Prospective, Single Center Randomized Control Trial to Evaluate the Safety and Feasibility of a Novel Allogenic Mesenchymal Precursor Cell Therapy in Patients with Hypoplastic Left Heart Syndrome
Presented During:
Saturday, May 6, 2023: 8:00AM - 8:15AM
Los Angeles Convention Center
Posted Room Name:
403B
Abstract No:
00LB4
Submission Type:
Late-Breaking Clinical Trial Abstract
Authors:
Rachel Wittenberg (1), Kimberlee Gauvreau (2), Jonah Leighton (2), Kenneth Borow (3), Gerald Marx (2), Sitaram Emani (2)
Institutions:
(1) Harvard Medical School, Boston, MA, (2) Boston Children's Hospital, Boston, MA, (3) Borow Consulting Group, LLC, Bryn Mawr, PA
Submitting Author:
Rachel Wittenberg
-
Contact Me
Harvard Medical School
Harvard Medical School
Co-Author(s):
Kimberlee Gauvreau
-
Contact Me
Boston Children's Hospital
Boston Children's Hospital
Jonah Leighton
-
Contact Me
Boston Children's Hospital
Boston Children's Hospital
Kenneth Borow
-
Contact Me
Borow Consulting Group, LLC
Borow Consulting Group, LLC
Gerald Marx
-
Contact Me
Boston Children's Hospital
Boston Children's Hospital
*Sitaram Emani
-
Contact Me
Boston Children's Hospital
Boston Children's Hospital
Presenting Author:
Rachel Wittenberg
-
Contact Me
N/A
N/A
Abstract:
Objective: To assess the safety and feasibility of low dose novel allogenic mesenchymal precursor cell (MPC) therapy as an adjunct to left ventricular (LV) recruitment for patients with hypoplastic left heart syndrome (HLHS) with borderline LV. In patients undergoing LV recruitment, MPC injections into the hypoplastic LV may stimulate local tissue neovascularization and LV remodeling, improving the likelihood of achieving biventricular (BiV) or 1.5 ventricle (1.5V) circulation.
Methods: Children <5 years with prior single ventricle palliation undergoing bidirectional Glenn and LV recruitment surgery (mitral valve repair, restriction) were randomized to ~20 million MPCs in ~11 injections in the LV endocardium/papillary muscles (MPC group) or standard-of-care (controls). Primary endpoint of safety was assessed at 12 months with pre-specified follow-up through 24 months for primary serious adverse events (SAEs), other adverse events (AEs), and anti-HLA panel reactive antibodies (PRA). Secondary endpoints included assessments of LV function by echocardiogram, cardiac MRI, and catheterization. Probability of BiV/1.5V conversion was estimated using Kaplan-Meier curves.
Results: 19 subjects were enrolled (15 HLHS, 4 unbalanced atrioventricular canal). Median age at LV recruitment surgery was 1.0 years (range 0.3, 3.4). 9 subjects were randomized to the MPC and 10 to the control group. 1 was lost to follow-up. There were 2 SAEs: 1 bradycardic arrest (day 8) and 1 mortality (21 months), both deemed unrelated to the trial. No cardiac tumors, intracardial hematomas or perioperative ventricular arrhythmias were detected. Median AEs per year was 1.6 for MPCs and 1.1 for controls (p=0.44). At baseline, 11/18 (61%) of patients had PRA>10% and 9/18 (50%) had PRA>90% with no difference in PRA% between groups at 12 months (Fig. 1A). In the full cohort, probability of BiV/1.5V conversion was 0.16 (95% CI: 0.05, 0.41) at 12 months and 0.54 (0.31, 0.79) at 24 months (Fig. 1B). At 12 months, LV mass, LVEDV, and LVEF on MRI were similar between the groups.
Conclusions: In a highly sensitized patient cohort undergoing LV recruitment, adjunct treatment with MPCs was safe and feasible. Over 50% underwent BiV/1.5V conversion within 2 years. Larger trials powered to detect efficacy are needed to further investigate the promising therapeutic potential of MPCs in this population. These may include dose escalation or assessment of the impact of baseline allosensitization on MPC effectiveness.
Methods: Children <5 years with prior single ventricle palliation undergoing bidirectional Glenn and LV recruitment surgery (mitral valve repair, restriction) were randomized to ~20 million MPCs in ~11 injections in the LV endocardium/papillary muscles (MPC group) or standard-of-care (controls). Primary endpoint of safety was assessed at 12 months with pre-specified follow-up through 24 months for primary serious adverse events (SAEs), other adverse events (AEs), and anti-HLA panel reactive antibodies (PRA). Secondary endpoints included assessments of LV function by echocardiogram, cardiac MRI, and catheterization. Probability of BiV/1.5V conversion was estimated using Kaplan-Meier curves.
Results: 19 subjects were enrolled (15 HLHS, 4 unbalanced atrioventricular canal). Median age at LV recruitment surgery was 1.0 years (range 0.3, 3.4). 9 subjects were randomized to the MPC and 10 to the control group. 1 was lost to follow-up. There were 2 SAEs: 1 bradycardic arrest (day 8) and 1 mortality (21 months), both deemed unrelated to the trial. No cardiac tumors, intracardial hematomas or perioperative ventricular arrhythmias were detected. Median AEs per year was 1.6 for MPCs and 1.1 for controls (p=0.44). At baseline, 11/18 (61%) of patients had PRA>10% and 9/18 (50%) had PRA>90% with no difference in PRA% between groups at 12 months (Fig. 1A). In the full cohort, probability of BiV/1.5V conversion was 0.16 (95% CI: 0.05, 0.41) at 12 months and 0.54 (0.31, 0.79) at 24 months (Fig. 1B). At 12 months, LV mass, LVEDV, and LVEF on MRI were similar between the groups.
Conclusions: In a highly sensitized patient cohort undergoing LV recruitment, adjunct treatment with MPCs was safe and feasible. Over 50% underwent BiV/1.5V conversion within 2 years. Larger trials powered to detect efficacy are needed to further investigate the promising therapeutic potential of MPCs in this population. These may include dose escalation or assessment of the impact of baseline allosensitization on MPC effectiveness.
Category:
Congenital
Image or Table
