Impact of the mobilization regimen and the harvesting technique on the granulocyte yield in healthy donors for granulocyte transfusion therapy

BACKGROUND: Granulocyte mobilization and harvesting, the two major phases of granulocyte collection, have not been standardized. STUDY DESIGN AND METHODS: The data on 123 granulocyte collections were retrospectively investigated for the effect of the mobilization regimen and the harvesting technique. After a single subcutaneous dose (600 µg) of granulocyte–colony‐stimulating factor (G‐CSF) with (n = 68) or without (n = 40) 8 mg of orally administered dexamethasone, 108 granulocyte donors underwent granulocyte collections. Moreover, 15 peripheral blood stem cell (PBSC) donors who had received 400 µg/m² or 10 µg/kg G‐CSF for 5 days underwent granulocyte collections on the day after the last PBSC collections (PBSC‐GTX donors). Granulocyte harvesting was performed by leukapheresis with (n = 108) or without (n = 15) using high‐molecular‐weight hydroxyethyl starch (HES). RESULTS: Granulocyte donors who received mobilization with G‐CSF plus dexamethasone produced significantly higher granulocyte yields than those who received G‐CSF alone (7.2 × 10¹⁰ ± 2.0 × 10¹⁰ vs. 5.7 × 10¹⁰ ± 1.7 × 10¹⁰, p = 0.006). PBSC‐GTX donors produced a remarkably high granulocyte yield (9.7 × 10¹⁰ ± 2.3 × 10¹⁰). The use of HES was associated with better granulocyte collection efficiency (42 ± 7.8% vs. 10 ± 9.1%, p < 0.0001). CONCLUSION: G‐CSF plus dexamethasone produces higher granulocyte yields than G‐CSF alone. Granulocyte collection from PBSC donors appears to be a rational strategy, since it produces high granulocyte yields when the related patients are at a high risk for infection and reduces difficulties in finding granulocyte donors. HES should be used in apheresis procedures.     

Treatment of severe neutropenic sepsis with granulocyte transfusion in the current era – experience from an adult haematology unit in Singapore

Objectives: Granulocyte transfusion's (GT) efficacy among adult severe neutropenic sepsis (SNS) patients remains uncertain. We assessed GT's efficacy and its determinants among SNS patients in an adult haematology unit. The feasibility and safety of granulocyte donation (GD) and determinants of granulocyte yield were also evaluated. Methods: Retrospective analysis of granulocyte donors and recipients from March 2008 to October 2009. Results: Donors: Sixty GDs with a median WBC yield (WBCY) of 65·49 (31·30–131·72) × 10⁹ were collected from 48 donors (9 repeat donors) using hydroxyethyl starch and intermittent flow centrifugation aphaeresis after receiving 8 mg dexamethasone and 300 mcg granulocyte colony‐stimulating factor, with no serious adverse reactions (SAR). Six donations were urgently collected <3 h after pre‐medication, the median WBCY of which was not significantly different from donations collected >12 h after pre‐medication [59·18 (45·68–62·90) × 10⁹ vs 67·45 (31·30–131·72) × 10⁹, P = 0·140]. Only pre‐GD absolute neutrophil count (ANC) correlated with WBCY. Patients: Fifteen patients (12 acute leukaemias, 1 severe AA, 1 myelodysplastic syndrome and 1 lymphoma) received median 3 (2–9) ABO/RhD‐matched GTs over 2–24 (median 7) days at 3–61 (median 28) days from severe neutropenia (SN) onset without SAR. They received intensive chemotherapies (N = 9), allogeneic transplant (N = 3), autologous stem cell rescue (N = 1) or immunosuppressants (N = 2). Fourteen had bacterial (N = 1) infections, fungal (N = 3) infections or both (N = 10) and one had severe viral pneumonitis; 63·6 and 30·8% of bacterial and fungal infections responded, respectively. Median ANC increase (ANC_increase) was 1·26 (0–9·25) × 10⁹ at 5–20 (median 11) h post‐GT. On multivariate analysis, each patient's median ANC_increase only significantly correlated positively with median WBC dose/kg (P = 0·013). Five (33·3%) patients survived to discharge; the rest had infection‐related mortality (IRM). IRM was significantly associated with inotropic requirement (P = 0·004), ventilatory requirement (P = 0·017) and persistent SN (P = 0·007). Conclusion: GD is safe and feasible with good WBCY obtainable using our protocol. The effect of shortening pre‐medication interval on WBCY which may prevent delay in initiating GT is worth evaluating. GT most likely benefits SNS patients with prospects of neutrophil recovery before haemodynamic deterioration. Large randomised trials investigating the role and timing of GT among such patients are required.     

