Interim Analysis of a Prospective Randomised Study Comparing a Therapeutic Platelet Transfusion Strategy with the Prophylactic Platelet Transfusion Standard in Patients after Autologous Peripheral Stem Cell Transplantation (ASCT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 577-577 ◽  
Author(s):  
Kerstin Schaefer-Eckart ◽  
Knut Wendelin ◽  
Martin Wilhelm ◽  
U. Mahlknecht ◽  
R. Conradi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Platelet Count ◽  
Stem Cell Transplantation ◽  
Interim Analysis ◽  
Platelet Transfusion ◽  
Transfusion Strategy ◽  
Randomised Study ◽  
Peripheral Stem Cell Transplantation ◽  
Significant Difference ◽  
Platelet Transfusions

Abstract We have previously shown, that a therapeutic platelet transfusion strategy is safe in patients after autologous peripheral stem cell transplantation(ASCT) and can reduce the number of platelet transfusions to about 50% compared with the prophylactic strategy (Wandt et al, BMT2006, 37, 387–392). To confirm these results, we started a randomised multicenter study in 2005 and present the results of the first planned interim analysis. In the prophylactic platelet transfusion arm (p) transfusions were given to patients if the morning platelet count was < 10/nl, while in the therapeutic transfusion arm (t) clinically stable patients (no sepsis or systemic inflammatory response syndrome II° or III° (SIRS), no invasive Aspergillosis or infection with Stenotrophomonas maltophilia) received platelet transfusions only in the case of clinically relevant bleeding. Apheresis platelets were recommended, but pooled platelet units were allowed as well. We now analysed the first 92 patients, 45 patients with a prophylactic and 47 patients with a therapeutic transfusion strategy. Both groups were well balanced according to age, gender, diagnosis and conditioning regimens. Median days of thrombocytopenia < 20/nl were 4 (0–14) in the prophylactic and 4 (0–20) in the therapeutic arm. The corresponding days regarding platelets below 10/nl were 1(p) (0–5) and 2(t) (0–14), respectively. The total number of days with thrombocytopenia <20/nl was 185 in the prophylactic arm and 239 in the therapeutic arm, resp. The number of days with a platelet count below 10/nl was 63 (p) vs. 110 (t). The number of days in hospital was 15 (p) (6–29) and 14 (t) (9–29), resp. Minor hemorrhages were observed in only 13 patients: 4 out of 45 patients in the prophylactic arm (8,9%) and 9 out of 47 patients in the therapeutic arm (19,2%). This difference was due to the protocol strategy and not significant. We observed no major clinically relevant bleedings. There was a significant difference in the number of transfused platelet units: 68 (p) vs 37 (t), (p=0,005). The median number of platelet units was 1(0–6) in the prophylactic arm and 0(0–5) in the therapeutic arm. More than 95% of the transfusions were single apheresis units. So the primary objective of the study, a reduction of platelet transfusions by 25% was reached, without significant difference in the number of major bleeding complications (secondary objective). 9 out of the 37 platelet transfusions (24%) in the therapeutic strategy arm were given because of sepsis or SIRS and in 4 out of the 37 (11%) transfusions there was no indication according to the protocol. There was a non-significant difference in the number of red blood cell transfusions: 59 (median 0, range 0–8) in the prophylactic arm versus 87 (median 2, range 0–12) in the therapeutic arm. With these first results of the randomised study we could confirm that a therapeutic platelet transfusion strategy is safe and can reduce the number of platelet transfusions by about 50%. The study will continue until 200 patients are included.

