Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor

Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.     

Administration of recombinant human granulocyte colony-stimulating factor to normal donors: results of the Spanish National Donor Registry. Spanish Group of Allo-PBT.

A Spanish National PBPC Donor Registry has recently been established for short- and long-term safety data collection in normal donors receiving rhG-CSF. To date, 466 donors have been included in the Registry. Median (range) dose and duration of rhG-CSF administration was 10 microg/kg/day (4-20) and 5 days (4-8), respectively. Donors underwent a median of two aphereses (range, 1-5). Adverse effects consisted mainly of bone pain (90.2%), headache (16.9%) and fever (6. 1%), but no donor discontinued rhG-CSF prematurely due to toxicity. Side-effects were more frequent in donors receiving >10 microg/kg/day than in those with lower doses (82.8% vs 61.8%; P = 0. 004). A significant decrease between baseline and post-apheresis platelet counts was the most important analytical finding (229 x 10(9)/l vs 140 x 10(9)/l; P < 0.0001), with a progressive reduction in platelet count with each apheresis procedure. One donor developed pneumothorax that required hospitalization due to central venous line placement. The mean CD34+ cell dose collected was 6.9 x 10(6)/kg (range, 1.3-36), with only 14 donors (2.9%) not achieving a minimum target of CD34+ cells of 2 x 10(6)/kg. No definitive information about potential long-term side effects is yet available. However, we hope this National Registry will serve as a useful basis for better monitoring of the efficiency and side-effects of cytokine administration in healthy people.     

Autologous transplantation with peripheral blood mononuclear cells collected after administration of recombinant granulocyte stimulating factor

Peripheral blood mononuclear cells (PBMC) were collected after the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and used as the sole source of hematopoietic stem cells after myeloablative therapy with busulfan (Bu) and cyclophosphamide (Cy). These studies were performed in 12 patients with malignancies (4 non-Hodgkin's lymphoma, 5 breast cancer, 1 testicular carcinoma, 1 Wilm's tumor, and 1 undifferentiated carcinoma) who had bone or bone marrow disease or had low marrow cellularity. rhG-CSF (16 micrograms/kg/d) was administered for 5 to 7 days by subcutaneous injection and PBMC were collected for 2 to 5 days beginning on day 4 after initiation of rhG-CSF, using continuous-flow blood-cell separators that processed 10 to 12 L of whole blood. From a median of three collections, a mean of 24.0 x 10(8) (+/- 10.5 SD) total nucleated cells/kg containing 12.6 x 10(8) (+/- 4.5 SD) mononuclear cells/kg, 7.3 x 10(6) (+/- 4.3 SD) CD34+ cells/kg and 20.5 x 10(4) (+/- 28.1 SD) granulocyte-macrophage colony-forming units (CFU-GM)/kg were harvested and cryopreserved. After the administration of Bu 14 to 17 mg/kg and Cy 120 to 150 mg/kg, PBMC were thawed and infused. One patient received rhG-CSF after the infusion of PBMC and the remaining 11 patients did not receive postinfusion growth factors. Mean days to recovery of neutrophil levels of 0.1, 0.5, and 1.0 x 10(9)/L were 11.4 (range, 9 to 13), 12.7 (range, 10 to 15), and 13.6 (range, 11 to 16) and the mean day to platelet transfusion independence was 13.3 (range, 7 to 49). Time to recovery of neutrophils to 0.5 and 1.0 x 10(9)/L and platelets to 20 x 10(9)/L was more rapid than in historical patients treated with Bu and Cy who received marrow alone or marrow followed by the posttransplant administration of rh-G or GM-CSF. No graft failures have been observed with a follow-up of 4 to 12 months. These results indicate that PBMC collected after rhG-CSF lead to rapid hematopoietic recovery after myeloablative chemotherapy.     

Three to six year follow-up of normal donors who received recombinant human granulocyte colony-stimulating factor