Lenograstim with or without dexamethasone for neutrophil mobilization in healthy donors: short-term kinetics of white blood cells and effects of granulocyte apheresis

Objectives : To determine the optimal time schedule for neutrophil collection after single mobilization with glycosylated recombinant granulocyte colony‐stimulating factor (G‐CSF, lenograstim) with or without dexamethasone (DXM). Donors and Methods : In this prospective randomized trial, 26 healthy volunteers were randomly assigned to a single subcutaneous dose of lenograstim 6 μg/kg plus 8‐mg DXM (G‐CSF/DXM, n = 13) or placebo (G‐CSF/placebo, n = 13). Hematological and biochemical parameters were analyzed before and 12, 15, 18, 21, 24, 27, 29, 36, 48, 60, 72, and 84 h and 7 and 30 days after mobilization. Six G‐CSF/DXM subjects underwent standard neutrophil apheresis (NA) 12 and 36 h after mobilization. Results : Polymorphonuclear neutrophil (PMN) counts 12 and 21 h after mobilization were 22.7 (16.6?32.8) × 10⁹/L and 22.4 (18.6?30.6) × 10⁹/L for G‐CSF/placebo versus 33.1 (24.2–44.9) × 10⁹/L and 32.5 (17.4–39.6) × 10⁹/L for G‐CSF/DXM. This mobilization plateau was followed by slow normalization at 72–84 h. The six NA subjects had median PMN yields of 62 (47–101) × 10⁹ and 39 (23–42) × 10⁹ per therapeutic unit. After the first apheresis, PMN counts sharply decreased to 21.1 (14.8–26.3) × 10⁹/L and then temporarily recovered to 25.9 (18.9–36.5) × 10⁹/L (P ≤ 0.001) over the next 8 h. Conclusions : Single doses of lenograstim with or without DXM induced a PMN plateau that lasted 9 h (12–21 h after mobilization), with PMN counts suitable for neutrophil collection. Lenograstim plus DXM made it possible to perform NA twice, 12 and 36 h after mobilization. © 2011 Wiley Periodicals, Inc.     

G-CSF mobilised granulocyte transfusions in 32 paediatric patients with neutropenic sepsis

Introduction In this retrospective, uncontrolled, observational study, the effect of granulocyte colony-stimulating factor (G-CSF)-stimulated granulocyte transfusions (GTX) in neutropenic paediatric patients with sepsis was evaluated.Patients and methods Granulocytes were collected from unrelated, ABO group-matched and cytomegalic-antibody compatible donors. For neutrophil mobilization, donors received a single subcutaneous dose of glycosylated G-CSF (Lenograstim, Chugai Pharma, Japan) plus oral dexamethasone (8 mg). In total, 168 (range 1–19 per patient) GTX were transfused in 32 children with a median age of 7.4 (0.25 to 16) years.Results The underlying diseases comprised predominantly haematooncological malignancies (31 children). In 15 of 32 patients, neutropenia was related to allogeneic stem cell transplantation. All children suffered from sepsis based on international criteria (fever, tachycardia, respiratory rate >2 SD above normal in the context of a suspected or proven infection). In ten children bacteria were isolated, in six children a fungal infection was diagnosed and four sepsis episodes were caused by viral infections. GTX contained a median neutrophil number of 6.3 (range 1.9–13.9)×10¹⁰ per transfusion and obtained a sustained haematological response after GTX. Nineteen out of 32 children survived the neutropenic sepsis, particularly nine out of 11 patients with bacterial sepsis.Discussion In contrast to the non-survivors, we observed a significant decrease in the C-reactive protein levels shortly after initiation of the GTX treatment in the surviving patients. A clear-cut benefit of GTX for children with neutropenic sepsis cannot be concluded from these data, but in children with (severe) bacterial sepsis refractory to antibiotic treatment, GTX were feasible, safe and could reduce mortality rates in this subgroup of patients.     

