Late transplant-associated thrombotic microangiopathy verified in bone marrow biopsy specimens is associated with chronic GVHD and viral infections.

OBJECTIVES: To describe late transplant-associated thrombotic microangiopathy (TA-TMA) as chronic endothelial complication in bone marrow (BM) after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: BM specimens along with conventional diagnostic parameters were assessed in 14 single-institutional patients with late TA-TMA (more than 100 days after HCST), including 11 late with history of early TA-TMA, 10 with early TA-TMA (within 100 days), and 12 non TA-TMA patients. Three non-HSCT patients served as control. The time points of BM biopsy were +1086, +798, +396, and +363 days after HSCT, respectively. RESULTS: Late TA-TMA patients showed an increase of CD34+ and von Willebrand Factor (VWF)+ microvascular endothelial cells with atypical VWF+ conglomerates forming thickened VWF+ plaque sinus in the BM compared to patients without late TA-TMA and non-HSCT. Severe chronic (p = .002), steroid-refractory GVHD (p = .007) and reactivation of HHV6 (p = .002), EBV (p = .003), and adenovirus (p = .005) were pronounced in late TA-TMA. Overall and relapse-free survival were shorter in late TA-TMA than in patients without late TA-TMA (5-year OS and RFS: 78.6% vs. 90.2%, 71.4% vs. 86.4%, respectively). CONCLUSION: Chronic allo-immune microangiopathy in BM associated with chronic, steroid-refractory GVHD and/or viral infections are key findings of late, high-risk TA-TMA, which deserves clinical attention.

Bone loss after allogeneic haematopoietic stem cell transplantation: a pilot study on the use of zoledronic Acid.

Purpose. Bone loss is a common phenomenon following allogeneic haematopoietic stem cell transplantation (allo-HSCT). The study aimed on tolerance and efficacy of zoledronic acid (ZA) in patients after allo-HSCT. Methods. 40 patients' with osteoporosis or osteopenia were recruited on this phase II study. ZA was given at a dose of 4 mg IV every 3 months for 2 years (yrs). BMD was determined by dual-energy X-ray absorptiometry (LS lumbar spine, FH femur hip). Patients were evaluated for deoxypyridinoline (Dpd) and calcium excretion by longitudinal measurements. Results. 36 patients who had received at least 3 doses of ZA were evaluable. 26 patients had at least two BMD measurements since baseline (BMD group). Among these patients, BMD increased from 0.97 ± 0.15 to 1.10 ± 0.18 g/cm² (LS baseline-2 yrs, Δ+11.6 ± 6.0%, P < 0.001) and from 0.82 ± 0.10 to 0.91 ± 0.10 g/cm(²) (FH baseline-2 yrs, Δ+7.5 ± 7.0%, P < 0.001). Factors associated with an increase in BMD were younger age, female donor sex, and immunosuppression with CSA/MTX. Conclusion. ZA was generally well tolerated; it increases BMD and reduces Dpd excretion significantly in patients with bone loss after allo-HSCT.

PUVA-bath photochemotherapy and isotretinoin in sclerodermatous graft-versus-host disease.

Chronic graft-versus-host disease (GVHD) is almost always associated with skin diseases appearing either as lichenoid GVHD, sclerodermatous GVHD (sGVHD) or as eosinophilic fasciitis-like disease. The two latter frequently result in severe and deep sclerosis. Immunosuppressive therapy is of little help in sclerodermatous or eosinophilic fasciitis-like types of GVHD. Based on data showing that PUVA-bath photochemotherapy is effective in the treatment of severe localized sclerosis of the skin, we investigated the efficacy of PUVA-bath photochemotherapy and isotretinoin in sGVHD. In a retrospective study we analyzed fourteen consecutive patients with sGVHD who received PUVA-bath photochemotherapy, five in combination with oral isotretinoin. Seven patients improved and four showed complete remission. Surprisingly, the therapy was complicated by the development of ulcers within the sclerotic plaques during the early periods of treatment. These ulcers cleared in most patients when PUVA-bath photochemotherapy was continued. Thus, PUVA-bath photochemotherapy alone or in combination with isotretinoin may resolve or improve GVHD associated sclerosis in selected patients.