Fresh or frozen grafts for allogeneic stem cell transplantation: conceptual considerations and a survey on the practice during the COVID-19 pandemic from the EBMT Infectious Diseases Working Party (IDWP) and Cellular Therapy & Immunobiology Working Party (CTIWP).

The COVID-19 pandemic has had a significant impact on medical practices, including the delivery of allogeneic hematopoietic cell transplantation (HCT). In response, transplant centers have made changes to their procedures, including an increased use of cryopreservation for allogeneic haematopoietic progenitor cell (HPC) grafts. The use of cryopreserved grafts for allogeneic HCT has been reviewed and analysed in terms of potential benefits and drawbacks based on existing data on impact on cell subsets, hematological recovery, and clinical outcomes of approximately 2000 patients from different studies. A survey of European Society for Blood and Marrow Transplantation centers was also conducted to assess changes in practice during the pandemic and any unnecessary burdens on HPC donors. Before the pandemic, only 7.4% of transplant centers were routinely cryopreserving HPC products, but this percentage increased to 90% during the pandemic. The results of this review and survey suggest that cryopreservation of HPC grafts is a viable option for allogeneic HCT in certain situations, but further research is needed to determine long-term effects and ethical discussions are required to balance the needs of donors and patients when using frozen allografts.

Trends in allogeneic haematopoietic cell transplantation for myelofibrosis in Europe between 1995 and 2018: a CMWP of EBMT retrospective analysis.

We performed a retrospective assessment of patient- and transplant-specific characteristics and outcomes for 4142 patients undergoing allogeneic haematopoietic cell transplant for myelofibrosis between 1995 and 2018 across 278 centres. Activity increased steadily across the four analysed eras (<2006, 2006-2010, 2011-2014 and 2015-2018). Median recipient age increased over time between the earliest and most recent cohort (49.4 years (range, 20.1-68) versus 59.3 years (range, 18.1-78.1). Increasing number of patients with a Karnofsky performance status <90 underwent transplant over time. Increased utilisation of matched unrelated donors was apparent (<2006, 22.5% versus 2015-18, 45.2%; p < 0.001). Decreased use of myeloablative conditioning, increased use of busulphan-based platforms and anti-thymocyte globulin was evident. Of note, rates of acute (a)GVHD grade II-IV by day +100 decreased over time (p = 0.027) as did rates of chronic (c) GVHD, predominantly extensive cGVHD (<2006, 36% (31-41%) versus 2015-18, 23% (21-25%); p = 0.001). Overall, significant factors associated with worse overall survival and non-relapse mortality (NRM) remained older age, use of donors other than matched sibling, recipient CMV seropositivity and a lower Karnofsky performance status (<90). Multivariable analysis demonstrated improvements in overall survival and reductions in relapse risk over time with stable NRM rates despite increasing numbers of older, less fit patients and use of unrelated donors.

EBMT prospective observational study on allogeneic hematopoietic stem cell transplantation in T-prolymphocytic leukemia (T-PLL).

Preliminary data suggest that allogeneic stem cell transplantation (allo-SCT) may be effective in T-prolymphocytic leukemia (T-PLL). The purpose of the present observational study was to assess the outcome of allo-SCT in patients aged 65 years or younger with a centrally confirmed diagnosis of T-PLL. Patients were consecutively registered with the EBMT at the time of transplantation and followed by routine EBMT monitoring but with an extended dataset. Between 2007 and 2012, 37 evaluable patients (median age 56 years) were accrued. Pre-treatment contained alemtuzumab in 95% of patients. Sixty-two percent were in complete remission (CR) at the time of allo-SCT. Conditioning contained total body irradiation with 6 Gy or more (TBI6) in 30% of patients. With a median follow-up of 50 months, the 4-year non-relapse mortality, relapse incidence, progression-free (PFS) and overall survival were 32, 38, 30 and 42%, respectively. By univariate analysis, TBI6 in the conditioning was the only significant predictor for a low relapse risk, and an interval between diagnosis and allo-SCT of more than 12 months was associated with a lower NRM. This study confirms for the first time prospectively that allo-SCT can provide long-term disease control in a sizable albeit limited proportion of patients with T-PLL.

Manipulating the stride length/stride velocity relationship of walking using a treadmill and rhythmic auditory cueing in non-disabled older individuals. A short-term feasibility study.

One target for rehabilitating locomotor disorders in older adults is to increase mobility by improving walking velocity. Combining rhythmic auditory cueing (RAC) and treadmill training permits the study of the stride length/stride velocity ratio (SL/SV), often reduced in those with mobility deficits. We investigated the use of RAC to increase velocity by manipulating the SL/SV ratio in older adults. Nine participants (6 female; age: 61.1 ± 8.8 years) walked overground on a gait mat at preferred and fast speeds. After acclimatization to comfortable speed on a treadmill, participants adjusted their cadence to match the cue for 3 min at 115% of preferred speed by either (a) increasing stride length only or (b) increasing stride frequency only. Following training, participants walked across the gait mat at preferred velocity without, and then with, RAC. Group analysis determined no immediate overground velocity increase, but reintroducing RAC did produce an increase in velocity after both conditions. Group and single subject analysis determined that the SL/SV ratio changed in the intended direction only in the stride length condition. We conclude that RAC is a powerful organizer of gait parameters, evidenced by its induced after-effects following short duration training.

Elderly adults delay proprioceptive reweighting during the anticipation of collision avoidance when standing.

The ability to reweight visual and proprioceptive information is critical for maintaining postural stability in a dynamic environment. In this study, we examined whether visual anticipation of collision avoidance (AV) while standing could facilitate the down-weighting of altered proprioception in young and elderly adults. Twelve young (24.91±6.44years) and 12 elderly (74.8±6.42years) participants stood upright for 180s under two task conditions: (a) quiet stance (QS) and (b) standing while anticipating virtual objects to be avoided. In order to disrupt the accuracy of proprioceptive input participants were exposed to bilateral Achilles tendon vibration during the middle 60s of standing in both tasks. Visual field dependence was assessed using the Rod and Frame Test (RFT). Elderly demonstrated significantly higher visual field dependence compared to the young participants. Analysis of the normalized Root Mean Square (RMS) of the Center of Pressure velocity (dCoP) revealed that young participants immediately reduced the sway velocity variability induced by tendon vibration during the anticipation of collision AV compared to the QS task. In the elderly, however, the modulating influence of visual anticipation was delayed and became significant only in the last two time intervals of the vibration phase. These results suggest that volitionally shifting reliance on vision when anticipating a collision AV event facilitates the down-weighting of altered proprioception. Elderly adults seem to be unable to dynamically exploit visual anticipation in order to down weight the altered proprioception possibly as a result of their more permanent up-weighting of the visual modality. Sensory reweighting seems to be a more time consuming process in aging which may have important clinical implications for falling.