Granulocyte concentrates prepared from residual leukocyte units produced by the Reveos automated blood processing system

BackgroundGranulocyte concentrates are mainly derived by apheresis technique from donors stimulated with granulocyte colony-stimulating factor and steroids. The automated blood processing system Reveos, which is now increasingly used across the world, separates whole blood into four components, including a residual leukocyte unit containing granulocytes. The aim of this study was to produce an alternative granulocyte concentrate from leukocyte units produced by the Reveos system, and to assess the function of the granulocytes.MethodsThe number of granulocytes was measured in residual leukocyte units, derived from whole blood donations, with different volumes ranging from 10 to 40 ml. After deciding the optimal volume of the leukocyte unit (30 ml), ten ABO-matched units were pooled to form a granulocyte concentrate. The function of the granulocytes from residual leukocyte units was assessed by analyzing surface markers, phagocytosis of yeast, and production of reactive oxygen species.ResultsResidual leukocyte units with a volume of 30 ml contained a median number of 0,7 × 10⁹ granulocytes, and granulocyte concentrates prepared from ten pooled 30 ml-leukocyte units contained a median number of 6,3 × 10⁹ granulocytes. Granulocytes derived from residual leukocyte units displayed surface markers associated with granulocyte function, and capability to phagocytose yeast and produce reactive oxygen species.ConclusionsGranulocyte concentrates prepared from residual leukocyte units contain in vitro functional granulocytes and may be considered as an alternative product in acute situations before regular granulocyte concentrates from stimulated donors are available.     

Successful neutrophil engraftment supported by granulocyte transfusion in adult allogeneic transplant patients with peri-transplant active infection

Active infection at the time of allogeneic hematopoietic stem cell transplantation (HSCT) is a risk for non-relapse mortality (NRM) after HSCT. Granulocyte transfusion (GTX) has been used to prevent or treat life-threatening infections in patients with severe neutropenia. However, data are limited on the clinical benefits of GTX during HSCT. We retrospectively analyzed the transplant outcomes of HSCT patients who had undergone GTX between 2012 and 2020. Altogether, 20 patients with documented infection had received 55 GTXs during HSCT. No adverse events were observed during the GTX infusion. The average number of granulocytes was 0.40 (range, 0.10–1.59) × 10⁹/kg. The median neutrophil increment one day after GTX was 515 (range, ?6 to 6630)/μl, which was significantly correlated with the infused granulocyte dose (p = 0.0007). A total of 17 of 20 patients achieved neutrophil engraftment. The number of infused granulocytes tended to higher in clinical responders (p = 0.12), and patients receiving ≥ 0.5 × 10⁹/kg showed trend toward to better transplant outcomes (GTX-high vs. GTX-low, 1-year OS; 33% vs. 11%, p = 0.19. 1-year NRM; 44% vs.77%, p = 0.11). The type of red blood sedimenting agents was significantly correlated with the amounts of granulocyte collection. In conclusion, GTX, especially with a high amount of containing granulocytes, could be a safe bridging therapy for neutrophil engraftment after HSCT in patients with active infection.     

