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Early Relapse (early + relapse)
Selected AbstractsProspective evaluation of intestinal homing memory T cells in ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 5 2004A. L. Hart Abstract Background: Intestinal homing (,7+) memory T cells reflect the mucosal environment in which they were primed. We hypothesized that prospective assessment of cytokine production by intestinal homing (,7+) memory T cells in ulcerative colitis patients followed from remission to early relapse may elucidate shifts in cytokine production relevant to the mucosal environment associated with the early phase of inflammation. Methods: Twelve patients with frequently relapsing ulcerative colitis (,2 relapses in the previous 12 months) were recruited in remission and followed prospectively until relapse. Antibody labeling of whole blood and flow cytometry were used to identify ,7+ cells and ,7, populations within CD3+CD45RA, leukocytes. Production of cytokines (IFN-,, TNF-,, IL-2, IL-10, TGF-,, and IL-4) was determined by intracellular labeling. Results: Early relapse of ulcerative colitis was associated with a shift of T cells from the naive to the memory T cell pool, and further the ratio of ,7+:,7, memory T cells was significantly reduced at relapse (p < 0.01). A greater proportion of intestinal homing ,7+ memory T cells produced IL-4 (p < 0.02) and TNF-, (p < 0.05) at disease relapse compared with remission. Non-intestinal homing ,7,memory T cells also showed a tendency toward an increased production of TH1 and TH2 cytokines. Conclusions: The earliest phase of intestinal inflammation in ulcerative colitis patients is associated with an increase in both TH1 (TNF-, and TH2 (IL-4) cytokines by intestinal homing ,7+ memory T cells. These data support the principles of targeting lymphocyte trafficking as therapies in ulcerative colitis. [source] Early relapse of JAK2 V617F-positive chronic neutrophilic leukemia with central nervous system infiltration after unrelated bone marrow transplantationAMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2007Shinichi Kako Abstract Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder characterized by a proliferation mainly of mature neutrophils. The prognosis is generally poor and an optimal therapeutic strategy remains to be determined. Allogeneic hematopoietic stem cell transplantation (HSCT) is expected to be the only curative therapy so far. We report a 46-year-old male with progressive CNL who underwent bone marrow transplantation from an HLA-matched unrelated donor. After engraftment was achieved on day 35, relapse of CNL was confirmed on day 50. The progression of CNL was very rapid afterward and infiltration to the central nervous system was observed. The Janus Kinase 2 (JAK2) V617F homozygous mutation was detected from the peripheral blood or bone marrow samples throughout the clinical course. From comparison with reports of successful HSCT for CNL in the literature, it was inferred that HSCT should be performed in a stable status before progression. Furthermore, JAK2 V617F-positive CNL may contain an aggressive disease entity in contrast to previous reports. Accumulation of experiences is required to establish a definite role of HSCT in the treatment of CNL and a prognostic significance of JAK2 mutation in CNL. Am. J. Hematol., 2007. © 2006 Wiley-Liss, Inc. [source] Prospective evaluation of intestinal homing memory T cells in ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 5 2004A. L. Hart Abstract Background: Intestinal homing (,7+) memory T cells reflect the mucosal environment in which they were primed. We hypothesized that prospective assessment of cytokine production by intestinal homing (,7+) memory T cells in ulcerative colitis patients followed from remission to early relapse may elucidate shifts in cytokine production relevant to the mucosal environment associated with the early phase of inflammation. Methods: Twelve patients with frequently relapsing ulcerative colitis (,2 relapses in the previous 12 months) were recruited in remission and followed prospectively until relapse. Antibody labeling of whole blood and flow cytometry were used to identify ,7+ cells and ,7, populations within CD3+CD45RA, leukocytes. Production of cytokines (IFN-,, TNF-,, IL-2, IL-10, TGF-,, and IL-4) was determined by intracellular labeling. Results: Early relapse of ulcerative colitis was associated with a shift of T cells from the naive to the memory T cell pool, and further the ratio of ,7+:,7, memory T cells was significantly reduced at relapse (p < 0.01). A greater proportion of intestinal homing ,7+ memory T cells produced IL-4 (p < 0.02) and TNF-, (p < 0.05) at disease relapse compared with remission. Non-intestinal homing ,7,memory T cells also showed a tendency toward an increased production of TH1 and TH2 cytokines. Conclusions: The earliest phase of intestinal inflammation in ulcerative colitis patients is associated with an increase in both TH1 (TNF-, and TH2 (IL-4) cytokines by intestinal homing ,7+ memory T cells. These data support the principles of targeting lymphocyte trafficking as therapies in ulcerative colitis. [source] Autoimmune liver diseases in a paediatric population with coeliac disease , a 10-year single-centre experienceALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010A. R. DI BIASE Summary Backgroud, Coeliac disease (CD) can be associated with liver disease. Gluten-free diet (GFD) normalizes cryptogenic forms, but most