First-time whole blood donation: A critical step for donor safety and retention on first three donations.

AIM OF THE STUDY: Whole blood donation is generally safe although vasovagal reactions can occur (approximately 1%). Risk factors are well known and prevention measures are shown as efficient. This study evaluates the impact of the donor's retention in relation to the occurrence of vasovagal reaction for the first three blood donations. MATERIAL AND METHODS: Our study of data collected over three years evaluated the impact of classical risk factors and provided a model including the best combination of covariates predicting VVR. The impact of a reaction at first donation on return rate and complication until the third donation was evaluated. RESULTS: Our data (523,471 donations) confirmed the classical risk factors (gender, age, donor status and relative blood volume). After stepwise variable selection, donor status, relative blood volume and their interaction were the only remaining covariates in the model. Of 33,279 first-time donors monitored over a period of at least 15 months, the first three donations were followed. Data emphasised the impact of complication at first donation. The return rate for a second donation was reduced and the risk of vasovagal reaction was increased at least until the third donation. CONCLUSION: First-time donation is a crucial step in the donors' career. Donors who experienced a reaction at their first donation have a lower return rate for a second donation and a higher risk of vasovagal reaction at least until the third donation. Prevention measures have to be processed to improve donor retention and provide blood banks with adequate blood supply.

An active haemovigilance programme characterizing the safety profile of 7437 platelet transfusions prepared with amotosalen photochemical treatment.

BACKGROUND: An active haemovigilance programme was implemented to survey adverse events (AE) associated with transfusion of platelets photochemically treated with amotosalen and ultraviolet A (PCT-PLT). The results of 5106 transfusions have already been reported. Here we report the results of an additional 7437 PCT-PLT transfusions. METHODS: The focus of this ongoing haemovigilance programme is to document all AEs associated with PCT-PLT transfusion. Data collected for AEs include: time of event after starting transfusion, clinical descriptions, vital signs, results from radiographs and bacterial cultures, event severity (Grade 0-4) and causal relationship to PCT-PLT transfusion. RESULTS: One thousand four hundred patients (mean 60 years, range 1-96) received PCT-PLT transfusions. The majority of the patients (53.4%) had haematology-oncology diseases and required conventional chemotherapy (44.8%) or stem cell transplantation (8.6%). Sixty-eight PCT-PLT transfusions were associated with AE. Acute transfusion reactions (ATR), classified as an AE possibly related, probably related, or related to PCT-PLT transfusions were infrequent (n = 55, 55/7437 = 0.7%) and most were of Grade 1 severity. Thirty-nine patients (39/1400 = 2.8%) experienced one or more ATRs. The most frequently reported signs/symptoms were chills, fever, urticaria, dyspnoea, nausea and vomiting. Five AEs were considered severe (> or = Grade 2); however, no causal relationship to PCT-PLT transfusion was found. Repeated exposure to PCT-PLT did not increase the likelihood of an ATR. No cases of transfusion-related acute lung injury and no deaths due to PCT-PLT transfusions were reported. CONCLUSIONS: Routine transfusion of PCT-PLT is well-tolerated in a wide range of patients. ATRs related to PCT-PLT transfusion were infrequent and most were of mild severity.

Guidelines for the transfusion of red cells.

The following recommendations, which aim at standardising and rationalising clinical indications for the transfusion of red cells in Belgium, were drawn up by a working group of the Superior Health Council. To this end, the Superior Health Council organised an expert meeting devoted to "Guidelines for the transfusion of red cells" in collaboration with the Belgian Hematological Society. The experts discussed the indications for red cell transfusions, the ideal red cell concentrate, the practical issues of administering red cells, and red cell transfusions in patients in a critical condition. The recommendations formulated by the experts were validated by the working group with the purpose of harmonising red cell transfusion in Belgian hospitals.

[Extracorporeal photochemotherapy: review of its mechanisms of action and clinical applications]. / La photochimiothérapie extracorporelle: revue de son mode d'action et de ses indications.

Extracorporeal photochemotherapy is an immunomodulatory treatment wich is carried out in three steps: first leukapheresis, then ex vivo PUVA treatment and finally autologous transfusion. Its current "evidence-based" indications are erythrodermic cutaneous lymphoma, graft versus host disease and cardiac graft rejection. However this treatment has already been used with success in many other diseases such as systemic sclerosis, multiple sclerosis, type 1 diabetes and various autoimmune dermatologic diseases. Randomised controlled studies are needed to confirm the efficacy of photopheresis in these diseases. We also review the different hypotheses explaining the mechanism of action of photopheresis.

