Thrombopoietic Agonists Show Efficacy in ITP Related to Allogeneic Stem Cell Transplantation,

Abstract Abstract 3292 Patients with refractory immune thrombocytopenia (ITP) have limited therapeutic options, with morbidity and mortality as often from infection as from bleeding. Thrombopoietin (TPO) mimetics allow an increase in the platelet count without causing immunosuppression. These agents may be especially useful in patients with secondary forms of ITP. We report three patients treated with TPO agonists for ITP post Allogeneic Stem Cell Transplants (SCT). Patient 1: MC, 37yrs, developed refractory ITP after a myeloablative allogeneic SCT for Accelerated Phase CML. He was unresponsive to standard treatments (figure 1a), requiring platelet transfusions 3x weekly for active bleeding. He started Eltrombopag 50mg/day in July 2009. He had a clinically significant increase in his platelet count (supported count increased to 40) so platelet transfusions were reduced to 2x weekly. Eltrombopag was increased to 75mg in November with a subsequent platelet increase to 90 and by December 2009 he was platelet independent, maintaining a platelet count 90–120 on Eltrombopag alone, 25mg/day, 5 days week. Patient 2: BT, 4yrs(12kg), underwent a myeloablative allogeneic PBSCT in September 2009 for JIA/HLH. She became thrombocytopenic in June 2010, presumed to be ITP. She had no response to prednisolone or rituximab and a only a minimal response to IVIG; requiring platelets 1x weekly. She started Eltrombopag 7mg OD in November 2010, escalated to 12mg by February 2011. This had a synergistic effect with IVIG and she became platelet independent after one month of Eltrombopag and IVIG, maintaining platelet counts 50–200 (figure1b). Patient 3: MG, 62yrs, underwent a reduced intensity allogeneic SCT in March 2010 for stage 3 Sezary syndrome. Post SCT he developed pancytopenia associated with EBV reactivation. He received daily GCSF, regular blood and weekly platelet transfusions. In July he developed GI bleeding from HSV colitis and his platelet transfusion requirements increased to alternate days. In October 2010 he was started on Romiplostim 250mcg, increased to 350mcg weekly, erythropoetin and GCSF. He had a clinically significant rise in his platelet counts and a reduction in his platelet requirements to 1x weekly within weeks of starting romiplostim. By December he was platelet independent, with counts persistently over 50, and romiplostim was stopped (figure1c). All three patients remain in remission at the time of submission of the abstract. Immune cytopenias are well-recognised post myeloablative allografts occurring in 5–37% of SCT recipients. The occurrence of ITP in SCT recipients has been reported, in which GVHD or the production of anti-platelet alloantibodies of recipient origin was considered to play major roles. Although small numbers, these case studies show efficacy of thrombopoietic agents (recently licensed for use in chronic ITP) in patients with thrombocytopenia post SCT refractory to standard therapies, with an early reduction and subsequent cessation in platelet transfusion requirements in all three patients. The lack of immune suppression with these agents may be particularly relevant in patients post SCT, in whom immune reconstitution is vital not only in preventing infections, but also in preventing rejection of the graft and in establishing a graft versus leukaemia effect. Given that TPO receptors are present on haematopoietic stem cells at all stages of development and that TPO provides a growth factor for stem cells, the use of these agents in patients treated for leukaemia requires caution. There was no evidence of progression of disease in these patients and TPO agents were only required for a period of time (patient 3 is off therapy and the others only receive minimal doses). Formal evaluation of these agents in allogeneic SCT is warranted. Disclosures: Cooper: GSK: Honoraria; Amgen: Honoraria.

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Transfusion Requirements in Nonmyeloablative Allogeneic Stem Cell Transplantation for Hematologic Malignancies.

