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PubMed2001

Activity and expression of the multidrug resistance proteins P-glycoprotein, MRP1, MRP2, MRP3 and MRP5 in de novo and relapsed acute myeloid leukemia.

The multidrug resistance proteins (MRPs) MRP1, MRP2, MRP3, MRP5 and P-glycoprotein (P-gp) act in concert with each other to give a net resultant pump function in acute myeloid leukemia (AML). The aim of the present study was to analyze the activity of these proteins, which might be upregulated at relapse as compared with de novo AML due to clonal selection. The mRNA expression and activity of P-gp and the MRPs were determined with RT-PCR and flow cytometry, in conjunction with phenotype, as measured with the monoclonal antibodies CD34, CD38 and CD33, in 30 paired samples of de novo and relapsed AML. P-gp and MRP activity varied strongly between the cases (rhodamine 123 efflux-blocking by PSC833: 5.4+/-7.7, and carboxyfluorescein efflux-blocking by MK-571: 4.3+/-6.7, n = 60). P-gp and MRP activity were increased in 23% and 40% of the relapse samples, and decreased in 30% and 20% of the relapse samples, respectively (as defined by a difference of >2 x standard deviation of the assays). Up- or downregulation of mRNA expression was observed for MDR1 (40%), MRP1 (20%), MRP2 (15%), MRP3 (30%), and MRP5 (5%). Phenotyping demonstrated a more mature phenotype in 23% of the relapsed AML cases, and a more immature phenotype in 23% of the relapses, which was independent of the karyotypic changes that were observed in 50% of the studied cases. P-gp and MRP activity correlated with the phenotypic changes, with higher P-gp and MRP activities in less mature cells (r = -0.66, P < 0.001 and r = -0.31, P = 0.02, n = 58). In conclusion, this study shows that P-gp and MRP activity are not consistently upregulated in relapsed AML. However, P-gp and MRP activities were correlated with the maturation stage as defined by immune phenotype, which was observed to be different in 46% of the relapses.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Leukemia lineage-specific chimerism analysis is a sensitive predictor of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome after allogeneic stem cell transplantation.

One of the major complications after allogeneic stem cell transplantation (SCT) in patients with malignant disease is a high frequency of relapse. We have prospectively analyzed the clinical impact of recipient-derived chimeric cells in 30 patients with acute myeloid leukemia and myelodysplastic syndrome after SCT. In order to improve sensitivity and specificity, all samples were cell-separated by using immunomagnetic beads according to the patient's leukemia phenotype, expressed at diagnosis or relapse before SCT. Twelve out of 30 patients experienced a clinical relapse after SCT. Median follow-up time for patients alive and without relapse (n = 15) was 30 (16-47) months. Mixed chimerism in peripheral blood (PB) and bone marrow (BM) > or =1 month post SCT, in the leukemia-affected cell lineage, was detected in 14/30 patients. Ten of these 14 patients relapsed as compared to 2/16 with donor chimerism (DC) (P <0.01). All eight patients with MC in peripheral blood > or =1 month after SCT relapsed vs 4/22 DC patients (P < 0.001). MC was detected a median of 66 (23-332) days before hematological relapse. No correlation was found between T cell MC and relapse. In this study, chimerism analysis showed a higher sensitivity and specificity vs morphological examination. In conclusion, this study may provide a rational basis for treatment with adoptive immunotherapy at an earlier time after SCT than at present, in patients with AML and MDS, in order to treat recurrences of malignant disease.

Acute Disease↗

PubMed2004

Is there a definition of remission in late-life depression that predicts later relapse?

Remission of depressive symptoms is the goal of all antidepressant therapy. Rating scales define remission in clinical trials, but it is unclear how well these definitions predict risk of later relapse. We measured the sensitivity and specificity of a range of Montgomery-Asberg Depression Rating Scale (MADRS) cutoff scores at 3- and 6-months, wherein scores above a given cutoff would predict relapse over an 18-month period. We examined 153 elderly depressed subjects exhibiting a MADRS < or = 15 after 3 or 6 months of antidepressant therapy. Subjects who subsequently exhibited a MADRS > 15 during the 18-month study period were defined as relapsed. Receiver operating characteristic (ROC) curves were developed and area under the curve (AUC) values calculated for the sensitivity and specificity of 3- and 6-month MADRS scores to predict future relapse. The 3-month ROC had an AUC value of 0.63; the 6-month ROC had an AUC value of 0.66. There was no MADRS cutoff found that could predict likelihood of relapse with good sensitivity and specificity. A post hoc analysis where relapse rate was adjusted by controlling for medical comorbidity, disability, and social support showed no change in the ROCs or AUC values. The higher the MADRS score at 3 and 6 months, the greater the likelihood of relapse. With no clean MADRS cutoff score, the goal of antidepressant therapy should be the lowest possible degree of depressive symptomatology to minimize risk of later relapse. Definitions of remission that are better associated with longer-term outcomes are needed.

