor with an inheritable genetic disorder. The data are not sufficient to support reliable estimates of the incidences of these events.
In a study of 364 patients, 15% of the patients developed engraftment syndrome.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C. Animal reproduction studies have not been conducted with HEMACORD. It is also not known whether HEMACORD 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. HEMACORD should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
8.4 Pediatric Use
HPC-C has been used in pediatric patients with disorders affecting the hem |