Safety and efficacy of therapeutic early onset granulocyte transfusions in pediatric patients with neutropenia and severe infections

BACKGROUND: Bacterial and fungal infections in profound neutropenia after chemotherapy are associated with high mortality despite appropriate antibacterial and antifungal treatment. Granulocyte transfusions are used as a therapeutic addendum, but concern regarding pulmonary reactions often results in delayed use in clinical practice. Accordingly, many patients are already at advanced stages of their infectious disease once granulocytes are transfused. Thus, a prospective Phase II trial was conducted to test the safety and efficacy of therapeutic early-onset granulocyte transfusions in immunocompromised children with neutropenia and severe infections. STUDY DESIGN AND METHODS: Twenty-seven children with hematologic disorder or malignancy and severe neutropenia with clinically and/or microbiologically documented severe infection unresponsive to standard treatment were included. They received granulocyte colony-stimulating factor (G-CSF)-elicited, crossmatched granulocyte concentrates every other day until complete recovery from infection was documented. RESULTS: A median of two granulocyte transfusions with a median of 8 x 10(8) granulocytes per kilogram of body weight were administered. All transfusions were well tolerated, and no pulmonary symptoms were observed. A total of 92.6 percent of our patients were able to clear their initial infection, and 81.5 percent were alive and without signs or symptoms of their infection 1 month later. All six children with aspergillosis cleared their infection. CONCLUSIONS: G-CSF-elicited, crossmatched granulocyte concentrates are a safe and efficient therapeutic addendum in immunocompromised children with prolonged neutropenia and severe infections. Early transfusion of granulocyte concentrates can lead to an overall response rate of 92.6 percent without adverse events. Randomized clinical trials with an early-onset design are required to determine appropriate clinical applications.     

Effect of granulocyte colony-stimulating factor on the candidacidal activity of polymorphonuclear neutrophils and their collaboration with fluconazole.

The effect of granulocyte colony-stimulating factor (GCSF) treatment of polymorphonuclear neutrophils (PMN) in vitro was studied with respect to their candidacidal activity. The candidacidal activity of PMN was found to be significantly increased when they were pretreated with GCSF. Fluconazole (1 microg/ml) was found to be highly fungistatic (90%) for Candida albicans Sh27 and collaborated with PMN for significantly increased killing. Collaborative killing by PMN significantly increased when they were treated with GCSF before and after fungal exposure. The enhancing activities of GCSF required optimization of the GCSF dose and were thus inoculum and strain dependent.     

The function and structure of granulocytes collected using the IBM 2997 separator

The effect of oral methylprednisolone and the sedimenting agent, hydroxyethyl starch, on granulocyte recovery, morphology, and function was studied in a volunteer donor programme. Using the IBM 2997, 10 litres of whole blood were processed, with an average procedure time of 2.4 hours and a collection volume of 300 ml. Donors not receiving methylprednisolone (n = 80) had a mean total granulocyte count of 3.5 × 10⁹/litre (range 1.6–5.3 × 10⁹/litre) and mean granulocyte yields were 1 × 10¹⁰ (range 0.2–3.0 × 10¹⁰). Those receiving 48 mg oral methylprednisolone 6–8 hours before the procedure (n = 320) had a mean granulocyte count of 6.3 × 109/litre (range 3.2–11.4 × 10⁹/litre) and significantly superior mean granulocyte yields of 2.0 × 10ln (0.3–6.5 × 10¹⁰) (P < 0.05). For both groups the mean packed cell volume of 0.08 litre/litre (range 0.02–0.17) and platelet contamination 1.9 × 10¹¹ (range 0.3–5.0 × 10¹¹). In all these procedures, hydroxyethyl starch was added to the blood entering the centrifuge channel. In none of the procedures were any untoward symptoms experienced by the donors. Light microscopy and ultrastructural studies showed no difference between control granulocytes and those collected following the addition of hydroxyethyl starch or after oral methylprednisolone. Similarly, granulocyte function measured with a random migration, chemotaxis. phagocytosis, and intracellular killing was not significantly different between control cells and those exposed to the sedimenting agent or the adrenocorticosteroids (P > 0.10). It is concluded that donor premedication with methylprednisolone significantly enhances granulocyte yields in the presence of hydroxyethyl starch and neither agent has any demonstrable effect on granulocyte morphology or function.     