Aged↗

PubMed1999

P-glycoprotein is an independent prognostic factor predicting relapse in childhood acute lymphoblastic leukaemia: results of a 6-year prospective study.

P-glycoprotein (P-gp), a cellular drug-efflux pump, is thought to be one of the major causes of multidrug resistance (MDR) in malignancies. Since therapeutic strategies are being developed to circumvent drug resistance by inhibiting P-gp function, large prospective studies evaluating the clinical relevance of P-gp in childhood acute lymphoblastic leukaemia (ALL) are warranted. P-gp expression was evaluated over a period of 6 years in 102 consecutive patients with de novo childhood ALL and in 35 children with relapse of ALL. Bone marrow and blood smears were studied immunocytochemically with two monoclonal antibodies at initial diagnosis and at relapse. P-gp expression was found in 14 (14%) patients at initial diagnosis. After induction treatment, complete remission was achieved in 100/102 patients (98%), of whom 19 relapsed. Cumulative event-free survival was significantly higher in the P-gp-negative group compared with the P-gp-positive population (Logrank P = 0.02). Multivariate analysis showed the results to be independent of age, WBC count and karyotype, and concomitantly underlined the importance of MDR1 phenotype detection in childhood ALL. P-gp expression was more frequently found at relapse (34%) than at primary diagnosis (P = 0.01). In the relapsed patient group, P-gp-positive patients had a 2-fold greater risk for adverse clinical outcome than the P-gp-negative relapsed patients. P-gp expression was not induced by exposure to previous chemotherapy since the majority of P-gp-negative patients remained negative at relapse. P-glycoprotein expression in newly diagnosed childhood ALL is an independent adverse prognostic parameter with a predictive value for relapse.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

CD34+ cell dose predicts relapse and survival after T-cell-depleted HLA-identical haematopoietic stem cell transplantation (HSCT) for haematological malignancies.

Seventy-eight patients with haematological malignancies, received T-cell-depleted stem cell transplants and cyclosporin followed by delayed add-back of donor lymphocytes to prevent leukaemia relapse. The source of stem cells was bone marrow in 50 patients and granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood in 28 patients. In univariate analysis, only the CD34+ cell dose (but not the stem cell source or the T lymphocyte dose) and disease status were predictive for transplant-related mortality, relapse and survival. Patients receiving >/= 3 x 106 CD34+ cells/kg had an overall actuarial survival of 68% compared with 52%, 35% and 10%, respectively, for cell doses of 2-2.99, 1-1.99 and < 1 x 106/kg. Multivariate analysis of risk factors for relapse identified disease risk and CD34+ cell dose as the only factors. Relapse was 62.5% in 38 patients at high risk of relapse vs. 25% for 40 patients at intermediate or low risk. CD34+ cell doses of >/= 3 x 106/kg were associated with a 13.5% relapse vs. 48% for recipients of lower doses. This favourable effect of CD34+ cell dose on relapse was apparent in both high- and intermediate- plus low-risk groups. Our results support the potential benefit of a high stem cell dose in lowering transplant-related mortality (TRM) and in reducing relapse after allogeneic marrow or blood stem cell transplants.

Adult↗

PubMed2000

The UK experience in treating relapsed childhood acute lymphoblastic leukaemia: a report on the medical research council UKALLR1 study.

