Abstract Background Safety, tolerability and efficacy of granulocyte colony-stimulating factor (G-CSF) for mobilization of hematopoietic stem and progenitor cells (HSPCs) from healthy donors have been conclusively demonstrated. This explicitly includes, albeit for smaller cohorts and shorter observation periods, biosimilar G-CSFs. HSPC donation is non-remunerated, its sole reward being “warm glow”, hence harm to donors must be avoided with maximal certitude. To ascertain, therefore, long-term physical and mental health effects of HSPC donation, a cohort of G-CSF mobilized donors was followed longitudinally. Methods We enrolled 245 healthy volunteers in this bi-centric long-term surveillance study. 244 healthy volunteers began mobilization with twice-daily Sandoz biosimilar filgrastim and 242 underwent apheresis after G-CSF mobilization. Physical and mental health were followed up over a period of 5-years using the validated SF-12 health questionnaire. Results Baseline physical and mental health of HSPC donors was markedly better than in a healthy reference population matched for ethnicity, sex and age. Physical, but not mental health was sharply diminished at the time of apheresis, likely due to side effects of biosimilar G-CSF, however had returned to pre-apheresis values by the next follow-up appointment after 6 months. Physical and mental health slightly deteriorated over time with kinetics reflecting the known effects of aging. Hence, superior physical and mental health compared to the general healthy non-donor population was maintained over time. Conclusions HSPC donors are of better overall physical and mental health than the average healthy non-donor. Superior well-being is maintained over time, supporting the favorable risk–benefit assessment of volunteer HSPC donation. Trial registration National Clinical Trial NCT01766934

To minimize donor risk and maintain public support, volunteer donor stem cell donation, whether by mobilized leukapheresis or marrow aspiration, requires careful donor eligibility assessment. Many contraindications to stem cell donation exist, yet analyses of donor deferral rates are not available. In a 36-month series encompassing 2493 potential stem cell donors, we analyzed frequencies and reasons for deferrals. All were presumed eligible by their registries because of previously submitted structured health questionnaire and formal telephone interviews. After assessment by our center's physicians, 3.3% of donors proved ineligible, but 5.6% more were eligible for only one of the collection methods. Higher deferral rates were associated with female sex, increasing age and mobilized stem cell donation vs marrow. Exclusion criteria were identified with approximately similar frequency by medical history, physical examination and laboratory testing. Reasons for deferrals almost exclusively served to protect donor safety; the rare recipient-directed safety concerns could be, and often were, overridden in agreement with the transplant center. As formal analyses have shown, with careful assessment, stem cell donation is acceptably safe, but the plethora of deferral reasons mandate that only physicians with specific experience should evaluate stem cell donors, that is, this task should not be delegated to paramedical personnel.

Background and Objectives G‐CSF‐mobilized peripheral blood stem cells have long replaced marrow as the major source for allogeneic transplants. Conclusive evidence questioning the long‐term safety of G‐CSF for donors has not been provided, but the cumulative number of followed donors remains insufficient to rule out rare adverse events. A long‐term active follow‐up study of G‐CSF‐mobilized healthy volunteer donors was therefore performed.Patients and Methods Two hundred and three successive donors were evaluated pre‐apheresis, subjected to G‐CSF‐mobilization/apheresis, and actively followed for 5 years by the same physicians and laboratories. Follow‐up laboratory work included standard biochemical/haematological tests and T‐cell phenotyping.Results Donor epidemiology was typical for reported stem cell donor cohorts. Acute adverse effects of G‐CSF and apheresis were mild and transient, consistent with the previous reports. Mean circulating CD34+ cells after nine doses of G‐CSF were 124 per μl. Other biochemical/haematological parameters were also altered, consistent with G‐CSF treatment. Spleen enlargement was modest. At first follow‐up, all clinical and laboratory parameters had normalized. Leucocyte/lymphocyte counts and CD4/CD8 ratios were the same as during premobilization work‐up and remained unchanged throughout. A single severe but likely unrelated adverse event, a case of papillary thyroid carcinoma, was reported.Conclusion The studies add an observation time of almost 500 donor years to the growing body of evidence of the long‐term safety of G‐CSF for allogeneic donor stem cell mobilization.

Background and Objectives G‐CSF mobilized peripheral blood stem/progenitor cells are frequently used for allogeneic transplantation. Available manual apheresis systems generate stem cell products of consistently high quality. Short‐comings include need for continuous interface monitoring/adjustment, interface instability in donors with inconsistent blood flow, high collection variability, high platelet loss, and failure to electronically document apheresis parameters. Material and Methods A fundamentally different, novel apheresis system, Spectra Optia v.5·0, featuring optical sensors, which provide real‐time automatic interface and product collect line control, and newly developed tubing sets, was designed to address these short‐comings. In a prospective validation study, 30 healthy volunteer stem cell donors were subjected to apheresis with Spectra Optia to test feasibility and effectiveness. Results were compared to 608 historic first‐day allogeneic aphereses with COBE Spectra MNC. Results Usability and function of automatic interface control of Spectra Optia were good. Most collection parameters, including collection efficiency and product size, were similar. Cells were viable and provided timely engraftment. Platelet loss with Spectra Optia was 25% less than with COBE Spectra MNC. Products contained fewer erythrocytes, but more granulocytes. Conclusion The automatic apheresis system Spectra Optia is functional and user‐friendly. Thus Spectra Optia aphereses are associated with similar, and equally variable, collection efficiencies as COBE Spectra MNC.