Blood ◽

10.1182/blood.v106.11.4178.4178 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4178-4178

Author(s):

Jason W. Brown ◽

Darrell J. Triulzi

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Blood Cell ◽

Red Blood Cell ◽

Platelet Transfusion ◽

Transfusion Requirement ◽

Hematologic Malignancies ◽

Packed Red Blood Cells ◽

Transfusion Requirements ◽

Cell Transplants

Abstract Nonmyeloablative allogeneic stem cell transplants (NM-ASCT) are increasingly being utilized to treat hematologic malignancies in settings where high dose, fully ablative regimens would not be tolerated. We identified 10 male and 13 female patients (n=23) ranging in age from 19 to 63 years old (mean=48) representing all patients whom had undergone NM-ASCT in the last five years. NM-ASCT were performed for acute myelogenous leukemia (n=7), non-Hodgkin’s lymphoma (n=6), Hodgkin’s disease (n=4), multiple myeloma (n=3), myelodysplastic syndrome (n=2), and acute lymphoblastic leukemia (n=1). The majority of patients had undergone at least one previous stem cell transplant (n=16). The mean number of stem cells infused per kilogram at time of transplant was 4.72 X 106 ±1.97 X 106 stem cells and mean time to engraftment was 15.8 ±5.15 days (3 consecutive days with ANC >500). All of the subjects required both platelet and red cell transfusion during the period of analysis. Mean transfusion requirements in the 7 days prior to transplantation were 3.1 ±5.9 units of platelets and 1.2 ±1.5 units of packed red blood cells. Mean platelet transfusion requirements 90 days post transplant were 73.7 ±79.7 units and mean red cell requirements 11.6 ±8.3 units. Total mean transfusion requirements during the time period analyzed were 76.9 ±82.2 units of platelets and 12.8 ±8.9 units of packed red blood cells. There was no significant correlation between the number of stem cells infused per kilogram on day of transplant, the number of previous transplants, or the time to engraftment with red blood cell or platelet transfusion requirements. Our data illustrate a higher proportion of patients requiring platelet transfusions (100% vs. 23%) and red blood cell transfusions (100% vs. 63%) as well as a higher platelet transfusion requirement (median 48 vs. 0 units) and packed red blood cell transfusion requirement (median 11 vs. 2 units) than other authors have reported in a 60 day period in HLA-matched sibling NM-ASCT [Weissinger et al. Blood 98(13):3584-8, 2001]. As is illustrated by the percentage of patients undergoing previous fully ablative stem cell transplants, our patients represent a heavily pretreated population and this may account for the higher transfusion requirements seen in this analysis. Although patients undergoing NM-ASCT receive reduced intensity therapy, in our analysis their transfusion requirements remain substantial.

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Characteristics and Financial Impact of Potentially Inappropriate Platelet Transfusion in the Inpatient Hospital Setting

Blood ◽

10.1182/blood-2019-125949 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2096-2096

Author(s):

Eric Mou ◽

Colin Murphy ◽

Jason Hom ◽

Lisa Shieh ◽

Neil Shah

Keyword(s):

