Blood 142 (2023) 702–705

The 65th ASH Annual Meeting Abstracts

ORAL ABSTRACTS

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401.BLOOD TRANSFUSION

Tranexamic Acid to Prevent Bleeding in Patients with Hematologic Malignancies and Severe Thrombocytopenia
(TREATT trial). a Randomized Placebo-Controlled Trial
Lise J Estcourt, DPhil,MBBChir 1,2, Zoe K McQuilten, MBBS, PhD FRACP, FRCPA 3,4, Peter Bardy, FRCP,FRCPath 5,
Merrole Cole-Sinclair, MBBS 6, Graham P. Collins, MBBS,DPhil 7, Philip J Crispin, MBBS, FRACP, FRCPA 8,9,
Jennifer Curnow, MBBS, FRACP, FRCPA, PhD 10, Amber Degelia, BS 11, Claire Dyer, MSc 12, Vanessa Fox, BSc 13,
Adam Friebe, FRCPA, FRACP, MBBS 14, Lajos Floro, MD 15, Effie Grand, MBChB, PhD 16, Cara Hudson, MSc 17,
Gail Jones, MD 18, Joanne Joseph, MBBS 19, Charlotte Kallmeyer, MD 20, Marina Karakantza, MBBS 21, Paul Kerr, MBChB,
PhD 22, Sara Last 23, Maria Lobo-Clarke, BSc 23, Matthew Lumley, MD 24, Mary Frances McMullin, MDFRCPath,FRCP 25,
Patrick G. Medd, MBBS, PhD 26, Suzy M Morton, MBBCh 27,28, Andrew David Mumford, PhD 29, Maria Mushkbar, MBBS,
FRCPath 30, Joe Parsons, BSc 17, Gillian Powter, BA 31, Mallika Sekhar, MBBS 32, Richard Soutar, MD 33,
William S. Stevenson, MBBS,PhD 34, Elango Subramoniapillai 35, Robyn Sutherland, BN, BSc 13, Jeff Szer, MBBS, FRACP 36,
Neil A Waters, BSc 37, Andrew H. Wei, MBBS,PhD 38, David Alan Westerman, MBBS, FRCPA, FRACP 39,
Sarah A Wexler, FRCP, FRCPath 40, Erica M. Wood, MD 41, Simon J Stanworth, MD DPhil 1,42,43
1
NHS Blood and Transplant, Oxford, United Kingdom
2
Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
3
Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
4
Department of Haematology, Monash Health, Melbourne, Australia
5
Royal Adelaide Hospital, Adelaide, AUS
6
St. Vincent’s Hospital, Fitzroy, AUS
7
Haematology, Oxford Cancer and Haematology Centre, Oxford, United Kingdom
8
Canberra Hospital, Canberra, AUS
9
Australian National University, CANBERRA, AUS
10
Westmead Hospital, Sydney, AUS
11
Monash University, Melbourne, AUS
12
NHS Blood and Transplant Clinical Trials Unit, NHS Blood and Transplant, Oxford, United Kingdom
13
Monash University, Melbourne, Australia
14
Andrew Love Cancer Center, Barwon Health, Geelong, Geelong, Australia
15
Kings College Hospital, London, GBR
16
Salisbury NHS Foundation Trust, Salisbury, United Kingdom
17
NHS Blood and Transplant Clinical Trials Unit, NHS Blood and Transplant, Bristol, United Kingdom
18
Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
19
St. Vincent’s Hospital, Sydney, AUS
20
United Lincolnshire Hospitals, Lincoln, United Kingdom
21
NHS Blood and Transplant, Leeds, United Kingdom
22
Royal Devon University Healthcare, Exeter, United Kingdom
23
NHS Blood and Transplant Clinical Trials Unit, NHS Blood and Transplant, Cambridge, United Kingdom
24
Department of Haematology, Birmingham Heartlands Hospital, Birmingham
25
Haematology, Belfast City Hospital, Queen’s University Belfast, Belfast, United Kingdom
26
University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom
27
University Hospitals Birmingham, Birmingham, United Kingdom
28
NHS Blood and Transplant, Birmingham, United Kingdom
29
School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom
30
Department of Haematology, University Hospital Coventry and Warwickshire, Coventry, United Kingdom
31
NHSBT Clinical Trials Unit, NHS Blood and Transplant, Oxford, United Kingdom
32
Royal Free Hospital, London, United Kingdom

702 5 DECEMBER 2023 | VOLUME 142, NUMBER Supplement 1 © 2023 by The American Society of Hematology
ORAL ABSTRACTS Session 401