One hundred and one donors who had received filgrastim (rhG-CSF) for the purpose of donating either granulocytes or peripheral blood stem cells (PBSC) for their relatives more than 3 years ago were contacted. All donors had received daily rhG-CSF at a median dose of 16 microg/kg/day (range 3-16) for a median of 6 days (range 3-15 days). All collection procedures were completed and short-term side-effects of rhG-CSF were mild in the majority of the donors. At a median time interval of 43.13 months (range 35-73), the donors were contacted to assess whether adverse effects related to rhG-CSF administration had occurred. Prior to rhG-CSF two donors had cancer, one had a myocardial infarction, one was hepatitis C virus positive, one had a history of sinusitis, one had Graves' disease and two had arterial hypertension. None worsened with the rhG-CSF administration but the donor with a history of infarction had an episode of angina following apheresis, and the donor with Graves' disease had a stroke 15 months after rhG-CSF. Two pregnancies occurred after the rhG-CSF administration and one donor was 2-3 weeks pregnant during rhG-CSF treatment. Three pregnancies resulted in two normal births and one in a spontaneous abortion of a pregnancy which occurred more than 2 years following rhG-CSF. In the time following rhG-CSF administration two donors developed cancer (breast and prostate cancer) at a follow-up of 70 and 11 months, respectively. One donor developed lymphadenopathy 38 months after the rhG-CSF, which spontaneously resolved. Blood counts were obtained in 70 donors at a median follow up of 40.4 months (range 16.8-70.8). Hematocrit was 43% (median, range 36.8-48), white blood cells were 5.7 x 109/l (median, range 3-14), granulocytes 3.71 x 109/l (median, range 1. 47-10.36), lymphocytes 1.67 x 109/l (median, range 0.90-3.96), monocytes 0.46 x 109/l (median, range 0.07-0.87) and platelet counts were 193.0 x 109/l (median, range 175.0-240.0). This study indicates that short-term administration of rhG-CSF to normal donors for the purpose of mobilizing the PBSC or granulocytes appears safe and without any obvious adverse effects more than 3 years after the donation. Bone Marrow Transplantation (2000) 25, 85-89.     

Tolerance of granulocyte donors towards granulocyte colony-stimulating factor stimulation and of patients towards granulocyte transfusions: results of a multicentre study

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.     

Autotransplantation of peripheral blood stem cells mobilized by chemotherapy and recombinant human granulocyte colony-stimulating factor in childhood neuroblastoma and non-Hodgkin''s lymphoma

Seven children with advanced neuroblastoma and non-Hodgkin's lymphoma were treated with myeloablative chemoradiotherapy (180 mg/m2 melphalan plus 12 Gy fractionated total body irradiation), followed by autotransplantation of peripheral blood stem cells (PBSC). Sufficient PBSC to restore bone marrow function were collected by a small number of leukaphereses during haematopoietic recovery after chemotherapy and recombinant human granulocyte colony-stimulating factor (rhG-CSF). Furthermore, rapid recovery of neutrophils was found in all patients by the administration of rhG-CSF following transplantation: median 10 d (range 8-12) to attain more than 0.5 x 10(9)/l neutrophils, and 27 d (range 14-73) to attain more than 50 x 10(9)/l platelets, respectively. Haematopoietic reconstitution has been maintained throughout the follow-up period (median 15 months; range, 6-22). Peripheral blood stem cells mobilized by chemotherapy and rhG-CSF can induce complete haematopoietic reconstitution after myeloablative chemoradiotherapy.     

Effective stimulation of donors for granulocyte transfusions with recombinant methionyl granulocyte colony-stimulating factor [see comments]

Effective granulocyte transfusion (GT) therapy has been hampered by the low yield of neutrophil granulocytes (PMN) obtainable from normal donors even by use of corticosteroid prestimulation, hydroxyethyl starch (HES), and modern leukapheresis (LA) techniques. To increase the PMN yield we performed LA in 22 healthy volunteer donors after a single subcutaneous administration of 300 micrograms of granulocyte colony- stimulating factor (G-CSF) 12 to 16 hours before LA. Five to 7 L of blood was processed within 1.9 to 3 hours using the standard CS- 3000Plus (Baxter, Deerfield, IL) LA protocol including HES. The mean number of PMN harvested was 44.32 +/- 15.5 x 10(9), corresponding to 6.88 +/- 2.1 x 10(9)/L of blood processed. In the final product PMN functions (in vitro: chemotaxis, phagocytosis, chemiluminescence, superoxide anion production; in vivo: chemiluminescence, half-life) were at least normal. In all donors G-CSF induced a consistent increase of white blood cell (mean 16.46 +/- 3.8 x 10(9)/L) and PMN counts (15.94 +/- 3.6 x 10(9)/L). No G-CSF-related side effects were observed and LA was well tolerated. G-CSF prestimulation allows to harvest three to five times higher numbers of functionally normal PMN by LA compared with corticosteroid pretreatment. This may help to overcome one of the major limitations of an effective PMN support.     

