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PubMed1994

Importance of effective central nervous system therapy in isolated bone marrow relapse of childhood acute lymphoblastic leukemia. BFM (Berlin-Frankfurt-Münster) Relapse Study Group.

Presymptomatic central nervous system (CNS) treatment in children with a late isolated first bone marrow (BM) relapse of acute lymphoblastic leukemia (ALL) was based on intermediate-dose systemic and intrathecal (IT) methotrexate (MTX) in the multicenter trial, ALL-REZ BFM 85. Because this was associated with an excess of overt second CNS relapses, cranial radiotherapy (cRT) plus prolonged triple IT therapy with MTX, cytarabine, and prednisone was instituted during the course of the subsequent trial, ALL-REZ BFM 87. Results of children with or without cRT, but otherwise identical chemotherapy, are presented here. Between April 1985 and March 1990, 93 children with their first late isolated BM relapse of ALL were entered on protocols ALL-REZ BFM 85M and ALL-REZ BFM 87. An intensive 6-month phase of multiagent chemotherapy that included 8 courses of systemic MTX (1 g/m2) plus IT MTX was followed by 2 years of conventional maintenance therapy with daily 6-thioguanine and biweekly MTX. Children with bone marrow transplantation excluded, 73 were in complete remission at the end of intensive polychemotherapy, 40 of whom received fractionated cRT plus triple IT therapy during the following 6 months; 11 did not receive cRT but prolonged triple IT; 22 received neither cRT nor prolonged triple IT. Except for a higher percentage of children who had received cRT in front-line protocols (29 of 33 v 20 of 40), the patient groups without or with salvage cRT were comparable. Of 33 children without salvage cRT, 26 relapsed, compared with 21 of 40 who had received cRT (P < .05). The difference was solely attributable to second relapses with CNS involvement (10 of 33 v 1 of 40; P < .01). Estimated 6-year event-free survival rates were .18 for children without cRT and .46 for children with cRT (P < .01). In patients without cRT, no impact of prolonged IT therapy could be shown. The data suggest that second CNS prophylaxis with cRT and prolonged triple IT therapy in children with late isolated BM relapse of ALL is effective in preventing CNS relapses, in reducing the overall relapse rate, and in increasing the overall survival rate.

Adolescent↗

PubMed1996

Predictive validity of Marlatt's relapse taxonomy versus a more general relapse code.

Marlatt's system for classifying relapses involves integrating information about the context of a relapse into a judgment about the most critical aspects of the situation. Constraints in this taxonomy, however, may limit its validity. On a sample of 300 subjects drawn from six treatment facilities, we compared the predictive validity of Marlatt's taxonomy with that of a coding scheme with fewer constraints. Marlatt's taxonomy does not significantly predict drinking outcome, nor does it predict time to relapse. There is weak evidence, however, that under some circumstances Marlatt's taxonomy can predict the type of relapse subsequently observed. The alternative coding system also does not seem useful for predicting drinking outcome, although a possible association was found between internal attribution and time to return to heavy drinking. The alternative system does seem to be able to detect repetitive aspects of subsequent relapse situations; lack of social interactions, family setting, anxiety and depression were most likely to repeat. It may be useful to consider these relapse attributes in treatment planning. The minimal predictive validity for both the Marlatt and the alternative relapse code may be due to weaknesses in the relatively unstructured interview used to gather the data, or to failure to assess the most critical dimensions relating to subsequent relapse.

Adult↗

PubMed2005

EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses.

Relapses, exacerbations or attacks of multiple sclerosis are the dominating feature of relapsing-remitting multiple sclerosis (MS), but are also observed in patients with secondary progressive MS. High-dose methylprednisolone is the routine therapy for relapses at present, but other treatments are also in current use. The objective of the task force was to review the literature on treatment of MS relapses to provide evidence-based treatment recommendations. Review was carried out on the literature with classification of evidence according to the EFNS guidelines for scientific task forces. Short-term, high-dose methylprednisolone treatment should be considered for the treatment of relapses of MS (level A recommendation). The optimal glucocorticoid treatment regimen, in terms of clinical efficacy and adverse events, remains to be established. A more intense, interdisciplinary rehabilitation programme should be considered as this probably further improves recovery after treatment with methylprednisolone (level B recommendation). Plasma exchange is probably efficacious in a subgroup of patients with severe relapses not responding to methylprednisolone therapy, and should be considered in this patient subgroup (level B recommendation). There is a need for further randomized, controlled trials in order to establish the optimal treatment regimen for relapses of MS.

Evidence-Based Medicine↗

PubMed2006

Relapses and subsequent worsening of disability in relapsing-remitting multiple sclerosis.