33
Glasgow Royal Infirmary, Glasgow, United Kingdom
34
Department of Haematology, Royal North Shore Hospital, Sydney, AUS
35
Royal Brisbane Hospital, Brisbane, Australia
36
Department of Clinical Haematology, Peter MacCallum Cancer Centre and the Royal Melbourne Hospital, Melbourne,
VIC, Australia, Melbourne, Australia
37
Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, AUS
38
Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, Australia
39
Peter MacCallum Cancer Inst., Melbourne, AUS
40
Royal United Hospitals Foundation Trust, Royal United Hospitals Foundation Trust, Bath, United Kingdom
41
Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
42
NIHR Blood and Transplant Research Unit in data driven transfusion practice, Oxford, United Kingdom
43
Oxford University Hospitals NHS Trust, Oxford, United Kingdom

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NB LJE & ZM and EMW & SJS contributed equally

Background Patients undergoing treatment for hematologic malignancies continue to have a high burden of clinically sig-
nificant bleeding (WHO grade 2 or above) despite receiving prophylactic platelet transfusions (43% in TOPPS trial, NEJM
2013).
One potential approach to reduce the burden of bleeding is antifibrinolytic therapy, which has been shown to reduce bleeding
and transfusion needs in patients undergoing surgery.
The Trial to EvaluAte Tranexamic acid therapy in Thrombocytopenia (TREATT) is a double-blind randomized controlled trial
evaluating the safety and efficacy of tranexamic acid (TXA) in patients with hematologic malignancies with severe thrombo-
cytopenia (EudraCT number 2014-001513-35).

Methods We enrolled adults with hematologic malignancies having intensive chemotherapy or a hematopoietic stem cell
transplant (HSCT) who were expected to have severe thrombocytopenia (platelet count ≤10x10 9 /L for ≥5 days) at 16 UK and
11 Australian sites. We stratified randomization by site.
We randomized participants to receive TXA (1g iv or 1.5g orally) or placebo (saline or capsule/tablet) 8-hourly from when
platelet count ≤30x10 9 /L or as soon as possible if the platelet count was already ≤ 30x10 9 /L (no later than 72 hours after
start of chemotherapy or HSCT). We stopped treatment if the unsupported platelet count reached ≥ 30x10 9 /L, thrombosis
occurred, or patient had received 30 days treatment.
Patients received red cell and platelet transfusions according to national transfusion guidelines. Bleeding assessments were
performed by trained research staff (inpatients) or via a patient diary, with significant bleeding reported to clinicians (outpa-
tients), using validated tools.
The primary outcome was the proportion of participants who died or had bleeding of WHO Grade 2 or above from study
day 1 ([D1], first day of treatment) to D30. We used marginal Cox proportional hazards regression modelling (adjusted for site
to account for clustering) to compare the two arms. Secondary outcomes included: safety outcomes (thrombotic events to
D120) and use of blood components.

Results Recruitment was affected by the COVID pandemic. We randomized 616 participants between June 2015 and February
2022 and included 597 in the modified intention to treat (mITT) analysis (platelet count ≤ 30x10 9 /L for ≥ 1 day and no exclusion
criteria). 16 participants were lost to follow-up prior to D120 (8 each arm); we included them in analyses if possible.
Participant mean age was 55.6 years (SD12.2), 38.2% (236/616) were women, 42.9% (264/616) had AML, 35.1% (216/626) auto-
graft and 25.4% (156/626) allograft.
There was no evidence of a difference in the risk of death or ≥ Grade 2 bleeding between the TXA and placebo arms (HR
0.92; 95% CI: 0.67, 1.27; p-value 0.62). 29.0% (87/300) of participants in the TXA arm and 32.7% (97/297) in the placebo arm
experienced ≥ Grade 2 bleeding, 66.0% (198/300) of participants in the TXA arm and 73.4% (218/297) in the placebo arm
experienced ≥ Grade 1 bleeding. There was no evidence of a difference in the risk of death to D30 (HR 2.72; 95% CI 0.29,
25.36; p-value 0.38), however there were only 11 deaths overall. No patient died from bleeding (to D30) or thrombosis (to
D120).
The proportion of participants surviving to D30 without a platelet transfusion was 8.3% in TXA arm (95% CI: 5.4, 11.9), 6.4%
placebo arm (95% CI 3.9, 9.7) (HR 0.92; 95% CI: 0.84, 1.02; p-value 0.10). The proportion of participants surviving to D30 without
a red cell transfusion was 29.4% in TXA arm (95% CI: 24.1, 34.8), 20.5% placebo arm (95% CI 16.0, 25.4) (HR 0.82; 95% CI: 0.72,
0.93; p-value 0.003).
13 participants developed thrombosis to D120: 2 arterial events (1 each arm), and 11 venous (7 TXA arm, 4 placebo). 5 partic-
ipants developed veno-occlusive disease (VOD) to D60 (3 TXA arm, 2 placebo).
Additional secondary outcomes (Table 1).