We have examined the toxicity and overall outcome of the Medical Research Council UKALL R1 protocol for 256 patients with relapsed childhood acute lymphoblastic leukaemia (ALL). Second remission was achieved in over 95% of patients. Two patients died during induction and seven patients died of resistant disease. The overall actuarial event-free survival (EFS) at 5 years for all patients experiencing a first relapse was 46% (95% CI 40-52). Duration of first remission, site of relapse, age at diagnosis and sex emerged as factors of prognostic significance. Five-year EFS was only 7% for children relapsing in the bone marrow within 2 years of diagnosis, but was 77% for those relapsing without bone marrow involvement > 2.5 years from diagnosis. All analyses in this report are by treatment received. For those receiving chemotherapy alone, the 5-year EFS was 48%; for autologous bone marrow transplantation (BMT), the 5-year EFS was 47%; for unrelated donor BMT, it was 52%; and for related donor BMT, the 5-year EFS was 45%. The groups, however, were not comparable with respect to risk factor profile, and therefore direct comparison of EFS is misleading. Adjustment for time to transplant and prognostic factors was used to reduce the effects of biases between treatment groups, but did not suggest benefit for any particular treatment. There was failure of our planned randomization scheme in this trial with only 9% of those eligible being randomized, which highlights the difficulties in running randomized trials especially in patients who have relapsed from a previous trial. The optimal treatment for relapsed ALL therefore remains uncertain. Alternative approaches are clearly needed for those with early bone marrow relapse if outcome is to improve.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Incidence and nature of CD20-negative relapses following rituximab therapy in aggressive B-cell non-Hodgkin's lymphoma: a retrospective review.

Re-treatment with rituximab for B-cell non-Hodgkin's lymphoma (NHL) relapsing after previous rituximab therapy has recently been shown to be clinically efficacious. Although the mechanism of resistance to rituximab re-treatment in non-responding patients is unknown, it is possible that loss of CD20 expression in the relapsed NHL could be important in some patients. We examined the incidence and nature of CD20 negative relapses following rituximab therapy in aggressive B-cell NHL treated at our institution. Of a total of 18 patients who received rituximab, 13 have relapsed, with 10 patients subsequently undergoing repeat tissue biopsy. Six of these 10 patients (60%) were shown to have lost CD20 expression by either immunohistochemistry and/or flow cytometry. Furthermore, three of the six patients who relapsed with CD20-negative NHL also suffered relapses at unusual anatomical sites. We conclude that loss of CD20 expression in aggressive B-cell NHL relapsing post-rituximab therapy is common. As such, repeat tissue biopsy should be undertaken to document CD20 expression by both flow cytometry and immunohistochemistry prior to considering repeated courses of rituximab in relapsed aggressive lymphomas.

Adult↗

PubMed2003

Minimal residual disease detection after allogeneic stem cell transplantation is correlated to relapse in patients with acute lymphoblastic leukaemia.

Minimal residual disease (MRD) assessments were performed retrospectively after allogeneic stem cell transplantation (SCT) in 32 patients (23 children and nine adults) with acute lymphoblastic leukaemia (ALL). Using immunoglobulin and T-cell receptor rearrangements as clonal markers, MRD was detected after SCT in nine patients, eight of whom have relapsed. The median time between first MRD detection and relapse was 5.5 (range 0.5-30) months. In 23 patients without MRD, six have relapsed to date: lower sensitivity, central nervous system relapse and clonal exchange of the leukaemic clone were factors that may explain the failure to detect MRD before relapse in these patients. In univariate analysis, factors associated with decreased risk of relapse were transplantation in first remission (P=0.02), the combination of acute and chronic graft-versus-host disease (P=0.03) and absence of MRD after SCT (P=0.005). In multivariate analysis, only MRD detection after SCT was significantly associated with increased risk of relapse (P=0.05). In conclusion, MRD detection after SCT is correlated with relapse and provides the opportunity for initiating immunotherapeutic intervention at an early stage when the tumour cell burden is still low.

Adolescent↗

PubMed2003

Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia.

