ACN_7.14_Full Issue digital | Page 21

Blood Advances in a Different Vein

NEWS day . This patient also had concurrent fever and cellulitis . Toxicities were reversible and tolerable , and there were no treatment-related deaths , the authors added
At 28 days after infusion , three patients ( 60 %) had achieved CR based on imaging and the remaining two patients showed evidence of stable disease . Of the patients with CR , one experienced disease progression at day 273 , one subsequently went on maintenance treatment at day 43 , and one remained in follow-up without maintenance therapy at day 520 . Four of the five initial patients were still alive at the last assessment ( the other patient was lost to follow-up ).
Researchers collected blood specimens during the 28-day post-infusion period from four of the five patients . Analysis revealed CAR T-cell expansion by flow cytometry as well as quantitative polymerase chain reaction . The investigators also noted a lack of CD19-positive B cells or systemic lymphoma .
An image series for a patient in CR showed a lesion prior to CAR T-cell infusion that was absent at 28 days following infusion . The investigators added that patients in CR also showed small lesions at baseline and hinted to the possibility “ that disease burden played a role in response to intravenous CD19-directed CAR T-cell therapy in the context of PCNSL .”
Cerebrospinal fluid ( CSF ) from one patient showed presence of CAR T cells and demonstrated that the intravenously administered therapy “ could traffic to the CSF despite the absence of systemic lymphoma ,” according to the researchers .
Limitations of this study included its small sample size and lack of a comparator or control arm . Additionally , the researchers explained that the study “ was originally designed for patients with systemic disease and thus , several aspects of the trial were not ideal for patients with PCNSL .” Despite these limitations , the investigators added that the data from this preliminary cohort suggest intravenously administered CD19-directed CAR T-cell therapy holds promise for the PCNSL patient population .
Study authors report no relevant conflicts of interest .
Reference Siddiqi T , Wang X , Blanchard MS , et al . CD19-directed CAR T-cell therapy for treatment of primary CNS lymphoma . Blood Adv . 2021 ; 5 ( 20 ): 4059-4063 .

Long-Term Hydroxyurea May Improve Cardiac Abnormalities in Young Patients With Sickle Cell Disease

Long-term hydroxyurea therapy in children with sickle cell disease ( SCD ) may reverse cardiac remodeling , according to new research findings . Lead study author Arushi Dhar , MD , of Northwell Health in New Hyde Park , New York , said that these findings emphasize “ the need for close cardiac monitoring of children with sickle cell anemia , including asymptomatic patients .” The findings from the study were published in Blood Advances .
Hydroxyurea is a U . S . Food and Drug Administration – approved disease-modifying treatment for SCD that has been employed for disease management for the past few decades . “ We hope to highlight the importance of timely initiation of treatment with hydroxyurea per the 2014 National Heart , Lung , and Blood Institute guidelines ,” said Dr . Dhar , “ which dictate that hydroxyurea should be offered to all children with sickle cell anemia starting at 9 months of age , regardless of disease severity .”
Despite the utility of hydroxyurea , there is currently a lack of robust long-term assessments of echocardiographic abnormalities in hydroxyurea-treated pediatric patients and young adults with SCD .
To close this research gap , Dr . Dhar and colleagues retrospectively evaluated the prevalence of echocardiographic abnormalities among 100 children and young adults with SCD who underwent routine cardiac screening at a single children ’ s medical center between 2010 and 2017 . Of this cohort , 60 patients had received hydroxyurea .
In the overall population , the mean age was 12 ± 4.9 years but ranged from 3 to 22 years . Approximately 58 % of the cohort was male . At baseline , half of all patients had dilated left ventricle ( LV ), defined as an LV end-diastolic ( LVEDd ) and / or LV enddiastolic volume ( LVEDv ) z-score of 2 or higher .
No difference was observed between patients who received or did not receive hydroxyurea in regard to LV size , LV mass , and tricuspid valve regurgitation velocity .
The researchers performed 169 serial echocardiograms in the 60 patients treated with hydroxyurea .
The mean duration of treatment at the last recorded visit was 630 ± 285 days . To determine whether the duration of hydroxyurea affected outcomes , Dr . Dhar and colleagues analyzed echocardiogram findings from the 25 patients ( 41.7 %) who were treated with hydroxyurea for less than one year and the 35 patients ( 58.3 %) who were treated for at least one year . Those who received hydroxyurea for less than one year had a significantly higher prevalence of LV dilation compared with patients who had received treatment for one year or more ( mean LVEDd z-score = 2.24 ± 1.3 vs . 1.57 ± 1.1 , respectively , p = 0.04 ; mean LVEDv z-score = 2.62 ± 1.5 vs . 1.72 ± 1.2 , p = 0.02 ; see TABLE ).

“ [ These findings emphasize ] the need for close cardiac monitoring of children with sickle cell anemia , including asymptomatic patients .”

Overall , treatment with hydroxyurea was associated with significant improvements in LV dilation and hypertrophy . The researchers also found that there was a negative correlation between duration of treatment with hydroxyurea and LV volume and mass .
While the study was limited by its “ inability to discern if poor patient medication adherence contributed to the lack of significant difference found
TABLE . Outcomes in Patients Treated With Hydroxyurea for < 1 Year Versus > 1 Year
Hydroxyurea < 1 Year
Hydroxyurea > 1 Year
p Value
Age , years
12 ± 4.2
13 ± 3.7
0.42
Hb , g / dL
9.23 ± 3.50
9.54 ± 2.90
0.36
MCV , fL
87.30 ± 10.80
95.50 ± 11.80
0.09
Platelet count , K / μL
365 ± 122
368 ± 144
0.92
HbF (%)
7.80 ± 6.20
11 ± 9.40
0.03
LVEDd z-score
2.24 ± 1.30
1.57 ± 1.10
0.04
LVESd z-score
1.28 ± 1.34
0.96 ± 0.95
0.28
LV volume z-score
2.62 ± 1.50
1.72 ± 1.20
0.02
LV mass z-score
1.09 ± 1.60
0.96 ± 1.40
0.24
TR , m / s
2.30 ± 0.20
2.40 ± 0.30
0.53
Hb = hemoglobin ; MCV = mean corpuscular volume ; LV = left ventricular ; LVEDd = LV end-diastolic ; LVES = LV end-systolic ; TR = tricuspid valve regurgitation velocity
— Arushi Dhar , MD
ASHClinicalNews . org ASH Clinical News
19