The use of dextran as an adjunct to granulocyte collection with the continuous-flow blood cell separator

High molecular weight dextran (dextran 110 or 150 in saline) was added to the input line of the continuous-flow blood cell separator during a series of procedures for the collection of granulocytes from normal donors. Compared with procedures in which dextran was not used, there was enhanced sedimentation of red blood cells within the centrifuge bowl, and analysis of serial samples taken from the white blood cell line showed that contamination of the buffy coat by red cells was reduced by 88 per cent at the point where the granulocyte count was highest. The total leukocyte yields were 1.0 × 10¹⁰ cells when dextran was not used (five procedures), 1.6 × 10¹⁰ cells with dextran 110 (28 procedures), and 2.3 × 10¹⁰ cells with dextran 150 (20 procedures), and there were corresponding increases in the numbers of granulocytes collected. The technique has proved safe and simple, and the addition of dextran is recommended as a means of increasing the leukocyte yield from normal donors while reducing the number of red blood cells collected.     

Human blood components. I. Preparation and characteristics of leukocyte concentrates from single units of human blood

The distribution of white blood cells in the packed cells remaining after removal of platelet-rich plasma has been examined. The top 50 ml, which includes the huffy coat, was expressed in 5 aliquots of 10 ml and analyzed. With ACD, the top SO ml contained 52 per cent of the total sedimented WBC but only 33 per cent of the available polymorphonuclear leukocytes (PMN). With CPD, the top 50 ml contained 65 per cent of the total sedimented WBC and 52 per cent of the available PMN. The PMN were relatively evenly distributed throughout the five aliquots, while the non-PMN leukocytes were concentrated in the first three aliquots. The hematocrit of the top layer of packed cells was consistently lower for units collected in ACD than for units collected in CPD anticoagulant. Standard curves for the volume dependence of the differential and hematocrit were generated from these data. The characteristics of leukocyte concentrates routinely prepared as part of component production from the top 35 ml of the packed cells have been analyzed. Leukocyte concentrates prepared with ACD had, on the average, lower hematocrit, a lower percentage of PMN and fewer total white blood cells than leukocyte concentrates prepared from CPD-anticoagu-lant. Using CPD-anticoagulant instead of ACD-anti-coagulant during source blood collection resulted in an increase of the mean PMN differential count of the leukocyte concentrates from 29.8 to 45.7 per cent and of the mean total number of PMN in the concentrates from 0.46 × 10⁹ to 0.74 × 10⁹. The application of these data to component preparation and use is discussed.     

The Transfusion of Leukocytes from Donors with Chronic Myelocytic Leukemia to Patients with Leukopenia*

Leukocytes were collected from donors with chronic myelocytic leukemia by plasmapheresis and transfused into severely leukopenic recipients. The median transfusion of 7 × 10¹⁰ granulocytes (range.15 to 35 × 10¹⁰) resulted in a median increase in circulating granulocytes of 1,000 per cu. mm. (range 0 to 19,000), one hour after injection. The posttransfusion increment was directly related to the number of cells injected. Only 4.8 per cent of the injected cells were recovered in the circulating blood volume at one hour (range 0–37 per cent). The per cent recovery was directly related to the pretransfusion granulocyte count of the recipient; the more severe the recipient's leukopenia, the lower was the per cent recovery of transfused cells. The transfused granulocytes disappeared from the recipients' circulation with a half time of 24 hours. A number of other factors were found to influence the results of transfusion, such as: the antileukemic drugs given, the presence of fever, the transfusion vehicle (i.e., saline concentrates or whole plasma), the ABO red cell compatibility of donor and recipient, and the sequence of transfusion. Clinical responses as measured by disappearance of fever were seen in 54 per cent of the recipients. The fraction of febrile patients responding increased as the dose of leukocytes transfused increased. Severe reactions, manifested by dyspnea, cyanosis, and lung infiltrates were seen in a small percentage, but febrile reactions occurred in 67 per cent of afebrile patients.     