We have reviewed the outcome after relapse in a cohort of 505 children with acute lymphoblastic leukaemia (ALL) seen at a single institution. The majority of relapses (74%) occurred within 3 years from diagnosis, and most involved the bone marrow alone or with overt extramedullary relapse. Early relapse was more common in children with T-ALL and those with unfavourable cytogenetics. Factors influencing second remission included length of first remission and type of relapse. Children who had not received previous cranial irradiation had a superior survival. The German relapse score involving length of first remission, site of relapse and immunophenotype was highly predictive of outcome: event-free survival with 95% confidence intervals at 6 years for patients who received modern treatment [intensive chemotherapy or bone marrow transplantation (BMT)] was 78% (51-92%) for standard risk, 41% (33-49%) for intermediate risk and 19% (10-31%) for highest risk. Retrospective comparison of BMT with chemotherapy showed no difference in the intermediate-risk group but a possible advantage in the highest risk group. Follow-up of 235 patients who relapsed after chemotherapy and received a third course of treatment showed an extremely high early attrition rate, but a small number of patients survived in third remission. We conclude that new approaches are needed to individualize therapy in intermediate-risk patients and to improve the outcome for those in the highest risk group. Only a small number of children can be treated effectively in third remission.

Bone Marrow Transplantation↗

PubMed2003

Childhood nephrotic syndrome in relapse is associated with down-regulation of monocyte CD14 expression and lipopolysaccharide-induced tumour necrosis factor-alpha production.

Interleukin-13 (IL-13) is a known modulator of monocyte function, down-regulating monocyte surface markers such as CD14 and proinflammatory cytokines. We have shown previously that lymphocyte IL-13 gene expression was up-regulated during relapses in children with steroid-responsive nephrotic syndrome (SRNS). In this study, we examined the monocyte mRNA expression and lipopolysaccharide (LPS)-stimulated intracellular production of tumour necrosis factor-alpha (TNF-alpha) and IL-8 in children with SRNS during relapse and remission. Additionally, we investigated CD14 mRNA levels, CD14 surface expression and its soluble component (sCD14) in serum. Our results showed that the percentages of TNF-alpha positive monocytes following LPS stimulation were significantly lower in nephrotic children in relapse (64.4 +/- 13.7%) compared to remission (81.6 +/- 9.0%, P < 0.005). This was associated with down-regulation of CD14 mRNA, as well as both membrane and sCD14 in patients with nephrotic relapse (82.9 +/- 10.1% and 1.23 +/- 0.30 micro g/ml, respectively) compared to remission (93.9 +/- 3.2% and 1.77 +/- 0.82 micro g/ml, respectively) (P < 0.003). Although we demonstrated a decrease in LPS-stimulated intracellular production of TNF-alpha in monocytes from patients with nephrotic relapse, we were unable to show a concomitant decrease in mRNA expression during relapses. This could be explained by down-regulation of gene expression at the translational rather than transcriptional level. In conclusion, it is conceivable that up-regulation of T-cell IL-13 production in children with active nephrotic relapse was associated with suppression of monocyte CD14 expression, down-regulating pro-inflammatory cytokine production, and could account for the increased susceptibility to bacterial sepsis seen in nephrotic children in active relapse.

Adolescent↗

PubMed2002

Outcome of relapse in lupus nephritis: roles of reversal of renal fibrosis and response of inflammation to therapy.

BACKGROUND: Renal relapse in lupus nephritis has been shown to have ominous prognostic significance with the majority of patients progressing to doubling of serum creatinine (CRX2). However, not all patients do so. This report explores the roles of response of inflammation to therapy and of glomerular scarring and interstitial fibrosis and their potential reversal to outcome of renal relapse. METHODS: Renal biopsies from 71 patients with lupus nephritis with an initial biopsy (Bx1) and systematic control biopsy (Bx2) after six months of therapy, as well as subsequent biopsies for clinical indications, were studied. The relationships of morphologic factors to renal relapse and its outcome as well as to CRX2 and end-stage renal disease (ESRD) were analyzed. Cox proportional hazards modeling was used to assess association of morphologic variables with outcomes. RESULTS: Renal interstitial fibrosis and glomerular segmental scarring were partially reversible in 17 and 11 patients, respectively. This decline was associated with an excellent prognosis, with only one patient in each group (5.9% and 9.1% respectively) progressing to CRX2. All 18 patients who progressed to CRX2 either failed to respond to therapy (7 patients) as defined by normalization of serum creatinine (SCr) and reduction of proteinuria to < or =1 g/day, or relapsed after initial response (11 patients), as defined by recent rise of SCr > 50% and/or proteinuria > 3.5 g/day. However, relapse also occurred in 11 of 47 other patients without progression to CRX2. These patients showed a greater initial response of inflammation and deposits to therapy and fibrous lesions partially reversed in the period prior to relapse, so that active lesions were superimposed on a lower level of chronic lesions. By contrast, chronic lesions mounted steadily in those who progressed to CRX2. Cox proportional hazards modeling indicated a strong association of inflammatory variables with renal relapse, CRX2 and ESRD. However, the extent of immunoglobulin deposits was not significantly associated with any outcome. Finally, we found that failure of disease to remit also is associated with a high rate of CRX2 (64.8% vs. 13.0%, P = 0.00034). CONCLUSIONS: Interstitial fibrosis and glomerular scarring in systemic lupus erythematosus are partially reversible, and this reversal is attended by an excellent outcome. The outcome of renal relapse is determined by the initial response of inflammatory and chronicity elements to therapy, those with prior partial reversal of interstitial and glomerular scarring having a good outcome, and those in whom fibrotic lesions have continued to increase and have a poor outcome. Inflammatory variables appear to be more important in determining outcome than immunoglobulin deposits.