Routine Prophylactic Platelet Transfusions Are Not Necessary for Patients in Clinically Stable Condition after Autologous Peripheral Stem Cell Transplantation(ASCT): Updated Results in 106 Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3636-3636
Author(s):  
Kerstin Schaefer-Eckart ◽  
Markus Frank ◽  
Martin Wilhelm ◽  
Hannes Wandt
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Platelet Count ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Platelet Transfusion ◽  
Median Number ◽  
Peripheral Stem Cell Transplantation ◽  
New Strategy ◽  
Platelet Transfusions

Abstract We present our extended experience with an only therapeutic platelet transfusion strategy in patients after autologous peripheral stem cell transplantation(ASCT). Clinically stable patients(fever < 38,5°Celsius, no local infections, no sepsis syndrome) received single donor apheresis platelet transfusions only in the case of bleeding WHO ≥ II°, while prophylactic platelet transfusions were given to clinically instable patients if the morning platelet count was < 10/nl. In a first analysis after 50 patients we have shown that this strategy was safe, with no bleeding greater than WHO II°. In a retrospective matched-pair analysis the total number of platelet units transfused was reduced to 50% compared to our former strategy with routine platelet transfusions given when the morning platelet count was below 10/nl. (ASH 2002). We now analysed 106 patients with a total number of 140 ASCTs. Median age was 54 years(19–70): The diagnoses were acute leukemia(17), lymphoma(34), solid tumors(9) and multiple myeloma(46). The conditioning regimens corresponded to standard protocols. Median days of thrombocytopenia < 20/nl and 10/nl were 6(0–92) and 3(0–62) respectively, with a total number of days with thrombocytopenia <20/nl and <10/nl of 989 and 508. Hemorrhages WHO I° and II° was observed in only 49 out of 140(35%) ASCTs. We observed no bleeding greater than WHO II°. The median number of platelet units was 1(0–18). 48 out of 140(34%) transplantations could be performed without platelet transfusions. In multiple myeloma this percentage was even higher: 32/68(47%). The indications for prophylactic transfusions were mainly FUO(21/61 – 34%) and mucositis with or without fever(19/61–31%). Considering age below or above the median age of 54 years or different diagnoses, there was no difference in days with platelets <10/nl, <20/nl, bleeding complications or median number of platelet units transfused. The total number of 234 transfusions in these 140 transplantations could have been even further reduced, because 15%(36/234) of the transfusions were given without a clear indication regarding the study regimen, because of a learning effect with this new strategy. This new strategy has shown to be very safe and prophylactic platetelet tansfusions are probably not necessary in clinically stable patients with fever as the only sign of an infection. We are just starting a multicenter randomised study comparing this new strategy with the former strategy of routine prophylactic platelet transfusion.

An Increase in the Immature Platelet Fraction Predicts Reconstitution of the Platelet Count and May Reduce Prophylactic Platelet Transfusions after Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3632-3632
Author(s):  
Samuel J. Machin ◽  
Dan Hart ◽  
Stefan Kunka ◽  
Carol Briggs ◽  
Laurence Corash
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Platelet Count ◽  
Platelet Transfusion ◽  
Thrombocytopenic Purpura ◽  
Platelet Recovery ◽  
Transplant Patients ◽  
Automated Method ◽  
Immature Platelet Fraction ◽  
Platelet Transfusions

Abstract A new automated method to reliably quantitate reticulated platelets, expressed as the immature platelet fraction (IPF), has been developed on an automated cell counter (XE-2100, Sysmex). The IPF is identified by flow cytometery using a polymethine dye, staining platelet RNA, in the reticulocyte channel; the results are available at the same time as the CBC. The IPF normal range is 1.1–6.1%, mean 3.4%, 2 SD 2.3%. Reproducibility and stability results over 48 hours were acceptable. The IPF is raised when there is increased peripheral consumption/destruction. In untreated idopathic thrombocytopenic purpura, n = 12, mean 22.3%, range 9.2–33.1% and active thrombotic thrombocytopenic purpura, n = 5, mean 17.2%, range 11.2–30.9%. Patients who may require prophylactic platelet transfusion, usually at threshold counts less than 10 x 109/L, to support periods of marrow aplasia were monitored daily for platelet count and IPF%. The recovery phase of thrombocytopenia in most chemotherapy (n=13) and stem cell/bone marrow transplant patients (n=15) was preceded by a rise in IPF% several days prior to platelet recovery, mean IPF 13.7%, range 7–27.3%. In particular, patients undergoing autologous transplantation (n=8) using peripherally collected stem cells have a very characteristic IPF% motif, with a rise 1 day prior to engraftment for all patients except one where it was 2 days prior. For bone marrow derived transplant patients the increase in IPF was more variable, the rise preceded the rise in platelet count by 2–7days. These patients suffer more septic episodes where there is a rise in the IPF with no immediate increase in the platelet count, and require more regular platelet transfusions. Following a platelet transfusion there is a 24-hour transitory fall in the IPF response, which may impede platelet recovery. A parameter that could predict the timing of platelet recovery could be used clinically to reduce the use of prophylactic platelet transfusion in these patients, thus minimising donor exposure, infection risk and allowing substantial financial savings. The IPF is a useful parameter in the evaluation of the thrombocytopenic patient and has the potential to allow more optimal transfusion of platelet concentrates.