OBJECTIVE: To investigate whether relapses contribute to the development of subsequent sustained increase of impairment and disability in patients with multiple sclerosis (MS). METHODS: In a random sampled subset of 256 relapsing-remitting MS (RRMS) patients from the placebo arms of 20 randomized, controlled clinical trials contained in the Sylvia Lawry Centre for MS Research (SLCMSR) open database (mean follow-up time 2.66 years), the authors tested whether time to an increase of the Expanded Disability Status Scale (EDSS) score (confirmed after 6 months) was related to the occurrence of prior relapses. In the primary analysis, EDSS progressions starting within the period used to calculate the on-study relapse rate (sacrifice period) were not counted. The result obtained was then validated in an independent validation part of the SLCMSR database (n = 320). RESULTS: Although in the first subset of 256 RRMS patients, occurrence of relapses in the first 4 months on study appeared to be the best predictor for a shorter time to subsequent sustained increase in the EDSS score (hazard ratio [HR] 2.26 [95% CI: 1.36 to 3.75]), this finding was not confirmed in the validation dataset (HR 1.35, one-sided Wald test, lower limit of the 95% CI: 0.90). CONCLUSION: Although relapses may result into permanent damage and Expanded Disability Status Scale (EDSS) progression, there is no consistent effect of on-study relapses on the subsequent development of sustained EDSS score increase during a typical clinical study observation period.

Adult↗

PubMed1994

Treatment of relapsing acute lymphoblastic leukemia in childhood. III. Experiences with 54 first bone marrow, nine isolated testicular, and eight isolated central nervous system relapses observed 1985-1989.

Of 54 children with acute lymphoblastic leukemia (ALL) and first hematological recurrence observed between 1985 and 1989, 31 relapsed while still on treatment and 23 after cessation of therapy. Of the former, only one survived. Of the latter, 11 children survived after a minimum follow-up of 25 months. During the same period, a first isolated testicular relapse was observed in nine boys, of whom six survived, and an isolated CNS relapse in eight patients, of whom three survived. As a rule, survivors of a bone marrow or testicular relapse were doing well while those surviving a CNS relapse had considerable neuropsychological sequelae. These results, compared with those of two preceding studies, suggest that with intensification of front-line treatments, it becomes more difficult to rescue children who relapse, particularly those with a bone marrow relapse while on therapy.

Adolescent↗

PubMed1987

Induction of synchronized relapses in SJL/J mice with chronic relapsing experimental allergic encephalomyelitis.

Chronic relapsing experimental allergic encephalomyelitis (CR-EAE) was induced in SJL/J mice by two injections of encephalitogenic emulsion. The majority of mice developed multiple relapses from day 22 to day 367 post injection. To induce synchronized relapses a third injection of the encephalitogenic emulsion was given. Almost all mice that received the third injection developed an acute, synchronized relapse with severe clinical signs within 7 to 11 days. Histologically, there was no difference between the lesions in the spontaneous versus the precipitated relapse. CR-EAE in SJL/J mice modified with the third injection offers an advantage of a reproducible and well-timed acute relapse, which allows precise dissection of the immunological events governing spontaneous relapses in chronic EAE.

Animals↗

PubMed1986

Chronic relapsing experimental autoimmune encephalomyelitis. Transient presence in blood of lymphocytes sensitised to encephalitogen at onset of inflammatory relapses.

Juvenile guinea pigs were immunised with homologous spinal cord and monitored daily over a 6-month period for neurological signs of chronic relapsing experimental autoimmune encephalomyelitis (CREAE). At various times animals were killed, numbers of leucocytes in their cerebrospinal fluid (CSF) quantified, and in vitro proliferative responses of blood lymphocytes to myelin basic protein (MBP) and its encephalitogenic nonapeptide (NP) determined. After recovering from initial acute clinical signs, animals suffered at least two major spontaneous relapses separated by remission periods of 4-5 weeks mean duration. In the early chronic phase, 5-12 weeks post-immunisation (pi), 63% of the animals recovered fully from relapses, whereas relatively irreversible neurological deficits predominated in the late chronic phase. During the acute and chronic phases, there was a highly significant correlation between clinical severity and CSF pleocytosis only in animals killed within 24 h of onset of a clinical exacerbation associated with more than 100 leucocytes/microliter of CSF. Guinea pigs with this degree of CSF pleocytosis were defined as suffering an inflammatory relapse. Blood lymphocytes responsive to MBP and NP were detected only in animals killed at the onset of clinical signs of either the acute or an inflammatory relapse. This dynamic relationship suggests that migration of encephalitogen-responsive lymphocytes via the blood to the central nervous system could produce certain relapses in CREAE. However, the relative paucity of CSF leucocytes in most animals killed during relapses between 15-26 weeks pi suggests that other factors may elicit neurological exacerbations in the late chronic phase.

Animals↗

PubMed1988

Alcoholics' attributions of factors affecting their relapse to drinking and reasons for terminating relapse episodes.