Platelet Count ◽

Patient Care ◽

Platelet Transfusion ◽

Bypass Surgery ◽

Hospital Setting ◽

Financial Impact ◽

Platelet Counts ◽

Cardiac Bypass ◽

Platelet Defects ◽

Platelet Transfusions

Introduction Platelets are transfused prophylactically to prevent hemorrhage in a variety of patient populations. However, guidelines indicate that prophylactic platelet transfusions in patients with platelet counts above 50k/uL are usually not indicated, with notable exceptions including those undergoing neurological or cardiac bypass surgery. Common minor procedures such as paracentesis, central line placement, and lumbar puncture have been safely performed at platelet counts below 50k/uL. Despite this evidence, our institution incurred approximately 10 million dollars (USD) in direct platelet costs in 2017, with nearly 40% of platelet transfusions are occurring when the patient's platelet count exceeded 50k/uL. Given the significant financial impact of, and potential adverse effects associated with inappropriate platelet transfusion, we implemented a best practice advisory (BPA) in our electronic medical record (EMR) in order to better characterize patterns of platelet transfusion orders in patients with platelet counts >50k/uL. Methods An EMR-embedded BPA was activated in the inpatient hospital setting of a large, tertiary care academic medical center on May 1, 2019, and triggered whenever a platelet transfusion order was placed on an admitted patient whose most recent documented platelet count was >50k/ul. To inform the comparative impact of BPA alerts on provider behavior, alerts were randomized at the patient level to trigger either in standard or silent fashion. For standard alerts, the BPA appeared on-screen, informing the provider that their platelet transfusion order was potentially inappropriate and citing supportive evidence. Providers had the option of following or overriding the alert (Figure 1). In case of alert override, a pre-specified or free text justification was requested. Pre-specified options included upcoming neurosurgery, cardiac bypass surgery, known qualitative platelet defects, or patients taking antiplatelet drugs. Charge data were based on charges for platelet transfusion orders as listed in the hospital charge master. Results From May 1, 2019 to July 30, 2019, the alert fired 181 times (Figure 2). Alerts were silently triggered in 64 (35%) cases. Of the 117 active alerts, 23 (20%) were followed and 94 (80%) were overridden. The most common reasons for alert override included prophylactic transfusions ahead of non-cardiac and non-neurosurgical operations (18%), upcoming cardiac bypass surgery (18%), qualitative platelet defects (12%), active central nervous system (CNS) bleeding (12%), and active non-CNS bleeding (7%). The estimated cost savings associated with followed alerts was $18,170 USD. Discussion Our BPA was effective in reducing instances of platelet transfusion orders by 20% over a three-month period, translating to an estimated annual savings of nearly $70,000 USD in hospital charges. Conversely, the 80% alert override rate indicates that platelet transfusion in patients with platelet counts >50k/uL remains common, occurring in a variety of contexts. Potentially appropriate reasons for platelet transfusions included orders in the setting of cardiovascular bypass surgery, active CNS bleeding, or qualitative platelet defects, representing circumstances in which platelet thresholds are often set higher than 50k/uL. Alternatively, 25% of alert overrides occurred in potentially inappropriate contexts, including patients undergoing non-cardiovascular/non-neurosurgical procedures and patients with non-CNS active bleeding, settings where routinely targeting a platelet threshold >50k/uL is not supported by evidence. As a result of our study's randomized design, future directions include comparative analyses between patient care encounters in which alerts were silently versus visibly triggered, allowing for rigorous determination as to whether providers' interaction with our BPA influences subsequent rates of potentially inappropriate platelet utilization as compared to a control group. Overall, our findings show that platelets are frequently ordered in potentially inappropriate settings, and that reducing these orders imparts significant financial savings. These results provide an impetus for interventions directed at educating providers on appropriate platelet ordering practices, in order to further reduce unnecessary expenditures and optimize patient care. Disclosures No relevant conflicts of interest to declare.

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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 ◽

10.1182/blood.v104.11.3636.3636 ◽

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.

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Transfusion Practice Following Intracranial Hemorrhage in Acute Leukemia: An Institutional Review

Blood ◽

10.1182/blood-2018-99-112718 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4740-4740

Author(s):

Shannon Nixon ◽

Dawn Maze ◽

Eshetu G Atenafu ◽

Danielle Brandys ◽

Cindy Susan Murray ◽

...

Keyword(s):

