We evaluated the safety and efficacy of high-dose, posttransplantation cyclophosphamide (Cy) to prevent graft rejection and graft-versus-host disease (GVHD) after outpatient nonmyeloablative conditioning and T cell-replete bone marrow transplantation from partially HLA-mismatched (haploidentical) related donors. Patients with advanced hematologic malignancies (n = 67) or paroxysmal nocturnal hemoglobinuria (n = 1) received Cy 50 mg/kg i.v. on day 3 (n = 28) or on days 3 and 4 (n = 40) after transplantation. The median times to neutrophil (>500/microL) and platelet recovery (>20,000/microL) were 15 and 24 days, respectively. Graft failure occurred in 9 of 66 (13%) evaluable patients, and was fatal in 1. The cumulative incidences of grades II-IV and grades III-IV acute (aGVHD) by day 200 were 34% and 6%, respectively. There was a trend toward a lower risk of extensive chronic GVHD (cGVHD) among recipients of 2 versus 1 dose of posttransplantation Cy (P = .05), the only difference between these groups. The cumulative incidences of nonrelapse mortality (NRM) and relapse at 1 year were 15% and 51%, respectively. Actuarial overall survival (OS) and event-free survival (EFS) at 2 years after transplantation were 36% and 26%, respectively. Patients with lymphoid malignancies had an improved EFS compared to those with myelogenous malignancies (P = .02). Nonmyeloablative HLA-haploidentical BMT with posttransplantation Cy is associated with acceptable rates of fatal graft failure and severe aGVHD or cGVHD.

The majority of diabetic foot ulcers have an underlying osteomyelitis that is clinically unsuspected. Leukocyte scans are highly sensitive for diagnosing osteomyelitis in diabetic foot ulcers and may be useful for monitoring the efficacy of antibiotic treatment. We recommend that diabetic patients with foot ulcers that expose bone should be treated for osteomyelitis. Diabetic patients with foot ulcers that do not expose bone should undergo leukocyte scanning, which eliminates the risk of bone biopsy in diagnosing osteomyelitis and allows for the diagnosis and treatment of this well-known but often silent precursor of lower extremity amputation.

No abstract

SUMMARY This phase I/II study was conducted to determine the maximum tolerated dose, toxicity, and efficacy of clofarabine in combination with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming (GCLAC), in the treatment of patients with relapsed or refractory acute myeloid leukaemia (AML). Dose escalation of clofarabine occurred without dose-limiting toxicity, so most patients were treated at the maximum dose, 25 mg/m2/day with cytarabine 2 g/m2/day, each for 5 days, and G-CSF 5 μg/kg, beginning the day before chemotherapy and continuing daily until neutrophil recovery. The complete remission (CR) rate among the 46 evaluable patients was 46% (95% confidence interval [CI] 31–61%) and the CR + CR but with a platelet count <100 x 109/l rate was 61% (95% CI 45–75%). Multivariate analysis showed that responses to GCLAC were independent of age, cytogenetic risk category, and number of prior salvage regimens. GCLAC is highly active in relapsed and refractory AML and warrants prospective comparison to other regimens, as well as study in untreated patients.

In situ saphenous vein bypass presents unique problems in wound management. A retrospective analysis of wound complications occurring after in situ bypass was undertaken in 93 patients who had 98 operations. For purposes of statistical analysis, only the first procedure was considered in patients having bilateral bypass. Fifty-nine percent of patients were male; the average age was 69 years. Medical risk factors surveyed included diabetes (64%), hypertension (52%), and smoking (53%). Ninety-one percent of the procedures were done for limb salvage; the mean ankle-brachial index was 0.43. Sixty percent of bypasses were infrapopliteal, and the mean duration of surgery was 4.6 hours. Continuous incision was used to expose the vein in 59% of cases. Skin closure was effected with staples in 44% and with sutures or both in the remainder. The mean postoperative hospital stay was 27 days. Wound problems developed in 31 cases, 11 of which were major. The thigh was the most common location. There was a significant association between continuous incision and anterior tibial bypass and wound complications. Anterior tibial bypass and staple closure were found to be independent predictors of wound problems with the use of stepwise logistic regression. Postoperative hospital stay was significantly prolonged; two bypasses failed and three lower extremities were amputated because of incisional complications. A discussion of the technical aspects of wound management is presented.