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![Page 1: Ding Wen Wu, Rachel Friedmann, Joan Uehlinger, Sadiqa ...c.ymcdn.com/sites/ · PDF fileDing Wen Wu, Rachel Friedmann, Joan Uehlinger, Sadiqa Karim, Etan Marks, Angie Bonzon-Adelson,](https://reader031.vdocument.in/reader031/viewer/2022030406/5a7fc8d57f8b9a9d308bc1b9/html5/thumbnails/1.jpg)
Ding Wen Wu, Rachel Friedmann, Joan Uehlinger, Sadiqa Karim, Etan Marks, Angie Bonzon-Adelson, Kala Mohandas, Evan Himchak, Ronald Walsh
May 5, 2017
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Abbreviations
T/R
Simple transfusion and/ or red cell exchange
Post-HCT
Hematocrit immediately after the T/R
Post- HbS
Hemoglobin S level immediately after the T/R
Pre – HbS
Hemoglobin S level immediately before the T/R
F/u- HbS
= Pre-HbS of next T/R
Highest HbS level between 2 consecutive T/Rs
FCR
Fraction of cell remaining
calculated based on the desired Post-HbS
FCR = post-HbS/ pre-HbS
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Background RCE Targets for SCA Patients
Clinical improvement
Post-HCT
≤ 30% traditionally
FCR
FCR = post-HbS/ pre-HbS
Post-HbS ≤ 30% traditionally
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Background SCA mgt guidelines 2014
In children with SCA who receive transfusions long-term, the goal of transfusion should be to maintain a HbS level of <30% immediately prior to the next transfusion
Strength of recommendation: Moderate
Quality of evidence: Moderate
Reference:
Yawn BP1, Buchanan GR2, Afenyi-Annan AN3, Ballas SK4, Hassell KL5, James AH6, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014 Sep 10;312(10):1033-48. doi: 10.1001/jama.2014.10517.
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New Challenge
How to maintain next pre-HbS ≤30% ?
Expert recommendation – none
Literature/ evidence – none
Thoughts: Monthly T/R with F/u-HbS ≤30%
- But how???
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How to maintain HbS <30%?
Current T/ R approaches for pediatric SCA pts:
Empirical
↓ post – HbS (i.e. post-T/R-HbS)
How low? 10-15%, or 15-20%
Or ↑ post-HCT
How much? Up to 36%
Why? Suppress erythropoiesis
For pts of how old?
Some recommend for all the ped SCA pts, up to 20 y/o
Evidence-based
None
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Our Study - Aims
↓ post – HbS How to predict F/u-HbS from post-HbS?
Can we predict it by calculation?
To identify a threshold
which keeps F/u HbS < 30%
↑ post-HCT
To determine if raising post-HCT to 30-36% can suppress F/u- HbS to < 30%
If yes, how to predict F/u HbS < 30% from post-HCT?
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Data Inclusion Criteria
Patients of genotype HbSS
Chronic monthly T/R
i.e. ~ 1 month (20-45 days) between 2 consecutive T/R events
Or a non-monthly T/R AND a F/u-HbS ~1 month later
AND no T/R event in between the post-HbS and the F/u HbS
June 2014 – Dec. 2015
Each event has at least a set of 3 documented parameters: post- HCT, and post-HbS, and F/u-HbS
To maximize the sample size for proof of concept, this study includes both pediatric and adult patients
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Data Exclusion Criteria
Patients with other hemoglobinopathies rather than genotype HbSS
Events with incomplete data points
Post-HbS > 30%
Post-HCT > 36%
SCA patients after allo-Stem Cell TxP
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Results
47 SCA patients
26 children, 21 adults
17 females, 30 males
247 T/R events
74 Pediatric events 173 adult events
190 events with HCT <30% 57 events with HCT 30-36%
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Results T
ab
le 1
. C
ha
racte
risti
cs o
f T
/R
SC
A p
ati
en
ts
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Results
- A moderate correlation - Lowering post-HbS lowers F/u-HbS. - However, the value of post-HbS does not predict F/u-HbS with accuracy.
Figure 1. Linear Regression Analysis
y = 1.03 x + 18.41 R² = 0.444
-5
5
15
25
35
45
55
65
0 10 20 30
F/u
-Hb
S (
%)
Post-HbS (%)
Post-HbS vs. F/u-HbS
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Figure 2. Linear Regression Analysis
_ Nearly no correlation between Post-HCT and F/u-HbS. _ Raising post-HCT does not lower F/u-HbS.
Results
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Results (Table 2, comparing F/u-HbS levels)
Post-HbS ≤10% effectively keeps F/u-HbS <30%;
Raising post-HCT to 30-36% does not lower F/u-HbS to <30%
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Results Table 3. Comparing frequency of 2 F/u-HbS levels in different post-HbS categories and post-HCT groups
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Results
Table 4. Frequency comparison of selected F/u-HbS levels in various post-HbS categories
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Results Table 5. Frequency comparison of selected F/u-HbS levels in SCA patients
Pediatric patients Adult patients
A similar trend in both Pediatric and adult SCA patients. (1) Post-HbS ≤10% keeps most of F/u-HbS <30% (2) Empirical Post-HbS 10-15% keeps only half of F/u-HbS <30% (3) Empirical Post-HbS 15-20% or above only keeps less than 10% of F/u-HbS <30% (4) Traditional Post-HbS 20-30% only keeps ≤ 85% of F/u-HbS <50%.
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Conclusions Identified a threshold
Post-HbS ≤10%
to keep most of F/u-HbS <30%
for pediatric SCA pts
Demonstrated that empirically raising post-HCT to 30-36% fails to lower F/u-HbS.
Identified an additional threshold
Post-HbS ≤20%
to keep nearly 100% of F/u-HbS <50%
for “refractory” adult SCA patients
who sometimes still have SCD crisis
when on monthly T/R
To our knowledge, this is the first evidence-based study demonstrating these results.
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Our Recommendations
Lower post-HbS to 5-10% for monthly T/R
for pediatric HgSS SCA patients
to maintain F/u-HbS < 30%
DO NOT raise post-Hct to >30-36%
It fails to suppress HbS production !!
It increases the risks of hyperviscosity and iron overload
Lower post-HbS to ≤ 20%
for refractory adult HgSS patients
to ensure F/u- HbS < 50%
A prospective randomized study
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Acknowledgement
Deepa Manwani, MD
Pediatric Hematology
Yungtai Lo, PhD, Statistician
Gurbakhash Kaur, MD
Hematology/ Oncology