Platelet Count ◽

Retrospective Study ◽

Acute Leukemia ◽

Intracranial Hemorrhage ◽

Platelet Transfusion ◽

Transfusion Practice ◽

Rank Test ◽

Transfusion Threshold ◽

Platelet Counts ◽

Platelet Transfusions

Abstract Background: Intracranial hemorrhage (ICH) is a common complication in acute leukemia that is associated with significant morbidity and mortality. While evidence supports prophylactic platelet transfusions at a threshold < 10 x 109/L to reduce the risk of bleeding in acute leukemia, there is little data to guide platelet transfusion practice in patients following ICH. The objectives of this study were to characterize the clinical features and outcomes of acute leukemia patients with ICH and to understand current platelet transfusion practice following ICH. Methods: This was a retrospective study conducted at a large, quaternary, academic cancer centre. We included all adult patients with a diagnosis of acute leukemia who had a documented ICH at our centre between January 1, 2009 and December 31, 2016. We assessed demographics, medications, infection and bleeding history in the week preceding ICH, characteristics of ICH including site of bleed, acute management, transfusion practice in the first 90 days, and clinical outcomes. Radiologic scans were re-assessed by neuroradiology to determine if the ICH was stable or if new or progressive bleeding had developed. Transfusion practice following the ICH was compared between the two groups with longitudinal data analysis using platelet counts as outcome. Kaplan-Meier product limit method was used to estimate overall survival (OS) rates as well as to obtain median survival; log-rank test was used to compare OS among those without new or progressive ICH vs. those with progression. Results: During the study period, of 2576 patients diagnosed with acute leukemia, 101 suffered from ICH and were included in the study. Most patients (94) had AML, of which 9 had APL, 6 had ALL, and 1 had MPAL. At the time of ICH, 61 patients were newly diagnosed or receiving induction chemotherapy, 33 had relapsed disease and 7 were in complete remission. Spontaneous ICH occurred in 76 patients. Within the week preceding ICH, 7 patients were on medications known to increase bleeding risk and 39 were on tranexamic acid. Sixty-four patients had clinical evidence of bleeding elsewhere and 22 had evidence of infection. On the day of ICH, the median platelet count was 16 x 109/L (range 0- 433 x109/L). Thirty-one patients had a platelet count < 10 x 109/L and 10 of these patients received a platelet transfusion prior to the bleed. Seventy patients had a platelet count ≥10 x109/L and 17 of these received a platelet transfusion prior to the bleed. Six patients (6%) exhibited evidence of platelet transfusion refractoriness. In the 90 days following ICH, 21% of platelet transfusions were given for a platelet count < 10 x 109/L, 55% were given with a platelet count between 10-29 x109/L, and 24% were given with a platelet count ≥ 30 x 109/L. New or progressive ICH occurred in 28 patients. The median platelet transfusion threshold was 19 x 109/L (range 0-114 x 109/L) for those without new or progressive ICH and 21 x 109/L (range 0-93 x 109/L) for those with progression (p=0.04; Figure 1). Of the 101 study patients, 79 have died. Median OS was 5.6 months for those without new or progressive ICH and 2.9 months for those with progression (p=0.002) (Figure 2). Cause of death was attributed to non-ICH causes in the majority of patients 65/79 (82%). Conclusions: In this retrospective study, we evaluated the outcomes of 101 patients with acute leukemia and ICH. At the time of the bleed, the majority of patients had active disease and more than two thirds had platelet counts of 10 x 109/L or higher. During 90 days of follow-up, nearly one third of patients developed new or progressive ICH. Platelet transfusion practice was variable and the median threshold was, in fact, higher in those who subsequently developed new or progressive bleeding. The reasons for this were unclear from our chart review, but we hypothesize that these patients may have had additional risk factors, e.g. fever, infection. The outcomes of patients with acute leukemia and ICH are poor. Factors other than platelet transfusion threshold likely contribute to secondary ICH events and the overall poor prognosis. Disclosures Maze: Novartis: Consultancy, Honoraria.

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Severe Thrombocytopenia Does Not Increase Bleeding Complications in Patients Undergoing Bronchoscopy

Blood ◽

10.1182/blood.v124.21.4293.4293 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4293-4293

Author(s):

Lakshminarayanan Nandagopal ◽

Muthu Veeraputhiran ◽

Tania Jain ◽

Ayman Soubani ◽

Charles A. Schiffer

Keyword(s):