Chronic Disease↗

PubMed2001

Two-year remission and subsequent relapse in children with newly diagnosed epilepsy.

PURPOSE: Although remission is the ultimate measure of seizure control in epilepsy, and epilepsy syndrome should largely determine this outcome, little is known about the relative importance of syndrome versus other factors traditionally examined as predictors of remission or of relapse after remission. The purpose of this study was to examine remission and relapse with respect to the epilepsy syndrome and other factors traditionally considered with respect to seizure outcome. METHODS: A prospectively identified cohort of 613 children with newly diagnosed epilepsy was assembled and is actively being followed to determine seizure outcomes. Epilepsy syndrome and etiology were classified at diagnosis and again 2 years later. Remission was defined as 2 years completely seizure-free, and relapse as the recurrence of seizures after remission. Multivariable analysis was performed with the Cox proportional hazards model. RESULTS: Five hundred ninety-four of the original 613 children were followed > or = 2 years (median follow-up, 5 years). Remission occurred in 442 (74%), of whom 107 (24%) relapsed. On multivariable analysis, idiopathic generalized syndromes and age at onset between 5 and 9 years were associated with a substantially increased remission rate, whereas remote symptomatic etiology, family history of epilepsy, seizure frequency, and slowing on the initial EEG were associated with a decreased likelihood of attaining remission. Young onset age (<1 year) and seizure type were not important after adjustment for these predictors. Relapses occurred more often in association with focal slowing on the initial EEG and with juvenile myoclonic epilepsy. Benign rolandic epilepsy and age at onset <1 year were associated with markedly lower risks of relapse. About one fourth of relapses were apparently spontaneous while the child was taking medication with good compliance, and more than half occurred in children who were tapering or had fully stopped medication. CONCLUSIONS: A large proportion of children with epilepsy remit. Symptomatic etiology, family history, EEG slowing, and initial seizure frequency negatively influence, and age 5-9 years and idiopathic generalized epilepsy positively influence the probability of entering remission. Factors that most influence relapse tend to be different from those that influence remission.

Age Factors↗

PubMed2004

Azathioprine and mesalamine for prevention of relapse after conservative surgery for Crohn's disease.

BACKGROUND & AIMS: Because the reoperation rate for Crohn's disease is high after resective surgery, use of conservative surgery has increased. Mesalamine was investigated for the prevention of postoperative relapse, with disappointing results. The role of azathioprine in the postoperative setting is unknown. We aimed to compare the efficacy and safety of azathioprine and mesalamine in the prevention of clinical and surgical relapse in patients who have undergone conservative surgery for Crohn's disease. METHODS: In a prospective, open-label, randomized study, 142 patients received azathioprine (2 mg. kg -1. day -1 ) or mesalamine (3 g/day) for 24 months. Clinical relapse was defined as the presence of symptoms with a Crohn's Disease Activity Index score >200 and surgical relapse as the presence of symptoms refractory to medical treatment or complications requiring surgery. RESULTS: After 24 months, the risk of clinical relapse was comparable in the azathioprine and mesalamine groups, both on intention-to-treat (odds ratio [OR], 2.04; 95% confidence interval [CI], 0.89-4.67) and per-protocol analyses (OR, 1.79; 95% CI, 0.80-3.97). No difference was observed with respect to surgical relapse at 24 months between the 2 groups. In a subgroup analysis, azathioprine was more effective than mesalamine in preventing clinical relapse in patients with previous intestinal resections (OR, 4.83; 95% CI, 1.47-15.8). More patients receiving azathioprine withdrew from treatment due to adverse events than those receiving mesalamine (22% vs. 8%; P = 0.04). CONCLUSIONS: While no difference was observed in the efficacy of azathioprine and mesalamine in preventing clinical and surgical relapses after conservative surgery, azathioprine is more effective in those patients who have undergone previous intestinal resection.