This study was designed to examine alcoholics' attributions about their relapses. The subjects were 36 male alcoholic participants in a study of the effectiveness of group behavioral marital therapy (BMT) for alcoholism. Subjects' treatment condition had been determined by random assignment to either the BMT, interactional marital therapy, or control group. At a two year posttreatment follow-up interview, subjects were asked what they thought the main reasons were for starting and stopping drinking in their two most recent relapses. Subjects' responses showed that both interpersonal and psychological factors were perceived to affect relapses, with some treatment group differences in how relapses were viewed. Subjects reported a variety of factors in their stopping drinking, with anticipation of negative consequences the most frequently reported reason. The treatment groups did not differ on their attributions for relapse termination. The results were interpreted as replicating and extending previous studies of relapse among alcoholics by showing the importance of spouse and other family members in subjects' attributions of relapse and their termination.

Adult↗

PubMed1993

Late relapses in Hodgkin's disease: outcome of patients relapsing more than twelve months after primary chemotherapy.

BACKGROUND: Patients with Hodgkin's disease whose initial complete remissions (CR) after primary chemotherapy were longer than 1 year are thought to have better prognoses than patients whose initial remissions were shorter than 1 year. However, only a few studies have analyzed the long-term survival in addition to the results of retreatment in patients relapsing after CR lasting more than 1 year. PATIENTS AND METHODS: We analyzed the data of 40 patients with Hodgkin's disease who were treated in a single institution and whose CR were > 1 year after primary chemotherapy. Therapy at relapse was not standardized: of 36 patients evaluable for response, 29 received second-line chemotherapy and 7 received radiotherapy alone. RESULTS: Sixty-five percent of the patients obtained CR (median duration: 21 months). Sixty-eight percent of the complete responders relapsed again; however, long-lasting third and fourth remissions were observed. All of the 7 patients whose retreatment consisted of radiotherapy alone obtained CR, but only 1 is in continuous CR. The presence of nodular sclerosing histologic subtype, the absence of extranodal involvement and the use of hybrid MOPP/ABVD or ABVD alone as salvage treatment are independently associated with a higher CR rate and a higher probability of 5-year survival. The 5-year survival for all 40 patients is 49%. For the patients obtaining CR, the 5-year survival and the 5-year relapse-free survival are 76% and 25%, respectively. However, the survival curve continues to fall in the succeeding years because of third and fourth relapses and the occurrence of secondary acute leukemia and non-Hodgkin's lymphoma. CONCLUSIONS: A high percentage of patients relapsing more than 12 months after primary chemotherapy can obtain second CR. Even if most of our patients eventually relapse, third and fourth CRs are not uncommon. However, the long-term survival is low and it is further diminished by secondary leukemia and non-Hodgkin's lymphoma.

Adult↗

PubMed1999

Relapsing membranous nephropathy. Response to therapy of relapses compared to that of the original disease.

BACKGROUND: Although controversial, treatment of membranous nephropathy appears to yield a reduction in the degree of proteinuria and conservation of renal function. METHODS: We report herein our experience with the treatment with steroids alone (group II, n = 13), or in combination with immunosuppressants (group III, n = 19) of patients with membranous nephropathy and the nephrotic syndrome, with a mean follow-up of 8.37 years. RESULTS: All patients underwent a first remission, with 24-hour urine protein excretion falling to 0.63 +/- 0.25 g in group II and 0.62 +/- 0.26 g in group III (p = NS) after 12.69 +/- 10.94 months of treatment in group II and 18.95 +/- 13.17 months in group III (p = NS). Three patients from group II (23%) and seven patients from group III (36.8%) experienced four and eight relapses, respectively (proteinuria in 24 h 4.0 +/- 0.80 g in group II relapsers and 4.4 +/- 0.87 in group III relapsers; p = NS). On treatment, all relapses remitted (second remission) after 7 +/- 6.93 months of therapy for group II and 8.6 +/- 6.70 months of treatment for group III (p = NS). Thereafter, no patients from group II, but 3 patients from group III (33.3%) had a second relapse. After treatment, all relapses remitted (third remission) in 3.3 +/- 1.53 months of therapy. CONCLUSIONS: These studies show that relapses, which occur in one-third of patients, respond favorably to treatment albeit remitting in approximately half the time, and that the duration of remission gets progressively longer in the later compared to the earlier remission.

Adult↗

PubMed2005

A comparison of patients relapsing to addictive drug use with non-relapsing patients following residential addiction treatment in Antigua.