Platelet Count ◽

Renal Dysfunction ◽

Platelet Transfusion ◽

Conflicts Of Interest ◽

Bleeding Complications ◽

British Thoracic Society ◽

Severe Thrombocytopenia ◽

Platelet Counts ◽

Number Of Patients ◽

Platelet Transfusions

Abstract Introduction Prophylactic platelet transfusions are often performed prior to bronchoscopy or broncho-alveolar lavage (BAL) to prevent bleeding in thrombocytopenic patients. There is a paucity of data to validate this approach, with a platelet transfusion threshold of <50,000/mm3 largely based on expert opinion. We conducted a retrospective study on the incidence of bleeding complications in thrombocytopenic patients undergoing bronchoscopy. Methods We identified 150 consecutive patients with platelet counts <100,000/mm3 who underwent bronchoscopy and/or BAL from January 2009 to May 2014 at our institution. Bronchoscopies performed in patients with frank hemoptysis and trans-bronchial lung biopsy procedures were excluded. Patient characteristics, underlying diagnosis, platelet count prior to bronchoscopy, administration of platelet transfusions and bronchoscopy details were recorded. Factors affecting bleeding risk including presence of renal dysfunction (defined as BUN >30 and/or Cr>2.0) and coagulation studies (PT, PTT, INR) were identified. The British Thoracic Society guidelines1 were used to categorize bleeding as a result of bronchoscopy. Data were analyzed using descriptive statistics. Results The median age was 59 years (range 27-90), with two-thirds of patients (63%) being male. One hundred and seventeen (78%) patients had underlying malignancy and 55 (37%) had thrombocytopenia related to malignancy. Fellows and residents under the supervision of a bronchoscopy certified attending performed all but 4 of the bronchoscopies. Infection (40%) was the primary indication for bronchoscopy with BAL performed in 127 (85%) patients. Fifty-eight of 89 (65%) patients with baseline platelet counts <50,000/mm3 received prophylactic transfusions compared to 8% of those with platelet counts >50,000/mm3. The platelet count did not rise to >50,000//mm3 in many transfused patients. Seventy patients (47%) had counts <50,000/mm3 and eighty patients (53%) had counts >50,000/mm3 at the time of bronchoscopy. 49% were receiving immunosuppressive medications, 45% had renal dysfunction and 8% had INR >1.5. Bloody lavage that resolved spontaneously without continuous suctioning (Grade 0) was observed in 9 (6%) patients. Bleeding that required continuous suctioning but then resolved spontaneously (Grade 1) was noted in 1 patient with a platelet count of 61,000/mm3. Of 10 total bleeding events, 7 occurred in patients who were intubated. Two additional patients with platelet counts of 30,000/mm3 and 53,000/mm3 had diffuse alveolar hemorrhage, which was present before bronchoscopy. “Old” blood and blood clots were observed in 6 patients. Discussion The low incidence of bleeding complications from bronchoscopy +/- BAL even in patients with platelet counts <30,000/mm3 (3 episodes in 31 patients, all grade 0) demonstrates that bronchoscopy can be safely done in severely thrombocytopenic patients. Adopting a lower threshold for prophylactic transfusions could save a considerable number of platelet units and translate into significant cost savings and decreased risk of transfusion-related complications. Table 1 Platelet count, transfusion history and bleeding complications during bronchoscopy Platelet count at the time of bronchoscopy Number (n) and percentage (%) of patients who underwent bronchoscopy Number of patients who received prior platelet transfusion Bleeding during bronchoscopy n % 0-15,000/mm3 9 6% (9/150) 5 Grade 0=1 pt 16-29 22 15% 16 Grade 0=2 pts 30-39 17 11% 9 Grade 0=1 pt 40-49 22 15% 9 Grade 0=3 pts 50-75 44 29% 14 Grade 1=1 pt 76-100 36 24% 10 Grade 0=2 pts Total 150 63 Grade 0=9 pts, Grade 1=1 pt. 1.Du Rand IA, Blaikley J, Booton R, et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE. Thorax. 2013:68 Suppl 1:i1-i44 Disclosures No relevant conflicts of interest to declare.

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

Blood ◽

10.1182/blood.v104.11.3632.3632 ◽

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.

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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 ◽

10.1182/blood.v108.11.577.577 ◽

2006 ◽

Vol 108 (11) ◽

pp. 577-577 ◽

Cited By ~ 3

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.

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Leukocyte and Platelet Counts Can Be Used To Guide Collection of Autologous Stem Cells after G-CSF Mobilization on the First Two Days of Leukapheresis but Not Beyond.

