Summary:Veno-occlusive disease of the liver (VOD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). To determine the incidence of, and the risk factors for the development of VOD, we performed a retrospective analysis of a series of 178 patients, who underwent allogeneic HSCT at our institution between 1990 and 1999. Busulfan and cyclophosphamide constituted the conditioning regimen most frequently administered. Bone marrow was the source of stem cells in 129 patients (73%), and peripheral blood (PBSC) in 49 patients (27%). Thirty-one patients of the PBSC group received CD34 + positively selected grafts. Most patients were given cyclosporin A and methotrexate (MTX) as graft-versus-host disease (GVHD) prophylaxis. Overall, 30 patients (17%) developed VOD. In univariate analyses, the incidence of VOD was significantly higher in recipients of unmanipulated grafts (20% vs 0%; P = 0.01), in patients with active malignant disease at transplantation (24% vs 9%; P = 0.03), in recipients of marrow from unrelated donors (33% vs 15%; P = 0.03), in patients grafted with bone marrow (21% vs 6%; P = 0.03), and in those receiving MTX as GVHD prophylaxis (21% vs 6%; P = 0.05). Under multivariate analysis, only CD34 + positive selection (P = 0.0004) and the status of the disease at transplant (P = 0.03) were statistically significant variables for the development of VOD. We conclude that CD34+ positively selected PBSC transplantation could result in a marked reduction in the incidence of VOD after allogeneic HSCT. Bone Marrow Transplantation (2001) 27, 983-988.

Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are an established treatment for patients with type 2 diabetes (T2D). Differences between GLP‐1RAs in pharmacokinetics, dosing regimens and clinical effects, including cardiovascular (CV) outcomes, mean there may be benefits to switching from one to another. However, clinical guidance on switching is lacking and data from clinical trials are limited. This article provides a clinical perspective and consensus on the benefits of switching between GLP‐1RAs, the triggers for switching and how best to manage this in clinical practice. Once weekly (OW) semaglutide is used as an example to illustrate how the authors might switch to a different GLP‐1RA in clinical practice. Methods Literature was searched and perspectives from 10 healthcare professionals with experience in switching patients with T2D to OW semaglutide from another GLP‐1RA were collated. Results Medical triggers for switching to another GLP‐1RA included HbA1c targets not being met, a desire for additional weight loss, poor adherence, patients moving to increased CV risk status and adverse effects with the current GLP‐1RA. Non‐medical triggers for switching included patient preference, cost, formulary changes and insurance mandates. Once the decision to switch is made, an individualised approach is recommended, based on considerations that include reimbursement requirements, treatment duration with (and dose of) previous GLP‐1RA, the patient's experience initiating the prior GLP‐1RA, any concomitant treatment and clinical characteristics. When switching, it is important to emphasise that treatment burden will not increase and that if gastrointestinal adverse effects occur, they are typically transient. Any transient gastrointestinal adverse effects that may occur (or recur) when switching to another GLP‐1RA can be reduced by slow up‐titration and advising patients to reduce food portion sizes and fat intake. Conclusion Switching from one GLP‐1RA to another, such as OW semaglutide, can provide clinical benefits and may delay the need for treatment intensification.

The contribution of residual malignant cells contaminating the autologous graft with the occurrence of post-transplant relapse in acute myeloid leukemia (AML) is still unclear. The presence of a specific molecular marker (the PML/RAR␣ rearrangement) in acute promyelocytic leukemia (APL) offers the opportunity to investigate better the pathogenesis of disease recurrence after transplant. We report an APL patient who received highdose chemotherapy and peripheral blood stem cell (PBSC) autograft in second hematologic remission. Two leukaphereses that tested PML/RAR␣ positive by RT-PCR were obtained during the post-reinduction hematopoietic recovery, while the patient also tested PCR positive in the BM, and was reinfused after myeloablative chemotherapy (BUCY4), when the patient had spontaneously converted to PCR negative in the marrow. At present, he remains in continuous molecular and hematologic remission 22 months after PBSC transplantation. This is the second report of an APL patient who was transplanted in molecular remission with a PML/RAR␣-positive PBSC autograft. As in the previous report, the prolonged clinical and molecular remission experienced post-transplant suggests that autologous PBSC infusion is still worthy of consideration for patients with APL in spite of the detection of PML/RAR␣-positive cells in the PBSC collections. Possible underlying mechanisms and the potential role of molecular monitoring of the graft, as well as the host, before and after transplant, in patients with APL undergoing autologous HSCT are also discussed.

In obese children, insulin resistance is associated with plasma lipid alterations suggestive of both decreased adipose tissue lipolysis and hepatic beta-oxidation and increased hepatic synthesis of triglycerides. Such a metabolic condition may facilitate fat storage and hinder weight loss.

AbstractAcute pancreatitis (AP) is a local inflammatory response with systemic effects and an adverse evolution in 20% of cases. Its mortality rate is 5–10% in sterile and 15–40% in infected pancreatic necrosis. Infection is widely accepted as the main reason of death in AP. The evidence to enable a recommendation about antibiotic prophylaxis against infection of pancreatic necrosis is conflicting and difficult to interpret. Up to date, there is no evidence that supports the routine use of antibiotic prophylaxis in patients with severe AP. Treatment on demand seems to be the better option, avoiding excessive treatment and selection of bacterial. In infected acute pancreatitis, antibiotics of choice are imipenem, meronem or tigecycline in patients allergic to beta-lactams. Also fluconazole must be given in determinate clinical situations.