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PubMedDate not supplied

Extended-release venlafaxine in relapse prevention for patients with major depressive disorder.

Many studies have demonstrated that venlafaxine is an efficacious and safe treatment for major depressive disorder (MDD). This double-blind, placebo-controlled study was performed to evaluate the efficacy of venlafaxine extended-release (XR) (75-225 mg/day) in the prevention of relapse of depression. Patients with MDD who responded to an 8-week course of venlafaxine XR treatment, i.e., had a score < or = 3 on the Clinical Global Impressions scale-Severity of Illness item (CGI-S) and a 21-item Hamilton Rating Scale for Depression (HAM-D(21)) score < or = 10, were randomly assigned to receive continuation treatment (up to 6 months) with venlafaxine XR (n=161) or placebo (n=157). The main efficacy outcome measure was the number of patients who experienced a relapse of depression. Relapse was defined by either a combination of a patient meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for MDD and a CGI-S score > or = 4, two consecutive CGI-S scores > or = 4, or a final CGI-S score > or = 4 for a patient who withdrew from the study. The cumulative probability of relapse was calculated using the Kaplan-Meier method of survival analysis. During the 6-month evaluation period, significantly more patients in the placebo group had a relapse of MDD than did patients who continued treatment with venlafaxine XR. Cumulative relapse rates at 3 and 6 months were 19 and 28%, respectively, for venlafaxine XR, and 44 and 52%, respectively, for placebo. This study demonstrates that venlafaxine XR is an effective and safe continuation therapy.

Adult↗

PubMed2004

Evolution of FLT3-ITD and D835 activating point mutations in relapsing acute myeloid leukemia and response to salvage therapy.

Internal tandem duplications (ITDs) of the juxtamembrane region of the FLT3 tyrosine kinase receptor are the most frequent genetic alterations in acute myeloid leukemia (AML). The presence of this mutation has been recognized as an independent poor prognostic factor. In this study, we compared the FLT3 mutational status between diagnosis and subsequent relapses in 31 patients with AML. At diagnosis, seven patients were identified to contain FLT3-ITD mutations and one patient to harbor the D835 mutation. Five patients remained FLT3-ITD positive throughout the disease course (+/+). Three patients lost the FLT3 gene mutation at first (one FLT3-ITD, one D835 mutation), or second relapse (one FLT3-ITD) (+/-). One additional patient lost a small FLT3-ITD positive clone at relapse and at the same time gained an apparently unrelated FLT3-ITD positive clone. One patient without FLT3 mutation at diagnosis relapsed with an FLT3-ITD mutation (-/+). A shorter median duration of first remission (6 months versus 11.5 months) and a higher relapse rate after salvage therapy (e.g. allogeneic peripheral blood stem cell transplantation) resulted in a lower leukemia-free survival in the FLT3 mutated group (11% versus 31%). The loss of a clone with a mutation in the FLT3 gene at relapse did not improve the prognosis.

Acute Disease↗

PubMed2005

Site of relapse after chemotherapy alone for stage I and II Hodgkin's disease.

BACKGROUND: Short course chemotherapy followed by radiotherapy is a standard treatment for early Hodgkin's disease. There is yet no consensus regarding the appropriate radiotherapy portal following chemotherapy. A good guide to the adjuvant radiotherapy field is the site of relapse in patients treated with chemotherapy alone. PATIENTS AND METHODS: From 1980 to 1996, 61 patients with stage I and II supradiaphragmatic Hodgkin's disease were treated with chemotherapy alone at the Royal Marsden Hospital. We undertook a retrospective review and failure analysis to define the pattern of recurrence. RESULTS: After a median follow-up of 6.5 years, 24 patients had relapsed giving a 5-year relapse rate of 40%. The 5 and 10-year actuarial survival rates were 94 and 89%, respectively with cause-specific survival being 94% at 5 and 10 years. Two-thirds of the relapses were nodal and supradiaphragmatic. Twenty patients (83%) relapsed in the initially involved sites of disease and this was the sole site of recurrence in 11 (45%) of patients. In retrospect, it appeared that at least 12 recurrences could have been prevented by involved field radiotherapy. Review of detailed imaging data (available in 9 out of 11 patients with recurrences in initial sites of disease) showed that the relapses were always in the initially involved nodes. CONCLUSION: After chemotherapy alone in early stage HD most initial recurrences are nodal. Loco-regional recurrences are in the originally involved nodes. Based on limited data it appears that involved nodal RT is equivalent to involved field radiotherapy and may halve the risk of recurrence.