G-CSF stimulated donor granulocyte collections for prophylaxis and therapy of neutropenic sepsis

Background: The administration of granulocyte colony-stimulating factor (G-CSF) increases the granulocyte count in normal donors and enables the collection of large numbers of mature myeloid cells by leukapheresis. This has potential value in the treatment of sepsis unresponsive to antibiotics in patients with severe neutropenia. Aim: To evaluate the tolerability of granulocyte collections in normal donors receiving G-CSF, the optimal method of collection and the clinical factors influencing the efficacy of granulocyte infusions. Methods: Analysis of the outcome of 55 granulocyte collections from 26 donors for progressive bacterial or fungal sepsis in neutropenic patients (n-8) or as prophylaxis in patients with recent fungal infections undergoing allogeneic bone marrow transplantation (BMT) (n=3). Results: G-CSF was well tolerated in most donors. Fatigue occurred commonly after the second collection. The median WCC per 200–220 mL bag was 351X10⁹7L. Collections were optimised with the use of a sedimenting agent (dextran) and a deepened interface setting on the cell separator. There was only a weak correlation between the number of granulocytes infused and the increment in the patient, but levels were usually maintained 0.5X 10⁹7L for the next 24 hours. The infusions were successful in three septic patients without multi-organ dysfunction and prophylactically, in two patients with localised fungal infections undergoing MBT The infusions were not beneficial in patients with septicaemia and established organ dysfunction or with extensive pulmonary aspergillosis. Conclusions: G-CSF mobilised granulocyte collections are feasible and the preliminary evidence suggests that the infusion of these cells may be useful early in the prophylaxis or treatment of severe neutropenic sepsis.     

Granulocyte transfusion in the G-CSF era

Granulocyte transfusions have been used since the 1960s with varying degrees of clinical success in the treatment of infection in patients with neutropenia or inherited granulocyte disorders. A number of studies have indicated that efficacy may well be associated with the dose of granulocytes delivered. Collection of granulocytes using modern apheresis machines and corticosteroid administration yields approximately 20 to approximately 30 x 10(9) neutrophils, unlikely to be adequate for treating an established infection. The administration of G-CSF to healthy donors has resulted in average granulocyte yields up to 8 x 10(10) cells. Normal or near normal blood neutrophil counts are often attained when these concentrates are transfused to neutropenic recipients, and these levels are sustained for up to 24 h. G-CSF-primed granulocytes appear to be functionally normal by both in vitro and in vivo measurements. Adverse effects experienced by recipients are similar to those seen with traditional doses of granulocytes. G-CSF administration to donors is well tolerated. Controlled clinical trials are needed to determine the therapeutic efficacy of G-CSF-primed granulocyte transfusions.     

Treatment of idiopathic neutropenia in the elderly with recombinant human granulocyte colony-stimulating factor.

We administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) intravenously for 2 weeks to 2 elderly patients with severe neutropenia. The absolute neutrophil count (ANC) recovered promptly after the initiation of rhG-CSF therapy and reached a peak (greater than 10 x 10(9)/l) on the 13th day. The ANC fell rapidly after rhG-CSF was discontinued, but it remained within the normal range after therapy. There were no side effects during the entire course of treatment. Therefore, rhG-CSF seems to be a most beneficial treatment in elderly patients with severe neutropenia.     

Stimulation of granulopoiesis by high-dose recombinant human granulocyte colony-stimulating factor in children with aplastic anemia and very severe neutropenia

We investigated the efficacy and safety of high-dose recombinant human granulocyte colony-stimulating factor (rhG-CSF) in treating 10 children with severe aplastic anemia and fewer than 0.05 x 10(9)/L neutrophils. Doses of rhG-CSF ranging from 400 to 2,000 micrograms/m2/d were administered as a 30-minute intravenous infusion daily for 4 weeks. In 6 of the 10 children, treatment increased the neutrophil count by 10- fold to greater than 60-fold (range, 0.21 to 1.8 x 10(9)/L). Bacterial or fungal infections that were present at study entry resolved in all 6 responders, who are still alive with a median survival of more than 27 months (range, 15 to 54 months) since the initiation of treatment. Three of 4 nonresponders died of infection, whereas 1 nonresponder received a bone marrow transplant and is alive. No serious toxicity was attributable to rhG-CSF. It was well tolerated at doses up to 2,000 micrograms/m2/d and effectively stimulated granulopoiesis. This agent thus offers promise as adjuvant treatment for severe infections in children with aplastic anemia and very severe neutropenia.     

In vivo stimulation of granulopoiesis by recombinant human granulocyte colony-stimulating factor.

