Rabbit antithymocyte globulin (rATG; thymoglobulin, Genzyme) in combination with cyclosporine, as first-line immunosuppressive therapy, was evaluated prospectively in a multicenter, European, phase 2 pilot study, in 35 patients with aplastic anemia. Results were compared with 105 age-and disease severitymatched patients from the European Blood and Marrow Transplant registry, treated with horse ATG (hATG; lymphoglobulin) and cyclosporine. The primary end point was response at 6 months. At 3 months, no patients had achieved a complete response to rATG. Partial response occurred in 11 (34%). At 6 months, complete response rate was 3% and partial response rate 37%. There were 10 deaths after rATG (28.5%) and 1 after subsequent HSCT. Infections were the main cause of death in 9 of 10 patients. The best response rate was 60% for rATG and 67% for hATG. For rATG, overall survival at 2 years was 68%, compared with 86% for hATG (P ‫؍‬ .009). Transplant-free survival was 52% for rATG and 76% for hATG (P ‫؍‬ .002). On multivariate analysis, rATG (hazard ratio ‫؍‬ 3.9, P ‫؍‬ .003) and age more than 37 years (hazard ratio ‫؍‬ 4.7, P ‫؍‬ .0008) were independent adverse risk factors for survival. This study was registered at www.clinicaltrials.gov as NCT00471848. (Blood. 2012;119(23): 5391-5396) IntroductionHistorically, horse antithymocyte globulin (hATG) has been the preferred animal source of ATG as first-line treatment for acquired aplastic anemia (AA) patients who are ineligible for hematopoietic stem cell transplantation (HSCT). For severe AA (SAA), the combination of ATG and cyclosporine (CSA) results in a response rate of 60% to 75% of patients, and the response is superior to using either agent alone. [1][2][3][4][5] The addition of G-CSF to the combination of ATG and CSA has shown no significant benefit either in terms of response or survival, 6-8 although it may reduce infectious complications and duration of hospital admission. 6 For patients with nonsevere AA (NSAA) who are transfusion dependent, the combination of ATG and CSA is superior to CSA alone, with a higher response rate, higher blood counts, and improved disease-free survival. 9 Rabbit ATG (rATG) is more commonly used for a second course after relapse or lack of response to a first course of hATG. Response to a second course for nonresponse to a first course varies from 30% to 77% 10,11 and only 11% in children. 12 In contrast, in patients relapsing after a first course, the response to a second course is 65%. 11,13 Until 2007, there were 2 preparations of hATG, namely, lymphoglobulin (Genzyme) and ATGAM (Pfizer). The most commonly used preparation of rATG (thymoglobulin, Genzyme) uses the same immunogen as lymophoglobulin; horses or rabbits are immunized with human thymocytes obtained at the time of cardiac surgery from newborn infants. rATG is more immunosuppressive than hATG; it results in more prolonged lymphopenia, 14 and it is more effective at preventing and treating acute renal allograft rejection. 15 We undertook a European study conducted by th...

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Alpha Interferon (IFN) is a biological agent used for the therapy of an increasing number of diseases, either as an established effective therapeutic tool or in the context of clinical trials. The use of IFN may be complicated by serious adverse reactions. We describe here the clinical course of a variety of vasculopathic complications in association with IFN-therapy in 12 patients with the diagnosis of chronic myeloid leukemia and 1 patient with malignant melanoma treated at our institute. Vascular manifestations in these patients include Raynaud's phenomena, digital ulcerations and gangrene, pulmonary vasculitis, pulmonary hypertension and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). These reactions occurred after 3 months to 3 years of 3-10 million units (MU) daily IFN therapy. Concomitant administration of hydroxyurea (HU) was noted in 5 patients. Discontinuation of IFN and initiation of immunosuppressive therapy brought about a complete resolution or arrested progression of these reactions. IFN-therapy may be complicated by severe vasculopathic/vasospastic complications that usually improve after its discontinuation. Possible underlying mechanisms for these complications are discussed. The early diagnosis of these complications may be vital and IFN should be immediately discontinued when early signs of these complications become evident.

There is unmet need for prediction of treatment response for chronic myeloid leukemia (CML) patients. The present study aims to identify disease-specific/disease-associated protein biomarkers detectable in bone marrow and peripheral blood for objective prediction of individual’s best treatment options and prognostic monitoring of CML patients. Bone marrow plasma (BMP) and peripheral blood plasma (PBP) samples from newly-diagnosed chronic-phase CML patients were subjected to expression-proteomics using quantitative two-dimensional gel electrophoresis (2-DE) and label-free liquid chromatography tandem mass spectrometry (LC-MS/MS). Analysis of 2-DE protein fingerprints preceding therapy commencement accurately predicts 13 individuals that achieved major molecular response (MMR) at 6 months from 12 subjects without MMR (No-MMR). Results were independently validated using LC-MS/MS analysis of BMP and PBP from patients that have more than 24 months followed-up. One hundred and sixty-four and 138 proteins with significant differential expression profiles were identified from PBP and BMP, respectively and only 54 proteins overlap between the two datasets. The protein panels also discriminates accurately patients that stay on imatinib treatment from patients ultimately needing alternative treatment. Among the identified proteins are TYRO3, a member of TAM family of receptor tyrosine kinases (RTKs), the S100A8, and MYC and all of which have been implicated in CML. Our findings indicate analyses of a panel of protein signatures is capable of objective prediction of molecular response and therapy choice for CML patients at diagnosis as ‘personalized-medicine-model’.

Matched related donor allo-SCT is the treatment of choice for patients with severe aplastic anemia (SAA) younger than 40 years of age. The standard conditioning regimen for such patients is cyclophosphamide with antithymocyte globulin. Unmanipulated BM is the best stem cell source for aplastic anemia patients going for SCT. Post-transplant GVHD prophylaxis with cyclosporine should be continued for 1 year. Early graft failure is rare but potentially life-threatening complication of SCT that can be managed with salvage SCT using more intense conditioning regimen.