Red Blood Cell Transfusion Thresholds and QOL in MDS

NCT02099669 | Unknown

• 1 other identifier: OCCMDS-005
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

Myelodysplastic syndromes (MDS) are bone marrow malignancies characterized by poor bone marrow function that may progress to acute myeloid leukemia. Many patients become red blood cell transfusion-dependent. Transfusion dependence is associated with inferior quality of life (QOL). However, the relationship between the degree of anemia and QOL is less clear. A commonly used transfusion strategy is to target the hemoglobin (Hb) in the range of 80-90 g/L (normal hemoglobin \> 120-130g/L). The question is: would a higher hemoglobin target lead to improvement in QOL despite the negative impact transfusion dependence may have on QOL (due to associated time commitments, expense, transfusion reactions etc). Several groups have prospectively shown that targeting hemoglobin levels of greater than 120 g/L (with hematopoietic growth factors (HGFs) and/or blood transfusions) or incremental increases of 15-20 g/L (with HGFs alone) were associated with improved QOL. The investigators MDS program has been conducting prospective assessments of QOL since 2007 in all registered and consented patients using a variety of validated questionnaires. Preliminary analysis (in 236 patients) revealed that, compared with an age-matched healthy general population, MDS patients have inferior QOL. Transfusion dependence and anemia were independently predictive of poor functioning, fatigue and decreased health utility. Furthermore, a hemoglobin level of ≥100 g/L seemed to be the key threshold for improvement in function and symptom scores. The investigators hypothesize that the target hemoglobins in transfusion dependent MDS patients are too low and this may account for their inferior quality of life. Our goal is to compare the effect on QOL of a restrictive strategy (which is the current standard of care), with a liberal transfusion strategy in a large randomized controlled trial of transfusion dependent MDS outpatients. Before embarking on such an endeavor, the investigators must first prove feasibility in a smaller pilot randomized controlled trial.

Conditions

Myelodysplastic Syndromes (MDS); Quality of Life; Red Blood Cell (RBC) Transfusions

Outcome Measures

Primary Outcomes (1)

• Percentage compliance of q2weekly hemoglobins

  The percentage compliance of q2weekly hemoglobins being within or above the target range of the RBC transfusion threshold assigned (after the 4 week run-in at study start as defined above). We will consider this study feasible and worthy of future development into a larger randomized trial (powered for QOL difference) if compliance is ≥70%. A compliance rate of 50-70%, would not exclude going forward with such an RCT but only after careful discussion and statistical planning

  3 months

Secondary Outcomes (7)

• Measures of feasibility

  3 months

• Quality of life

  3 months

• Adverse events

  3 months

• Alloimmunization rates

  3 months

• Hemosiderosis

  3 months

Study Arms (2)

Liberal transfusion strategy

EXPERIMENTAL

Intervention: Red Blood Cell transfusions. Transfuse pRBC at a higher threshold- maintain Hb level between 110 and 120 g/L: to achieve this, 2 units of pRBCs are transfused when Hb level is \< 105 g/L and 1 unit of RBCs when Hb level is 105-110 g/L. Transfusions administered more frequently.

Other: Red Blood Cell Transfusions

Restrictive transfusion strategy

ACTIVE COMPARATOR

Intervention: Red Blood Cell transfusions. Transfuse pRBC at standard of care thresholds- maintain Hb level between 85 and 100 g/L: to achieve this, 2 units of packed red blood cells (pRBCs) will be transfused when the Hb level is \< 80 g/L and 1 unit of pRBCs when Hb level is 80-85 g/L: standard administration

Other: Red Blood Cell Transfusions

Interventions

Red Blood Cell Transfusions OTHER

Liberal transfusion strategy; Restrictive transfusion strategy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients with MDS ≥18 years of age
• Transfusion dependent: at least 1 transfusion per month in the last 8 weeks
• Hb \<100g/L pre transfusion
• Life expectancy \> 6 months

You may not qualify if:

• Unstable cardiac disease (Canadian Cardiovascular Society (CCS) III/IV angina or New York Heart Association (NYHA) III/IV congestive heart failure) requiring the transfusion target range to remain \>85-100 g/L at all times
• ECOG ≥3
• Patients with red cell antibodies against high frequency antigens or multiple antibodies (would potentially delay finding blood)
• Patients on ESA's or disease modifying agents (like azacitidine) for their MDS

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Princess Margaret Hospital, Canada: collaborator
• Juravinski Cancer Center: collaborator

Study Sites (3)

Juravinski Cancer Centre

Hamilton, Ontario, Canada

RECRUITING

Princess Margaret Hospital

Toronto, Canada

RECRUITING

Sunnybrook Health Sciences Centre/Odette Cancer Centre

Toronto, Canada

RECRUITING

Related Publications (2)

• Carson JL, Stanworth SJ, Dennis JA, Fergusson DA, Pagano MB, Roubinian NH, Turgeon AF, Valentine S, Trivella M, Doree C, Hebert PC. Transfusion thresholds and other strategies for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2025 Oct 20;10(10):CD002042. doi: 10.1002/14651858.CD002042.pub6.

  PMID: 41114449 DERIVED

• Carson JL, Stanworth SJ, Dennis JA, Trivella M, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2021 Dec 21;12(12):CD002042. doi: 10.1002/14651858.CD002042.pub5.

  PMID: 34932836 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Erythrocyte Transfusion

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Blood Component Transfusion; Blood Transfusion; Biological Therapy; Therapeutics

Study Officials

• Rena Buckstein, MD

  Sunnybrook Health Sciences Centre/Odette Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Gallagher

CONTACT

jennifer.gallagher@sunnybrook.ca

Geetha Yogendron

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2014
• First Posted: March 31, 2014
• Study Start: March 1, 2014
• Primary Completion: December 1, 2018
• Study Completion: January 1, 2019
• Last Updated: April 26, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)