A Therapeutic Platelet Transfusion Strategy without Routine Prophylactic Transfusion Is Feasible and Safe and Reduces Platelet Transfusion Numbers Significantly: Preliminary Analysis of a Randomized Study in Patients after High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 286-286 ◽  
Author(s):  
Hannes Wandt ◽  
Knut Wendelin ◽  
Kerstin Schaefer-Eckart ◽  
Markus Thalheimer ◽  
Mario Stephan Schubert ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Risk Factor ◽  
Platelet Count ◽  
Platelet Transfusion ◽  
Additional Risk Factor ◽  
Transfusion Strategy ◽  
Bleeding Events ◽  
Additional Risk ◽  
Mucosal Bleeding ◽  
Platelet Transfusions

Abstract We performed a multicenter randomized trial comparing the traditional prophylactic platelet transfusion strategy -arm P- (trigger: morning platelet count ≤ 10/nL) with an experimental therapeutic transfusion strategy -arm T- where patients (pts) received platelet transfusions only if they experienced clinically relevant bleeding (more than petechias or minimal mucosal bleeding). The morning platelet count was no trigger in arm T for transfusion as well as fever per se. Fever was no additional risk factor for bleeding in thrombocytopenic pts treated with our therapeutic transfusion strategy as published recently. (Wandt, H et al. Bone Marrow Transplant2006; 37:387–392) For safety reasons prophylactic transfusion was recommended in arm T, however, for pts with invasive aspergillosis, sepsis syndrome and unexpected headache. Randomisation was stratified according to age (&lt;50 years), sex and center. Different diagnoses (multiple myeloma, non Hodgkin’s lymphoma, Hodgkin’s disease, acute leukemia) were well balanced between both arms. One hundred seventy one consecutive pts with a median of 56 years (19–68) who signed informed consent were included in the study. Primary objective was a reduction of platelet transfusions of 15–25%; secondary objectives were safety, duration of leuko- and thrombocytopenia, hospitalisation, and numbers of red blood cell transfusion. Red blood cells should be transfused when hemoglobin level dropped below 8 g/dL or as clinically indicated. Results: Platelet transfusions could be reduced significantly by 27% in arm T compared with arm P (p0.004). In arm T 46% of pts did not need any platelet transfusion and this was more than the double compared to arm P (0.001). Between younger and older pts there was no difference in numbers of platelet transfusions needed. Overall, adherence to the protocol was good. Since clinically relevant bleeding (more than petechias and minimal mucosal bleeding) was the trigger for platelet transfusion in arm T consequently more such hemorrhages occured in arm T (28.7% vs 9.5%). No life threatening or fatal bleeding was registered. Hemorrhages were mainly (21.8%) epistaxis or mucosal, 6.9% were minor bleedings (e.g. vaginal, hematochezia, hemoptysis, hematuria). One pt with sudden headache had a minor cerebral hemorrhage (subarachnoid) documented by ct-scan without any clinical sequelae. Days with hemorrhage overall were rare but significantly increased in arm T (0.69 vs 0.17 days per pt). Age was no risk factor for bleeding. As already expected by our former experience we could show that fever and infection were no additional risk factor for bleeding in arm T compared with arm P despite the very stringent platelet transfusion strategy in the experimental transfusion arm. In pts with multiple myeloma bleeding events were very rare compared to other diagnoses (p &lt;0.0001). Numbers of red blood cell units were not significantly different between the two arms, as well as the duration of leukocytopenia and hospitalisation. In contrast duration of thrombocytopenia &lt;20/nL was significantly longer in arm T (median 5 vs 3 days; p 0.004) as expected. We conclude that our therapeutic platelet transfusion strategy is cost effective and safe in pts after autologous stem cell transplantation. Despite more minor hemorrhages in the experimental arm compared with the traditional prophylactic strategy all bleeding events could be safely controlled by consecutive platelet transfusion. Development of major bleeding could be prevented by the therapeutic transfusion strategy according to our protocol.

