Stem Cells mobilization and collection in allogeneic related and unrelated donors: a single center experience with focus on plerixafor.

INTRODUCTION: Poor CD34 + cells mobilization in allogeneic donors could affect transplant outcome. In a subgroup of patient mobilization with granulocyte colony-stimulating factor (G-CSF) alone is unsatisfactory, and Plerixafor could be used to enhance CD34 + cells release from bone marrow niche. MATERIALS AND METHODS: We conducted a retrospective single-center, cohort study on healthy allogeneic donors both related and unrelated, treated by Udine Transfusion Center over the last 10 years (2012-2022). In the 195 allogeneic donors treated we analyzed age, sex, body weight, BMI, comorbidities, G-CSF dosage and even baseline white blood cell count as possible predictor of insufficient CD34 + cells mobilization on day 5. In the subgroup of related donors we evaluated even baseline CD34 + cells (measured before mobilization start). Processed donor blood volume, collection efficiency and apheresis product were examined. Additionally a comparative analysis was conducted between G-CSF alone treated donors and poor mobilizing ones, in which Plerixafor was administered at a dose of 0.24 mg/kg as a pre-emptive or rescue agent. RESULTS: In 9 donors, due to poor mobilization (defined as CD34 + < 20/µL or estimated yield < 1 ×106 kg/recipient body weight), the use of plerixafor was necessary. PLX at a dose of 0.24 mg/kg was administered 5 h before collection, inducing an average increase of 5.1 (1.7-12.6) in CD34 + circulating cells. In this subgroup of patients, BMI and weight were significantly lower (p = 0.03). Interestingly, baseline CD34 + cells (measured before the onset of mobilization) also seems to predict poor mobilization (p = 0.003). In donors additionally treated with Plerixafor compared to those who received G-CSF alone, collection efficiency was higher (p = 0.02) and CD34 + cells collected were comparable (p = 0.2). Side effects related to the administration of plerixafor, if they occurred, were well tolerated. CONCLUSIONS: Plerixafor is a safe and effective drug in the rescue and prevention of poor mobilization. New prospective studies on allogeneic donors should be performed to increase the treatable population to avoid inadequate collection and mobilization. New laboratory predictors such as baseline CD34 + cells should be investigated in larger cohorts and then used as early screening.

Impact of Cryopreservation of Peripheral Blood Stem Cells (PBSC) in Transplantation from Matched Unrelated Donor (MUD).

Background: Cryopreservation of PBSC for allogenic hematopoietic stem cell transplantation (allo-HSCT) was implemented due to the current Coronavirus 2019 pandemic. The impact of match unrelated donor (MUD) graft freezing on the outcome of allo-HSCT in terms of hematological recovery, graft versus host disease (GVHD), and survival are still controversial. Methods: In this study, we compared graft composition, clinical characteristics, and outcome of 31 allo-HSCT from MUD cryopreserved PBSC (Cryo Group) with 23 matched-pair allo-HSCT from fresh MUD PBSC (Fresh Group) performed in our center between January 2020 and July 2021. Results: No significant differences were recognized in clinical characteristics of patients, donors, and transplants between the Cryo and Fresh groups except for a better prognostic comorbidity index (HCT-CI) of the Cryo group. In the Cryo Group, the median time from apheresis to cryopreservation was 46.0 h (range 23.8−53.5), while the median time from cells collection and reinfusion was 13.9 days (range 5.8−28.1). In the Fresh Group, median time from apheresis to reinfusion was 35.6 h (range 21.4−51.2). The number of viable (7-AAD negative) CD34+ cells per kg patient infused was significantly lower in the Cryo Group (5.2 ± 1.9 × 106/kg vs. 7.0 ± 1.3 × 106/kg; p < 0.001). Indeed, there was a 36% (11−70) median loss of viable CD34+/kg cells after freezing. All patients engrafted: median time to neutrophil engraftment (>0.5 × 109/L) was 13.5 days (range 12−15) for Cryo Group and 14 days (range 13−16) days for Fresh Group (p = 0.522), while the median time to platelet engraftment (>20 × 109/L) was, respectively, 14 (range 12−18) and 15 (range 12−17) days (p = 0.904). The incidence of grade ≥ 2 acute GVHD was similar in the two groups (56.5% Cryo Group vs. 60.0% Fresh Group; p = 0.832) and no differences in terms of OS (p = 0.090), PFS (p = 0.200) and TRM (p = 0.970) were observed between the Cryo and Fresh groups. Conclusions: In our series, no differences between the Cryo and Fresh groups were found in engraftment, grade ≥ 2 acute GVHD incidence, OS, PFS, and TRM despite a lower CD34+ infused dose in the Cryo Group. Frozen PBSCs could be considered a safe option also for allo-HSCT from MUD but a higher amount of PBSC should be collected to warrant an adequate viable CD34+ post-thawing.

Direct Oral Anticoagulants for Very Elderly People With Atrial Fibrillation: Efficacy and Safe Enough?

BACKGROUND: Four direct oral anticoagulants (DOACs) have been licensed for the treatment of atrial fibrillation (AF); efficacy and safety have been shown in clinical trials, but its real use in elderly and very elderly people is still unclear. AIM: To evaluate the impact of DOACs in our patients (pts) aged ≥75 years and switched from other treatments. METHODS: From September 2013 to May 2015, all consecutive pts aged ≥75 years, males and females, in treatment for AF and switched to DOACs are considered in this study. Follow-up (FU) was scheduled after 3 and 6 months by phone and after 12 months by visit. RESULTS: Two hundred thirty-two pts in treatment for AF were switched to DOACs, among these 143 (61.6%) pts aged ≥75 years (mean age, 81 years). The medium FU was 9.6 months, during which 4 minor bleedings in 4 different pts and 1 clinically relevant nonmajor bleeding were reported, all treated with temporary cessation or reduction in DOACs. Two strokes occurred in pts in treatment with dabigatran 110 mg, both resolved without serious sequelae; 2.8% of pts had nausea, itching, vomiting, or discomfort, half of these returned to acenocumarol, and the remaining switched to other DOAC. Four pts died, but the deaths were not related to anticoagulation. CONCLUSION: As reported for general people, also in our elderly population, DOACs resulted in a good alternative to old antithrombotic therapies. Efficacy and safety associated with a higher compliance by pts bring these drugs to be the first choice for long-term anticoagulation.