Fludarabine-Based Reduced Intensity Conditioning for Stem Cell Transplantation of Fanconi Anemia Patients from Fully Matched Related and Unrelated Donors

AbstractReduced intensity conditioning has been suggested as a desirable therapeutic modality for the treatment of patients with malignant and nonmalignant indications, but it seems particularly attractive for patients with Fanconi anemia due to their increased sensitivity to chemoradiotherapy. Between November 1996 and September 2003, 7 patients (1 male and 6 female; age range, 3-31 years; median age, 9.5) were conditioned with a fludarabine-based protocol for stem cell transplantation without radiation. In vivo T-cell depletion was accomplished with anti-thymocytic globulin or Campath-1H (alemtuzumab). Graft-versus-host disease prophylaxis consisted of low-dose cyclosporine alone. Eight transplantations were carried out for 7 patients using bone marrow, peripheral blood, and/or cord blood as sources of stem cells. All patients received transplants from HLA-A, -B, -C, and -DR matched donors, 5 from family members and 2 from matched unrelated donors. One patient did not engraft her first matched unrelated donor and underwent a second transplantation from another matched unrelated donor, after which she engrafted well. All 7 patients are alive and well, fully reconstituted with donor cells, and with 100% performance status. In conclusion, fludarabine-based preparative protocols are well tolerated, facilitate rapid engraftment with minimal toxicity, and should be considered an essential component of choice for patients with Fanconi anemia

Irradiated mononuclear cells express significant in vitro cytotoxic activity: Promise for in vivo clinical efficacy of irradiated mismatched donor lymphocytes infusion

Background: Relapse of the original disease remains the most common cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-SCT). Patients who relapse post-allo-SCT can achieve prolonged remission after donor lymphocyte infusion. Donor lymphocyte infusion as well as other immunotherapeutic strategies are usually complicated by severe graft versus host disease. Aim: In the present study, we examined the effect of irradiation on the cytotoxic activity of mononuclear cells (MNCs). Materials & methods: Cytotoxic activity of fresh and irradiated MNCs from healthy donors was tested against the leukemic cell line K562 and against fresh leukemic cells from patients with acute myeloid leukemia. Cytotoxicity was assessed by using a flow-cytometry assay. Results & discussion: Interestingly, we observed that 25 Gy irradiated MNCs retain significant cytotoxic activity against K562. Based on these in vitro data, the safety and efficacy of irradiated haploidentical, IL-2-activated lymphocytes were tested in six patients after allo-SCT. Acute skin graft versus host disease developed in two patients and was resolved after a short course of steroids. One patient with mixed chimera converted to full donor chimera after infusion of irradiated donor cells. Conclusion: The efficacy of irradiated haploidentical lymphocytes should be further tested in a larger number of patients. © 2014 Future Medicine Ltd

Machine learning in user modeling

It is generally recognized that information systems are becoming more complex and, therefore, intelligent user interfaces are needed to improve user interaction with these systems. Furthermore, the exponential growth of the Internet makes it difficult for the users to cope with the huge amount of available on-line information. The challeng