Osmotic pumps containing Escherichia coli-derived recombinant human granulocyte colony-stimulating factor (rhG-CSF) were attached to indwelling jugular vein catheters and implanted subcutaneously into Golden Syrian hamsters. Within 3 days, peripheral granulocyte counts had increased greater than 10-fold with a concomitant 4-fold increase in total leukocytes. Microscopic examination of Wright-Giemsa-stained blood smears from rhG-CSF hamsters showed that only the neutrophil subpopulation of granulocytes had increased. No significant changes in lymphocyte or monocyte counts were observed during the course of continuous rhG-CSF treatment. After subcutaneous injection at rhG-CSF doses of up to 10 micrograms X kg-1 X day-1 only granulocyte counts were affected. However, at higher dose levels, a transient thrombocytopenia was noted. Erythrocyte had lymphocyte/monocyte counts remained unaffected by rhG-CSF over the entire dose range (0.3-300 micrograms X kg-1 X day-1) studied. Total leukocyte counts increased 3-fold within 12 hr after a single s.c. injection of rhG-CSF. This early effect was associated with an increase in the total number of colony-forming cells and the percent of active cycling cells in the marrow. A sustained elevation of peripheral leukocyte and marrow progenitor counts was observed following seven daily s.c. injections of rhG-CSF. The ability of rhG-CSF to increase the production and release of granulocytes from the marrow may underlie the beneficial effect it produced on the restoration of peripheral leukocyte counts in hamsters made leukopenic by treatment with 5-fluorouracil.     

Phase I/II trial of neutrophil transfusions from donors stimulated with G-CSF and dexamethasone for treatment of patients with infections in hematopoietic stem cell transplantation

We examined the feasibility of a community blood bank granulocyte transfusion program utilizing community donors stimulated with a single-dose regimen of subcutaneous granulocyte colony-stimulating factor (G-CSF) plus oral dexamethasone. The recipients of these transfusions were neutropenic stem cell transplantation patients with severe bacterial or fungal infection. Nineteen patients received 165 transfusions (mean 8.6 transfusions/patient, range 1-25). Community donors provided 94% of the transfusions; relatives accounted for only 6% of the transfusions. Sixty percent of the community donors initially contacted agreed to participate, and 98% of these individuals indicated willingness to participate again. Transfusion of 81.9 +/- 2.3 x 10(9) neutrophils (mean +/- SD) resulted in a mean 1-hour posttransfusion neutrophil increment of 2. 6 +/- 2.6 x 10(3)/microL and restored the peripheral neutrophil count to the normal range in 17 of the 19 patients. The buccal neutrophil response, a measure of the capacity of neutrophils to migrate to tissue sites in vivo, was restored to normal in most patients following the transfusion. Chills, fever, and arterial oxygen desaturation of >/= 3% occurred in 7% of the transfusions, but these changes were not sufficient to limit therapy. Infection resolved in 8 of 11 patients with invasive bacterial infections or candidemia. These studies indicate that transfusion of neutrophils from donors stimulated with G-CSF plus dexamethasone can restore a severely neutropenic patient's blood neutrophil supply and neutrophil inflammation response. Further studies are needed to evaluate the clinical efficacy of this therapy.     

Development of a practical oral dexamethasone premedication schedule leading to improved granulocyte yields with the continuous-flow centrifugal blood cell separator.

Studies were conducted to improve the yield of granulocytes collected for transfusion from normal donors by means of the continuous-flow centrifugal blood cell separator. Nonleukapheresed donors were medicated with varying schedules of corticosteroids to learn the magnitude and duration of granulocytosis. Normal donors were medicated with varying schedules of corticosteroids prior to a 4-hr leukapheresis and the granulocyte yields determined. It was found that maximum yields (32.2 x 10(9) granulocytes) were obtained by use of dexamethasone given orally 12 and 3 hr prior to leukapheresis. There was a good correlation between the yields and the circulating granulocyte count at the start and during the procedure.     

