Stem cell donor registry activities during the COVID-19 pandemic: a field report by DKMS.

The COVID-19 pandemic has serious implications also for patients with other diseases. Here, we describe the effects of the pandemic on unrelated hematopoietic stem cell donation and transplantation from the perspective of DKMS, a large international donor registry. Especially, we cover the development of PBSC and bone marrow collection figures, donor management including Health and Availability Check (HAC), transport and cryopreservation of stem cell products, donor recruitment and business continuity measures. The total number of stem cell products provided declined by around 15% during the crisis with a particularly strong decrease in bone marrow products. We modified donor management processes to ensure donor and product safety. HAC instead of confirmatory typing was helpful especially in countries with strict lockdowns. New transport modes were developed so that stem cell products could be safely delivered despite COVID-19-related travel restrictions. Cryopreservation of stem cell products became the new temporary standard during the pandemic to minimize risks related to transport logistics and donor availability. However, many products from unrelated donors will never be transfused. DKMS discontinued public offline donor recruitment, leading to a 40% decline in new donors during the crisis. Most DKMS employees worked from home to ensure business continuity during the crisis.

Reevaluation of reference values for bone marrow differential counts in 236 healthy bone marrow donors.

Despite the increasing role of molecular markers, differential counts and morphology of hematopoietic cells in the bone marrow (BM) remain essential diagnostic criteria in hematological diseases. However, the respective reference values for BM myelogram commonly used came from small series with limited numbers of healthy individuals. We evaluated the myelograms of 236 healthy individuals who underwent unrelated bone marrow donation. Health check-ups were performed 4 weeks prior to harvest. Samples for this study, taken from the first aspiration, were stained according to the standard Pappenheim method. Three experienced investigators assessed cellularity, megakaryopoiesis, and differential counts independently. The median donor age was 31 (range 18-51) years. Predonation tests did not reveal any relevant morbidity. Thirty-seven out of 42 hypocellular marrow samples were from younger donors up to 39 years. Content of megakaryocytes was normal in 210 specimens (89%). Gender and body mass index had significant impact on hematopoiesis, whereas age had not. The number of erythroblasts was higher (about 32%) and the proportion granulopoiesis slightly lower (about 50%) compared with previous studies. Differential counts showed also some differences with respect to individual maturation stages in these lines. Interrater comparisons showed greater reliability for the assignment of cells to the different hematopoietic cell lines than for single-cell diagnoses. This study largely confirms the results for cell counts in normal human bone marrow available from previous reports and provides some insights into factors that affect individual cell populations. It also reveals substantial variability among even experienced investigators in cytological diagnoses.

Immunogenetics in stem cell donor registry work: The DKMS example (Part 2).

DKMS is a leading stem cell donor registry with more than 9 million donors. Donor registry activities share many touch points with topics from immunogenetics or population genetics. In this two-part review article, we deal with these aspects of donor registry work by using the example of DKMS. In the second part of the review, we focus on donor typing of non-HLA genes, the impact of donor age, gender and CMV serostatus on donation probabilities, the identification of novel HLA, KIR and MIC alleles by high-throughput donor typing, the activities of the Collaborative Biobank and pharmacogenetics in the donor registry context.

Immunogenetics in stem cell donor registry work: The DKMS example (Part 1).

Currently, stem cell donor registries include more than 35 million potential donors worldwide to provide HLA-matched stem cell products for patients in need of an unrelated donor transplant. DKMS is a leading stem cell donor registry with more than 9 million donors from Germany, Poland, the United States, the United Kingdom, India and Chile. DKMS donors have donated hematopoietic stem cells more than 80,000 times. Many aspects of donor registry work are closely related to topics from immunogenetics or population genetics. In this two-part review article, we describe, analyse and discuss these areas of donor registry work by using the example of DKMS. Part 1 of the review gives a general overview on DKMS and includes typical donor registry activities with special focus on the HLA system: high-throughput HLA typing of potential stem cell donors, HLA haplotype frequencies and resulting matching probabilities, and donor file optimization with regard to HLA diversity.

Retrospective Analysis of 37,287 Observation Years after Peripheral Blood Stem Cell Donation.

