Single-Agent High-Dose Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Human Leukocyte Antigen-Matched Reduced-Intensity Peripheral Blood Stem Cell Transplantation Results in an Unacceptably High Rate of Severe Acute Graft-versus-Host Disease.

High-dose cyclophosphamide given early after allogeneic hemopoietic cell transplantation has been shown to be effective prophylaxis against graft-versus-host disease (GVHD) in the setting of HLA-matched myeloablative bone marrow grafts, allowing avoidance of long-term immunosuppression with calcineurin inhibitors in some patients. Whether this approach is feasible using granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell grafts is unknown. We conducted an exploratory phase 2 trial of cyclophosphamide given at 50 mg/kg i.v. on days 3 and 4 after transplantation as sole GVHD prophylaxis in recipients of G-CSF-mobilized peripheral blood stem cell grafts from HLA-matched related or unrelated donors after reduced-intensity conditioning therapy with fludarabine, carmustine, and melphalan. Five patients, ages 52 to 67 years, with high-risk hematologic malignancies were enrolled. Four of the 5 developed severe acute GVHD of grades 3 to 4, requiring treatment with methylprednisolone and cyclosporine; 3 were steroid refractory and were given salvage therapy. One of these 4 patients died of hepatic GVHD, one died of sepsis, and 2 survived. We conclude that post-transplantation cyclophosphamide is inadequate as sole GVHD prophylaxis in the context of peripheral blood reduced-intensity conditioning transplantations from HLA-matched donors. This trial is registered at ACTRN12613001154796.

Outpatient rituximab, ifosfamide, etoposide (R-IE) in patients older than 60 years with relapsed or refractory diffuse large B-cell lymphoma who are not candidates for stem cell transplantation.

Patients with relapsed-refractory diffuse large B-cell lymphoma (RR-DLBCL) ineligible for autologous stem cell transplantation (autoSCT) have poor survival. Thirty transplant-ineligible patients older than 60 years were administered rituximab 375 mg/m2 day 1, ifosfamide 1333 mg/m2 days 1 to 3, and etoposide 80 mg/m2 days 1 to 3 (R-IE) every 21 days for 6 cycles plus 2 doses of rituximab. Revised international prognostic index 3-4 was seen in 53% and prior rituximab exposure in 60%. The complete and overall response rates were 55% and 76%, respectively. Median progression free survival (PFS) and overall survival were 23 and 24 months, respectively. Patients relapsing within 12 months of prior treatment had a median PFS of 2.5 months compared to 23 months for those relapsing beyond 12 months. Grade 3-4 thrombocytopenia and neutropenia occurred in one and eight patients, respectively. R-IE is an effective, well tolerated regimen in RR-DLBCL patients not fit for autoSCT.

Foot problems in Maori with diabetes.

AIM: The prevalence of diabetes and its associated manifestations is higher in New Zealand Maori than New Zealand Europeans. There is no current evidence regarding podiatric clinical characteristics of Maori with diabetes. The aim of this study was to determine the clinical and foot characteristics of Maori with diabetes using a podiatry-specific assessment tool. METHOD: This study used a cross-sectional design. Participants with diabetes were recruited from two Maori Primary Health Organisations. Podiatric-specific characteristics (vascular, neurological and musculoskeletal) were recorded. Patient demographics and general medical conditions were also recorded. RESULTS: Fifty-three participants were recruited and displayed risk factors for diabetes-related complications (mean disease duration 12 years, mean HbA1c 8.3%) including 49% of participants with hypertension. Podiatric-specific characteristics revealed unremarkable neurovascular results. However, many participants presented with pre-ulcerative lesions and current pedal ulceration (53% and 8% respectively). Although many participants had good foot-care knowledge (>85%), a modified classification tool of foot risk status determined that a high percentage of participants required regular podiatric management and screening (60%). CONCLUSION: Despite this population living with a chronic condition for more than 10 years and displaying poor long-term glycaemic control, there was no evidence of microvascular or macrovascular complications in the lower limb. However, there was a high prevalence of pre-ulcerative lesions which unmonitored and undetected may predispose the foot to ulceration. The detection of current ulceration in this study alongside other risk factors for diabetes-related complications necessitates the need for appropriate podiatric screening and podiatry management.