A brief, telephone-administered CBT intervention developed for HSCT survivors is an efficacious treatment for reducing illness-related PTSD symptoms and general distress.
In this study, we explored dermal dendritic cell (DC) homeostasis in mice and humans both in the steady state and after hematopoietic cell transplantation. We discovered that dermal DCs proliferate in situ in mice and human quiescent dermis. In parabiotic mice with separate organs but shared blood circulation, the majority of dermal DCs failed to be replaced by circulating precursors for >6 mo. In lethally irradiated mice injected with donor congenic bone marrow (BM) cells, a subset of recipient DCs remained in the dermis and proliferated locally throughout life. Consistent with these findings, a large proportion of recipient dermal DCs remained in patients' skin after allogeneic hematopoietic cell transplantation, despite complete donor BM chimerism. Collectively, our results oppose the traditional view that DCs are nondividing terminally differentiated cells maintained by circulating precursors and support the new paradigm that tissue DCs have local proliferative properties that control their homeostasis in the steady state. Given the role of residual host tissue DCs in transplant immune reactions, these results suggest that dermal DC homeostasis may contribute to the development of cutaneous graft-versus-host disease in clinical transplantation.
Summary This study examined barriers to mental health service use and their demographic, medical, and psychosocial correlates among hematopoietic stem cell transplant (HSCT) survivors. A sample of 253 HSCT survivors who were 1- to 3-years post-transplant completed measures of demographic, physical, psychological, and social characteristics as well as a newly modified measure of barriers to mental health service use. Only 50% of distressed HSCT survivors had received mental health services. An exploratory factor analysis of the barriers to mental health service use scale yielded four factors: Scheduling Barriers, Knowledge Barriers, Emotional Barriers, and Illness-related Barriers. Patients with higher social constraints (perceived problems discussing the illness experience with significant others) reported higher levels of all four types of barriers. General distress and transplant-related posttraumatic stress symptoms were positively associated with emotional, knowledge, and illness-related barriers to mental health service use, whereas physical and functional well-being were inversely associated with these barriers. Having more knowledge barriers and more emotional barriers predicted a lower likelihood of receiving mental health services, as did lower levels of education and general distress. Results suggest that a significant number of HSCT survivors may benefit from education about mental health services that is tailored to individual barriers.
Calcineurin inhibitor-induced thrombotic microangiopathy (TMA) has been described in up to 14% of solid-organ transplant recipients. Sirolimus has recently been described in two reports in association with TMA. Sirolimus is known to potentiate cyclosporine-induced nephrotoxicity, but such effect has not been shown with tacrolimus. We report two intestinal transplant patients who developed TMA while on a tacrolimus and sirolimus immunosuppressive regimen. This syndrome appeared soon after institution of or increase in sirolimus dosage and improved only after this medication was discontinued.
Nonmyeloablative allogeneic peripheral blood progenitor cell transplantation with low-dose total body irradiation (TBI; 200 cGy) plus fludarabine followed by cyclosporine and mycophenolate mofetil results in modest graft rejection rates. Acute and chronic graft-versus-host diseases (GVHD) are also seen and may not differ substantially from those that occur after fully ablative transplantation. Adding antithymocyte globulin (ATG) to pretransplant conditioning produces substantial immunosuppression. Because of its persistence in the circulation, ATG can achieve in vivo T-cell depletion. Twenty-five patients who were not eligible for conventional fully ablative allogeneic stem cell transplantation by virtue of age or comorbidities underwent nonmyeloablative allogeneic transplantation with ATG 15 mg/kg/d days -4 to -1, TBI 200 cGy on a single fraction on day -5, and fludarabine 30 mg/m(2)/d on days -4 to -2. Oral mycophenolate mofetil 15 mg/kg every 12 hours and cyclosporine 6 mg/kg every 12 hours were started on day -5. Grafts were unmanipulated peripheral blood progenitor cells mobilized with filgrastim 10 microg/kg/d and collected on day 5. The median age of the recipients was 57 years (range, 30-67 years); diagnoses were non-Hodgkin lymphoma (n = 11), acute myeloid leukemia (n = 6), multiple myeloma (n = 3), acute lymphoblastic leukemia (n = 2), severe aplastic anemia (n = 1), paroxysmal nocturnal hemoglobinuria (n = 1), and myelodysplastic syndrome (n = 1). The median CD34(+) and CD3(+) contents of the grafts were 7.6 x 10(6)/kg and 1.6 x 10(8)/kg, respectively. Five patients received voluntary unrelated donor grafts. Three patients, 2 with voluntary unrelated donor grafts and 1 with a sib donor, received a 1 antigen-mismatched graft. The rest were fully matched. Twenty-two of 25 patients were evaluable for chimerism. Sixteen had >/=95% donor chimerism. Four patients displayed 80% to 90% donor chimerism, 1 displayed 78%, and 1 displayed 64%. Eleven patients relapsed with their original disease. One patient rejected the graft at 180 days. The median hospital stay was 27 days. Complications included GVHD in 6 patients (3 patients had grade I or II GVHD of skin and liver, and 3 patients had grade III or IV GVHD of liver and gut). Two of the patients with GVHD had mismatched grafts. Transplant-related toxicity was seen in 4 patients and infection in 5 patients. The median length of follow-up was 162 days (range, 17-854 days). Complete remissions were seen in 10 patients. Four patients remained in complete response (CR) at 280 to 595 days. One patient relapsed with non-Hodgkin lymphoma after a CR of 728 days. Of the 25 patients, 16 died (6 of relapsed disease, 4 of GVHD, 3 of infection, and 3 of transplant-related toxicity) and 9 are alive (6 with CR-2 of them after donor leukocyte infusion-and 3 with relapsed disease). The addition of ATG to low-dose TBI and fludarabine nonmyeloablative conditioning was well tolerated and resulted in >80% donor engraftment in this small cohort. As in other series of truly nonmyeloab...
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