Single-stage treatment of infected tibial non-unions and osteomyelitis with bone marrow granulocytes precursors protecting bone graft.

PURPOSE: Infected non-unions present a clinical challenge, especially with risk of recurrent infection. Bone marrow contains granulocyte precursors identified in vitro as colony forming units-granulocyte macrophage (CFU-GM) have a prophylactic action against infection. We therefore tested the hypothesis that bone marrow concentrated granulocytes precursors added to a standard bone graft could decrease the risk of recurrence of infection when single-stage treatment of infected tibial non-unions is performed with bone graft. METHODS: During a single-stage procedure 40 patients with infected tibial non-union received a spongious bone graft supercharged with granulocytes precursors after debridement (study group). A control group (40 patients) was treated in a single stage with local debridement and standard bone graft obtained from the iliac crest. The antibiotic therapy protocol was the same (60 days) in the two groups. CFU-GM progenitors were harvested from bone marrow aspirated on the opposite iliac crest of the site where the cancellous bone was obtained. Union (radiographs and CT scan), a recurrence of clinical infection, and need for subsequent surgery were evaluated. RESULTS: Thirty-eight (95%) patients who received graft supercharged with granulocytes precursors achieved successful union without recurrence of infection during the seven-year follow-up versus 28 (70%) control patients; for the control group the mean graft resorption volume was 40%, while no bone graft resorption was found for the study group. CONCLUSION: Supercharging the cancellous bone graft with bone marrow granulocytes precursors protect the site of infected non-union from recurrence of infection and bone resorption of the graft.

Local transplantation of bone marrow concentrated granulocytes precursors can cure without antibiotics infected nonunion of polytraumatic patients in absence of bone defect.

PURPOSE: Infected, long bone non-unions present a significant clinical challenge. New and alternative therapies are needed to address this problem. The purposes of this study were to compare the number of circulating granulocyte-macrophage colony-forming units (CFU-GM) in the peripheral blood of polytraumatic patients with infected tibial non-unions and in the peripheral blood of control patients with the hypothesis that their number was decreased in polytraumatic patients; and to treat their infection without antibiotics and with local transplantation of bone marrow concentrated granulocytes precursors. METHODS: Thirty (18 atrophic and 12 hyperthrophic ) infected tibial non-unions (without bone defect) that occurred after open fractures in polytraumatic patients were treated without antibiotics and with percutaneous injection of autologous bone marrow concentrate (BMC) containing granulocytes precursors (CFU-GM). CFU-GM progenitors were assessed in the bone marrow aspirate, peripheral blood, and fracture site of these patients. The number of these progenitors was compared with the CFU-GM progenitors of control patient samples (healthy donors matched for age and gender). Outcome measures were: timing of union, callus formation (radiographs and CT scan), and recurrence of clinical infection. RESULTS: As compared to control patients, the number of CFU GM derived colonies was lower at peripheral blood in patients with infected nonunions. The bone marrow graft injected in nonunions contained after concentration 42 621 ± 20 350 CFU-GM-derived colonies/cc. Healing and cure of infection was observed at six months for 25 patients and at one year follow up for 30 patients. At the median ten year follow-up (range: 5 to 15), only one patient had clinical recurrent infection after healing (between 6 months and last follow-up). CONCLUSION: The peripheral blood of these polytraumatic patients with infected nonunions had a remarkable decrease in CFU-GM-derived colonies as compared with normal controls. Local transplantation of concentrated CFU-GM-derived colonies aspirated from bone marrow allowed cure of infection and healing without antibiotics.

Factors affecting neutrophil recovery after autologous bone marrow-derived stem cell transplantation in patients with acute myeloid leukemia.

Bone marrow is currently regarded as the most appropriate source of stem cells for patients with acute myeloid leukemia (AML) undergoing autologous transplants. A total of 55 adult patients with AML in first complete remission receiving autologous bone marrow-derived stem cell (BMSC) transplantation (BMSCT) were analyzed to determine factors affecting the rate of neutrophil recovery. All patients were treated with standard induction and three to four courses of consolidation chemotherapy and, after collection of BMSC, conditioned with BuCy2. The median time to neutrophil reconstitution was 30 (10-62) days and was delayed in 24 patients. Neutrophil recovery was faster in patients who had received granulocyte-macrophage progenitors (CFU-GM) dose >23.5 x 10(4)/kg, CD34(+) cells >3.2 x 10(6)/kg, and mononuclear cells (MNCs) >3 x 10(8)/kg. The speed of neutrophil recovery correlated with the number of transplanted CFU-GM progenitors (P = .0077) and MNCs (P = .0015). CFU-GM progenitors dose was the only factor close to significance in univariate analysis of neutrophil engraftment. Probability for neutrophil recovery was higher in patients transplanted with a higher dose of MNCs. These data suggested that the content of CFU-GM progenitors and MNCs within the bone marrow graft was the most important factor for the quality of neutrophil recovery after autologous BMSCT in AML patients.