We present results of peripheral blood stem cell (PBSC) mobilization, collection, and follow-up from 3928 consecutive unrelated stem cell donors. Assessments were performed prospectively at baseline, ...leukapheresis, 1 month, 6 months, and annually after PBSC donation. During follow-up, side effects were recorded by return post questionnaires. The median CD34+ cell counts on day 5 were 67.5/μL in male and 51/μL in female donors. Bone pain and headache were the most common side effects of recombinant human granulocyte-colony stimulating factor. Central venous access was required for 23 donations (0.6%). Throughout the follow-up, the absolute neutrophil counts were slightly below the initial baseline values but remained within the normal range. The majority of the donors reported good or very good health. Malignancies occurred in 12 donors (0.3%), among whom were 1 case of acute myeloid leukemia, 1 case of chronic lymphatic leukemia, and 2 cases of Hodgkin disease. Only the incidence of Hodgkin lymphoma differed significantly from an age-adjusted population. In conclusion, 7.5 μg/kg per day lenograstim proved to be safe and effective for mobilizing hematopoietic stem cells for allogeneic transplantation. Long-term monitoring of healthy PBSC donors remains important to guarantee the safety standards of PBSC mobilization and collection.
Abstract Human leukocyte antigen (HLA) haplotype frequency distributions in specific populations can be applied to optimize both individual stem cell donor searches and donor registry planning. We ...present allele and haplotype frequencies derived from a data set of 8862 German stem cell donors who were typed at high resolution for the HLA-A, HLA-B, HLA-C, and HLA-DRB1 genes upon registration. Calculated haplotype frequencies were used to estimate the probability p to find matching donors subject to donor registry size n . The impact of various matching standards on p ( n ) was analyzed. When high-resolution matching for HLA-A, HLA-B, HLA-C, and HLA-DRB1 is required, p (1,000,000) is 0.678. The corresponding value for n = 7,000,000 is 0.859. In a scenario with low-resolution matching and no consideration of HLA-C, p (1,000,000) is 0.863 and thus larger than p (7,000,000) in the scenario with stricter matching requirements. As recent findings support the importance of high-resolution matching of HLA-A, HLA-B, HLA-C, and HLA-DRB1 for outcomes of hematopoietic stem cell transplantation, our results are highly relevant for strategic planning and resource allocation of donor centers and registries.
BACKGROUND: Recombinant human G–CSF is widely used to mobilize PBPCs in healthy donors for allogeneic transplantation. There have been concerns about donor safety because of splenic ruptures during ...G–CSF application. To address this problem, changes in splenic size in 91 healthy donors during G–CSF mobilization of allogeneic PBPCs were investigated.
STUDY DESIGN AND METHODS: For mobilization, G–CSF in a dosage of 7.5 μg per kg per day was administered for 5 days and PBPC collection started Day 5. Splenic size was determined by ultrasound before G–CSF application was started and on the day of the first apheresis.
RESULTS: The mean increase in splenic length was 11 mm (range, 0‐28 mm; p<0.0001), whereas a mean increase of 5 mm in width (range, 0‐14 mm; p<0.0001) was measured. No major side effects could be observed. There was no significant correlation between the increase in splenic size and the hematologic values, or the age and body‐mass index. In a multivariant analysis, no independent risk factor for the development of a spleen enlargement over 19 mm in length and 9 mm in thickness was found in 20 percent of investigated donors.
CONCLUSION: In this prospective trial, a significant spleen enlargement was observed in healthy donors during G–CSF mobilization of allogeneic PBPCs. Further investigations are needed to define the degree of spleen enlargement with higher G–CSF dosages to improve donor safety.
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.
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.
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.
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.
