Clinical, radiological and molecular responses to combination chemotherapy with MAPK pathway inhibition in relapsed and refractory Langerhans cell histiocytosis.

Optimal therapeutic approaches for advanced Langerhans cell histiocytosis (LCH) are not known. We assessed the safety and efficacy of combined chemotherapy with MAPK pathway inhibition in 10 patients with refractory systemic disease and/or LCH-associated neurodegeneration. Overall response rate was 9/10 (90%) for the entire cohort: 5/5 (100%) for patients with systemic disease and 6/7 (86%) for patients with central nervous system disease. BRAFV600E+ peripheral blood fraction decreased in 5/6 (83%). Toxicities included fever, skin rash, myalgias, neuropathy, cytopenias and hypocalcaemia. Prospective trials are required to optimize combination strategies, determine potential to achieve cure and compare outcomes to chemotherapy or MAPK inhibitor monotherapy.

Thyroid hormone use during cardiac transplant organ procurement.

BACKGROUND: Acute hypothyroidism after brain death results in hemodynamic impairments that limit availability of donor hearts. Thyroid hormone infusions can halt that process and lead to increased utilization of donor organs, but prolonged use of thyroid replacement has not been well studied. METHODS: We developed a 15-question survey regarding policies, procedures, and reporting of thyroid hormone use by organ procurement organizations (OPOs). The survey was posted for 5 weeks on the Association of OPOs Portal. RESULTS: We received 29 responses, representing 24 OPOs. Seventy-two percent reported their OPOs use thyroid hormone for all potential donors and 90% have a protocol for thyroid hormone use. There is a large variation in the maximum dose of thyroid hormone used, and many OPOs have no weaning protocol. Most OPOs do not collect data on total thyroid hormone administered during procurement and would favor more detailed report of thyroid hormone use. CONCLUSIONS: Thyroid hormone use can have important implications for organ selection and cardiac function before and after transplantation. Protocols vary widely with respect to why and how to use and wean thyroid hormone. We believe there should be more detailed reporting of thyroid hormone use for future studies to ensure appropriate donor management.

Obliterative bronchiolitis in lung allografts removed at retransplant for intractable airway problems.

BACKGROUND AND OBJECTIVE: The role of large airway ischaemia, with resultant airway narrowing, in the development of post-lung transplant bronchiolitis obliterans has not been defined. A determination of clinical bronchiolitis obliterans syndrome (BOS), which is defined as a decline in FEV(1) from a stable post-transplant baseline, is difficult in the setting of airway complications. The aim of this study was to assess the evidence for histological bronchiolitis obliterans in lung allografts removed during retransplantation for severe recurrent airway narrowing. METHODS: Case records and histological findings in allograft lungs removed at retransplantation were retrospectively reviewed. RESULTS: Five lung transplant recipients, who had undergone retransplantation because of severe recalcitrant airway stenosis, were identified. In each case, explant allograft lung pathology revealed evidence of bronchiolitis obliterans. CONCLUSIONS: There is a possible link between airway ischaemia, large airway stenosis and the development of bronchiolitis obliterans, which is the most common cause of death in lung transplant recipients after the first year. These findings may provide an impetus for evaluation of the role of bronchial artery revascularization techniques in the prevention of bronchiolitis obliterans.

Mobilization of Ph chromosome-negative peripheral blood stem cells in a child with chronic myeloid leukemia after imatinib-induced complete molecular remission.

Chronic myelogenous leukemia (CML) is rare in the pediatric population. Allogeneic stem cell transplant remains the only curative therapy; however, identifying a fully matched donor is not always possible. Imatinib mesylate has been shown to induce hematologic and cytogenetic response in adults and children with CML. We describe a child who achieved molecular remission with imatinib mesylate. BCR-ABL negative peripheral blood stem cells (PBSC) were successfully collected after mobilization with filgrastim.

Clinical experience with a new removable tracheobronchial stent in the management of airway complications after lung transplantation.

BACKGROUND: Airway complications are among the most challenging problems after lung transplantation. This article describes the use of a new tracheobronchial stent that can be placed and removed easily by flexible bronchoscopy. METHODS: A retrospective review was done of 24 consecutive patients requiring tracheobronchial stent placement after lung transplantation. A new self-expanding hybrid nitinol stent was used, and changes in airway diameter and spirometry were assessed. Stent related complications were recorded. RESULTS: Between February 2007 and April 2008, 24 patients underwent stent placement, and 49 stents were placed for 36 anastomoses at risk. Indications included bronchial stenosis in 12, bronchomalacia in 12, bronchial stenosis plus bronchomalacia in 20, and partial bronchial dehiscence in 5. Adjunctive procedures included electrocautery in 1, balloon dilatation in 7, and electrocautery plus balloon dilatation in 4. The average degree of stenosis decreased from 80% to 20%. After stent placement, the average increase was 0.28 liters in forced vital capacity and 0.44 liters in forced expiratory volume in 1 second. Complications included granulation tissue formation in 10 stents, migration in 9, thick mucus formation in 2, and fracture in 3. CONCLUSION: Airway complications in lung transplant patients were effectively palliated. Our complication rate with this new stent is comparable with other airway stents. This stent has the advantage of easy removability during flexible bronchoscopy if complications from the stent outweigh the benefits of palliation.