Favorable recovery profiles and good reliability among youngest unrelated stem cell donors supports lowering the minimum donor registration age.

INTRODUCTION: Younger donor age in hematopoietic cell transplantation has been associated with improved overall and disease-free survival. Safety data on peripheral blood stem cell (PBSC) and bone marrow (BM) donation is well established, including in the <18-year old age group in the related setting. In response, Anthony Nolan became the first stem cell donor registry to lower the minimum age for unrelated donors to 16-years. MATERIALS AND METHODS: This retrospective study reviewed unrelated donors donating PBSC or BM for the first time between April 2015 and October 2017 since adoption of the lowered recruitment age. Data were collected from registry electronic database and structured follow-up questionnaires. Primary outcomes were turnaround time from VT to donation, optimal cell yield achievement, and physical and emotional recovery. RESULTS: Out of a total of 1013 donors, there were no differences between the different age groups in proportion of donors achieving optimal CD34+ or TNC (PBSC and BM, respectively). There was no increased central line requirement for younger donors or increased emergency telephone support. Youngest donors were more likely to report physical recovery 2 and 7 days post-PBSC (P = .024 and P = .015, respectively) as well as an earlier emotional recovery (P = .001) and fewer physical symptoms 1 week BM donation (P = .04). CONCLUSION: This study shows that younger donors are as reliable as older donors, and have favorable recovery profiles without need for increased support at any stage of the donation, supporting Anthony Nolan recruitment strategy and offering reassurance to donor registries considering the same.

Outcomes After Donor Lymphocyte Infusion in Patients With Hematological Malignancies: Donor Characteristics Matter.

In the context of T-cell depletion, failing to achieve full donor chimerism (FDC) entails higher risk of graft loss and disease relapse. Donor lymphocyte infusion (DLI) is an adoptive immunotherapy for mixed chimerism (MC) or relapsed disease after reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (HSCT). Nevertheless, little is known of factors associated with attaining FDC or disease remission. We carried out a retrospective study with 100 adult patients to identify patient and donor factors that can predict achievement of FDC and disease remission and describe complications after DLI. Indications for DLI were T-cell MC in 61 patients and relapsed disease in 39 patients. Forty patients (65.6%) with MC attained T-full donor chimerism (T-FDC), with higher responses seen in patients whose donors were female (81.5% versus 52.9%, P = .004) and cytomegalovirus negative (76.5% versus 52%, P = .004). However, only patients with younger donors (<30 years old) compared to older donors (94.4% versus 53.5%, P = .013) and those attaining unfractionated whole blood (UWB) FDC after DLI (76.6% versus 28.6%, P < .001) had a survival benefit and subsequently a better graft-versus-host disease (GvHD)-free/relapse-free survival. Nineteen of 39 patients (48.7%) with relapsed disease achieved remission after DLI. In this cohort, attaining T-FDC impacted favorably in disease control (76.7% versus 12.5%, P = .012) and improved survival (45.5% versus 12.5%, P = .007). In the whole population, the cumulative incidence of acute GvHD (aGvHD) at day 100 after DLI was 23%, and chronic GvHD (cGvHD) at 1 year after DLI was 22%. In the whole population, donor age was also a determining factor for aGvHD, because patients with younger donors had a lower incidence of aGvHD (8% versus 36%, P = .021). The cGvHD was more likely to occur in patients who converted to T-FDC (34% versus 10.3%, P = .025). Donor characteristics are increasingly considered when deciding approaches for HSCT. Donor age should be considered when planning HSCT, as well as doses and scheduling of DLI. As per our experience, this should be done alongside T/UWB chimerism to achieve the maximal clinical benefit with less associated toxicity. Selection of younger male donors from stem cell registries can minimize the risk of GvHD and improve survival.

The role of ibrutinib in COVID-19 hyperinflammation: A case report.

Immune modulation in COVID-19 is emerging as an important therapeutic strategy as increasing evidence suggests that inflammatory pathways are implicated in lung damage. Bruton tyrosine kinase inhibitors (BTKi), such as ibrutinib, are commonly used to treat indolent B-cell neoplasms and chronic graft-versus-host disease (GvHD). Given their potential to suppress pulmonary inflammatory cytokines and lessen acute lung injury, this could be applicable in the context of hospitalised COVID-19 patients. We describe an 81 year-old male receiving ibrutinib for Waldenstrom macroglobulinaemia (WM) who was hospitalised with COVID-19. On stopping the BTKi due to concerns of additional immunosuppression, he required non-invasive ventilation (NIV) in the intensive care unit (ICU) and demonstrated prompt clinical recovery when ibrutinib was reinstated. Continuing ibrutinib in patients with COVID-19 may be advantageous given its immunomodulatory properties and withdrawal of ibrutinib therapy may be detrimental. Further evidence is required to explore the potential therapeutic impact of BTKis and other immunomodulatory agents on the clinical course of COVID-19 as is currently being carried out in a number of clinical trials.

Vitamin D: is it important in haematopoietic stem cell transplantation? A review.

Vitamin D has effects on several body systems, from well-established role in bone metabolism to emerging effects on the immune system. Increasing evidence supports an immunomodulatory effect including inhibition of the pro-inflammatory lymphocyte subsets while enhancing their anti-inflammatory counterpart, in favour of a more tolerogenic status. Vitamin D deficiency is increasingly recognised in association with autoimmune and inflammatory diseases, also with evidence from the field of asthma where vitamin D supplementation may overcome steroid resistance. In the HSCT setting, vitamin D deficiency has been variably associated with increased complications, including graft-versus-host disease (GvHD), with a potential impact on survival outcomes. In this review we provide an overview and critical appraisal of the current literature of the role of vitamin D (and its deficiency) in relation to immunity in both allogeneic and autologous HSCT settings. We conclude that the evidence base is mixed, but a greater understanding of the role of vitamin D in relation to immune reconstitution following HSCT is warranted. Given its potential benefits, its inexpensive cost and favourable side effect profile, consideration of vitamin D levels and its supplementation could be easily incorporated into prospective studies in GvHD, including clinical trials of novel therapeutics, supportive care and biomarkers.