In Utero Hematopoietic Stem Cell Transplantation for Alpha-thalassemia Major (ATM)

Summary

The investigators aims to evaluate the safety of in utero hematopoietic stem cell transplantation in fetuses with alpha-thalassemia major performed at the time of in utero transfusion of red blood cells.

Timeline

Start

2017-10-05

Primary completion

2024-04-30

Completion

2024-12-31

Outcome

Outcome not reported

Stopped (Enrollment): “Enrollment ended early due to interim data suggesting a lack of efficacy. Interim data did demonstrate that IUHSCT was safe and well tolerated, but the PI and DSMB agreed that enrollment should not continue under the current treatment protocol.”

Publications

• Background Derderian SC, Jeanty C, Walters MC, Vichinsky E, MacKenzie TC. In utero hematopoietic cell transplantation for hemoglobinopathies. Front Pharmacol. 2015 Jan 12;5:278. doi: 10.3389/fphar.2014.00278. eCollection 2014.
• Background Vichinsky E. Advances in the treatment of alpha-thalassemia. Blood Rev. 2012 Apr;26 Suppl 1:S31-4. doi: 10.1016/S0268-960X(12)70010-3.
• Background MacKenzie TC. Fetal Surgical conditions and the unraveling of maternal-fetal tolerance. J Pediatr Surg. 2016 Feb;51(2):197-9. doi: 10.1016/j.jpedsurg.2015.10.059. Epub 2015 Nov 4.
• Background MacKenzie TC, David AL, Flake AW, Almeida-Porada G. Consensus statement from the first international conference for in utero stem cell transplantation and gene therapy. Front Pharmacol. 2015 Feb 10;6:15. doi: 10.3389/fphar.2015.00015. eCollection 2015. No abstract available.
• Background Jeanty C, Derderian SC, Mackenzie TC. Maternal-fetal cellular trafficking: clinical implications and consequences. Curr Opin Pediatr. 2014 Jun;26(3):377-82. doi: 10.1097/MOP.0000000000000087.
• Background Nijagal A, MacKenzie TC. Clinical implications of maternal-fetal cellular trafficking. Semin Pediatr Surg. 2013 Feb;22(1):62-5. doi: 10.1053/j.sempedsurg.2012.10.011.
• Background Nijagal A, Flake AW, MacKenzie TC. In utero hematopoietic cell transplantation for the treatment of congenital anomalies. Clin Perinatol. 2012 Jun;39(2):301-10. doi: 10.1016/j.clp.2012.04.004. Epub 2012 May 8.
• Background Nijagal A, Wegorzewska M, Le T, Tang Q, Mackenzie TC. The maternal immune response inhibits the success of in utero hematopoietic cell transplantation. Chimerism. 2011 Apr;2(2):55-7. doi: 10.4161/chim.2.2.16287.
• Results Kreger EM, Singer ST, Witt RG, Sweeters N, Lianoglou B, Lal A, Mackenzie TC, Vichinsky E. Favorable outcomes after in utero transfusion in fetuses with alpha thalassemia major: a case series and review of the literature. Prenat Diagn. 2016 Dec;36(13):1242-1249. doi: 10.1002/pd.4966. Epub 2016 Dec 7.
• MacKenzie TC, Lianoglou BR, Gonzalez J MD, Dvorak CC, Kharbanda S, Herzeg A, Canepa E, Kreger EM, Frascoli M, Sper R, Gupta A, Leung J, Tang Q, Sinha R, Worthington AK, Gano D, Coco Bakkour S, Chafets D, Keller RL, Shimotake J, Lal A, Glenn OA, Moon-Grady A, Vichinsky EP. In Utero Hematopoietic Cell Transplantation in Fetuses with Alpha Thalassemia Major: A Phase 1 Clinical Trial. Blood Adv. 2026 Apr 15:bloodadvances.2026019655. doi: 10.1182/bloodadvances.2026019655. Online ahead of print.
• Borges B, Canepa E, Chang IJ, Herzeg A, Lianoglou B, Kishnani PS, Harmatz P, MacKenzie TC, Cohen JL. Prenatal Delivery of Enzyme Replacement Therapy to Fetuses Affected by Early-Onset Lysosomal Storage Diseases. Am J Med Genet C Semin Med Genet. 2025 Sep;199(3):203-217. doi: 10.1002/ajmg.c.32132. Epub 2025 Jan 31.

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