likely not autoimmune hepatitis (AIH). For this condition, immunosuppressants represent the treatment. However, when these are stopped, AIH generally relapses. Aim, To determine in CD children liver test abnormality frequency, the effect of GFD alone, or plus prolonged immunosuppressants on AIH course. Methods, Coeliac disease patients with abnormal transaminases were selected; if transaminases <5 × UNL (upper normal limits), GFD alone was administered; if >5 × UNL, liver examinations and biopsy were performed. In AIH, immunosuppressants were administered (5 years). Treatment was stopped only if patients remained in remission during the entire maintenance period and normalized liver histology. Results, A total of 140 out of 350 CD children had hypertransaminaemia: 133 cryptogenic disease, 7 AIH. GFD normalized only cryptogenic hepatitis. During treatment, all AIH persistently normalized clinical and biochemical parameters; after withdrawal, six patients maintained a sustained remission (follow-up range: 12,63 months), while one relapsed. Conclusions, In CD children with AIH, only GFD plus immunosuppressants determines a high remission rate. When clinical remission is reached, a prolonged immunosuppressive regimen induces a high sustained remission rate after treatment withdrawal, indicating that this regimen may prevent early relapse. Aliment Pharmacol Ther,31, 253,260 [source] Altered intestinal permeability is predictive of early relapse in children with steroid-responsive ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2007E. MIELE SUMMARY Aim To determine if small bowel involvement at diagnosis could predict early relapse in children with ulcerative colitis. Methods Children with newly diagnosed ulcerative colitis were evaluated prospectively at three time points: within 1 month, 6 months and 1 year after diagnosis. Clinical activity indices were used to measure disease activity. Laboratory studies were performed at each visit and/or at the time of relapse. At diagnosis, all patients underwent colonoscopy and a cellobiose/mannitol small intestinal permeability study. Some children were further investigated with an upper gastrointestinal endoscopy. Results Thirty-three patients completed the 1-year study. Overall, nine patients (27.3%) relapsed within 6 months of diagnosis, one patient (3%) within 1 year, whereas 23 patients (69.7%) did not relapse. The mean clinical activity indices, laboratory parameters, extent of colonic involvement, upper and lower gastrointestinal histological features were not predictive of early relapse. Results of the cellobiose/mannitol small intestinal permeability study were significantly higher in children who relapsed within 6 months compared with children who did not relapse (P < 0.013). The cellobiose/mannitol small intestinal permeability study was abnormal in 77.8% of early relapsers compared with only 8.3% of non-relapsers. Conclusion Abnormal small intestinal permeability in children with ulcerative colitis could predict a more relapsing disease. [source] Continuous infusion of intermediate-dose cytarabine and fludarabine with idarubicin for patients younger than 60 years with resistant acute myeloid leukemia: A prospective, multicenter phase II study,AMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2009Hawk Kim We assessed continuous infusion (CI) of fludarabine and cytarabine (FLAG) plus idarubicin for patients under 60-years old with resistant acute myeloid leukemia (AML). Induction chemotherapy consisted of idarubicin (12 mg/m2 iv infusion over 30 min on Days 1,3), plus fludarabine (30 mg/m2/day) and cytarabine (1,000 mg/m2/day) on Days 1,5 as a 24-hr CI. G-CSF was added on Days 1,5. The 29 patients enrolled were of median age 40 years (range, 18,57 years); of these, 8 (27.6%) had primary refractory disease, 19 (65.5%) were in early relapse, and 1 each (3.4%) was in multiple relapse and relapse after SCT. In response to induction, 8 patients (27.6%) achieved CR, 2 (6.9%) achieved CRp, and 19 (65.5%) failed treatment; of the latter, 14 had aplasia, three had an indeterminate course, and two showed resistance. Seven patients remain alive, while two were lost to follow-up. Nineteen patients died, 14 of infection, one of toxicity during consolidation, three of relapse after SCT, and two of persistent disease. These findings indicate that although CI of FLAG plus idarubicin was effective for eradicating blasts, it carried a high risk of toxicity. Reduced doses are recommended for CI of FLAG plus idarubicin. Am. J. Hematol., 2009. © 2008 Wiley-Liss, Inc. [source] Most proteinase3- and myeloperoxidase-antineutrophil cytoplasmic antibodies enzyme-linked immunosorbent assays perform less well in treated small-vessel vasculitis than in active diseaseAPMIS, Issue 2009JUDY SAVIGE Antineutrophil cytoplasmic antibodies (ANCA) levels have been thought to follow disease activity, with levels being high at presentation, declining with treatment and increasing just before relapse. However, we have shown that ANCA often persist for many years in patients with clinically inactive Wegener's granulomatosis. ANCA assays are less sensitive for treated disease than for active disease, and the levels in treated patients produce different results in different assay systems. ANCA often persist for years without relapse, and the risk of relapse probably depend on levels that are critical for any individual patient. The capture enzyme-linked immunosorbent assays may be more sensitive in detecting early