Claudia Rutt

Safety and efficacy of hematopoietic stem cell collection from mobilized peripheral blood in unrelated volunteers: 12 years of single-center experience in 3928 donors

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/microL in male and 51/microL 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 microg/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.

Spleen enlargement in healthy donors during G–CSF mobilization of PBPCs

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.

Estimation of high-resolution HLA-A, -B, -C, -DRB1 allele and haplotype frequencies based on 8862 German stem cell donors and implications for strategic donor registry planning.

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.

High-resolution human leukocyte antigen allele and haplotype frequencies of the Polish population based on 20,653 stem cell donors

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*25:01 g, B*18:01 g, 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.

Second donation of hematopoietic stem cells from unrelated donors for patients with relapse or graft failure after allogeneic transplantation

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative approach for a variety of hematologic malignant and non-malignant disorders. With the rising number of stem cell transplantations from unrelated donors over the last years,[1][1] the occurrence of graft failure or disease

Second donation of granulocyte–colony-stimulating factor–mobilized peripheral blood progenitor cells: risk factors associated with a low yield of CD34+ cells

BACKGROUND:  There are still limited data on the efficacy and safety of repeated donations of granulocyte–colony‐stimulating factor (G–CSF)‐mobilized peripheral blood progenitor cells (PBPCs) for allogeneic transplantation.

Making the Case for Private Cord Blood Banking: Mission Failed!

In their review [1], Hollands and McCauley present arguments for private cord blood (CB) banking. We think their arguments require critical reassessment. The authors state that the main value of privately stored CB units for hematopoietic stem cell transplantation (HSCT) lies, contrary to the marketing statements of most private banks and the focus of critic by professional bodies, in allogeneic related instead of autologous use. This assessment is plausible as there are general limitations of HSCT with autologous CB units [2]: Autologous transplantation is not suited for the treatment of genetic disorders. In leukemia patients, the use of autologous CB units is suboptimal because of the missing graft-versus-leukemia effect. Besides, abnormal cells with the potential to induce leukemia could be present in the CB unit. Consistently, Hollands and McCauley refer to an analysis that identifies 46 allogeneic transplantations among 52 transplantations from privately stored CB units. A similar ratio (9 autologous and 41 allogeneic transplantations) was observed in a recent study [3]. Interestingly, the CB was collected to treat an already known disease of the patient in 36 of the allogeneic transplantations. Such targeted CB collections are common practice and should be clearly distinguished from purely prophylactic private CB storage. Ballen et al. [2] refer to various estimates for the probability of autologous use of stored CB units. These estimates range from 0.0005% to 0.04%. Under current indications, a study of the Center for International Blood and Marrow Transplant Research (CIBMTR) estimated the likelihood of receiving an autologous transplant to 0.02% by age 20, 0.05% by age 40, and 0.23% by age 70 [4]. Without changes of indications, these probabilities can be seen as upper bounds for autologous use of stored CB as low cell counts may, especially for adult patients, frequently prevent the use of the stored units [5]. According to Hollands and McCauley, the benefits of privately stored cord blood for HSCT result mainly from higher survival rates after allogeneic related compared to unrelated CB transplantation [6]. However, in the vast majority of cases where an HLAidentical CB unit that was stored in a private bank is available for transplantation, an HLA-identical related bone marrow (BM) transplantation from the same donor would also be possible. Harvesting BM is a safe procedure [7] that is carried out in several thousand allogeneic donors per year, including many unrelated donors. In order to assess the benefits of private CB banking, it is, therefore, primarily relevant to compare the output of related CB and related BM transplantation. Hollands and McCauley cite a study by Rocha et al. that identified lower risks for acute and chronic graft-versus-host disease (GVHD) after related CB transplantation compared to related BM transplantation [8]. The significant delay in granulocyte and platelet engraftment after related CB transplantation that was observed in the same study is not mentioned in the review. Risks of death after related CB and BM transplantation did not differ significantly in the A. H. Schmidt (*) : C. Rutt DKMS German Bone Marrow Donor Center, Tübingen, Germany e-mail: schmidt@dkms.de