Adolescent↗

PubMed2001

[The effect of a bacterial immunostimulant (human Enterococcus faecalis bacteria) on the occurrence of relapse in patients with].

The following double-blind, placebo-controlled, multicenter study investigated the influence of a bacterial immunostimulant (Symbioflor 1, cells and autolysate of human Enterococcus faecalis) on the occurrence of relapses in patients with chronic recurrent bronchitis (n = 136; placebo n = 66, verum n = 70) in a 6 months treatment period and a follow-up period of 8 months, compared to placebo. Under verum 39 incidents of relapses were recorded, which was about 60% the number observed among the patients treated with placebo (66 incidents). The verum preparation exhibited superior clinical efficacy compared to placebo (p = 0.001) in the Kaplan-Meier test. This better clinical efficiency of the test preparation was particularly observed during the treatment period, with 12 vs. 27 relapses (p = 0.013), but less during the follow-up observation period, with 27 vs. 39 relapses (p = 0.127). In addition, the time span until occurrence of the first relapse was clearly longer under verum (699 days) than under placebo (334 days) and after the end of the observation period 91% of patients under verum experienced only one relapse compared to 62% in the placebo group (p = 0.01). Severity of relapses under verum was also reduced significantly (chi 2; p = 0.001. Only 4 patients under verum required antibiotic therapy compared to 13 patients under placebo. Verum was equally well tolerated as placebo, with no serious side effects in either group. No changes in laboratory tests--haematology and clinical chemistry--were observed. It can be concluded, that previously demonstrated immunomodifying effects of the test preparation have clinical relevance for the treatment of chronic recurrent bronchitis because not only the number but also the severity of acute relapses could be clearly reduced. This is discussed in view of the current literature.

Adjuvants, Immunologic↗

PubMed1996

Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease.

BACKGROUND: Patients with Crohn's disease may have periods of remission, interrupted by relapses. Because fish oil has antiinflammatory actions, it could reduce the frequency of relapses, but it is often poorly tolerated because of its unpleasant taste and gastrointestinal side effects. METHODS: We performed a one-year, double-blind, placebo-controlled study to investigate the effects of a new fish-oil preparation in the maintenance of remission in 78 patients with Crohn's disease who had a high risk of relapse. The patients received either nine fish-oil capsules containing a total of 2.7 g of n-3 fatty acids or nine placebo capsules daily. A special coating protected the capsules against gastric acidity for at least 30 minutes. RESULTS: Among the 39 patients in the fish-oil group, 11 (28 percent) had relapses, 4 dropped out because of diarrhea, and 1 withdrew for other reasons. In contrast, among the 39 patients in the placebo group, 27 (69 percent) had relapses, 1 dropped out because of diarrhea, and 1 withdrew for other reasons (difference in relapse rate, 41 percentage points; 95 percent confidence interval, 21 to 61; P < 0.001). After one year, 23 patients (59 percent) in the fish-oil group remained in remission, as compared with 10 (26 percent) in the placebo group (P = 0.003). Logistic-regression analysis indicated that only fish oil and not sex, age, previous surgery, duration of disease, or smoking status affected the likelihood of relapse (odds ratio for the placebo group as compared with the fish-oil group, 4.2; 95 percent confidence interval, 1.6 to 10.7). CONCLUSIONS: In patients with Crohn's disease in remission, a novel enteric-coated fish-oil preparation is effective in reducing the rate of relapse.

Adult↗

PubMed2001

Prospective multicenter study of relapse after treatment for acute asthma among children presenting to the emergency department.

