Autologous bone marrow mononuclear cell therapy for critical limb ischemia is effective and durable

Tiffany W. Liang, Andrea Jester, Raghu Motaganahalli, Michael G. Wilson, Patricia G'Sell, George A. Akingba, Andres Fajardo, Michael Murphy

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objective: We have previously shown that autologous bone marrow mononuclear cell (ABMNC) therapy improves measures of limb perfusion, rest pain, wound healing, and amputation-free survival (AFS) at 1 year in patients with critical limb ischemia (CLI). Long-term durability of ABMNC therapy for CLI remains unknown. The objective of the current study was to evaluate long-term clinical outcomes 5 years after treatment. Methods: Data were retrospectively gathered from a database and via a patient survey and review of medical records of patients previously enrolled in this phase I/II trial. AFS, freedom from major amputation, and freedom from major adverse limb events (MALE) were calculated using the product-limit estimate. The incidence of cardiac, malignant, and other medical events relevant to the safety of cell therapy were tabulated during the time from treatment to follow-up. Results: Twenty-one of the 24 patients (88%) who completed the initial 1-year phase I/II trial were available for the 5-year analysis; AFS was 74% (95% confidence interval [CI], 0.53-0.87), freedom from major amputation was 78% (95% CI, 0.58-0.90), and freedom from MALE was 65% (95% CI, 0.45-0.80). Three patients (14%) had major cardiac events. There were no incidences of malignancies or diagnoses of clinically significant proliferative retinopathy. Fifteen patients (71%) report continued improvement in pain-free walking. Nineteen (90%) patients believed that the study was of significant medical value and would participate again. Conclusions: ABMNC therapy provides long-term freedom from AFS, major amputation, and MALE that are comparable with other reports of patients who underwent surgical and endovascular interventions for CLI. Furthermore, no patients developed tumorigenesis or clinically significant retinopathy. Because of the limited number of patients studied, our findings will need to be followed up in a larger phase III trial.

Original languageEnglish (US)
JournalJournal of Vascular Surgery
DOIs
StateAccepted/In press - Oct 8 2015

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Cell- and Tissue-Based Therapy
Bone Marrow Cells
Ischemia
Extremities
Amputation
Survival
Confidence Intervals
Incidence
Wound Healing
Walking
Medical Records
Carcinogenesis
Perfusion
Databases
Safety
Pain
Therapeutics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Autologous bone marrow mononuclear cell therapy for critical limb ischemia is effective and durable. / Liang, Tiffany W.; Jester, Andrea; Motaganahalli, Raghu; Wilson, Michael G.; G'Sell, Patricia; Akingba, George A.; Fajardo, Andres; Murphy, Michael.

In: Journal of Vascular Surgery, 08.10.2015.

Research output: Contribution to journalArticle

Liang, Tiffany W. ; Jester, Andrea ; Motaganahalli, Raghu ; Wilson, Michael G. ; G'Sell, Patricia ; Akingba, George A. ; Fajardo, Andres ; Murphy, Michael. / Autologous bone marrow mononuclear cell therapy for critical limb ischemia is effective and durable. In: Journal of Vascular Surgery. 2015.
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abstract = "Objective: We have previously shown that autologous bone marrow mononuclear cell (ABMNC) therapy improves measures of limb perfusion, rest pain, wound healing, and amputation-free survival (AFS) at 1 year in patients with critical limb ischemia (CLI). Long-term durability of ABMNC therapy for CLI remains unknown. The objective of the current study was to evaluate long-term clinical outcomes 5 years after treatment. Methods: Data were retrospectively gathered from a database and via a patient survey and review of medical records of patients previously enrolled in this phase I/II trial. AFS, freedom from major amputation, and freedom from major adverse limb events (MALE) were calculated using the product-limit estimate. The incidence of cardiac, malignant, and other medical events relevant to the safety of cell therapy were tabulated during the time from treatment to follow-up. Results: Twenty-one of the 24 patients (88{\%}) who completed the initial 1-year phase I/II trial were available for the 5-year analysis; AFS was 74{\%} (95{\%} confidence interval [CI], 0.53-0.87), freedom from major amputation was 78{\%} (95{\%} CI, 0.58-0.90), and freedom from MALE was 65{\%} (95{\%} CI, 0.45-0.80). Three patients (14{\%}) had major cardiac events. There were no incidences of malignancies or diagnoses of clinically significant proliferative retinopathy. Fifteen patients (71{\%}) report continued improvement in pain-free walking. Nineteen (90{\%}) patients believed that the study was of significant medical value and would participate again. Conclusions: ABMNC therapy provides long-term freedom from AFS, major amputation, and MALE that are comparable with other reports of patients who underwent surgical and endovascular interventions for CLI. Furthermore, no patients developed tumorigenesis or clinically significant retinopathy. Because of the limited number of patients studied, our findings will need to be followed up in a larger phase III trial.",
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