Therapeutic transfusions of granulocytes collected by simple bag method for children with cancer and neutropenic infections: results of a single-centre pilot study

BACKGROUND AND OBJECTIVES: Granulocyte transfusion therapy (GTX) can be effective for life-threatening infections unresponsive to conventional antimicrobial therapies in severely neutropenic children with cancer. We developed a new granulocyte collection method, named the 'bag method', in which apheresis, hydroxyethyl starch (HES) or dexamethasone are not used. We undertook a pilot study to determine the feasibility and the safety of GTX collected by the bag method for children with cancer and life-threatening infections. MATERIALS AND METHODS: A total of 25 GTX were administered to 13 patients (median age 3 years, range: 0.3-17; median weight 10.6 kg, range: 4.5-49.8) with neutropenia-related infections. Thirteen blood-relative donors received granulocyte colony-stimulating factor (G-CSF) (5-10 microg/kg), subcutaneously, 14 h before collection. Major end-points were granulocyte yields, post-transfusion absolute neutrophil counts (ANC) in patients, donor and patient safety, and clinical outcome on day 30. RESULTS: The median yield of ANC per 400 ml of processed whole blood was 6.2 x 10(9) (range: 2.5-15.0 x 10(9)). Patients received a mean of 6.4 +/- 0.8 x 10(8) granulocytes per kg of body weight per transfusion. The 1-h and 24-h post-transfusion ANC rose to 607 +/- 124/microl and 704 +/- 300/microl, respectively, from the baseline of 21/microl before the first GTX. Adverse reactions were observed in five of 13 donors (bone pain, headache, vasovagal reaction; all < or = grade 2) and in two of 25 transfusions of 13 patients (transient hypoxia; grade 3). Ten patients had favourable responses, and infection resolved in nine patients. CONCLUSIONS: The bag method without apheresis relieves the physical load of donors and enables patients with a low body weight to provide an adequate dose of granulocytes.     

Autologous peripheral blood stem cell transplantation after high dose therapy in patients with advanced lymphomas.

Thirty-eight patients with refractory or relapsed non-Hodgkin's lymphoma (19 patients) or Hodgkin's disease (19 patients) were treated with salvage therapy. The peripheral stem cell collection was performed during hematologic recovery after myeloablative chemotherapy. In eight patients with Hodgkin's disease the number of CFU-GM collected was less than 0.5 x 10(4)/kg and these patients were excluded for stem cell transplantation. In the remaining 30 patients, a median of 4 x 10(4) CFU-GM/kg was collected (range 0.8-100 x 10(4)/kg) by three leukaphereses in 25 patients and six to 11 leukaphereses in five patients. Conditioning regimens were CBV (eight), BEAM (six), BEAC (10) and cyclophosphamide + total body irradiation (TBI) (six). Without TBI, the mean time for reaching a granulocyte count greater than 0.5 x 10(9)/l was 18 days and for a platelet count greater than 50 x 10(9)/l was 19 days in 23 out of 24 patients. With TBI, in five patients the mean time for reaching a granulocyte count greater tahn 0.5 x 10(9)/l was 37 days and for a platelet count greater than 50 x 10(9)/l was greater than 100 days. Complications were minor. There was only one toxic death. The outcome in these patients was similar to that observed in patients who received autologous bone marrow transplantation for advanced lymphomas. In conclusion, we observed good hematologic recovery except when TBI was used in the conditioning regimen.     

Prophylactic platelet transfusions from healthy apheresis platelet donors undergoing treatment with thrombopoietin

Many patients receiving dose-intensive chemotherapy acquire thrombocytopenia and need platelet transfusions. A study was conducted to determine whether platelets harvested from healthy donors treated with thrombopoietin could provide larger increases in platelet counts and thereby delay time to next platelet transfusion compared to routinely available platelets given to thrombocytopenic patients. Community platelet donors received either 1 or 3 microg/kg pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) or placebo and then donated platelets 10 to 15 days later. One hundred sixty-six of these platelet concentrates were then transfused to 120 patients with platelets counts 25 x 10(9)/L or lower. Pretransfusion platelet counts (11 x 10(9)/L) were similar for recipients of placebo-derived and PEG-rHuMGDF-derived platelets. Early after transfusion, the median platelet count increment was higher in patients receiving PEG-rHuMGDF-derived platelets: 19 (range, -12-66) x 10(9)/L, 41 (range, 5-133) x 10(9)/L, and 82 (range, -4-188) x 10(9)/L for placebo-, 1-microg/kg-, and 3-micro/kg-derived platelets, respectively. This difference was maintained 18 to 24 hours after transfusion. Transfusion-free intervals were 1.72, 2.64, and 3.80 days for the recipients of the placebo-, 1-microg/kg-, and 3-micro/kg-derived platelets, respectively. The rate of transfusion-related adverse events was not different in recipients of placebo-derived and PEG-rHuMGDF-derived platelets. Therefore, when transfused into patients with thrombocytopenia, platelets collected from healthy donors undergoing thrombopoietin therapy were safe and resulted in significantly greater platelet count increments and longer transfusion-free intervals than platelets obtained from donors treated with placebo.     

