Allogeneic peripheral blood stem cell transplantation using reduced intensity versus myeloablative conditioning regimens for the treatment of leukemia.

Reduced intensity conditioning (RIC) have allowed the application of transplantation to older patients and to patients with underlying medical problems. Between October, 1999, and June, 2003, 61 patients with acute leukemia or chronic myeloid leukemia received allogeneic peripheral blood hematopoietic stem cell transplantation (HSCT) from HLA-identical siblings. Thirty-four were conditioned with myeloablative protocols and twenty-seven with RIC regimens. The patients in the myeloablative group were younger (29 vs. 37 years; p < 0.0003), most of them were transplanted in complete remission (74% vs. 59%; p < 0.03), had a shorter interval between diagnosis and HSCT (12 vs. 21 months; p < 0.02) and a greater proportion belonged to standard-risk prognosis (68% vs. 48%; p < 0.1). The median times to neutrophil, platelet and red blood cell engraftment for the myeloablative and RIC groups were 14 versus 11 days (p < 0.009), 17 versus 9 days (p < 0.0001), and 19 versus 12 days (p < 0.007), respectively. Transfusion requirements were lower in the RIC group. Severe mucositis was present in 32% and 7%, respectively (p < 0.01). The proportion of patients having acute graft versus-disease (GVHD), chronic GVHD, and infections was the same, as well as early and late mortality, disease-free survival, and overall survival. Analyzing all the patients together, three factors significantly influenced overall survival: standard risk patients, complete remission at transplant, and the absence of severe acute GVHD. In conclusion, our data suggest that even in high-risk patients, RIC transplantation seems to be as useful as ablative HSCT.

Molecular heterogeneity of prolactin in the plasma of patients with systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) has been associated with high levels of prolactin in the circulation of some patients. Although prolactin stimulates immune responses, the relationship between hyperprolactinemia and the pathophysiology of SLE remains controversial. This study was undertaken to investigate whether circulating bioactive prolactin isoforms are associated with the activity of SLE. METHODS: The molecular heterogeneity of prolactin was studied in the plasma of patients with active and inactive SLE and in healthy volunteers by radioimmunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), Nb2-cell bioassay, and immunoprecipitation-Western blots. The specificity of the bioassay determinations was assessed by neutralization of growth-promoting effects with antiserum to human prolactin. RESULTS: Significantly higher prolactin levels were detected by bioassay and by ELISA than by RIA in both subsets of SLE patients and in normal individuals. Plasma prolactin levels in the SLE patients were significantly greater than those in the normal controls when measured by ELISA, but not by RIA or bioassay. The bioassay:ELISA and bioassay:RIA ratios were similar between SLE patients and controls, suggesting that prolactin biopotency was not altered with the disease, and none of the 3 assays detected a difference in prolactin levels between patients with active SLE and those with inactive SLE. However, the prolactin detected in plasma was associated with immunoreactive proteins of 130 kd and 23 kd, and the concentration of the 130-kd prolactin-like species was 10-fold higher in inactive SLE versus active SLE patients. CONCLUSION: Discrepancies among assays substantiate the molecular heterogeneity of circulating prolactin. The prolactin isotype that is found in association with inactive SLE could be of potential use as a marker for the inactive form of the disease and as an index for the efficacy of treatment.

High dose intravenous immunoglobulin (IVIg) in severe refractory rheumatoid arthritis: no evidence for efficacy.

OBJECTIVE: A number of reports have recently suggested that high doses of intravenous immunoglobulins may exert beneficial effects in rheumatoid arthritis. One proposed mechanism for this effect is suppression of the generation of pro-inflammatory cytokines, particularly tumor necrosis factor alpha (TNF alpha). We have undertaken a prospective open study of IVIg in patients with severe refractory RA who have failed at least four second line drugs, including methotrexate, and who were receiving NSAIDs and prednisone only. METHODS: Four patients, 3 males and 1 female, with an average age of 58.25 years (range 41-69 years) and a mean disease duration of 13 years (range 9-14 years), were given IVIg at a dose of 1 g per day for 2 days once a month for 3 months. All patients had active disease at baseline as indicated by an average tender joint count of 15 and an average swollen joint count of 15.25. Clinical assessments were performed according to the WHO/ILAR recommendations at baseline and at monthly intervals up to 4 months after the initiation of IVIg therapy. Patients were classified as responders or non-responders according to the Paulus criteria. Laboratory assessment included a CBC, ESR, and whole blood cytokine ELISA for TNF alpha, TNF R1, and TNF R2 at baseline, 1 day, 7 days and 3 months after the initiation of therapy. RESULTS: None of the patients met the Paulus criteria for either improvement or worsening. Furthermore, increased TNF alpha production in lipopolysaccharide (LPS) stimulated whole blood assays was consistently noted in 3 out of the 4 patients during the course of therapy which, together with the lack of clinical efficacy, prompted us to curtail further evaluation of this therapy. CONCLUSION: We were unable to discern any beneficial effects of IVIg therapy, and suggestions that it may enhance TNF alpha generation as well as its substantial cost mandate caution in the future use of this agent in RA.

An open study of pentoxifylline in the treatment of severe refractory rheumatoid arthritis.

OBJECTIVE: Recent data implicates the cytokine, tumor necrosis factor alpha (TNF-alpha), in the pathophysiology of rheumatoid arthritis (RA). In vitro data suggest that pentoxifylline may possess anti-TNF-alpha properties. We have therefore carried out a prospective 3-month open evaluation of pentoxifylline in a group of adult patients with RA refractory to conventional disease remittive therapies. METHODS: Nineteen patients with RA were included and clinical assessments were performed according to the World Health Organization/International League of Associations for Rheumatology (WHO/ILAR) criteria at baseline, and one and 3 months after the initiation of therapy. Laboratory assessments included a complete blood count, erythrocyte sedimentation rate (ESR), and whole blood assays of TNF-alpha production. TNF-alpha was assayed using ELISA and semiquantitative polymerase chain reaction methodologies. RESULTS: A significant diminution in number of tender and swollen joints as well as the ESR was noted after 3 months (p < 0.05) although no consistent effects on TNF-alpha production were observed. Furthermore, whole blood assays of TNF-alpha production shortly after initiation of pentoxifylline therapy were not predictive of the clinical response to this agent. CONCLUSION: Although pentoxifylline may possess therapeutic properties in RA, any beneficial effects appear to be unrelated to changes in TNF-alpha generation in whole blood assays.

Research in rheumatology: a six-month review of selected medical journals.

Research in rheumatology has dramatically increased in the past decades, and researchers can choose among over 20,000 journals to publish their findings. The purpose of this study was to examine the current extent and impact of rheumatological research on the medical literature. The tables of contents of 1,158 biomedical journals were analyzed during a 6-month period and those with a rheumatology-related title were selected. In total, 2,549 articles from 406 journals were related to rheumatology. The 10 rheumatology journals selected for the analysis contained 769 articles (30% of the total); thus, over two-thirds of the information on rheumatology topics was provided by non-rheumatology journals. Over 65 different journals included information about rheumatoid and systemic lupus erythematosus. It is concluded that research in rheumatology is extensive and widespread. Since articles in rheumatology are scattered over a variety of journals, it is suggested that the periodic publication of a rheumatology reference index may assist rheumatologists in updating information from various sources.