Use of Cryopreserved Allogeneic PBSC Results in Delayed Engraftment and Increased Incidence of Poor Graft Function

Use of Cryopreserved Allogeneic PBSC Results in Delayed Engraftment And Increased Incidence of Poor Graft Function

Introduction: During COVID Pandemic, national and international transplant centres agreed to use cryopreserve the donor PBSC as a safer option to deliver allogeneic transplants. Published data suggests that use of cryopreserved allogeneic PBSC is safe and comparable to use of fresh PBSC but cryopreservation of stem cells may lead to cell loss and hence efficacy. During COVID pandemic, use of cryopreserved allogeneic PBSC was adopted as policy on 01/06/2020. This look back analysis evaluates the impact of change in policy.

Aims: Evaluate Engraftment time, compare with historical data, blood component support, and use of growth factors

Methods and Materials: Data was collected from health records (paper and electronic) and laboratory records. Transplant features and engraftment kinetics were analysed.

Results: Group A June 2020 to November 2020, 19 patients [M: 13; F: 6; median age: 50yr (range: 23-69)] who received cryopreserved allogeneic PBSC were compared to 35 patients [M:24; F:11; median age: 59yr (range: 21-71)] receiving fresh allogeneic PBSC for engraftment kinetics. There were no differences between two groups regarding underlying diagnosis (p=0.31), sex mismatch, CMV mismatch, blood group mismatch, reduced intensity conditioning [RIC](p=0.28), type of donor (p=0.98) or use of Alemtuzumab (p=0.88). Median infused Cell dose in group A was 5.3 (3.4-7.16) and in group B 4.9 (1.03-6.85), [p=0.11]. Neutrophil engraftment was significantly faster with fresh PBSC as compared to cryopreserved PBSC (16d vs. 25d, p=0.0025) predominantly with MUD (18d vs. 27d, p=0.009) and RIC (16d vs. 25d, p=0.009). Platelet engraftment to 25 was faster with fresh PBSC (13d vs. 20d, p=0.021) with delayed engraftment in MUD (20d vs. 13d, p=0.006) and RIC (23d vs. 13d, p=0.039). Day to engraftment per unit CD34 was shorter with fresh PBSC for neutrophils (median: 3.2, range: 2.0-7.7 vs. 5.3, range: 2.5-16.7; p=0.006) and platelets (median: 2.4, range: 1.7-25 vs. 3.8, range: 2.2-25; p=0.001) but only for MUD. This suggests 35-40% less efficiency with use of cryopreserved PBSC. There was no difference in the need for transfusion support [RBCs (6 units vs. 3 units, p=0.32); platelets (5 pools vs. 7 pools, p=0.33)]. G-CSF use was higher with cryopreserved PBSC in RIC (54% vs. 20%, p=0.031). Two patients experienced TRM before day 90 (3.7%). At day 90, 17/52 (32.7%) had cytopenia in one lineage and 8/52 (16%) had cytopenia in more than one lineage. Delayed engraftment was observed in 10 of 33 patients (30.3%) transplanted in 2020 and the only significant association was use of cryopreserved PBSC (0% vs. 53%, p=0.001). There was no difference in the incidence of aGVHD, hepatic VOD, microangiopathy and bacterial infections. Numbers are not sufficient to make disease specific comparisons.

Conclusion: Cryopreserved PBSC result in delayed neutrophil and platelet engraftment predominantly with MUDS and RIC. Incidence of delayed engraftment and poor graft function is higher. Per unit CD34 dose, cryopreserved PBSC are 30-40% less efficient to achieve engraftment. Delayed engraftment with cryopreserved PBSC especially in MUD raises the possibility that time from harvest to cryopreservation contributes to reduced efficacy. Based on these findings it was decided to infuse higher CD34 dose (6-7x10^6/kg as compared to usual 4-5x10^6/kg) for cryopreserved MUD PBSC.