Comparison of different transfusion strategies for red blood cell transfusion dependent MDS and MPN patients - a cross-over study with remote patient monitoring

There are no completed trials in the outpatient setting comparing restrictive
vs. liberal transfusion strategies for transfusion-dependent hemato-oncologic
patients. Moreover, there is little data in general about the value of
outpatient transfusions.
In order to optimize red cell transfusion in RBC transfusion-dependent patients
both the risks and the benefits should be known and carefully weighted. The
results of trials conducted in other patient groups (surgical and ICU patients)
indicated that RBC transfusion may have a negative impact on patient outcome
and therefore a restrictive transfusion strategy is recommended for these
groups of patients. Hardly any research, however, has been done in chronically
transfusion dependent patients. A restrictive transfusion policy may be less
optimal for this patient category since the goal of the transfusion is the
improvement of the quality of life (QOL), rather than survival or vital support
as in the critical ill. QoL, however, is hard to substantiate and a patient
specific parameter. To understand the full balance between risks and benefits
of a red cell transfusion policy in RBC transfusion dependent patients, we need
to assess objective clinical relevant outcomes including QoL. While so far QoL
was quantified by questionnaire based scoring, nowadays wearable artificial
intelligence (AI) technology might add objective parameters like transfusion
modulation on physical, cardio-pulmonary activity and cognition to the QoL
equation.

Current standard of transfusion care in transfusion-dependent patients is based
on a restrictive Hb trigger-based policy for regular RBC transfusions, which
typically includes multiple (2-4) units every 2-4 weeks. As said, clinically
relevant endpoints such as QOL and cognition, are currently not taken into
account when the decision to give a transfusion is made. Patient vital signs
and functional activity are more patient specific transfusion indicators and,
therefore, may enable personalized timing and dosing of RBC transfusion. To
date, however, no published randomized trials have examined the impact of
different RBC transfusion policies on functional outcomes in chronic recipients
of RBC transfusions, since continuous monitoring in the outpatient setting was
not possible. Nowadays, wearables can effectively collate vital signs and
functional activity after transfusion and this could result in an optimal
transfusion policy for any individual patient without a significant change in
overall healthcare costs, but better overall individual quality of life.

after completion of the first 12 patients we will do an interim analysis. To
account for the increased risk of Type I error due to multiple testing, the
threshold for statistical significance will be halved.

Compare the effect of three different RBC transfusion strategies* (Standard of
care (SoC), SoC+1 and SoC+2**) on heart rate in a population of chronically
transfused patients (with on average at least 1 RBC transfusion each 8 weeks as
personal standard of care).
Secondary:
- Compare the effect of three different RBC transfusion strategies* (Standard
of care (SoC), SoC+1 and SoC+2**) on physical activity, QoL and cognition in a
population of chronically transfused patients (with on average at least 1 RBC
transfusion each 8 weeks as personal standard of care).
- Compare QoL by questionnaires with wearable based cognition, vital and
physical activity parameters and their correlation with transfusion induced
Hb-level changes.

** An exception will be made for those patients that normally receive 3 or more
RBC's as SoC. To prevent circulatory overload, instead of +2 RBC's, they will
receive one RBC less than their SoC.

This is a multicentre, single blind, cross-over trial in which 24 patients will
be included.
Upon inclusion, the treating physician will be asked what the patient*s SoC
Hb-trigger is and what the standard amount of RBC products transfused to that
specific patient is. This will then be called a SoC transfusion.
Patients will receive, in randomized order, 1. a SoC transfusion, 2. a SoC+1
RBC transfusion and 3. SoC+2 RBC transfusion. In the case that a SoC
transfusion for a patient is >=3 units, SoC+2 will change into SoC-1 (one RBC
unit less than SoC) to avoid cardiac overload and logistical issues due to too
many units to transfuse. Between all study transfusions, a SoC transfusion will
be given as a means of wash-out. This cross-over design in which patients are
their own control reduces bias by adjudication order. Blood will be drawn <72hr
before and <2hr after transfusion to measure Hb. Patients will complete a
QoL-questionnaires (QUALMS and MFI) and a Rapid Visual Information Processing
test (RVP) from the Cambridge Neuropsychological Test Automated Battery
(CANTAB) 2 days before and 7 days after transfusion and again 2 days before the
next transfusion. at the same timepoints, patients will measure their
bloodpressure and pulse with a Withings BPM connect. They also will wear a
Withings Steel HR smartwatch during the 3 red blood cell transfusion cycles.
Patients will start wearing the smartwatch 7 days prior to a planned RBC
transfusion to generate baseline data and continue to wear the device at least
until the next transfusion. At the end of a transfusion cycle, the patient
will fill out a short questionnaire on their experience of the last transfusion
cycle. Both the questionnaires and completion of the cognitive tasks can be
monitored remotely. Patients missing a measurement will be sent a reminder to
make up for a missed task.

1 or 2 extra RBCs added to a standard of care transfusion

15 questionnaires, 9 cognitive games and venapuncture of 3 x 3 ml spread over
2-6 months

Furthermore 3 times a period of 2-8 weeks of wearing the smartwatch(dependent
of transfusion regime of patient)

Part 2: (optional) Qualitative interview (30-45 min) and focus group (45-60
min)