Vassiliki Kitra

HLA-matched sibling stem cell transplantation in children with β-thalassemia with anti-thymocyte globulin as part of the preparative regimen: the Greek experience.

BU combined with CY, the preferred preparatory regimen for thalassemic patients, is associated with a substantial incidence of graft rejection especially in patients with advanced disease stage. This study retrospectively analyzes the outcome of 75 consecutive pediatric patients with β-thalassemia who underwent HLA-matched sibling transplantation after anti-thymocyte globulin (ATG)-containing myeloablative conditioning regimens. With a median follow-up of 9 years (range 1–15 years), the overall survival (OS) and thalassemia free survival (TFS) rates were 96% and 92%, respectively. Both the estimated TRM and the cumulative incidence of rejection/failure were 4%. The cumulative incidences of acute GVHD grade II–III and grade III were 20% and 5.3%, respectively. No patient developed acute GVHD grade IV. Only two patients developed extensive chronic GVHD. The estimated OS and TFS for patients with Class 1 and 2 disease according to Pesaro criteria were 96.3% and 94.4%, whereas for patients with Class 3 disease they were 94.1% and 88.2%, respectively. In our series, the use of myeloablative conditioning regimens, which include ATG for the transplantation of thalassemic children from matched sibling donors, resulted in excellent outcomes with very low incidences of TRM and rejection.

Severe anemia and neutropenia associated with hyperzincemia and hypercalprotectinemia.

Calprotectin, also known as the S100A8/A9 or MRP8/14 complex, is a major calcium-binding protein in the cytosol of neutrophils, monocytes, and keratinocytes. It differs from other S100 proteins in its zinc-binding capacity. The authors describe a 4-year-old girl with severe anemia, neutropenia, inflammation, and severe growth failure. Bone marrow examination showed moderate dyserythropoiesis. No hemolysis, iron deficiency, hemoglobinopathies, immunologic diseases, or autoantibodies were detected. Serum levels of copper and ceruloplasmin were within the normal range, although the serum zinc concentration was markedly increased (310 μg/dL). Urinary zinc excretion and erythrocyte zinc concentrations were within the normal range. Family studies showed normal zinc and copper plasma levels. The patients plasma calprotectin concentration showed a 6,000-fold increase (2,900 mg/L) compared with normal values. The calprotectin concentration is known to be elevated in many inflammatory conditions but is generally below 10 mg/L and thus far below the levels reported in this patient. The authors describe this case as an inborn error of zinc metabolism caused by dysregulation of calprotectin metabolism, which mainly presented with the features of microcytic anemia and inflammation.

Extracorporeal photopheresis in the treatment of chronic graft-versus-host disease. The Hellenic experience: a study by the Hellenic association of hematology.

The Hellenic experience regarding the efficacy of extracorporeal photopheresis (ECP) in the treatment of 58 patients with chronic graft-versus-host disease (cGVHD) is presented in this article. All 58, except one patient, had failed at least one line of immunosuppressive treatment including steroids. Thirty-three out of 58 patients showed an objective overall response to ECP in a median time of 10 weeks after the onset of treatment. The cumulative incidence of overall response was 65.1%. In multivariate analysis, the presence of severe chronic GVHD was the only parameter associated with a significantly lower probability of response to treatment (RR=0.4, CI 95% 0.2-0.9, p=0.03). Responders to treatment with ECP were more likely to discontinue immunosuppression, had a lower probability of non-relapse mortality (RR=0.2, CI 95% 0.1-0.5, p=0.002), and a higher probability of overall survival (RR=7.8, CI 95% 3-20, p<0.001) in comparison with non-responders. Eight out of 58 patients experienced relapse of the original disease. The cumulative incidence of relapse in the group of responders to ECP was 6%, while it was 25% in the group of non-responders to ECP. In multivariate analysis, response to treatment with ECP was the only parameter statistically associated with a significantly decreased hazard of relapse (RR=0.1, CI 95% 0.1-0.7, p=0.02). ECP should be tested as first-line treatment in patients with cGVHD with the aim to minimize the duration of immunosuppression and the rate of relapse of the malignant disease.

Culture of bone marrow CD105+ cells allows rapid selection of pure BM-stromal cells for chimerism studies in patients undergoing allogeneic bone marrow transplantation.

Stromal tissue derived from adult bone marrow (BM) contains clonogenic progenitor cells (CFU-F), some of which are considered to be multi-potent MSCs, capable of differentiating into a range of mesenchymal cell lineages.1 Current methods for the isolation of BM-MSCs rely upon the rapid adhesion of the stromal progenitor populations to tissue culture plastic and their subsequent rapid proliferation in vitro,2 resulting, however, in a heterogeneous starting population of adherent BM cells. A significant proportion of the latter represent adherent monocytic cells, the major cause of false-positive results in studies investigating the origin of BM-stromal cells following SCT.3 In addition, BM-MNCs from patients post allogeneic transplantation show a significant impairment in the ability to generate confluent SC-layers in long-term Dexter-type cultures preventing molecular assessment of chimerism.4, 5 Therefore, studies based on these methods are limited by monocyte-macrophage contamination and defective SC growth.

Acute disseminated encephalomyelitis after allogeneic bone marrow transplantation for pure red cell aplasia – A case report and review of the literature

ADEM is a rare inflammatory demyelinating disease of the CNS, which usually presents after a viral infection or a vaccination. We report a 15‐yr‐old boy who was diagnosed with ADEM after an HLA‐identical sibling allogeneic BMT for transfusion‐dependent PRCA. His course was complicated with GVHD affecting the skin and lungs. Five months post‐BMT, he developed neurological symptoms including sudden mental status alteration, dysarthria, facial nerve palsy, and acute paraplegia. The MRI revealed multifocal hyperintense lesions mainly in the subcortical white matter of the cerebrum, the brainstem, the basal ganglia, and the thalami. CSF examination was normal. There was no laboratory evidence of infection. The typical MRI findings and an acute monophasic clinical course were consistent with the diagnosis of ADEM. Clinical and radiological improvement was observed after treatment with high‐dose steroids and IVIG. Complete neurologic recovery was achieved six months after the onset of symptoms. We present a rare case of ADEM post‐BMT and review of the literature.

Resolution of Hematocolpos in Adolescents Affected with Graft vs Host Disease

BACKGROUND Bone marrow transplantation is a lifesaving procedure for a range of serious benign or malignant hematological conditions. A proportion of patients, however, will develop graft vs host disease (GVHD), acute or chronic, with serious long-term sequalae. CASES We present 2 cases of hematocolpos that developed in adolescence because of vaginal synechiae due to GVHD. The condition was initially asymptomatic, resolved spontaneously at first and recurred. In 1 girl blunt lysis of the adhesions was performed with the patient under general anesthesia, followed thereafter by local hydrocortisone and estriol treatment. SUMMARY AND CONCLUSION Genital symptoms might not be readily reported by adolescents after bone marrow transplantation. Physicians should be aware of possible late effects of GVHD on genitalia, inquire about symptoms, and be acquainted with addressing complications, such as vaginal obstruction.

Infectious complications following allogeneic stem cell transplantation by using anti-thymocyte globulin-based myeloablative conditioning regimens in children with hemoglobinopathies.

Anti‐thymocyte globulin (ATG) has been used to prevent graft failure/rejection in the setting of allogeneic stem cell transplantation (allo‐SCT) for hemoglobinopathies; however, epidemiology data for transplant‐related infections in this population are scarce.