Influence of post-transplant recombinant human granulocyte colony-stimulating factor administration on peritransplant morbidity in patients undergoing autologous stem cell transplantation

This study evaluated of the effect of post-transplant recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration on the parameters of peritransplant morbidity. Three sequential and consecutive cohorts of 20 patients each received either post-transplant rhG-CSF at a dose of 5 micro g/kg/d i.v. in the morning, starting on d 0, d 5, or no rhG-CSF. Patients who received rhG-CSF starting on d 0 and 5 recovered granulocytes more rapidly than those not receiving rhG-CSF (P < 0.001 for ANC >or= 0.5 and 1 x 10(9)/l). RhG-CSF administration was not significantly associated with more rapid platelet engraftment. RhG-CSF administration starting on d 0 and 5 was significantly associated with a decreased duration of fever (P = 0.002 and 0.001 respectively), antibiotic administration (P < 0.001 and 0.006 respectively) and shorter hospitalization (P < 0.001 and 0.001 respectively) compared with the reference group. There was no difference between the d 0 and d 5 arms regarding the parameters of peritransplant morbidity. In conclusion, rhG-CSF administration was associated with a faster granulocyte recovery, shorter hospitalization, and shorter period of fever and non-prophylactic antibiotic administration. This study also showed that starting rhG-CSF administration on d 5 may be as effective as d 0 on the clinical outcome and may be an economical approach in routine clinical practice in this cost-conscious era.     

Treatment and prophylaxis of severe infections in neutropenic patients by granulocyte transfusions

Bacterial and fungal infections are the main cause of morbidity and mortality in neutropenic patients. To resolve infections, an adequate number of functional granulocytes is required. Successful treatment of severe infections with granulocyte transfusions is strongly dependent on an adequate number of transfused cells. In this study, 42 neutropenic patients received rhG-CSF-stimulated granulocyte transfusions (GTXs). Of these patients, 18 with severe infections during neutropenia and 8 in a high-risk situation, as defined by severe infections during previous periods of neutropenia or increasing infectious parameters during prolonged neutropenia, received a median of three GTXs (range 1-25), containing a median total of 2.62x10(10) leukocytes (range 0.3-8.61x10(10)). A further 16 patients in a pilot study received prophylactic GTX, consisting of a median of three GTXs (range 1-4) containing a median total of 3.20x10(10) leukocytes (range 0.73-8.51x10(10)). Out of 18 patients with severe infections, 12 improved clinically or showed a resolution of infection after GTX. All 8 patients in a high-risk situation showed a stable clinical course without serious infections. Prophylactic GTX did not result in significant differences with regard to infectious parameters. The median number of transfused platelet units during the course of cytopenia was significantly reduced (13.5 units vs 22.0 units, P<0.02) compared to the control group. For the treatment of infections during neutropenia, rhG-CSF-stimulated granulocyte transfusions are safe and a promising approach.     

Granulocyte transfusion as a treatment for enterococcal meningoencephalitis after allogeneic bone marrow transplantation from an unrelated donor

Bacterial meningoencephalitis occurring in the pre-engraftment period after bone marrow transplantation (BMT) is a rare complication, and the feasibility of granulocyte transfusion (GTX) in such cases remains to be elucidated. A 37-year-old man developed enterococcal meningoencephalitis during a severely granulocytopenic pre-engraftment period after BMT. Despite therapy with appropriate antibiotics, cultures of blood and cerebro-spinal fluid (CSF) continued to grow Enterococcus faecalis, and he developed rapid mental deterioration and seizure. Granulocytes were collected from his HLA-mismatched, ABO-matched sibling with subcutaneous injection of granulocyte colony-stimulating factor (G-CSF) and oral dexamethazone. Transfusion of 4.4 x 10(10) granulocytes resulted in a 12-h post-transfusion granulocyte increment of 2.0 x 10(9)/l, and maintained peripheral blood granulocyte counts above 0.5 x 10(9)/l for 3 days. A rapid increase of granulocytes in CSF was also observed, and cultures of blood and CSF became negative after GTX. A transient worsening of seizure was observed as a potential side effect of GTX. The patient subsequently developed septic shock because of Pseudomonas aeruginosa and died. Further studies are warranted to evaluate the clinical efficacy of GTX for the treatment of uncontrolled infections in granulocytopenic stem cell transplant recipients.