relapse. Relapse is more common when ANCA levels are high but, although elevated, ANCA levels are lower in relapse than at presentation. Standardized ANCA levels for the definitions of remission and relapse may not be possible, and the optimal ANCA testing protocol for treated disease remains unclear. [source] Association of RANTES promoter polymorphism with juvenile rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 4 2009Tsung-Chieh Yao Objective We recently reported that RANTES was a key molecule in the pathogenesis of juvenile rheumatoid arthritis (JRA) in a longitudinal cohort. This study was undertaken to investigate genetic associations between the RANTES ,28 C/G and ,403 G/A polymorphisms and JRA in a well-documented cohort of patients who were followed up prospectively. Methods Patients with JRA (n = 107) and healthy children (n = 139) were genotyped through use of a polymerase chain reaction,based assay. Association of the RANTES promoter polymorphisms with results of laboratory tests, clinical variables, outcome after clinical remission, and response to intraarticular triamcinolone injection was evaluated in patients who were followed up for >1 year. Results JRA patients had a significantly higher frequency of the RANTES ,28 G/G genotype, as compared with ethnically matched healthy controls. The RANTES ,28 C/G polymorphism was associated with the duration of clinical remission, with patients carrying the RANTES ,28G allele experiencing only 49% of the duration of remission experienced by patients who were RANTES ,28 C/C homozygous. The RANTES ,28 C/G polymorphism was associated with the duration of clinical response to intraarticular triamcinolone injection, with patients carrying the RANTES ,28G allele showing shorter duration of clinical response. No significant association between the RANTES ,403 G/A polymorphism and JRA was found in this Chinese population. Conclusion Our findings indicate that the RANTES ,28 C/G polymorphism represents a genetic risk factor for JRA. It is noteworthy that this RANTES promoter polymorphism was also associated with an early relapse of disease after clinical remission and a shorter duration of clinical response to intraarticular administration of corticosteroids. [source] WT1 gene expression: an excellent tool for monitoring minimal residual disease in 70% of acute myeloid leukaemia patients , results from a single-centre studyBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2004Mette Østergaard Summary Following induction chemotherapy for acute myeloid leukaemia (AML), sensitive determination of minimal residual disease (MRD) in patients achieving complete remission (CR) should enable the detection of early relapse and allow intervention at a more favourable stage than at overt relapse. We have determined the expression levels of the Wilms' tumour gene (WT1) by real-time quantitative polymerase chain reaction (RQ-PCR) in peripheral blood and bone marrow in 133 newly diagnosed AML patients and compared them with those in healthy volunteers. At diagnosis, the WT1 level exceeded normal expression in 118 of 133 (89%) patients, and was high enough to allow for detection of a WT1 decrease of least 1000-fold in 98 of 133 (74%) patients following induction therapy. Concomitant monitoring of fusion transcripts (PML-RAR,, AML1-ETO, MLL-MLL, CBF, - MYH11, or DEK-CAN) in 38 patients identified different relationships between WT1 and fusion transcript levels, the AML1-ETO group showing remarkably low levels of WT1 compared with fusion transcript. In 32 patients analysed longitudinally there was close concordance between relapse and increased WT1 levels. Parallel longitudinal monitoring of WT1 and fusion transcript showed close correlation in 18 of 18 patients. We conclude that WT1 expression by RQ-PCR may be employed as a tool to detect MRD in the majority of fusion transcript-negative AML patients. [source] A single high dose of idarubicin combined with high-dose ARA-C for treatment of first relapse in childhood ,high-risk' acute lymphoblastic leukaemia: a study of the AIEOP groupBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2002Anna Maria Testi Summary. The outcome of children with acute lymphoblastic leukaemia (ALL) and early relapse remains unsatisfactory. In January 1995, the AIEOP (Associazione Italiana di Oncologia ed Ematologia Pediatrica) group opened a trial for children with ALL in first isolated or combined bone marrow relapse defined at high risk according to the length of first remission and the immunophenotype. The treatment plan included the combination of a single high-dose idarubicin and high-dose cytarabine as induction therapy followed by an intensive consolidation and stem cell transplant (SCT). In total, 100 children from 16 Italian centres were enrolled; 80 out of the 99 evaluable patients (81%) achieved second complete remission; eight (8%) died during induction and 11 (11%) failed to respond. A total of 42 out of the 80 responders (52·5%) received a SCT: 19 from an identical sibling, 11 from a matched unrelated donor and 12 from umbilical cord blood cells. The estimated 4-year overall survival and event-free survival were 25% and 21% respectively. Disease-free survival at 4 years was 25·8% for the 80 responders. At 4 years, 39 out of 100 children remain alive, with 27 of them free of leukaemia. This induction therapy has shown antileukaemic efficacy with acceptable toxicity; moreover, all responders proved eligible for intensive consolidation. [source] | ||||||||||