Conclusions Prophylactic TXA had no effect on the incidence of WHO Grade ≥2 bleeding or death when given in addition to
prophylactic platelet transfusions to severely thrombocytopenic patients undergoing therapy for hematologic malignancies.

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ORAL ABSTRACTS Session 401

The results are consistent with those of a similar trial (A-TREAT, Blood 2022). These results indicate no role for TXA to prevent
WHO ≥ Grade 2 bleeding in this patient population. There was no evidence that TXA increases the risk of venous or arterial
thrombosis, or VOD, despite use for up to 30 days.

Disclosures McQuilten: BeiGene: Research Funding; Gilead Sciences: Research Funding; Roche: Research Funding; Janssen-
Cilag: Research Funding; AstraZeneca: Research Funding; Bristol-Myers Squibb: Research Funding; Antengene: Research
Funding; Takeda: Research Funding; CSL Behring: Research Funding. Collins: Roche: Consultancy, Honoraria, Speakers Bu-
reau; Gilead: Consultancy, Honoraria, Speakers Bureau; Beigene: Consultancy, Honoraria, Research Funding, Speakers Bu-
reau; Astra Zeneca: Consultancy, Honoraria, Research Funding; Pfizer: Research Funding; Amgen: Research Funding; BMS:
Research Funding; Daiichi Sankyo: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau. McMullin: No-
vartis: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an
entity’s Board of Directors or advisory committees; AbbVie: Membership on an entity’s Board of Directors or advisory commit-
tees, Speakers Bureau; AOP: Speakers Bureau; Incyte: Membership on an entity’s Board of Directors or advisory committees,
Speakers Bureau; CTI: Membership on an entity’s Board of Directors or advisory committees; Sierra oncology: Membership

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on an entity’s Board of Directors or advisory committees; GSK: Membership on an entity’s Board of Directors or advisory
committees. Mushkbar: Astellas Pharma Ltd: Consultancy. Stevenson: Imago Biosciences, Inc., a subsidiary of Merck & Co.,
Inc., Rahway, NJ, USA: Research Funding. Szer: Sanofi: Consultancy, Honoraria, Membership on an entity’s Board of Direc-
tors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity’s Board of Directors or advisory
committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees,
Speakers Bureau; Prevail Therapeutics: Honoraria, Membership on an entity’s Board of Directors or advisory committees,
Speakers Bureau; Apellis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bu-
reau; Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity’s Board of Directors or advisory committees,
Speakers Bureau. Wei: Aculeus: Consultancy; Walter and Eliza Hall Institute of Medical Research: Patents & Royalties; BMS:
Consultancy, Honoraria, Research Funding, Speakers Bureau; Syndax: Research Funding; Astellas: Consultancy, Honoraria,
Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Servier: Consultancy, Honoraria,
Patents & Royalties: MCL1 use, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding;
Roche: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria,
Research Funding, Speakers Bureau; Beigene: Consultancy, Honoraria; Shoreline: Consultancy; Amgen: Consultancy, Hono-
raria, Research Funding; Gilead: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria, Research Funding; Novartis:
Consultancy, Honoraria, Research Funding, Speakers Bureau. Wood: Roche: Research Funding; BeiGene: Research Fund-
ing; Antengene: Research Funding; AstraZeneca: Research Funding; Bristol-Myers Squibb: Research Funding; CSL Behring:
Research Funding; Gilead Sciences: Research Funding; Janssen-Cilag: Research Funding; Takeda: Research Funding.

OffLabel Disclosure: Tranexamic Acid (TXA) is an antifibrinolytic agent. Intravenous TXA is licensed by the FDA for prevention
and treatment of bleeding in patients with hemophilia during and following tooth extraction (short-term use for 2 to 8 days.
Oral TXA is licensed by the FDA to treat heavy menstrual bleeding (maximum 5 days use per cycle).

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Session 401

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Figure 1

https://doi.org/10.1182/blood-2023-180720
ORAL ABSTRACTS

ABSTRACTS