Blood ◽

10.1182/blood.v106.11.5278.5278 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5278-5278

Author(s):

Adi Gidron ◽

Jayesh Mehta

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Platelet Count ◽

Leukocyte Count ◽

Allogeneic Transplantation ◽

Hematologic Malignancies ◽

Platelet Counts ◽

Peripheral Blood Cd34 ◽

Collection Data ◽

Stem Cell Collection

Abstract We have shown recently that when healthy donors are treated with G-CSF to collect stem cells for allogeneic transplantation, the combination of a pre-apheresis leukocyte count of ≥25 x 109/L and a pre-apheresis platelet count of ≥100 x 109/L is associated with excellent mobilization as measured by an absolute peripheral blood CD34+ cell count (PBCD34) of ≥20/μL, and can be used to guide harvest timing (Tomblyn et al. Bone Marrow Transplantation advance online publication 01 August 2005; doi: 10.1038/sj.bmt.1705117). We wanted to see if this observation could be extended to patients receiving 10–16 μg/kg G-CSF daily as the sole mobilizing agent for autologous stem cell collection. Data from 161 leukapheresis procedures (65 day 1 collections, 47 day 2 collections, and 49 collections done beyond day 2) were analyzed to determine correlation between pre-apheresis leukocytes, platelets, and PBCD34. Overall, leukocytes (4.5–86.3; median 29.2) and platelets (26–452; median 121) correlated with PBCD34 (0.6–515.5; median 8.6); r=0.38 and 0.41 respectively (P<0.0001 for both). With leukocytes ≥25 and platelets ≥100, PBCD34 was 2.9–515.5 (median 31.8); significantly (P<0.0001) higher than PBCD34 of 0.6–226.0 (median 6.0) when leukocytes were <25 and/or platelets were <100. Among day 1 collections, with leukocytes ≥25 and platelets ≥100, PBCD34 was ≥20 in 63% of the time compared to 16% of the time if leukocytes were <25 and/or platelets were <100 (P=0.0001). On day 1, PBCD34 ≥10 was seen 78% of the time with leukocytes ≥25 and platelets ≥100, compared with 36% of the time with lower leukocyte or platelet counts (P=0.001). Similarly, PBCD34 levels of ≥20 and ≥10 were obtained 63% and 87% of the time with day 2 collections when leukocytes were ≥25 and platelets ≥100, compared with 19% and 35% of the time when leukocytes were <25 and/or platelets were <100 (P=0.003 and 0.001 respectively). For collections done beyond day 2, with leukocytes ≥25 and platelets ≥100, PBCD34 was ≥20 50% of the time compared with 7% when leukocytes were <25 and/or platelets were <100 (P=0.047). Beyond day 2, PBCD34 was ≥10 50% of the time with leukocytes ≥25 and platelets ≥100 compared with 8% of the time when leukocytes were <25 and/or platelets were <100 (P=0.18). Our data suggest that in patients with hematologic malignancies receiving G-CSF for mobilization of autologous stem cells, the combination of a leukocyte count of ≥25 and a platelet count of ≥100 is associated with excellent mobilization of stem cells as measured by PBCD34 in the majority of patients on the first and second harvest days. However, the relationship between good counts and PBCD34 is not as strong from the third day onwards, and a good leukocyte-platelet count combination is less powerful at predicting good mobilization. Conversely, lower leukocyte and/or platelet counts strongly predict for poor mobilization beyond the second day, but somewhat less strongly on the first two days. Thus, on the first and second days of stem cell collection in patients mobilized with G-CSF, apheresis can be initiated based on favorable hematologic parameters without necessarily awaiting PBCD34 levels. However, beyond the second day, PBCD34 levels should guide apheresis rather than surrogate markers such as leukocyte and platelet counts.

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

Blood ◽

10.1182/blood.v98.5.1346 ◽

2001 ◽

Vol 98 (5) ◽

pp. 1346-1351 ◽

Cited By ~ 70

Author(s):

Lawrence T. Goodnough ◽

David J. Kuter ◽

Jeffrey McCullough ◽

Sherrill J. Slichter ◽

John DiPersio ◽

...

