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Haemophagocytic lymphohistiocytosis (HLH) is a possibly life-threatening syndrome of immune dysregulation and can be divided into primary (hereditary) and secondary forms (including malignancy-associated HLH (M-HLH)). We retrospectively analysed epidemiological, clinical, virological and laboratory data from patients with M-HLH treated at our department between 1995 and 2014. Out of 1.706 haemato-/oncologic patients treated at our department between 1995 and 2014, we identified 22 (1.29%) patients with secondary HLH (1.3–18.0, median 10.1 years; malignancy induced n = 2; chemotherapy induced n = 20). Patients with acute myeloblastic leukaemia (AML) developed HLH significantly more often than patients with acute lymphoblastic leukaemia (ALL) (10/55, 18.2% vs. 6/148, 4.1%, p = 0.0021). As possible viral triggers, we detected BKV (53.8% of the tested patients), HHV-6 (33.3%), EBV (27.8%), CMV (23.5%), ADV (16.7%) and PVB19 (16.7%) significantly more frequently than in haemato-/oncologic patients without HLH. Despite lacking evidence of concurrent bacterial infection, C-reactive protein (CRP) and procalcitotnin (PCT) were elevated in 94.7 and 77.7% of the patients, respectively. Ferritin and sIL2R were markedly elevated in all patients. HLH-associated mortality significantly (p = 0.0276) decreased from 66.6% (1995–2004) to 6.25% (2005–2014), suggesting improved diagnostic and therapeutic management. Awareness of HLH is important, and fever refractory to antibiotics should prompt to consider this diagnosis. Elevated ferritin and sIL2R seem to be good markers, while inflammatory markers like CRP and PCT are not useful to discriminate viral triggered HLH from severe bacterial infection. Re-/activation of several viruses may play a role as possible trigger.

Between 1990 and 2001, 68 patients with advanced Hodgkin's disease (HD) and 86 patients classified as low-/intermediate-grade B non-Hodgkin's lymphoma (NHL) were reported to the Austrian Stem Cell Transplantation Registry (ASCTR). Following autologous stem cell transplantation (SCT) for HD, overall survival was 56% [95% confidence interval (CI): 40-72%] with a disease-/progression-free survival of 49%, reaching a plateau at 5 years. Using multivariate Cox regression analysis BEAM conditioning (carmustine, cytarabine, etoposide and melphalan) was predictive for favourable outcome, better disease-/progression-free survival and a significantly lower risk for relapse. The cumulative incidence of relapse was 30%, even for patients in complete remission at time of SCT. The cumulative risk for developing a secondary malignancy increased continuously over time, achieving 20% at 7 years and 46% at 10 years with previous radiotherapy as the only risk factor in the multivariate analysis. Overall survival for NHL patients was 45% (95% CI: 26-64%) with a disease-/progression-free survival of 26% at 7 years. In the multivariate Cox regression analysis stage of disease at time of SCT was the most powerful parameter for overall survival, disease-/progression-free survival and relapse. Mantle cell lymphoma, greater than or equal to three lines of previous therapy, and a conditioning regimen other than BEAM were also predictive for death. The main reason for treatment failure was relapse (cumulative incidence 54-75%). Because of the high risk of relapse/progression in both disease categories and the additional high rate of second malignancies in HD patients, allogeneic stem cells should be considered a valuable alternative for selected patients. The efficacy of allotransplantation following reduced-intensity conditioning should be tested in randomised trials.

Severe aplastic anemia (SAA) has been related in most cases to underlying autoimmune conditions. Various immunosuppressive regimens have been recommended in the absence of an HLA-identical bone marrow donor. Prednisolone, antithymocyte globulin, and cyclosporin A have been shown to be effective. This report describes the successful treatment of a 23-year-old woman suffering from severe aplastic anemia who had become multiresistant against previously administered immunosuppressive agents, using a monoclonal IL-2-receptor blocking antibody. The patient responded within 4 weeks. The time to the next relapse was 8 months; however, another remission with a second course of horse-antithymocyte globulin was achieved and has been maintained for 27 months to date with low doses of cyclosporin A. Although this is an anecdotical report, IL-2-receptor blockade using a monoclonal antibody might be considered as a further alternative in multi-resistant SAA, perhaps increasing the susceptibility to further immunosuppressive trials.

Umbilical cord blood is capable of hematopoietic stem cell reconstitution in children. However, the major limitation of cord blood is a relatively low content of pluripotent progenitor cells. Thus, safe engraftment for adolescents and for adults is still not predictable and a technology for ex vivo expansion of umbilical cord blood cells is desirable. In a first step, four different methods of red cell depletion followed by magnetic cell sorting of CD34+ cells were evaluated in this study in order to assess the efficacy and safety of optimal stem cell recovery. A modified two-step Ficoll gradient separation and a hydroxyethyl starch separation tended to produce a better WBC/MNC recovery (median 94.2+/-2.44% vs. 90.2+/-5. 8%) as compared with standard Ficoll gradient separation and a gelatin-based procedure (median 78.35+/-7.1% vs. 67.2+/-5.5%). However, the recovery of CD34+ cells after magnetic cell sorting did not reach a statistically significant difference after the four different methods of red cell depletion, indicating that the recovery of WBC/MNC is not predictably correlated with the recovery of stem cells within these fractions. In a second step, we established three different cytokine combinations by adding the megakaryocyte growth and development factor +/- erythropoietin and granulocyte colony-stimulating factor to a fetal calf serum containing medium with Flt 3, stem cell factor, and interleukin-3. Net expansion of total colony-forming cells 20- to 50-fold and expansion of colony-forming cells after 5 weeks of culture 1.5- to 3-fold were obtained over a period of 7-14 days. These results demonstrate that cord blood stem cells can be expanded substantially in this short-term culture system.

Two siblings with evidence of disseminated T-cell lymphoma at the time of diagnosis of familial hemophagocytic lymphohistiocytosis (FHL) are reported, an association which has not been described previously. The first child with typical clinical and laboratory features of FHL died shortly after admission, before diagnosis could be established. Retrospective analysis of autoptic tissue revealed marked hemophagocytosis as well as morphological and immunohistochemical features suggestive of disseminated T-cell lymphoma. In the second child, FHL was diagnosed in time. Subsequent histologic investigation of bone marrow biopsies displayed a focal infiltration by T-cell lymphoma. DNA hybridization studies provided evidence of a monoclonal T-cell receptor beta chain gene rearrangement. Following conventional chemotherapeutic induction for FHL, the patient received an allogeneic bone marrow transplant (BMT) from a related healthy donor. Currently, 17 months after BMT, the boy is in unmaintained remission from FHL and T-cell lymphoma. The current pathogenetic concepts for FHL and a possible relationship between T-cell lymphoma and FHL are discussed.