Effect of Post-Thaw Washing Prior to Transplantation of Umbilical Cord Blood Units (UCB) That Were Depleted of Plasma but Not of Red Blood Cells.

Background: Washing after thawing of frozen UCB used for hematopoietic stem cell transplantation (HSCT) is widely practiced for the purpose of removal of the cryoprotectant DMSO and free hemoglobin from lysed red cells; however, frozen peripheral blood stem cells with similar loads of free hemoglobin and DMSO are often thawed and infused directly without washing. Recently, similar clinical outcome and post-thaw viability were seen with the standard red cell depleted (RCD) UCB whether washing was employed after thawing or not. However, no data exist on the utility of post-thaw washing for UCB that were depleted of plasma (PD) but not depleted of red blood cells.

Hypothesis: Myeloid and platelet engraftment, speed of engraftment, overall survival (OS), disease-free-survival (DFS), and transplant related mortality (TRM) will be similar in two comparable groups of patients who received frozen PD CBU that were washed (W) or not washed (NW) after thawing.

Methods: A retrospective analysis was performed on the outcomes of 84 patients in remission without history of prior transplants, who received either washed (n=43) or non-washed (n=40) PD UCB units for HSCT.

Results: Adverse events of any grade occurring more than once during infusion include hemoglobinuria (9NW, 1W), hypertension (6NW, 4W), hives (1NW, 1W), nausea/vomit (2NW) and dyspnea (1NW, 1W). One patient developed seizure and encephalopathy, although relationship to infusion was uncertain. Total nucleated cell recovery after thawing is higher for NW (median 95% vs. 75%). Unadjusted cumulative incidence (C.I.) of neutrophil engraftment was similar for both groups, 91±5% for NW (n=36) versus 93±4% for W (n=41), but median time to neutrophil (20 vs 26 days) and platelet engraftment (platelet 20K 47 vs. 55 days & platelet 50K 55 vs 63 days) occurred earlier for NW. Additionally, C.I. for platelet 20K engraftment was higher for NW (n=28; 92±6%) than W (n=39; 75±7%). Acute grade III–IV GVHD were 10% (NW) and 19% (W), and extensive chronic GVHD were 0% (NW) and 22% (W). TRM was 18±6% for NW and 20±7% for W, with the relapse rate for malignant cases at 11±7% for NW and 25±8% for W. One-year OS was 75±7% (n=40) versus 72±8% (n=43), and 1-year DFS was 69±10% (n=23) versus 54±9% (n=34) for NW and W respectively.

Conclusion: No clear benefits of post-thaw washing for PD UCB prior to HSCT was found, except for the anticipated lower incidence of transient hemoglobinuria. HSCT with NW PD CBU was at least as efficacious as that using W PD units with respect to neutrophil engraftment, TRM, relapse rate, 1-year OS and DFS. Moreover, washing may have a negative impact on C.I. of platelet engraftment and the speed of neutrophil and platelet engraftment. The questions of PD versus RCD UCB and post-thaw W versus NW have important clinical consequences and prospective randomized studies are needed to clarify these issues.