Keyword(s):

Platelet Count ◽

Adverse Events ◽

Growth And Development ◽

Platelet Transfusion ◽

Intensive Chemotherapy ◽

Platelet Concentrates ◽

Platelet Counts ◽

Development Factor ◽

Healthy Donors ◽

Platelet Transfusions

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 μg/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 × 109/L or lower. Pretransfusion platelet counts (11 × 109/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) × 109/L, 41 (range, 5-133) × 109/L, and 82 (range, −4-188) × 109/L for placebo-, 1-μg/kg–, and 3-μ/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-μg/kg–, and 3-μ/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.

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Patients Receiving Palifermin in Conjunction with Melphalan 200 Required Fewer Platelet Transfusions: Analysis of a Retrospective Cohort Study.

Blood ◽

10.1182/blood.v108.11.5261.5261 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5261-5261

Author(s):

Donald A. Hutcherson ◽

Amelia Langston ◽

Cheryl H. Lin ◽

Christopher Flowers ◽

Mary Jo Lechowicz ◽

...

Keyword(s):

Platelet Count ◽

Platelet Transfusion ◽

Conditioning Regimen ◽

Control Group ◽

Indirect Measure ◽

Platelet Recovery ◽

Autologous Transplant ◽

Transfusion Requirements ◽

Severity Scores ◽

Platelet Transfusions

Abstract Background: Mucosal injury and concomitant associated side effects represents a major toxicity of autologous transplant for myeloma. The use of Palifermin has been demonstrated to reduce mucositis severity scores and duration in randomized trials. We sought to evaluate the effect of palifermin on overall platelet transfusion requirements as an indirect measure of reduced GI toxicity. Since palifermin has been shown to decrease mucosal damage caused by conditioning regimens for PBSCT, it was theorized that palifermin’s protective effects might lead to a reduction in the platelet transfusion requirements for these patients. Methods: Thirty six consecutive myeloma PBSCT patients conditioned with melphalan 200 mg/m2 plus palifermin (dosed per manufacturers recommendations) were retrospectively evaluated for platelet transfusion requirements following autologous transplant. As a historical control, data were retrospectively collected on thirty eight consecutive myeloma PBSCT patients conditioned with the same regimen prior to the routine use of palifermin. Platelet support consists of transfusion of leukoreduced irradiated single donor pheresis products. Platelet transfusions were dictated by standard clinical practice on the transplant service either for a routine platelet count <10K or 20k when patients had evidence for bleeding. Identical platelet transfusion criteria were used in the control and palifermin groups. The number of platelet transfusions required from the time of transplant until platelet recovery was analyzed for each patient. Patients who did not have adequate platelet recovery (Platelets <100,000) at the initiation of transplant conditioning were excluded from analysis in both groups. Results: The palifermin and control patients were of similar age and renal function. Baseline median platelet count was higher in the palifermin group (260 vs 213.5; p=.01), but both groups had mean platelet counts well above the normal range. Patients in the palifermin group required an average of 1.11 platelet transfusions compared with 2.42 transfusions for the control group (p=.055). In the palifermin group, 17 (46%) of the patients required no platelet transfusions compared to only 8 (21%) in the control group (p=.017). When analyzing only the patients who had normal platelet count (> 150,000) prior to start of the conditioning regimen, the palifermin patients (33) required an average of 1.1 transfusions compared to 1.7 transfusions in the control patients (33). The numbers of patients requiring only 1 transfusion were 11 (31%) in the palifermin group and 13 (34%) in the control group. The time to platelet engraftment was similar in both the 2 groups (14.5 days in the palifermin group and 15 days in the control group). Conclusion: The use of palifermin is associated with reduced platelet transfusion requirements among a group of patients who received melphalan 200 mg/m2 conditioning and autologous transplant for myeloma. Further cost analysis and quality of life analysis are needed to further justify this approach for all patients.

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