Comparison of Two Methods of Transfusion for Stroke Prevention in Sickle Cell

II. Objective. Compare differences in RMPET versus ST.

III. Specific Aims:

1. To compare key predictive hematologic factors (hematocrit, hemoglobin, hemoglobin S
quantification, blood volume and alloantibodies) for relative risk of stroke utilizing
two methods of blood transfusion therapy.

2. To determine the nursing time to administer straight versus manual exchange transfusion
therapy.

3. To survey patient satisfaction for both procedures.

IV: Background/Significance:

Stroke occurs in 10% of Sickle Cell Disease (SCD) patients before the age of 20 Years.
Current standard of care for secondary overt stroke prevention in patients with SCD is
chronic red blood cell (RBC) transfusions. Stroke recurs in ~ 60% of patients without chronic
RBC therapy and in ~ 20% of patients with chronic transfusion while maintaining a hemoglobin
S percentage of less than 30%. Indefinite transfusion therapy is practiced as discontinuation
after short-term or long-term prophylactic transfusions leads to recurrent overt strokes and
more ensuing CNS damage, even with transition to hydroxyurea. Chronic transfusions also
prevent initial stroke in high-risk patients identified by transcranial Doppler (TCD)
ultrasound. The Stroke Prevention Study in Sickle Cell Disease (STOP) demonstrated a 92%
stroke risk reduction among 63 of 130 children with abnormal TCD results. Rates of stroke
declined significantly since implementing routine TCD screening and primary prophylactic
transfusion therapy. The subsequent STOP 2 trial supports the use of chronic transfusion
indefinitely because discontinuation resulted in an increased rate of abnormal TCD conversion
and development of overt stroke. Discontinuing transfusions on the STOP 2 trial was also
associated with a higher occurrence of silent cerebral infarcts, documented in 3 of 37
patients (8.1%) in the continued-transfusion group compared with 11 of 40 (27.5%) in the
transfusion-halted group. More recent studies demonstrate that SCD patients are also at risk
for silent cerebral infarcts. An association between worsening vasculopathy shown by magnetic
resonance angiography and progressive overt and silent infarcts on magnetic resonance imaging
has been found. More aggressive magnetic resonance imaging screening may be indicated and
this could result in more patients with SCD treated with chronic transfusion.

Common chronic transfusion modalities include ST or RMPET. The goal of therapy is to reduce
the hemoglobin S level either by diluting the blood (ST) or by removing and replacing the
blood with non-sickle hemoglobin (RMPET). To prevent further brain injury, the goal of
transfusion therapy is to lower the hemoglobin S quantification to less than 30% on a routine
basis, usually monthly transfusion procedure. There are many large centers that utilize
erythrocytapheresis which is considered the preferable method if available.

The investigator's study will focus on the types of RBC exchange therapy currently utilized
in the investigator's Infusion Clinic at T.C. Thompson Children's Hospital. The investigators
will determine which transfusion method is best for each participant for achieving the
hematologic parameters of lower hemoglobin S quantification.The investigators will also
measure the amount of nursing time for each procedure and which method is preferred by
participants. The investigators will share the institutional observations with other
institutions who may intend to switch between RMPET and ST.

V. Methods:

Study Design: Prospective observational cohort study

The investigators will utilize the institution's current population of 8 eligible chronically
exchanged transfused participants at the T.C. Thompson Children's Infusion Clinic. The
eligible participants will be invited to participate in a cross over design study so that
each participant serves as its own control. Eight participants will be randomly assigned
(blinded envelope) whereby four participants will start with rapid manual partial exchange
transfusion: 3 months will be spent in a wash out period, then 3 months of data collection
for RMPET. This group will then be switched to simple transfusion with a wash out period of
three months, then data collection for three months. The second group of four participants
will start with simple transfusion and have an identical study design over 12 months (3
months of collected data during simple transfusion, a 3 month wash out period, switch to
rapid manual partial exchange transfusion for three months, then 3 months of data collection
for RMPET).

The investigators will optimize all therapy to achieve the post transfusion goal of <30%
hemoglobin S and post transfusion Hb <12g/DL.with each transfusion performed for best
practice in avoiding sickle cell complications.

Inclusion Criteria:

1. Participants between 3 and 25 years of age

2. Diagnosis of Hemoglobin SS or SBeta thalassemia

3. On chronic exchange for stroke prevention

4. Performance status: Lansky play score of 100%, and if over 16 years of age,
Karnofsky=100%

Exclusion Criteria:

1. Participant has experienced more than one stroke and has a modified Rankin Scale of
>3.

2. Diagnosis of Hemoglobin SC disease

3. Participants on chronic transfusion for priapism.