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Ding Wen Wu, Rachel Friedmann, Joan Uehlinger, Sadiqa Karim, Etan Marks, Angie Bonzon-Adelson, Kala Mohandas, Evan Himchak, Ronald Walsh
May 5, 2017
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
Background RCE Targets for SCA Patients
Clinical improvement
Post-HCT
≤ 30% traditionally
FCR
FCR = post-HbS/ pre-HbS
Post-HbS ≤ 30% traditionally
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.
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???
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
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?
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
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
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%
Results T
ab
le 1
. C
ha
racte
risti
cs o
f T
/R
SC
A p
ati
en
ts
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
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
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%
Results Table 3. Comparing frequency of 2 F/u-HbS levels in different post-HbS categories and post-HCT groups
Results
Table 4. Frequency comparison of selected F/u-HbS levels in various post-HbS categories
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%.
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.
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
Acknowledgement
Deepa Manwani, MD
Pediatric Hematology
Yungtai Lo, PhD, Statistician
Gurbakhash Kaur, MD
Hematology/ Oncology
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