Adolescent↗

PubMed2006

Isolated lymph node relapse of epithelial ovarian carcinoma: outcomes and prognostic factors.

BACKGROUND: Relapses of epithelial ovarian carcinoma (EOC) have a poor prognosis. Isolated lymph node relapses (ILNR) are considered of relatively good prognosis with intensive therapy. METHODS: This retrospective study aimed to describe incidence, characteristics, outcomes and prognostic factors of ILNR treated over 15 years. RESULTS: Twenty-seven patients (4.2%) experienced an ILNR among 640 patients. Median age was 59 years, tumour stages included stage I (n=4), II (n=5), III (n=15) and IV (n=3). After initial optimal treatment, median progression-free survival (PFS) was 26 months. Sites of relapse were retroperitoneum (n=15), left supraclavicular (n=7), mediastinum (n=4), iliac (n=4) and inguinal (n=3). ILNR locations were unique in 63% of patients (n=17) and multiple in 37% (n=10). Treatment modalities were surgery in eight patients (30%), chemotherapy in 15 (55%) and radiotherapy in 5 patients (18%), alone or in combination. Seven patients without tumour-related symptoms (26%) were not treated. Median overall survival (OS) after ILNR was 26 months. Median OS from initial diagnosis was 68 months. 25% of patients had a very long survival (>100 months), independent of their initial staging or PFS. There was no difference in 2-year survival after ILNR between the groups of early relapse (before 24 months) and late relapse (after 24 months). In the seven non-treated patients, median OS was 91 months. CONCLUSION: ILNR is a rare event in EOC. Time to relapse may not have its usual prognostic value. Immediate or delayed therapy should be discussed in case of asymptomatic ILNR.

Adult↗

PubMed1999

Management of interferon relapsers.

Relapse in patients who have evidenced an initial response to a course of interferon monotherapy for chronic hepatitis C virus (HCV) infection has been a major frustration. At least 70% of responders will relapse after a 6-month course of treatment and more than 50% will relapse after a 12-month course of treatment, usually within the first 3 to 6 months after treatment discontinuation. At most, half of patients relapsing after an initial 6-month course will have a sustained response to a second, 12-month course of interferon monotherapy. A more promising second-line regimen is the combination of interferon plus ribavirin. A recent multicenter international trial has shown that this regimen results in a sustained virologic response rate of nearly 50%, fully 10-fold higher than the sustained response rate observed with a second 6-month course of interferon alone (49% vs 5%, respectively). In patients with non-1 genotype and viral levels no greater than 2 million copies/mL, the likelihood of sustained response to the second course of combination therapy was 100%. Biochemical and virologic responses (normalization of liver enzymes and disappearance of HCV RNA from the serum) were frequently accompanied by histologic improvement. HCV-RNA levels < or = 2 million copies/mL and non-1 viral genotype predicted treatment response, whereas age, gender, body weight, source of infection, type of interferon used for the first round of treatment, and elapsed time since first treatment had no effect. Based on these data, combination therapy with interferon and ribavirin is now considered the treatment of choice for relapsers. It is not clear whether 12 months of combination therapy might have produced even better rates of viral eradication in relapsed patients.

Antiviral Agents↗

PubMed2000

Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI.

BACKGROUND & AIMS: This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection. METHODS: In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model. RESULTS: Cumulative relapse rates (+/-SE) after 18 months were 24.5% +/- 3.6% and 31.4% +/- 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% +/- 5.6% vs. 39.7% +/- 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003). CONCLUSIONS: Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease.

Adult↗

PubMedDate not supplied

The limitations of antipsychotic medication on schizophrenia relapse and adjustment and the contributions of psychosocial treatment.

Whether psychosocial treatment adds substantially to the prophylactic efficacy of maintenance antipsychotic monotherapy requires a more accurate estimate of relapse risks than those contained in recent reviews. A reappraisal of the literature suggests a 1-year, post-hospital, relapse rate of 40% on medication, and a substantially higher rate among patients who live in stressful environments, rather than earlier estimates of 16%. Relapse rates of 65% at 1 year and over 80% by 2 years among drug discontinued or placebo substituted outpatients are also more accurate than the 53% relapse rate previously estimated. When psychosocial treatment is added to maintenance chemotherapy, there is compelling evidence that relapse rates are reduced by as much as 50% compared with relapse associated with medication and standard care. However, psychosocial treatment without medication is as ineffective as placebo. The additive effects appear greater for recent, theoretically based psychosocial approaches than earlier atheoretical, altruistic forms of caring. However, effects vary according to the patient's clinical state, the nature and timing of the intervention, and the presence of environmental stressors. Regarding adjustment, very little definitive information regarding psychosocial treatment effects has existed until recently. A novel, disorder-relevant approach has now been shown to have broad and significant effects on social adjustment compared with medication and support. However, the magnitude of effects is not fully realized until a third year of treatment: a distinct challenge in the era of managed care. Atypical antipsychotics and more definitive psychosocial strategies that target social cognitive deficits hold promise for enhanced outcomes in the next generation of studies.

