Clinical trial NCT02099669: Red Blood Cell Transfusion Thresholds and QOL in MDS
Official title: Red Blood Cell Transfusion Thresholds and QOL in MDS (EnhanceRBC): a Pilot, Feasibility Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Myelodysplastic Syndromes (MDS)
Quality of Life
Red Blood Cell (RBC) Transfusions
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Princess Margaret Hospital, Canada
name: Juravinski Cancer Center
First posted: 2014-03-31
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage compliance of q2weekly hemoglobins
timeFrame: 3 months
Secondary outcomes:
measure: Measures of feasibility
timeFrame: 3 months
measure: Quality of life
timeFrame: 3 months
measure: Adverse events
timeFrame: 3 months
measure: Alloimmunization rates
timeFrame: 3 months
measure: Hemosiderosis
timeFrame: 3 months
measure: Overall utilization of blood
timeFrame: 3 months
measure: Time commitment
timeFrame: 3 months
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre/Odette Cancer Centre
Study officials:
affiliation: Sunnybrook Health Sciences Centre/Odette Cancer Centre
name: Rena Buckstein, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.