A "no-wash" albumin-dextran dilution strategy for cord blood unit thaw: high rate of engraftment and a low incidence of serious infusion reactions

Abstract

Preparation of cord blood (CB) units for infusion by albumin-dextran dilution without centrifugation may be advantageous for adult patients to minimize cell loss and, unlike a bedside thaw, is still conducted in the controlled laboratory environment. Therefore, we studied CB transplantation (CBT) using this technique in 54 consecutive CBT recipients >20 kg. Patients (median age=42 years [range: 7-66 years]; median weight=71 kg [range: 24-109]) were transplanted for high-risk hematologic malignancies with myeloablative (n=35) or nonmyeloablative (n=19) conditioning and 4-6/6 human leukocyte antigen (HLA)-matched double-unit grafts. One hundred seven units were thawed with dilution, whereas 1 red blood cell (RBC)-replete unit was washed. A 5:1 dextran 40%/25% albumin solution was used. RBC-depleted units (n=104) were diluted >or=5.5-fold (median final volume 200 mL [range: 200-500]), whereas RBC-replete units (n=3) were diluted >or=4-fold (median final volume 400 mL [range: 400-535]). Total nucleated cell (TNC) recovery was 86%; the median infused TNC dose was 2.17x10(7)/kg/unit. Although 35 patients (65%) had a total of 45 infusion reactions (6 nausea, 31 hypertension, 3 pain, 1 rigors/fever, 2 transient hypoxia, 2 renal impairment) requiring additional therapy, there were no infusion-related serious adverse events, and reactions were not related to dimethyl sulfoxide (DMSO) dose/kg. Cumulative incidence of sustained donor engraftment was 94% (95% cumulative incidence [CI]: 87-100) with neutrophil recovery occurring at a median of 25 days (range: 13-43) in myeloablative and 10 days (range: 7-36) in nonmyeloablative recipients. CB thaw with albumin-dextran dilution reduces unit manipulation, and minimizes cell loss, speeds time to infusion, is associated with a tolerable infusion reaction profile, and a high rate of sustained engraftment in CBT recipients >or=20 kg.

Figure 1. Distribution of infused DMSO doses/kg with double unit CB grafts prepared with albumin dilution and incidence of infusion reactions in 53 patients

To most accurately represent the DMSO dose with two unwashed units the single patient who received one washed unit is excluded from this analysis.

Figure 2. Cumulative incidence of sustained neutrophil engraftment (2A) and platelet engraftment (2B) after CBT with double unit grafts prepared with albumin-dextran dilution

Recipients of ablative and non-myeloablative conditioning are shown separately. While early recovery in recipients of non-myeloablative conditioning was due to transient autologous recovery all engrafting patients shown converted to sustained donor-derived hematopoiesis.

Figure 2. Cumulative incidence of sustained neutrophil engraftment (2A) and platelet engraftment (2B) after CBT with double unit grafts prepared with albumin-dextran dilution

Recipients of ablative and non-myeloablative conditioning are shown separately. While early recovery in recipients of non-myeloablative conditioning was due to transient autologous recovery all engrafting patients shown converted to sustained donor-derived hematopoiesis.

Figure 3. Kaplan-Meier probabilities of overall survival and disease-free survival after CBT with double unit grafts prepared with albumin-dextran dilution