Antipsychotic Agents↗

PubMed1997

The effect of intrathecal MBP synthetic peptides containing epitope P85 VVHFFKNIVTP96 on free anti-MBP levels in acute relapsing multiple sclerosis.

Acute relapses of multiple sclerosis (MS) are characterized by elevated Free (F)/Bound (B) anti-MBP ratios during the initial phase, followed by a steady decline of F antibody as the recovery/remission phase develops. The (human) MBP epitope for MS anti-MBP is: Pro85-Val-Val-His-Phe-Phe-Lys-Asn-Ile-Val-Thr-Pro96. In phase one clinical research, synthetic peptides (p) containing this epitope, namely pMBP86-95 and/or pMBP82-98, were intrathecally administered to MS patients with monosymptomatic or polysymptomatic relapses to determine the dosage, frequency and duration of administration which will immediately neutralize F circulating CSF anti-MBP. Patients with monosymptomatic relapses required 50 mg of peptide administered daily for 4-5 days. In patients with polysymptomatic relapses, F anti-MBP can be neutralized with dosages between 50 mg peptide daily for 4 days up to 100 mg twice a day for 2 days; however due to the prolonged nature of polysymptomatic relapses, antibody neutralization could not be maintained by these short courses of intrathecal peptide administration. Intravenous administration of these same peptides did not prevent occurrence of future relapses.

Acute Disease↗

PubMed1994

Pattern of failure and survival of patients with metastatic urothelial tumors relapsing after cis-platinum-based chemotherapy.

Cis-platinum-based chemotherapy combinations have improved the outcome of patients with metastatic urothelial tumors, since two-thirds of these patients respond to treatment. Nevertheless, the majority of such patients have relapse within a median of 12 months. To define the pattern of failure and subsequent outcome, we retrospectively assessed 58 consecutive patients with relapse after prior response to cis-platinum-based combination chemotherapy. Of the patients who presented initially with local-regional metastases, 74% had relapse with involvement of a similar site, while only 26% of these patients had visceral metastases at relapse. The median survival after relapse was 9 months, and parameters associated with longer survival were local-regional relapse (10.7 months) and response to salvage chemotherapy (12.6 months). These data suggest that select patients with urothelial tumors and local-regional metastases may benefit from consolidation therapy with surgery or radiotherapy after maximum response to chemotherapy.

Adult↗

PubMed2002

[Major depressive episode: a study of remission and relapses].

BACKGROUND: Our objective was to study the rates of remission and relapse over more than two years in a sample of Spanish outpatients with DSM-III-R criteria of unipolar major depressive episodes. PATIENTS AND METHODS: In the first assessment, we used the structured clinical interview for DSM-III-R (SCID). Forthcoming visits were held monthly. A survival analysis was used to assess partial and complete remission in the original sample of 356 patients. The probability and prediction of relapses were calculated in 186 patients who finished the 2 year follow-up period. Evolution stages were recorded using the Hamilton Depression Rating Scale (HDRS), after applying the Frank criteria. Patients were treated following standardized pharmacological protocols at our center. RESULTS: After 6 months of follow-up, 50% of patients had attained a complete remission; it was partial in 25% of cases. Rate of relapses for patients on complete remission was 12,18%, whereas it was 67,61% for patients on partial remission. Risk of relapses was 2,84 times greater after partial remission than after complete remission. Partial remission was the most powerful predictor of relapses. CONCLUSIONS: Partial remission after a depressive episode seems to be an important predictor of relapses.

Major Depressive Disorder↗

PubMed2002

Neural substrates of conditioned-cued relapse to drug-seeking behavior.