Donor safety is of utmost importance in the setting of hematopoietic stem cell donation. Follow-up is indicated to detect potential long-term risks for donors. We sent a follow-up questionnaire to 15,445 donors of peripheral blood stem cells (PBSCs) or bone marrow (BM) within a retrospective study design. The return rate was 91.3%, resulting in 37,287 observation years for PBSC donors and 25,656 for BM donors. Most donors assessed their health conditions as very good or good and had not been hospitalized or received long-term medical treatment including prescribed medication for more than 4 weeks since donation. Although there were no differences in the frequency of reported health events, BM donors more often rated their general health as very good or good. Ninety-five percent of donors after BM or PBSC donation would consider a second stem cell donation. In total, 93 malignancies were reported. The standardized incidence ratio (SIR) for a diagnosis of any type of cancer after PBSC donation was .94 (95% CI, .70 to 1.24) with a SIR below 1 indicating a lower risk than in the age- and sex-matched population. The SIR for a diagnosis of leukemia was 0 (95% CI, 0 to 1.88). In summary, we found no evidence that either PBSC or BM donation are associated with increased risks of malignancies or other severe health problems.

Assessment of dysplastic hematopoiesis: lessons from healthy bone marrow donors.

BACKGROUND: According to WHO 2008 guidelines, the required percentage of cells manifesting dysplasia in the bone marrow to qualify as significant is 10% or over in one or more hematopoietic cell lineages, but this threshold is controversial. No 'normal' values have been established. Therefore, we investigated dyshematopoiesis in bone marrow aspirate squash preparations of 120 healthy bone marrow donors. DESIGN AND METHODS: Bone marrow squash slides of 120 healthy unrelated bone marrow donors were examined independently by 4 experienced morphologists. Samples were taken from the first aspiration during the harvest. Bone marrow preparation and assessment were performed according to WHO recommendations and ICSH guidelines. RESULTS: More than 10% dysmyelopoiesis could be detected in 46% of bone marrow aspirate squash preparations with 26% in 2 or more cell lineages and 7% in 3 cell lineages in healthy bone marrow donors. Donors under the age of 30 years exhibited more dysgranulopoietic changes and dysmegakaryopoietic changes (P<0.001) compared to the older donors. Female donors showed more dysgranulopoietic changes than male donors (P = 0.025). The concordance rate between the 4 investigators was modest in dysgranulopoiesis but poor in dyserythropoiesis and dysmegakaryopoiesis. CONCLUSIONS: The poor reliability of the 10% cut off was partly related to the proximity of the current criteria to the observed cut-off mean values of the normal population. These findings question the current WHO threshold of the 10% or over necessary for the percentage of cells manifesting dysplasia to be considered significant, and suggest that either a higher threshold would be more appropriate or different thresholds should be set for each lineage.

Losing the genetic twin: donor grief after unsuccessful unrelated stem cell transplantation.

BACKGROUND: Stem cell transplantations from related or unrelated donors are used to cure leukaemia and other blood diseases. When a patient dies after an unsuccessful transplantation, interested unrelated donors are informed about the failure by their donor centre. Studies focussing on failed related donations show that donors undergo an intense grieving process. As there are only two investigations about reactions from unrelated donors, knowledge about their reactions is less comprehensive. METHODS: We conducted a prospective study of reactions of unrelated donors to the information of failed transplantations, subject to various communication methods (letter, phone). Questionnaires were sent to 395 unrelated donors who received the news of their recipients' deaths between November 2005 and August 2006. In addition, twelve in-depth interviews with selected donors were carried out. RESULTS: Unrelated donors were emotionally affected by the recipients' deaths, and it is appropriate to speak about a "Donor Grief" phenomenon, as the results of 325 returned questionnaires (return rate 82.3%) and in-depth interviews show. Donors demonstrated a range of feelings such as sadness, disappointment, grief, and helplessness. These feelings were often unexpectedly intense given the fact that the recipient was a stranger. Although the news caused grief, donors underlined that they nevertheless wanted to be informed. They preferred knowledge of the failure to uncertainty. The method of providing the information is only of secondary importance. Most donors favoured the way of communication they had experienced. CONCLUSION: This result indicates that both phone and letter communication can be justified. However, phone communication seems to be superior with respect to aspects of sensitivity. In spite of transplantation failure and the associated negative feelings, most donors were happy to have donated and would be willing to do so again. Our results underline the special responsibility of donor centres for informing and supporting unrelated volunteer donors in case their recipients have died.

Single-dose pegfilgrastim for the mobilization of allogeneic CD34+ peripheral blood progenitor cells in healthy family and unrelated donors.

BACKGROUND AND OBJECTIVES: Short-term treatment with granulocyte colony-stimulating factor (G-CSF) has been established as the standard regimen for mobilizing allogeneic peripheral blood progenitor cells (PBPC) from healthy donors. The pegylated form of filgrastim (pegfilgrastim) has a longer elimination half-life because of decreased serum clearance and might be a convenient alternative for stem cell mobilization. DESIGN AND METHODS: Twenty-five family (n=15) or unrelated (n=10) healthy donors received a single-dose of 12 mg pegfilgrastim for mobilization of allogeneic PBPC. Donors with inadequate mobilization (blood CD34+ cells