Data of 507 granulocyte donations from 183 donors were evaluated. No severe granulocyte colony-stimulating factor (G-CSF)-related side-effects were observed. Three donors complained of severe itching following infusion of hydroxyethyl starch (HES). A high proportion (85%) of the donors stated that they would donate granulocytes again. The mean granulocyte yield was 4.3 x 10(10). High-molecular-weight HES resulted in a significantly higher yield compared with low-molecular-weight HES. Mild, but no severe, adverse transfusion reactions were observed in 16% of the recipients. A leucocyte alloimmunization rate of 24% was found. G-CSF stimulation and transfusion of G-CSF-mobilized granulocytes were well tolerated by donors and recipients, respectively.
The use of peripheral blood stem cells (PBSC) as a source of hematopoietic stem cells is steadily increasing and has nearly supplanted bone marrow. The present article reviews mobilization and collection of PBSC as well as its side effects. Specialized harvesting strategies such as large volume leukapheresis (LVL) and pediatric PBSC collection are included in this overview. Under steady state conditions, less than 0.05% of the white blood cells (WBC) are CD34+ cells. Chemotherapy results in a 5-15-fold increase of PBSC. Combining chemotherapy and growth factors increases CD34+ cells up to 6% of WBC. In the allogeneic setting, granulocyte-colony stimulating factor is used alone for PBSC mobilization. Several factors affect the mobilization of PBSC: age, gender, type of growth factor, dose of the growth factor and in the autologous setting, patient's diagnosis, chemotherapy regimen and number of previous chemotherapy cycles or radiation. Harvesting of PBSC can be performed with various blood cell separators using continuous or discontinuous flow technique. Continuous flow separators allow the processing of more blood compared with intermittent flow devices resulting in higher yields of CD34+ cells for transplantation. LVL can be used to increase the CD34+ yield in patients with low CD34+ pre-counts. Processing of more blood in LVL is achieved by an increase of the blood flow rate and an altered anticoagulation regimen. Specialized strategies were developed for pediatric PBSC collection considering the main limiting factors, extracorporeal volume and vascular access. Adverse events in PBSC collection can be subdivided in apheresis associated and mobilization associated side effects. Citrate reactions due to hypocalcemia are frequent during apheresis, especially in pediatric PBSC collection and LVL. Thrombocytopenia is often observed in patients after termination of apheresis due to platelet loss during PBSC harvesting. Muscle and bone pain are frequent adverse events in allogeneic stem cell mobilization but are usually tolerated under the use of analgesics. Spleen enlargement followed by rupture is a serious complication in allogeneic donors.
The plateletpheresis systems studied allow the collection of WBC-reduced SDPs. In-line filtration resulted in the best WBC reduction. Some SDPs collected with the devices studied had a WBC content >1 x 10(6) per unit. Platelet yield was significantly higher in SDPs from the Amicus device.
The detection of HNA-3a antibody specificities could be integrated into the new LABScreen MULTI assay; however, we detected only 90%. In addition, we detected further HNA antibodies, such as HNA-1c, HNA-1d, and some HNA-3b and HNA-4a antibodies. The new generation of LABScreen MULTI is a great step toward feasible high-throughput testing for HNA antibodies. Nevertheless, GIFT and GAT remain the gold-standard methods for the differentiation of rare and currently unknown HNA specificities.
Background: Despite availability of potent anti-bacterial, anti-mycotic drugs and hematopoietic growth factors invasive bacterial or fungal infections remain a severe threat to neutropenic patients after chemotherapy or hematopoietic stem cell transplantation (HSCT). Granulocyte transfusions (GT) from granulocyte colony stimulating factor (G-CSF)-stimulated donors have been shown to increase the leukocyte count prior to expected hematopoietic regeneration, resulting in a shorter period of neutropenia and thus offer a therapeutic option for the control of severe infections. However, published studies rely on clinical observations of individual cases as no statistical comparison with control groups could have been established. The aim of this study was to define the clinical benefit and the leukocyte increment/duration of neutropenia after randomized administration of leukocyte transfusions in immunocompromized neutropenic patients. Patients and methods: Between 1999 and 2005 80 patients with underlying hematological diseases with or without allogeneic or autologous HSCT were randomized to receive either G-CSF, anti-infective treatment according to local standards with or without therapeutic or prophylactic application of GT from G-CSF-stimulated volunteer donors. The mean age was 47 years (range, 14 – 62 y). Indications were either fever in neutropenia and pulmonary infiltrates or soft tissue infiltration (therapeutic) or the history of invasive fungal infection during episodes of neutropenia following earlier chemotherapy courses and anticipated neutropenia of > 10 days (prophylactic). Results: 10 centers participated in the trial, however only five centers recruited patients (n=80) for randomization during the study period. This corresponds to ~50% of the expected sample size of 160 patients, hence results are statistically insignificant. Patient characteristics were comparable within the randomized cohorts (underlying disease, stage of disease, indication for GT, lenght of neutropenia). No significant difference in the clinical outcome was found between patients who received either therapeutic or prophylactic GT from G-CSF stimulated donors or no GT. The probability of survival on day 28 was 85% in both groups. Furthermore, no difference in the incidence and causes of death could be identified within the compared cohorts. Conclusion: The high percentage of infection clearance and survival in patients with severe infections in both groups contrasts with published results and own experiences. We speculate whether this is due a bias in including predominantly patients into the randomized study who presented with relatively favourable prognostic factors, as in the observation period numerous GT were performed in the participating centers without randomization. Most likely, existing clinical evidence for the benefit of this therapeutic measure was sufficient in many cases to exclude patients in serious conditions from randomization. Although well designed, a randomized trial may not always provide the expected results.
Hyperleukocytosis is a complication of various leukemias and can result in life-threatening leukostasis. Critical white blood cell (WBC) counts are conventionally defined as higher than 100 × 109/l in acute myeloid leukemia and > 300 × 109/l in acute lymphatic leukemia and other leukemic disorders (e. g. chronic myeloid leukemia). Leukocytapheresis is a therapeutic tool to reduce leukocyte counts in patients with symptomatic or threatening leukostasis until induction chemotherapy works. In patients with temporary contraindications against cytotoxic drugs, e.g. during pregnancy, leukocytapheresis can be used as a bridging therapy until conventional chemotherapy can be started. Therapeutic leukocytapheresis should be performed in specialized centers by experienced, well-trained staff. Thorough monitoring of the patients is extremely relevant. During a single procedure, WBC count can be reduced by 10–70%. Treatment should be repeated daily and can be discontinued when the symptoms of leukostasis have been resolved and/or leukocyte counts have fallen below the critical thresholds. There are no prospective studies evaluating the clinical efficacy of therapeutic leukocytapheresis in patients with hyperleukocytosis. It can be concluded from retrospective studies that leukocytapheresis might have some beneficial effect in early morbidity and mortality of patients with newly diagnosed AML but has no influence on overall long-term survival. Induction chemotherapy is the most important treatment in these patients and must never be postponed.
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