Relapse to drug use following abstinence is a significant impediment in the long-term treatment of drug abuse and dependence. Conditioned stimuli are believed to be critically involved in activating drug craving and relapse to compulsive drug-taking behavior. Studies in humans and animal models have recently begun to identify the fundamental neural circuitry that mediates relapse following withdrawal from chronic drug self-administration. The current review summarizes key findings in this area that have converged on the amygdalar complex and regions of the frontal lobe as critical structures in conditioned-cued relapse. It is proposed that the amygdala is a key regulator of discrete stimulus-reinforcer associations, while the anterior cingulate and orbitofrontal cortex are critical regulators of relapse evoked by conditioned stimuli that predict drug availability. This corticolimbic circuitry may form the neural basis of multiple long-term conditioned associations produced by a variety of drugs of abuse ranging from psychostimulants to opiates. Future studies aimed at discerning the functional roles of these pathways will provide critical direction for the development of treatments for the prevention of relapse.

Animals↗

PubMed2001

HIV-1 and recurrence, relapse, and reinfection of tuberculosis after cure: a cohort study in South African mineworkers.

BACKGROUND: The proportion of recurrent tuberculosis cases attributable to relapse or reinfection and the risk factors associated with these different mechanisms are poorly understood. We followed up a cohort of 326 South African mineworkers, who had successfully completed treatment for pulmonary tuberculosis in 1995, to determine the rate and mechanisms of recurrence. METHODS: Patients were examined 3 and 6 months after cure, and then were monitored by the routine tuberculosis surveillance system until December, 1998. IS6110 DNA fingerprints from initial and subsequent episodes of tuberculosis were compared to determine whether recurrence was due to relapse or reinfection All patients gave consent for HIV-1 testing. FINDINGS: During follow-up (median 25.1 months, IQR 13.2-33.4), 65 patients (20%) had a recurrent episode of tuberculosis, a recurrence rate of 10.3 episodes per 100 person-years at risk (PYAR)-16.0 per 100 pyar in HIV-1-positive patients and 6.4 per 100 pyar in HIV-1-negative patients. Paired DNA fingerprints were available in 39 of 65 recurrences: 25 pairs were identical (relapse) and 14 were different (reinfection). 93% (13/14) of recurrences within the first 6 months were attributable to relapse compared with 48% (12/25) of later recurrences. HIV-1 infection was a risk factor for recurrence (hazard ratio 2.4, 95% CI 1.5-4.0), due to its strong association with disease caused by reinfection (18.7 2.4-143), but not relapse (0.58; 0.24-1.4). Residual cavitation and increasing years of employment at the mine were risk factors for relapse. INTERPRETATION: In a setting with a high risk of tuberculous infection, HIV-1 increases the risk of recurrent tuberculosis because of an increased risk of reinfection. Interventions to prevent recurrent disease, such as lifelong chemoprophylaxis in HIV-1-positive tuberculosis patients, should be further assessed.

Adult↗

PubMed1984

Steroid-hormone receptors and survival after first relapse in breast cancer.

Oestrogen receptors were measured in the primary breast tumours of 508 patients and progesterone receptors in those of 486 patients. Survival from mastectomy was significantly longer in patients with receptor-positive tumours. There was no significant difference between patients with receptor-positive and receptor-negative tumours in the relapse-free interval, but survival from first relapse was longer in patients with receptor-positive tumours. Axillary node status and tumour size indicated the probability of relapse but did not influence the length of survival after relapse. Response to tamoxifen or ovarian ablation was known in 65 of the 137 patients who relapsed. Survival from first relapse was significantly longer in patients who both responded to hormone therapy and had receptor-positive tumours. Patients who did not respond to hormone therapy and had receptor-positive tumours had the same survival characteristics as those with receptor-negative tumours who did not respond.

Breast Neoplasms↗

PubMed1984

Yield of unpredicted bone-marrow relapse diagnosed by routine marrow aspiration in children with acute lymphoblastic leukaemia. A report from the Children's Cancer Study Group.

1466 children with acute lymphoblastic leukaemia had routine bone-marrow aspiration at the end of each 84-day cycle of maintenance therapy. Relapses detected by routine bone-marrow aspiration were classified according to whether or not they could be predicted by clinical signs or peripheral blood counts. In the low-risk, moderate-risk, and high-risk leukaemic patients 0.4%, 0.5%, and 0.8%, respectively, of the total routine bone-marrow aspirations yielded an unpredicted bone-marrow relapse. 19.4% of relapses were detected by routine surveillance marrow aspirations before any clinical signs of relapse on physical examination or peripheral blood count. The median survival after relapse in the predicted group was significantly shorter than that in the unpredicted group, but the eventual outcome was the same in both groups, 95% of all patients dying within 24 months of relapse.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1985

How should acute lymphoblastic leukaemia relapsing after bone-marrow transplantation be treated?