The value and practicality of granulocyte transfusion: a single oncology centre experience

There is an increased risk of infection in patients with neutropaenia, especially in those with neutrophil counts of less than 0·5 × 10⁹/L, and neutropaenia‐associated infection remains a limiting factor in treating malignancy especially of haematopoietic origin. Transfusing donor neutrophils is a logical approach to these problems, but granulocyte transfusion (GTx), a practice first advocated in the 1960s, is underused and although now enjoying resurgence, remains controversial. The aim of this study was to determine the practical aspects of GTx and clinical responses in patients receiving them. This is an observational retrospective review of GTx in patients undergoing therapy for predominantly haematological malignancies. We reviewed blood bank records and identified patients who received therapeutic granulocytes procured by leukapheresis and linked these recipients with their granulocyte donors. We determined the reasons for GTx and their clinical and relevant haematological responses to the transfusions. We identified 22 patients receiving at least three continuous days of GTx and who had adequate clinical and haematological data. Most donors were relatives and ABO matched with their respective recipients. Mean age of the patients was 28·8 years. Severe aplastic anaemia was the most common diagnosis, occurring in 9 patients (40·9%), followed by acute myeloid leukaemia in 6 (27·3%). Disseminated fungal infection was the most common reason for GTx, occurring in 16 patients (73%), followed by febrile neutropaenia in 7 patients. Fifteen (68·2%) patients showed clinical improvement. This uncontrolled retrospective observational study provides some evidence that procurement and use of GTx is safe for both donors and recipients and is probably an effective supportive therapy for patients with febrile neutropaenia     

FOLFOX chemotherapy can safely be given to neutropenic patients with early-stage colorectal cancer for higher dose intensity and fewer visits

Purpose

How does giving adjuvant FOLFOX chemotherapy to patients with early-stage colorectal cancer (ESCRC) regardless of the day-before absolute neutrophil counts (ANC) effect chemotherapy-induced febrile neutropenia (CIFN) rates, received dose intensity (RDI), and chemotherapy cycle delay? Does an ANC level predict future neutropenia?

Methods

A retrospective chart review was conducted on all patients receiving adjuvant chemotherapy for ESCRC at a mid-sized community hospital in Toronto, Ontario, Canada between April 2005 and May 2014. All patients were under one medical oncologist. Day-before CBC data were collected along with other patient characteristics. CIFN was confirmed by hospital records. Inclusion criteria were met by 132 patients. Overall, 1074 cycles of chemotherapy were analyzed.

Results

Six episodes of CIFN were observed. There was a significant difference in the average day-before ANC between patients who developed CIFN (1.4 × 10⁹/L, 95 % CI 0.76–2.0 × 10⁹/L) and those who did not (2.9 × 10⁹/L, 95 % CI 2.8–3.0 × 10⁹/L, p = 0.03). The RDI for oxaliplatin was 0.95 and for 5-fluorouracil (5-FU) was 0.96. A total of 170 cycles were given at day-before ANC <1.5 × 10⁹/L (range 0.1 × 10⁹/L–1.4 × 10⁹/L), and 24 were delayed for 1 week for hematologic reasons. Cycles given with grade 2 neutropenia predicted higher grades of neutropenia with a sensitivity of 0.22 (95 % CI 0.12–0.38).

Conclusions

Adjuvant FOLFOX chemotherapy may be given in the setting of low day-before ANC to patients with ESCRC. The benefits include higher RDI and a reduced number of clinic visits for the patient.