High-dose chemotherapy and autologous CD34-positive blood stem cell transplantation for multiple myeloma in an HIV carrier.

The epidemiology and clinical outcome of multiple myeloma in human immunodeficiency virus (HIV)-positive patients is poorly documented. There are uncertainties concerning the optimal management of this rare disorder. We report on the use of myeloablative chemotherapy with autologous stem cell transplantation in an HIV-positive patient with multiple myeloma.

[The immunology-hematology-transfusion department]. / Le Service d'Immunologie-Hématologie-Transfusion.

New immunotherapies derived from biotechnology offer fascinating perspectives in different fields of medicine including anti-infectious vaccines, cancer, organ transplantation and autoimmune diseases. In this paper, we illustrate how the Department of Immunology can contribute to the development of these new treatments within a academic hospital such as the Erasme Hospital at the Université Libre de Bruxelles.

[Anti-tumor immunotherapy based on dendritic cells]. / L'immunothérapie anti-tumorale à base de cellules dendritiques.

In cancer immunotherapy, the use of dendritic cells (DC) loaded with tumor-associated antigens (TAA) emerged as a promising strategy. We initiated 3 pilot clinical trials with immunological endpoints using TAA loaded autologous DC. These trials showed that this approach was safe and associated with the induction of potent TAA specific IFN-gamma responses, which were transient despite the providing a further help through KLH presentation. Subcutaneous (s.c.) IL-2 administration was associated with long-lasting TAA specific IL-5 production. Clinical responses were observed in about 1/3 of the patients. Further improvements will take advantage of the use of a new type of DC cells (IL-3/IFN-beta DC) and of tumor cell-DC hybrids.

Transient expansion of peptide-specific lymphocytes producing IFN-gamma after vaccination with dendritic cells pulsed with MAGE peptides in patients with mage-A1/A3-positive tumors.

Assessment of T-cell activation is pivotal for evaluation of cancer immunotherapy. We initiated a clinical trial in patients with MAGE-A1 and/or -A3 tumors using autologous DC pulsed with MAGE peptides aimed at analyzing T-cell-derived, IFN-gamma secretion by cytokine flow cytometry and ELISPOT. We also tested whether further KLH addition could influence this response favorably. Monocyte-derived DC were generated from leukapheresis products. They were pulsed with the relevant MAGE peptide(s) alone in group A (n=10 pts) and additionally with KLH in group B (n=16 pts). A specific but transient increase in the number of peripheral blood T lymphocytes secreting IFN-gamma in response to the vaccine peptide(s) was observed in 6/8 patients of group A and in 6/16 patients of group B. We conclude that anti-tumor vaccination using DC pulsed with MAGE peptides induces a potent but transient anti-MAGE, IFN-gamma secretion that is not influenced by the additional delivery of a nonspecific, T-cell help.

Generation of immature autologous clinical grade dendritic cells for vaccination of cancer patients.

BACKGROUND: Dendritic cell (DC)-based vaccine is a promising approach for cancer therapy. Pioneer trials have been conducted using DC generated in research conditions. There is now a need for generating DC in clinical grade conditions, including the use of closed systems, avoidance of FCS and respect of good manufacturing practices (GMP). METHODS: DC were generated from 84 leukapheresis products of 27 cancer patients enrolled in two Phase I/II trials of vaccination of either MAGE+tumors (n = 24) or prostate cancer (n = 3). Monocytes were seeded in culture bags in a serum-free medium supplemented with IL-4 and GM-CSF. After a 7 day culture, DC were collected and most were pulsed with various MAGE-derived peptides. RESULTS: After a short leukapheresis (mean time: 66 min; mean processed blood: 5 L), a mean of 6 x 10(9) WBC were collected, from which 2.25 x 10(9) were seeded. The culture procedure yielded a large number of DC (mean: 62 x 10(6) DC) harboring the expected phenotype of immature DC (CD1a(+) CD14(-) HLA-DR(+) CD80(+) CD86(+) CD83(-)). This phenotype was not altered by peptide loading. These DC, either fresh or thawed, were functionally effective invitro. Their s.c. and i.v. injections were devoid of any short-term side effect and associated with the induction of immune responses in the patients. DISCUSSION: Large numbers of functional immature clinical grade DC can be generated in a closed system from leukapheresis products in cancer patients. These results provide the basis for large-scale studies of cancer immunotherapy under improved safety conditions.

