Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans.
BACKGROUND
The short-term clinical benefits of bone marrow mononuclear cell transplantation have been shown in patients with critical limb ischemia. The purpose of this study was to assess the long-term safety and efficacy of bone marrow mononuclear cell transplantation in patients with thromboangiitis obliterans.


RESULTS
Eleven limbs (3 with rest pain and 8 with an ischemic ulcer) of 8 patients were treated by bone marrow mononuclear cell transplantation. The patients were followed up for clinical events for a mean of 684+/-549 days (range 103 to 1466 days). At 4 weeks, improvement in pain was observed in all 11 limbs, with complete relief in 4 (36%). Pain scale (visual analog scale) score decreased from 5.1+/-0.7 to 1.5+/-1.3. An improvement in skin ulcers was observed in all 8 limbs with an ischemic ulcer, with complete healing in 7 (88%). During the follow-up, however, clinical events occurred in 4 of the 8 patients. The first patient suffered sudden death at 20 months after transplantation at 30 years of age. The second patient with an incomplete healing of a skin ulcer showed worsening of the lesion at 4 months. The third patient showed worsening of rest pain at 8 months. The last patient developed an arteriovenous shunt in the foot at 7 months, which spontaneously regressed by 1 year.


CONCLUSIONS
In the present unblinded and uncontrolled pilot study, long-term adverse events, including death and unfavorable angiogenesis, were observed in half of the patients receiving bone marrow mononuclear cell transplantation. Given the current incomplete knowledge of the safety and efficacy of this strategy, careful long-term monitoring is required for future patients receiving this treatment.
Miyamoto
Koji
K
Department of Medicine, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
Nishigami
Kazuhiro
K
Nagaya
Noritoshi
N
Akutsu
Koichi
K
Chiku
Masaaki
M
Kamei
Masataka
M
Soma
Toshihiro
T
Miyata
Shigeki
S
Higashi
Masahiro
M
Tanaka
Ryoichi
R
Nakatani
Takeshi
T
Nonogi
Hiroshi
H
Takeshita
Satoshi
S
D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D010865:Pilot Projects; D013919:Thromboangiitis Obliterans / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D014182:Transplantation, Autologous