     

A pilot study on impact of use of medium molecular weight hydroxyethyl starch in granulocyte apheresis using Spectra Optia

IntroductionGranulocyte transfusion (GT) is a therapeutic option for prolonged neutropenic patients with severe bacterial or fungal infections. Efficient apheresis based granulocyte collection may be better achieved by infusion of high-molecular-weight (HMW) hydroxyethyl starch (HES). But multiple adverse incidents have been reported with HMW-HES. Due to availability issues and adverse incidents related to it, use of HMW-HES has become limited. Few studies have mentioned about medium molecular weight HES (MMW-HES) (130 kDa) as efficient for this purpose with minimal adverse incidents. So, the aim was to assess the impact of the use of MMW-HES in granulocyte apheresis when using Spectra Optia.MethodologyIn this observational study, donors who received MMW-HES during granulocyte harvest were included in HES group and another group who did not receive HES were grouped as non-HES. Injection G-CSF 10 microgram/kg and tablet dexamethasone 8 mg given 12 h before for non-HES group and 6 – 8 h in case of HES group blood donors. Number of adverse incidents observed were noted. Donor/procedure parameters were compared using Mann–Whitney U test / unpaired t test.ResultsGranulocyte yield was significantly higher in the HES group (2.5 × 10¹⁰ vs. 1.75 × 10¹⁰, p < 0.01) and was attributed to the difference in collection efficiency (22.61% vs. 10.15%, p < 0.01). There were no significant differences in occurrence of adverse events between HES and non-HES groups.ConclusionOur results clearly indicate that sufficient number of granulocytes can be harvested by using MMW-HES in Spectra Optia apheresis system even after short interval between mobilization to harvest.     

Efficacy and safety of plateletpheresis by donors with low-normal platelet counts

Our practice is to defer donors with blood platelet (PLT) counts of <180 × 10⁹/L because PLT yields are low, when compared to PLT units collected from donors with higher counts. In an attempt to minimize deferral, we determined whether 33 donors, who repeatedly demonstrated low-normal PLT counts (150–180 × 10⁹/L) on multiple occasions during the prestudy period, might safely donate satisfactory apheresis PLT units simply by extending the apheresis collection time by 20 min (men) and 40 min (women). Repeat plateletpheresis procedures were scheduled at ≥28-day intervals. The mean PLT yield (N = 92) was 5.8 × 10¹¹ with 97% of units containing ≥4.0 × 10⁹ PLTs. Although donors entered the study only after they had repeatedly exhibited predonation PLT counts of <180 × 10⁹/L, PLT counts were not always below this level at the time of study collections. However, analyzing only donations with true predonation PLT counts of <180 × 10⁹/L (N = 35), the mean PLT yield was excellent—5.4 × 10¹¹ with 97% of units containing ≥4.0 × 10¹¹ PLTs. The average fall in donor blood PLT counts (pre- vs. postdonation) was 36%, with only ten of 99 postdonation counts being <100 × 10⁹/L; the lowest was 69 × 10⁹/L. Thus, extending the apheresis collection time permitted donors who in the past were routinely deferred because of low PLT counts to safely donate satisfactory PLT units.     

European data on stem cell mobilization with plerixafor in patients with nonhematologic diseases: an analysis of the European consortium of stem cell mobilization

