Autologous stem cell-based therapy for sickle cell leg ulcer: a pilot study.

Recurrent chronic leg ulcers are among the most severe vasculopathic complications of sickle cell disease (SCD). Their treatment remains a challenge. Stem cell therapy with bone marrow mononuclear cells (BMMC) is a promising new therapeutic option for other forms of chronic ulcers. This prospective pilot study was performed to evaluate safety and feasibility of BMMC implantation in patients with SCD and chronic leg ulcers (SCLU). Ulcer closure, recurrence and local pain were evaluated. BMMC were successfully administered to 23 SCLU patients and no serious adverse events occurred. During the 6-month follow-up period, 91·3% of patients had improved ulcer pain compared with baseline and 29·2% of the treated ulcers achieved total healing. The frequency of progenitor stem cells (CD34CD45low and fibroblast colony-forming units) in BMMC was found to be significantly reduced in SCLU patients and compared to SCD patients without ulcers (P < 0·004 and P < 0·01, respectively). No relationship was observed between treatment outcome and the number of implanted BM progenitor stem cells. In conclusion, BMMC implantation is a feasible and safe procedure, showing favourable outcomes for the treatment of SCLU, and encouraging further controlled clinical trials.

Markers of severe vaso-occlusive painful episode frequency in children and adolescents with sickle cell anemia.

OBJECTIVE: To identify factors associated with frequent severe vaso-occlusive pain crises in a contemporary pediatric cohort of patients with sickle cell anemia (SCA) enrolled in a prospective study of pulmonary hypertension and the hypoxic response in sickle cell disease. STUDY DESIGN: Clinical and laboratory characteristics of children with SCA who had ≥3 severe pain crises requiring health care in the preceding year were compared with those of subjects with <3 such episodes. RESULTS: Seventy-five children (20%) reported ≥3 severe pain episodes in the preceding year, and 232 (61%) had none. Frequent pain episodes were associated with older age (OR, 1.2; 95% CI, 1.1-1.3; P < .0001), α-thalassemia trait (OR 3.5; 1.6-6.7; P = .002), higher median hemoglobin (OR 1.7; 95% CI: 1.2-2.4; P < .003), and lower lactate dehydrogenase concentration (OR 1.82; 95% CI: 1.07-3.11; P = .027). Children with high pain frequency also had an increased iron burden (serum ferritin, 480 vs 198 µg/L; P = .006) and higher median tricuspid regurgitation jet velocity (2.41 vs 2.31 m/s; P = .001). Neither hydroxyurea use nor fetal hemoglobin levels were significantly different according to severe pain history. CONCLUSIONS: In our cohort of children with SCA, increasing age was associated with higher frequency of severe pain episodes as were α-thalassemia, iron overload, higher hemoglobin and lower lactate dehydrogenase concentration, and higher tricuspid regurgitation velocity.