21 of 63 patients given bone-marrow transplantation (BMT) for acute lymphoblastic leukaemia (ALL) relapsed between day 75 and day 1126 after BMT. 19 patients were given leukaemic induction treatment with standard combination chemotherapy. 7 patients achieved a sustained remission, of whom 5 are alive in remission 88-1240 days after relapse; the 2 others died during a second BMT. 2 of the remaining 14 obtained partial remission but all 14 ultimately died with relapsed leukaemia. A favourable outcome for ALL relapsing after BMT was predicted by the pace of the disease: the 5 survivors had an interval between diagnosis and first relapse of more than 2 years and a disease-free period after BMT of 500 days or more. These results indicate that further conventional chemotherapy should be used rather than a second marrow transplant to prolong disease-free survival in patients with ALL relapsing after BMT.

Adolescent↗

PubMed1994

Effect of systemic adjuvant treatment on first sites of breast cancer relapse.

Adjuvant systemic treatment for resectable breast cancer changes the natural history of the disease but provides only a small and delayed effect on survival. Evaluation of the types of first relapse avoided by available treatments may explain why effects on mortality are small and appear late during follow-up. In randomised clinical trials done by the International Breast Cancer Study Group (IBCSG) between 1978 and 1985, 2108 patients with node-positive disease received more-effective treatments (6 or more cycles of cyclophosphamide, methotrexate, fluorouracil and prednisone; with or without tamoxifen, or tamoxifen and prednisone alone), and 722 patients received less-effective treatments (no treatment or a single cycle of chemotherapy). 3 main categories of first site of relapse were defined and evaluated by cumulative incidence analysis: local or regional, and distant soft tissue, bone, and viscera. The more-effective treatments reduced the cumulative incidence of first relapse in local or regional and distant soft tissue sites at 10 years from 36% to 18% (p = 0.0001); first relapse in bone and viscera was not altered by the more-effective treatments. These results were similar for premenopausal and postmenopausal women, and for patients with oestrogen-receptor-positive or oestrogen-receptor-negative tumours. Adjuvant systemic treatments in current use improve patient outcome mainly by reducing the incidence of first local or regional and distant soft-tissue relapses, while first recurrences in bone or viscera are influenced much less. More intensive treatments at present being tested in clinical trials might affect bone and visceral relapses and have a greater and earlier influence on survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

Truncated STAT proteins are prevalent at relapse of acute myeloid leukemia.

Signal transducer and activator of transcription (STAT) proteins are implicated in the control of cell survival, proliferation and differentiation in response to hematopoietic cytokines. C-terminally truncated STAT isoforms (STATbeta), as opposed to the full length form (STATalpha), have a competitive or even transdominant negative effect on gene induction mediated by the STAT pathway. We have previously demonstrated that while constitutively active STAT proteins were detected in ten of 36 (28%) for STAT3 and eight of 36 (22%) for STAT5 in pretreatment samples from newly diagnosed acute myeloid leukemia (AML) patients, a significantly larger fraction of samples [21 of 27 (78%)] expressed STATbeta proteins. To determine whether STATbeta expression was maintained or increased after relapse in AML, we compared STAT activity and isoform expression at diagnosis and at relapse in 17 patients. In this selected group, constitutively active STAT3 was detected in 13 of 17 (76%) AML samples at diagnosis but was detected in only four of these patients at relapse. Constitutively active STAT5 was detected in three of 17 (18%) AML samples at diagnosis; but only two at relapse. In contrast, STATbeta protein expression was observed in 12 of the 17 pretreatment samples (71%) and in 16 of 17 samples at relapse. Only one patient did not express STATbeta at relapse. Our results suggest that STATbeta isoform expression, rather than level of constitutive activity, may be involved in disease progression in AML.

Adult↗

PubMed1997

Shortened survival after relapse in T-cell acute lymphoblastic leukemia patients with p16/p15 deletions.

p16 Alterations were detected in > 60% of 103 primary T-ALL samples. In paired diagnosis-relapse patient samples, 80% of the relapse samples with p16 deletion were deleted at diagnosis. When p16 was homozygously deleted, p15 gene alterations were found in 72% of the diagnosis T-ALL patient samples, increasing significantly to 100% at relapse. Alterations of p18 were not detected. No clinical significance of p15/p16 gene deletion in diagnosis T-ALL was found with respect to white blood cell (WBC) count, incidence of mediastinal mass, rate of relapse, duration of first remission or event-free survival. In relapse T-ALL, however, patients with p16 deletion experienced a significantly shorter duration of post-relapse survival, demonstrating that p16 deletion is clinically significant in T-ALL.

Carrier Proteins↗