BACKGROUND: Plerixafor with granulocyte–colony‐stimulating factor (G‐CSF) has been shown to enhance stem cell mobilization in patients with multiple myeloma and lymphoma with previous mobilization failure. In this European named patient program we report the experience in insufficiently mobilizing patients diagnosed with nonhematologic diseases. STUDY DESIGN AND METHODS: Thirty‐three patients with germ cell tumor (n = 11), Ewing sarcoma (n = 6), Wiscott‐Aldrich disease (n = 5), neuroblastoma (n = 4), and other nonhematologic diseases (n = 7) were included in the study. Plerixafor was limited to patients with previous or current stem cell mobilization failure and given after 4 days of G‐CSF (n = 21) or after chemotherapy and G‐CSF (n = 12) in patients who mobilized poorly. RESULTS: Overall, 28 (85%) patients succeeded in collecting at least 2 × 10⁶/kg body weight (b.w.) CD34+ cells (median, 5.0 × 10⁶/kg b.w. CD34+ cells; range, 2.0 × 10⁶‐29.5 × 10⁶/kg b.w. CD34+ cells), and five (15%) patients collected a median of 1.5 × 10⁶/kg b.w. CD34+ cells (range, 0.9 × 10⁶‐1.8 × 10⁶/kg b.w. CD34+ cells). Nineteen patients proceeded to transplantation. The median dose of CD34+ cells infused was 3.3 × 10⁶/kg b.w. (range, 2.3 × 10⁶‐6.7 × 10⁶/kg b.w. CD34+ cells). The median numbers of days to neutrophil and platelet engraftment were 11 (range, 9‐12) and 15 (range, 10‐25) days, respectively. CONCLUSION: These data emphasize the role of plerixafor in combination with G‐CSF or chemotherapy and G‐CSF as an effective mobilization regimen with the potential of successful stem cell collection. Accordingly, plerixafor seems to be safe and effective in patients with nonhematologic diseases. Larger prospective studies are warranted to further assess its use in these patients.     

Released washed platelet concentrates are effective and safe in patients with a history of transfusion reactions

Background

Plasma removal by washing is an effective approach to prevent transfusion reactions by platelet concentrates (PCs). Recently, washed PCs were released by the Japanese Red Cross Society (JRCS).

Combined granulocyte and platelet transfusions. Development of alloimmunization as reflected by decreasing cell recovery values

Twenty-three patients undergoing induction therapy for acute myelogenous leukemia (AML) received a total of 191 combined prophylactic granulocyte (PMN) and platelet (PLT) concentrates on alternate days (median 8, range 3–12 per patient). Each transfusion was assessed by monitoring the patient for reactions and by estimating the recovery of PMN in the circulation at 1 hour and of PLT at 1 and 20 hours. Seventeen patients developed alloimmunization to PLT from at least one donor, defined as either a PLT recovery of less than 15 percent at 1 hour and/or less than 10 percent at 20 hours. In this group there was a progressive reduction in PMN and PLT recovery with increasing transfusion number, strongly suggesting alloimmunization to both cells. Thirty-four transfusions were accompanied by transfusion reactions, thirty-two of which occurred in ten patients who had PMN recoveries of less than 5 percent after at least one transfusion (median 2.5, range 1–6 transfusions per patient). Actuarial calculations predicted that 70 percent of patients would become alloimmunized to PLT from at least two individuals after receiving 11 transfusions. These results suggest that combined PMN and PLT transfusion are associated with the rapid development of alloimmunization.     

Collection of platelets and peripheral progenitor cells with the Fresenius AS.TEC 204 blood cell separator

The aim of the present study was to clinically evaluate the blood cell separator AS. TEC 204. One hundred fifteen platelet collections were carried out with the dual or single needle procedure. Platelet yield was 3.21 ± 0.80 × 10¹¹ (mean ± standard deviation) and 59.1% of the collections showed platelet counts >3.0 × 10¹¹. Leukocyte contamination was 1.77 ± 2.81 × 10⁶ and 89.0% of the platelet concentrates had a white blood cell content <5 × 10⁶. Using a dual needle technique with an alternating interface adjustment, all of the products were contaminated with less than 1 × 10⁶ leukocytes. Furthermore, 23 peripheral progenitor cell collections were performed in 12 patients and three allogeneic donors. Median numbers of harvested CD 34 antigen expressing cells/kg body weight were 0.78 (range 0–4.7) and 3.67 × 10⁶ (range 2.2–5.23), respectively. We conclude that platelet and progenitor cell collections can be carried out with efficient results. The collections were well tolerated by the donors. J. Clin. Apheresis 12:126–129, 1997. © 1997 Wiley-Liss, Inc.