Blood transfusion practice in Belgium. As assessed by a national survey.

In April 1995 the Ministry of Public Health invited all Belgian hospitals to participate to a survey on the use of blood transfusion. The questionnaire presented two parts, the first one devoted to products transfused and the second one to the transfusion organisation in the hospital. 71 hospitals answered: 7 university and 64 general hospitals. All hospitals reported the use of red cells, 31 of them still used whole blood. Surgical departments transfused the greatest absolute amount of units, but the highest intensity (units/bed/year) was observed in intensive care units. 52 hospitals mentioned the use of autologous predeposit. The highest consumption of platelets occurred in medicine but intensive care showed the highest intensity of platelet transfusion. In 41 hospitals platelets were obtained by cytapheresis. The number of plasma units transfused was highly correlated with the quantities of packed red cells and whole blood transfused. Ten hospitals didn't report the use of any blood conservation technique. Returning unused units to the blood bank was allowed in 80% of the hospitals, their return to the transfusion center was permitted in 65% of the hospitals. A transfusion committee existed in only 11 hospitals. Transfusion should be improved by a better education of all physicians and nurses involved with transfusion and by improving standardisation, by better documentation, better reporting and information of all health care workers involved.

Isolation and infusion of donor CD34+ bone marrow cells in cadaver kidney transplantation.

BACKGROUND: Infusion of donor bone marrow cells induces tolerance in allograft models. CD34+ stem cells present in human bone marrow could be endowed with tolerogenic properties. METHODS: CD34+ stem cells were isolated from bone marrow extracted from vertebral bodies of cadaveric donors. Donor CD34+ cells (0.6-3.7 x 10(6)/kg) were infused during surgery in 10 kidney transplant recipients receiving OKT3 as induction therapy. Chimerism was investigated using nested PCR for donor-specific HLA alleles. RESULTS: The infusion of CD34+ stem cells was perfectly tolerated. Five patients remained free of acute rejection at follow-up, 47-325 days post-operatively. The five other patients underwent a single episode of corticosensitive acute rejection. Long-term chimerism was not induced in the seven patients investigated for the persistence of donor DNA. CONCLUSIONS: Infusion of donor CD34+ stem cells in kidney transplantation is safe. The clinical usefulness of the procedure remains to be established.

Autologous stem cell infusion for acute myeloblastic leukemia in an HIV-1 carrier.

We present the case of an asymptomatic HIV carrier, who presented with acute myeloblastic leukemia in third relapse and successfully underwent autologous stem cell transplantation as a rescue treatment. This observation supports the conclusion that tolerance of autologous bone marrow or stem cell transplant in patients with HIV may correlate with a low viral burden and relatively good immune function.

Clinical evidence for an engraftment syndrome associated with early and steep neutrophil recovery after autologous blood stem cell transplantation.

Seventy autologous peripheral blood stem cell transplants (APBSCT) performed in 61 cancer patients were retrospectively analyzed. Patients were heterogenous with regard to malignancy, conditioning regimens and use of growth factors after transplantation. Six patients developed a non-infectious fever, fluid retention and pulmonary interstitial infiltrates during the early phase of neutrophil recovery. Diarrhea was observed in four of these patients and cutaneous rash in three. The clinical condition improved spontaneously in one patient, and within 48 h after steroid therapy in four. One patient died from multiple organ failure. Age, sex (all patients were female; P = 0.07), and time to platelet recovery did not distinguish the six courses complicated by the hypothetical engraftment syndrome (ES) from the other 64 courses taken as controls. However, neutrophil recovery > 0.5 x 10(9)/l occurred earlier (P = 0.01), and the neutrophil count increment during the early phase of recovery was steeper in ES patients (P = 0.003). ES was also associated with infusion of a high number of CD34+ progenitors (P = 0.03) and conditioning with busulfan (P = 0.03). Although all ES patients received G-CSF after transplantation, an association of ES with G-CSF use could not be demonstrated, possibly because of the small number of courses not supported by G-CSF. However, in one patient, ES did not recur after a second transplant unsupported by growth factors. Our study supports the idea of an engraftment syndrome associated with an early and steep neutrophil recovery after APBSCT.