A “Single” Dose of G-CSF after Autologous Stem Cell Transplantation in Patients with Malignant Lymphoma - Third Interim Analysis of Multicentre Randomized Trial Comparing Standard Schedule with Delayed Application and Placebo.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2925-2925
Author(s):  
Edgar Faber ◽  
Robert Pytlik ◽  
Marek Trneny ◽  
Jiri Slaby ◽  
Tomas Kozak ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Malignant Lymphoma ◽  
Cell Transplantation ◽  
Interim Analysis ◽  
Bone Marrow Involvement ◽  
Cd 34 ◽  
Significant Difference ◽  
The Impact ◽  
Neutrophil Engraftment

Abstract The optimal schedule of G-CSF given after autologous peripheral stem cell transplantation (ASCT) has not been defined yet. Here we present results of the third interim analysis of randomized multicentre trial comparing standard application of G-CSF from day +5 (arm A) with delayed dosing (G-CSF was started when WBC reached 0,5x109/l and neutrophil count 0,1x109/l; arm B) and placebo (arm C). In order to eliminate the influence of diagnosis and conditioning and to minimize the impact of graft quality only patients with malignant lymphoma conditioned by BEAM and with graft harvested in maximum 3 aphereses containing at least 5,0x106 CD 34+cells/kg were included. Patients signed informed consent before registration into the study that had been approved by local ethical and national health care authorities. 115 patients at median age 45 (range 21 – 64) were randomized by July 15th, 2004. The data of 97 patients were analysed. There was no difference in age, lymphoma bone marrow involvement at diagnosis, number of chemotherapy cycles and the use of radiotherapy before transplantation and CD 34+ cells content in graft between any two of the three arms. Duration of neutropenia below 0,5x109/l and 1,0x109/l and number of days to neutrophil engraftment over 0,5x109/l and 1,0x109/l are listed in the table. A significant difference in duration of neutropenia and time to neutrophil engraftment was found between the arms A and B (p=0,002 – 0,005), the arms A and C (p&lt;0,0001) and also between the arms B and C (p=0,04–0,0001). A trend for delayed platelet engraftment was observed in both arms with G-CSF (A and B). Duration of hospitalisation was significantly longer in placebo group (arm C), however, there was no prolongation of fever or antibiotic use. The delayed „single” application of G-CSF (usually with one or two doses sufficient for full neutrophil recovery) appears to be safe and cost effective. Comparing with standard G-CSF schedule only one day delay in median neutrophil engraftment was observed. We hope to finish the study within the year 2004. Supported by the grant MSN 15110004. Arm A / G-CSF from day +5 (n=33) Arm B / Tailored initiation of G-CSF (n=32) Arm C / Placebo (n=32) * median(range) Days with neutropenia &lt;0,5x109/l (days) 7 (4–10)* 8 (6–11)* 10 (6–30)* Days with neutropenia &lt;1,0x109/l (days) 8 (5–15)* 9 (7–11)* 11,5 (6–30)* Neutrophil engraftment &gt;0,5x109/l (day +) 10 (9–12)* 11 (9–15)* 14 (9–30)* Neutrophil engraftment &gt;1,0x109/l (day +) 11 (9–22)* 12 (9–15)* 15 (10–30)* Platelet engraftment &gt;20x109/l (day +) 12 (2–33)* 12 (7–30)* 11 (7–24)* Platelet engraftment &gt;50x109/l (day +) 17,5 (8–100)* 16,5 (9–115)* 13 (8–32)*

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