OBJECTIVE: Single-center studies have reported varying relapse rates after treatment of patients with acute asthma. We determined the relapse rate after emergency department (ED) treatment in a cohort of children. DESIGN: This was a prospective inception cohort study performed during 1997-1998. SETTING: The study was performed in 44 EDs including both general and pediatric centers. PATIENTS: Children (n = 1184) aged 2 to 17 years who had been admitted to EDs, with acute asthma restricted to 881 patients discharged from the ED. MAIN RESULTS: Two weeks after discharge, families were telephoned to determine relapse. Follow-up data were available for 762 (86%) of the children with a 10% incidence of relapse. On univariate analysis several factors were associated with relapse including current medications and markers of asthma severity. On multivariate analysis the factors associated with relapse were age (OR 1.4 per 5-year increase), use of second-line asthma medications (OR 3.7), exposure to cigarette smoke (OR 0.5), and ED visits within the past year (OR 1.2 per 5 ED visits). CONCLUSIONS: The incidence of relapse among children is lower than that observed among adults and varies with age. Other risk factors such as frequent ED visits are likely markers of chronic asthma severity. Further research should focus on ways to decrease the relapse rate among patients at high risk.

Asthma↗

PubMed1990

Molecular relapse in chronic myelogenous leukemia patients after bone marrow transplantation detected by polymerase chain reaction.

Relapse of chronic myelogenous leukemia after bone marrow transplantation can be detected by using clinical, cytogenetic, or molecular tools. A modification of the polymerase chain reaction can be used in patients to detect low levels of the BCR-ABL-encoded mRNA transcript, a specific marker for chronic myelogenous leukemia. Early detection of relapse after bone marrow transplantation could potentially alter treatment decisions. We prospectively evaluated 19 patients for evidence of molecular relapse, cytogenetic relapse, and clinical relapse after bone marrow transplantation. We used the polymerase chain reaction to detect residual BCR-ABL mRNA in patients followed up to 45 months after treatment (median, 15 months; range, 6-45 months) and found 4 patients with BCR-ABL mRNA expression following bone marrow transplantation. In 2 patients BCR-ABL mRNA was detected in all samples, and both have developed cytogenetic relapse. In 1 patient BCR-ABL mRNA was detected transiently during the first month after transplant but was undetectable thereafter. The fourth patient had BCR-ABL mRNA 6 months after bone marrow transplantation but not in prior samples. Fifteen patients did not express detectable BCR-ABL mRNA. All 19 patients remain in clinical remission. In this prospective study of chronic myelogenous leukemia patients treated with bone marrow transplantation, molecular relapse preceded cytogenetic relapse in those patients who persistently express BCR-ABL mRNA. We recommend using standard clinical and cytogenetic testing to make patient care decisions until further follow-up determines the clinical outcome of those patients with residual BCR-ABL mRNA transcripts detected by polymerase chain reaction.

Base Sequence↗

PubMed1998

A clinical and flow cytometric model to study remission and relapse in psoriasis.

The aim of the present study has been to analyse remission and relapse characteristics in psoriasis vulgaris. In 15 patients, two different psoriatic lesions (clinical and flow cytometric study) were treated with clobetasol propionate until clearance for maximally 23 days. In the clinical study only cleared lesions were divided into three test sectors with different post-clearance treatment: (1) alcoholic solution under occlusion, (2) occlusion only, and (3) no treatment. In the flow cytometric study, biopsies were taken from the test lesion before clobetasol therapy (i), at clearance (ii), and at relapse from both visibly affected and unaffected skin (iii, iv). Epidermal proliferation, differentiation and inflammation were quantified by multiparameter flow cytometry. The clinical evaluation worked well and could discriminate between the different therapy modalities. After 28 days, 80% of untreated sectors showed a relapse. Occlusion decreased this percentage to 50%. Application of the alcoholic solution further decreased this percentage to 30%. The flow cytometric analysis demonstrated a very low proliferative activity of the basal compartment at clearance. This activity was higher in the visibly unaffected skin at relapse, whereas highest values were assessed in the affected skin at relapse. Interestingly, at relapse the proliferative activity in the suprabasal compartment of the visibly unaffected skin had increased to values identical to the affected skin. The present model allows standardized comparison of different approaches for maintenance therapy in psoriasis vulgaris. We demonstrate that occlusion has an inhibitory effect on the tendency to relapse after successful treatment with clobetasol propionate. Quantitative information on remission and relapse of psoriasis can be obtained by multiparameter flow cytometry.

Administration, Topical↗