Abstract We present high-resolution allele and haplotype frequency (HF) estimations of the Polish population based on more than 20,000 registered stem cell donors. Sequencing-based donor human ...leukocyte antigen (HLA) typing led to unambiguous typing results in most cases (between 94.3% for HLA-DRB1 and 96.9% for HLA-B). HF estimations were carried out with a new, validated implementation of the expectation–maximization algorithm that allowed processing of data with ambiguities. Our results confirm several earlier results, for example, the relative commonness of the haplotype A*25:01g, B*18:01g, C*12:03, DRB1*04:01 in the Polish population. Because of the large sample size, we were able to obtain results of unprecedented accuracy. The estimated population-specific HFs were then used to analyze questions of strategic donor registry planning. Simulated matching probabilities by donor file size suggest that there is a need for intense donor recruitment efforts in Poland despite the large German donor registry and the genetic relatedness of both populations. Based on the current German registry size of approximately 4 million donors, the recruitment of 100,000 Polish donors would produce a stronger increase in matching probabilities for Polish patients than the recruitment of 3.3 million additional German donors.
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.
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 <or=5/microL on day 3 or <or=20/mL on day 4) were given additional daily doses of 10 mg/kg conventional filgrastim. Leukapheresis was planned to start on day 5.
All harvests were completed successfully. In 20 out of 25 donors (80 %) only a single apheresis was necessary. Additional non-pegylated filgrastim had to be given to only one 74-year old family donor. The maximum concentration of circulating CD34+ cells occurred on day 5 (median 67/microL, range 10-385/mL). The median yield of CD34+ cells was 9.3 (range 3.2-39.1)x10(6)/kg of the recipient's body weight. The median number of T cells in the apheresis products was 3.9 (range 2.7-10.8)x10(8)/kg. Bone pain, headaches and transient elevations of alkaline phosphatase and lactate dehydrogenase were the main adverse events.
The study shows that collection of allogeneic PBPC after administration of a single dose of pegfilgrastim is feasible. The toxicity profile, graft composition and impact on the recipients' outcome need further investigation.
Background: Peripheral blood progenitor cells (PBPCs) are routinely applied worldwide for allogeneic related and unrelated stem cell transplantation. Factors influencing the mobilisation of PBPC's in ...healthy donors are poorly understood. The database of the Apheresis Centre at the University of Dresden was evaluated to identify predictors of PBPC mobilisation.
Methods: 4050 PBPC collections (3928 first donations, 122 second donations) of healthy unrelated donors between 1/1996 and 1/2008 were carried out according to a standardized protocol and prospectively documented in a database. Peripheral blood CD 34 counts were performed before each leukapheresis. CD 34 yield of every PBPC product was calculated in absolute numbers and per kg body weight of the recipient. All parameters are presented as median and range. Mann-Whitney test was performed for discrete variables. Correlation analysis by Pearson was applied for continuous variables. Multivariate regression analysis was carried out to detect factors independently predicting mobilization efficacy.
Results: The range of peripheral CD 34+ haematopoietic stem cells obtained on day 5 was 8.7–285/μl (median 67.5/μl) in male and 6–282/μl, (median 51/μl) in female donors. The median CD 34 yield from the first leukapheresis was 5.88 ×108. Inadequate CD34-yields (< 2 × 106/kg) were obtained only in 18 donors (0.45%). Peripheral CD 34 count at day 5 is significantly correlated with (positive linear regression): BMI, baseline platelet count, male sex, G-CSF application (split dose), baseline leukocyte count. Peripheral CD 34 count at day 5 correlates negatively with: female sex, single dose G-CSF application, regular alcohol consumption and regular smoking status. Linear regression analyses revealed no significant influence of donor age. Multivariate correlation analysis included sex, BMI, baseline platelets, G-CSF-application, baseline leukocytes, age and smoking. This model explained 21.2 % of the variabilityA strong correlation exists between peripheral CD 34-counts at day 5 and apheresis yield (70% of the variability explained).
Conclusions: A dose of 7.5 μg/kg/d lenograstim proved to be safe and effective in a large cohort of unrelated donors for mobilizing sufficient haematopoietic progenitor cells for allogeneic transplantation. Our analysis of 4050 donations revealed significant, but very weak correlations of the peripheral CD 34-counts with donor characteristics and life style parameters. No single parameter derived from donor baseline investigation reliably predicts CD 34 yield. Further evaluation of healthy donors including comprehensive genomic linkage analysis is necessary to elucidate the variable efficiency of PBPC mobilization
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