Summary:Tacrolimus has been shown to be more effective than cyclosporine for prevention of acute graft-versus-host disease (GVHD). A number of transplant centers have therefore adopted tacrolimus as standard prophylaxis, but with additional experience, current management of tacrolimus differs from that in the clinical studies. Therefore, a consensus conference was convened to assess the current practices. For prevention of GVHD, conference participants recommended administering tacrolimus at 0.03 mg/kg/day (by lean body weight) i.v. by continuous infusion from day ؊1 or ؊2 pretransplant, with day ؊2 used especially for pediatric patients. Therapeutic drug monitoring was considered essential in the management of patients on tacrolimus. The consensus target range for the whole blood concentration was 10-20 ng/ml. Doses were modified for blood levels outside the target range or for nephrotoxicity, and tacrolimus was discontinued for intolerable tremor, hemolytic uremic syndrome, leukoencephalopathy or other serious toxicity. Tacrolimus was employed most frequently in combination with minimethotrexate (5 mg/m 2 i.v. days 1, 3, 6 and 11). Tapering was individualized according to center practice. No patient category was excluded from use of tacrolimus based on age, extent of disease, patient-donor histocompatibility or stem cell source. Tacrolimus was also used successfully for treatment of chronic GVHD. The responsiveness of steroidrefractory acute GVHD was marginal, so it was deemed more prudent to use tacrolimus for prophylaxis instead. Keywords: tacrolimus; graft-versus-host disease; allogeneic marrow transplantation; therapeutic drug monitoring Tacrolimus was first evaluated in marrow transplant recipients in 1990.1 The initial clinical experience demonstrated its activity for treatment of chronic graft-versus-host disease (GVHD) resistant to cyclosporine and other immunosuppressive drugs, but the limitations in its use for treat- ment of refractory acute or chronic GVHD were readily apparent. Subsequently, three randomized studies conducted in 17 North American centers and 21 Japanese centers compared tacrolimus and cyclosporine in combination with standard-dose methotrexate for prevention of GVHD after HLA-identical sibling or unrelated donor marrow transplantation.2-4 The studies revealed that tacrolimus was superior to cyclosporine for prevention of acute GVHD in these settings, although long-term leukemia-free survival was not affected. For many of the participating centers, the randomized studies were their first experience with tacrolimus.Several centers have since adopted tacrolimus as the standard agent for GVHD prophylaxis, and more than 500 patients have been treated outside the sponsored trials. 5-11Investigators from these centers were convened at a consensus conference in Key West in November 1998 to review the current practices by those experienced with tacrolimus for prevention of GVHD, determine if there is a consensus in the use of tacrolimus, and identify where additional information is needed....

tension with ascites frequently accompanies these histologiHepatic venoocclusive disease (VOD) is a common, lifecal changes and contributes to the clinical manifestations of threatening complication of bone marrow transplantathis syndrome. A wedged hepatic venous pressure gradient tion (BMT). Portal hypertension is usually present and greater than 10 mm Hg is highly specific for the diagnosis of accounts for many of the clinical manifestations of this VOD in this setting. 6,7 Similar histological and clinical syndrome. We describe the results of transjugular intrachanges may be seen with other causes of hepatic venous hepatic portosystemic shunt (TIPS) for the management outflow obstruction, i.e., Budd-Chiari syndrome. 8 of VOD after BMT. TIPS was performed in six patientsVarying degrees of liver dysfunction occur with VOD. Cowith histologically confirmed VOD who had progressive agulopathy, hepatic encephalopathy, and intractable ascites jaundice and ascites. Portal hypertension was improved requiring large volume paracentesis may occur. Rapidly inby TIPS in all patients (mean portal pressure gradient creasing levels of serum bilirubin and marked weight gain before TIPS, 20.2 { 4.6 vs. 6.7 { 1.9 mm Hg post-TIPS, P are predictors for the development of severe VOD. 9 Mild to õ .004). Three patients who underwent TIPS late in the moderate VOD may spontaneously resolve, whereas severe course of VOD did not demonstrate any clinical improve-VOD results in the relentless progression to multiorgan failment after TIPS and expired within 2 weeks of the proceure, with a mortality rate approaching 100%. 2 There is no dure. The remaining three patients had less advanced satisfactory treatment for VOD, and management remains disease and demonstrated decreases in serum bilirubin, largely supportive. Infusions of heparin, prostaglandins, or improvement in coagulopathy, and decreased ascites tissue plasminogen activating factor have been used either after TIPS. Two patients subsequently expired, one with prophylactically or as therapy for established VOD in an atpersistent histological changes of VOD. The lone survitempt to improve blood flow through the terminal hepatic vor continues to do well with resolution of ascites, jaunvenule. [10][11][12][13][14] While some of these interventions resulted in a dice, and coagulopathy as of her last outpatient visit. decreased incidence of VOD or clinical improvement in estab-TIPS was an effective method for portal decompression lished VOD, significant side effects have been reported and, in patients with VOD after BMT, and was associated at this time, none of these modalities are considered to be with clinical improvement in some patients. However, standard therapy for VOD. these effects may be transient and may not improve Both VOD and Budd-Chiari syndrome cause centrilobular overall survival. (HEPATOLOGY 1996;24:588-591.) congestion within the liver. In Budd-Chiari syndrome, this congestion is associated with hepatocellular necrosis and proHepatic venoocclusive disease (VOD) is a clini...

A comprehensive supportive care approach was associated with a low treatment-related mortality rate of less than 1%. With the observed reduction in treatment-related mortality, it is reasonable to evaluate the efficacy of HDC in women with less than 10 positive nodes and stage II disease in well-designed clinical trials.

Plasmacytoid dendritic cells (pDCs) bridge innate and adaptive immune responses and have important roles in hematopoietic engraftment, GvHD and graft-versus-leukemia responses following allogeneic hematopoietic cell transplantation (HCT). In addition, pDCs mediate antiviral immunity, particularly as they are the body’s primary cellular source of type I interferon. Given their pleiotropic roles, pDCs have emerged as cells that critically impact transplant outcomes, including overall survival. In this article, we will review the pre-clinical and clinical literature, supporting the crucial roles that pDCs assume as key immune effector cells during HCT.