Metabolic syndrome and cardiovascular disease following hematopoietic cell transplantation: screening and preventive practice recommendations from CIBMTR and EBMT.

Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31-49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal of reviewing literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.

High prevalence of early-onset osteopenia/osteoporosis after allogeneic stem cell transplantation and improvement after bisphosphonate therapy.

Osteopenia/osteoporosis (O/O) has been associated with allogeneic stem cell transplantation (alloSCT). We retrospectively reviewed 102 patients undergoing a first alloSCT from 2000 to 2005 at our center to evaluate the prevalence of O/O < or =6 and >6 months post-alloSCT. Fifty-six patients did not have a dual energy X-ray absorptiometry (DXA) scan following alloSCT. Approximately half (n=13/27) of those with a first DXA scan < or =6 months post-alloSCT had O/O and a similar rate (n=9/19) was seen in those with a first DXA scan >6 months. There were no significant differences in patient characteristics between the normal and O/O groups. The dual femur (DF) appeared to be more vulnerable to alloSCT-induced bone mineral density (BMD) loss than the lumbar spine (LS), regardless of screening time. O/O patients were treated with bisphosphonates and 41% had a repeat DXA scan post-treatment. No patient developed jaw osteonecrosis and significant BMD improvement was seen at the LS (mean BMD, 1.03+/-0.13 vs 1.08+/-0.12, P=0.004) but not the DF (mean BMD, 0.84+/-0.06 vs 0.85+/-0.08, P=0.29), indicating BMD loss at the DF is more resistant than the LS to antiresorptive therapy. Our results demonstrate that O/O is an early and late complication post-alloSCT and bisphosphonate treatment reverses BMD loss at the LS.

Two cases of hepatic zygomycosis in allogeneic stem cell transplant recipients and review of literature.

Gastrointestinal zygomycosis is a rare condition with a high mortality rate. We present 2 fatal cases of hepatic zygomycosis following allogeneic hematopoietic stem cell transplantation and review the literature.

Successful treatment of disseminated fusariosis with posaconazole during neutropenia and subsequent allogeneic hematopoietic stem cell transplantation.

We report the case of a 16-year-old girl with acute myelogenous leukemia with disseminated fusariosis, who responded to salvage posaconazole therapy. She subsequently received additional cytotoxic chemotherapy and allogeneic hematopoietic stem cell transplantation with posaconazole continued as secondary prophylaxis. Despite intensive immunosuppressive therapy for graft-versus-host disease, no recrudescence of infection occurred.

Leflunomide failure to control recurrent cytomegalovirus infection in the setting of renal failure after allogeneic stem cell transplantation.

Cytomegalovirus (CMV) reactivation is common in the allogeneic stem cell transplant setting but the incidence of CMV organ disease and mortality has been dramatically reduced by prophylactic or preemptive antiviral therapy. We report the case of a CMV-seropositive 46-year-old man with non-Hodgkin's lymphoma who underwent an unrelated allogeneic stem cell transplant from a CMV-seronegative HLA-matched unrelated donor. CMV encephalitis and colitis developed that was refractory to single-agent therapy. The CMV isolate demonstrated genotypic resistance to both ganciclovir and foscarnet. CMV disease was controlled by prolonged combination ganciclovir and cidofovir therapy, but severe renal dysfunction developed. Leflunomide was selected as a last resort to avoid the nephrotoxicity of cidofovir. CMV antigenemia rapidly increased following leflunomide administration, necessitating discontinuing this agent and resuming prior antiviral therapy. The pharmacokinetics of leflunomide in the setting of renal insufficiency is presented. Options for salvage therapy in refractory CMV disease in allogeneic stem cell transplant recipients are briefly reviewed.

Long-term stability of a patient-convenient 1 mg/ml suspension of tacrolimus for accurate maintenance of stable therapeutic levels.

Tacrolimus (Prograf, FK506, Fujisawa Healthcare) is a widely used immunosuppressive agent that is used both for the prevention and treatment of solid organ transplant rejection as well as for the prevention and treatment of graft-versus-host disease after allogeneic blood and marrow transplant. Oral preparations of tacrolimus are commercially available in 0.5, 1 and 5 mg gelatin capsules. Previously, only a 0.5 mg/ml oral suspension has been demonstrated to be stable for use in pediatric patients. On our bone marrow transplant service, we found that using this concentration of tacrolimus led to confusion, with patients and their caregivers confusing milligrams and milliliters, thus increasing errors with this formulation. We postulated that a 1 mg/ml oral formulation of tacrolimus would decrease the potential for medication errors. Our findings support new stability information of approximately 4 months for an extemporaneous oral suspension of tacrolimus at a concentration of 1 mg/ml.