Secondary acute myeloblastic leukemia following myelodysplasia (sAML) is mainly seen in elderly patients beyond the age of 40 years. It is frequently associated with cytogenetic abnormalities known to carry a high risk for resistance to chemotherapy [5]. With conventional chemotherapy complete remission is induced in an average of only 36% of patients. Remission duration is usually short leading to overall survival rates of less than 10% at three years.

The incidence of systemic fungal infections in neutropenic patients with malignant hematological diseases is increasing (Beck-Sague and Jarvis 1993; Bodey, Bueltmann, et al. 1992). Patients at highest risk for these life-threatening infections are those with prolonged periods of neutropenia after intensified chemotherapy, usually patients with acute leuke-mia or after bone marrow transplantation (Denning 1998). Particularly increasing are invasive infections with Aspergillusspecies, showing high mortality rates and, if the patient survives, also considerable complications often limiting further antileukemic therapies (Denning 1998). The paragon of antifungal therapy, Amphotericin B, is toxic; chemoprophylaxis against Aspergillus species is therefore controversially discussed and not generally recommended or practiced (Schwartz, Behre et al. 1999).

The increasing incidence of invasive aspergillosis, a life-threatening infection in immunocompromised patients, emphasizes the need to improve the currently limited diagnostic tools. Using a recently developed two-step polymerase chain reaction (PCR) assay to detect 10 fg of Aspergillus DNA, corresponding to 1-5 colony-forming units (CFU)/ml of spiked samples in vitro, we prospectively examined 197 bronchoalveolar lavage (BAL) samples from 176 subjects, including 141 neutropenic, febrile patients with lung infiltrates, at risk for invasive fungal disease. Underlying diseases of these patients were haematological malignancies; 93 patients suffered from acute leukaemias. Thirty-one of these immunocompromised patients (17.6%) were PCR positive, correlating with positive BAL culture, positive histology from lung surgery or from autopsy, positive computerized tomography scans or positive galactomannan enzyme-linked immunosorbent assay. Six patients (4.3%) of this group had positive PCR results without any correlation to clinical or other diagnostic data, probably owing to contamination of the samples by ubiquitous Aspergillus spores. The samples of two patients (1.4%) with a subsequent histologically proven mould infection were PCR negative. All 102 immunocompromised patients (72.3%) with a negative PCR showed no evidence of invasive fungal disease. From 35 patients without immunodeficiency, four (11.4%) showed positive results, without evidence of invasive or non-invasive pulmonary aspergillosis. In this haematological population, the sensitivity and specificity values of the test reached 93.9% and 94.4%, the positive predictive value 83.8%, the negative predictive value 98.1%. Our data support the considerable clinical value of this PCR assay for confirming and improving diagnosis of pulmonary aspergillosis in high-risk patients.

Background: Although several diagnostic methods are available for the surveillance of patients at risk of human cytomegalovirus (CMV) infection and disease, little data is available on their comparative performances in the diagnostic setting. Objectives: To compare different assays for CMV detection, especially assays based on (quantitative) DNA and mRNA detection. Study design: Eight allogeneic bone marrow and stem cell transplant recipients at high risk for developing CMV disease (donor CMV-negative, recipient positive) were regularly tested for 7-20 weeks post-transplant by spin-amplification rapid culture from urine (viruria), antigenemia (pp65 assay), pp67 mRNA in whole blood (NASBA). and CMV DNA both qualitatively tin-house PCR, whole blood) and quantitatively tin-house PCR, plasma, Cobas Amplicor(TM) CMV Monitor Test, plasma and whole blood, Hybrid Capture(TM), whole blood). Results: Four patients (50%) suffered CMV reactivation during follow-up. Out of 104 sample dates, 41 (39.4%) yielded a positive CMV result in at least one assay. Out of the 28 samples tested by all assays, the highest percentage of positive results was obtained with the in-house quantitative PCR (60.7%), followed by the Hybrid Capture(TM) system (39.3%), the Cobas Amplicor(TM) CMV Monitor Test, plasma version (35.7%), the Cobas Amplicor(TM) CMV Monitor Test, whole blood version (32.1%), in-house qualitative PCR (28.6%), and the mRNA assay (21.4%). Viruria was positive in one sample and pp65 antigenemia was found in two samples. Conclusions: Despite a considerable incidence of CMV reactivations, pre-emptive anti-CMV chemotherapy prevented the development of CMV disease with the exception of one case. The molecular assays had superior sensitivity to conventional ones. The antigenemia assay proved unsuitable for the surveillance of hematological transplant patients. However, none of the tests recognized all timepoints with CMV reactivation. Further comparative studies are needed to determine their respective diagnostic values. (C) 2001 Elsevier Science B.V. All rights reserved.