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.

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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.

Leukocyte scanning is superior to MRI in detecting clinically unsuspected osteomyelitis in diabetic foot ulcers.

Reports of reconstructive surgery for peripheral vascular disease have been relatively uncommon in patients with end-stage renal disease. Between 1980 and 1989, 39 patients with end-stage renal disease underwent revascularization of 56 limbs. Fifty-two primary infrainguinal and four secondary infrainguinal bypass grafts were performed. In addition, nine thrombectomies were performed. At the time of surgery 37 patients were on dialysis; three had functioning kidney transplants. The indications for revascularization were gangrene, rest pain, or ulceration in all except three limbs with disabling claudication. Reversed, nonreversed, or in situ vein was used in 25 of the 52 primary infrainguinal revascularizations performed. Polytetrafluoroethylene was used in 25. Two procedures used a combination of polytetrafluoroethylene and vein. The primary patencies for all infrainguinal procedures at 1 and 2 years were 77% and 68%, respectively. Four perioperative deaths occurred in the infrainguinal group (7.7%). An additional death occurred after thrombectomy for late graft closure. Three deaths were a result of myocardial infarction. One patient on peritoneal dialysis developed uncontrolled sepsis. At 3 years 39% of patients were alive, and 84% of the limbs were salvaged. Among the cases studied no group was identified that represented unacceptable operative risk. Results compared well with reported patencies for patients subjected to infrainguinal revascularization procedures. Limb revascularization in patients with end-stage renal disease may be performed by use of similar criteria to those used for other patients with peripheral vascular disease.

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