Simplification of the blood stem cell transplantation (BSCT) procedure: large volume apheresis and uncontrolled rate cryopreservation at -80 degrees C.

Very high-dose chemotherapy with autologous blood stem cell (BSC) rescue becomes more and more widely performed. In order to simplify the technique, a large volume apheresis programme combined with an uncontrolled rate cryopreservation at -80 degrees C was developed. Twenty-six patients suffering from multiple myeloma (n = 8), non-Hodgkin's lymphoma (n = 7), dysgerminoma (n = 4), breast cancer (n = 3), Hodgkin's disease (n = 2), acute lymphoblastic leukaemia (n = 1) and acute myelocytic leukaemia (n = 1) were autografted after a classical high-dose chemotherapy regimen. A single large volume apheresis was sufficient to obtain the threshold value of CD34+ BSC in 24/26 transplantations. The haematological recovery was favourably comparable with the previously published data obtained with controlled rate frozen BSC: median time to granulocytes > 1000/microL and to a self-supporting platelet count > 20,000/microL, respectively, 10.5 and 12 d. The treatment-related mortality was confined to 1/26 BSCT. These results indicate that this easy and cost-saving policy of BSCT is efficacious and safe: sustained long-term haematopoiesis, reduced morbidity and mortality were observed.

[Novel autograft method using positive selection of CD34 stem cells]. / Méthode nouvelle d'autogreffe par sélection positive de cellules souches sanguines CD34.

High dose chemotherapy with autologous blood stem cell rescue becomes widely used for patients with hematologic malignancies and solid tumors. Recently, it has been demonstrated that stem cells characterized by the CD34 antigenic marker could be positively selected using an anti CD34 monoclonal antibody and an avidin biotin immunoabsorption device. We report our experience of twelve selections and ten grafts. A CD34+ cells enrichment of 1.9 log (purity: 72%) and a CFU-GM cells concentration of 1.6 log have been obtained. In ten transplanted patients, the hematological recovery was similar to that obtained with non selected blood stem cells. The CD34+ cells purification allows mini graft infusion and purge of residual tumor cells implicated in relapse after autologous stem cells transplantation.

Transplanted sickle-cell disease patients with autologous bone marrow recovery after graft failure develop increased levels of fetal haemoglobin which corrects disease severity.

Bone marrow transplantation (BMT) is the only curative therapy for sickle-cell disease (SCD), but is not devoid of failure risk. Nine patients with severe SCD were grafted in our institution between 1988 and 1993. Six patients successfully engrafted, but three failed to engraft and had delayed autologous recovery. All patients had, prior to BMT, low levels of fetal haemoglobin (HbF < or = 3.5%). No change in HbF occurred in successfully grafted patients. In the three patients with graft failure HbF increased and remained persistently present at a high level (> or = 22%) 14 months, 16 months and 39 months post BMT, although two of the three patients were homozygous for either the Benin or the Central African Republic haplotype, a characteristic associated with low HbF level. Of interest, these three previously severely affected patients remain free of vaso-occlusive events. The mechanism responsible for the expression of high levels of HbF in our three patients with graft failure is not understood, but it protects them from the recurrence of severe vaso-occlusive crises.

Optimal blood stem cell mobilization using 10 micrograms/kg granulocyte colony-stimulating factor (G-CSF) alone for high-dose melphalan intensification in multiple myeloma: an intrapatient controlled study.

A recent randomized multicentric French study has shown that intensification with stem cell rescue improves the response rate and progression-free survival in multiple myeloma. Transplantation with primed peripheral blood stem cells (PBSC) displays a faster hematological recovery, especially for platelets, as compared with a bone marrow stem cell graft. In multiple myeloma, the optimal mobilization method for PBSC is unknown. The present study compares mobilization with cyclophosphamide 4 g/m2 + G-CSF 5 micrograms/kg versus G-CSF 5 micrograms/kg alone versus G-CSF 10 micrograms/kg alone in two cases of multiple myeloma, using an intrapatient controlled evaluation of the amount of CD34-positive cells obtained during each leukapheresis. In both cases, the highest CD34-positive cells yield was obtained with G-CSF at 10 micrograms/kg. Despite the low number of cases, this method, devoid of life-threatening toxicity, might be of greatest interest in multiple myeloma.