The outcome of a 29-day residential addiction treatment programme for persons from Antigua and Barbuda with addiction to drugs or alcohol was assessed. All 100 patients entering the drug and alcohol treatment programme at Crossroads Centre Antigua between November 1998 and October 2002 were included. All patients were assessed with regards to drug or alcohol use or abstinence in November 2002 using telephone and mail follow-up as well as informal follow-up with families and other community contacts. Crossroads Centre Antigua is a 35 bed, 29-day residential treatment centre for drug and alcohol addiction serving patients from developed countries (85%) and from the Caribbean region (15%). Patients records were also reviewed to obtain age, gender, ethnicity, drug of choice, years of problematic use, completion of the 29 day programme, family member participation at Crossroads Centre Antigua (a four-day programme) and acceptance of halfway house placement. Of the 100 Antiguan patients admitted, 46 (46%) were abstinent (non-relapsers) at average 20.7+/-14.7 months after treatment. Abstinence did not have to be continuous. Forty-nine were known to be using drug or alcohol (49%) and five (5%) were lost to follow-up and considered to be using drugs (relapsers). Age (37.5 vs 41.1 years), gender (28% vs 22% female), ethnicity (87% vs 87% Afro-Caribbean), years of harmful use (12.7 vs 12.5 years) did not differ significantly between relapsers and non-relapsers. Crack cocaine use (67% vs 65%) and alcohol use (26% vs 31%) as primary addiction did not differ significantly between relapsers and non-relapsers. Relapsers were significantly less likely to complete the 29- day programme (81% vs 100%, p < 0.01), have family members participate at Crossroads (32% vs 54%, p < 0.05) or accept halfway house placement (4% vs 54%, p < 0.001). In conclusion, abstinence was achieved in 46% of those entering treatment, in 51% completing treatment, in 60% whose families participated and in 92% of those accepting halfway house placement.

Adult↗

PubMed1991

Treatment of adult acute lymphoblastic leukemia with allogeneic bone marrow transplantation. Multivariate analysis of factors affecting acute graft-versus-host disease, relapse, and relapse-free survival.

Between February 1972 and December 1987, 192 adults (greater than or equal to 18 years old) with acute lymphoblastic leukemia were transplanted using genotypically HLA-identical marrow donors. Median patient age was 23 years. Eighty-nine patients were in marrow remission and 103 were in relapse. Conditioning regimens included chemotherapy alone (three patients) or in combination with 9.2-17.5 Gy total body irradiation (189 patients). Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate and/or cyclosporine. Seventy-nine patients developed grades II-IV acute GVHD and 28 of 122 patients who survived at least 100 days developed chronic GVHD. Relapse-free survival at 5 years was 21% for patients transplanted in first remission, 15% for those in greater than or equal to 2nd remission, and 12% for those transplanted in relapse. Patient and donor characteristics were evaluated in multivariate analyses for their effect on development of acute GVHD, survival, relapse, and relapse-free survival. An increased risk of developing acute GVHD was associated with increasing donor age. Variables significantly associated with both increased survival and relapse-free survival included transplantation in first remission, younger patient age, and not developing interstitial pneumonia. A decreased probability of relapse was associated with transplantation in first remission, male patient sex, and grades II-IV acute GVHD.

Acute Disease↗

PubMed1987

Treatment of relapsing acute lymphoblastic leukemia in childhood. I. Experiences with 82 first bone marrow and 17 isolated central nervous system relapses observed 1968-1980.

Of 99 patients with acute lymphoblastic leukemia in first bone marrow or isolated CNS relapse seen between 1968 and 1980, 48 were treated without standardized protocol and 51 according to a relapse protocol. Of 16 patients with bone marrow relapse after cessation of the initial treatment 6 survived 8 1/2 years or more, of 66 with bone marrow relapse while on therapy only 4 survived. All of the latter were low risk patients with an initial WBC of less than 20 x 10(9)/l and no enlargement of the mediastinum. All of the 17 patients with isolated CNS relapse died. The relapse protocols used probably improved the chances of children with first bone marrow but not of those with isolated CNS relapse.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Isolated extramedullary relapse in children with acute lymphoblastic leukemia: a comparison between treatment results of chemotherapy and bone marrow transplantation. BFM Relapse Study Group.

The purpose of this study was to determine the therapeutic efficacy of different treatment strategies, namely chemotherapy, allogeneic and autologous bone marrow transplantation (BMT), for extramedullary relapse of acute lymphoblastic leukemia (ALL) in children in second or subsequent remission. Between 1983 and 1993, 165 patients up to 19 years of age with extramedullary relapse of ALL were registered in the multicenter ALL-REZ BFM trials. One hundred and thirty four children received chemotherapy only; 17 children were grafted from HLA-identical sibling donors 152 days (46-392 days) after diagnosis of relapse, and 14 children underwent autologous BMT after a median time of 137 (range 23-300) days. Event-free survival (EFS) at 5 years was 0.47 +/- 0.05 for patients receiving chemotherapy: 0.76 +/- 0.07 for late, 0.33 +/- 0.08 for early and 0.33 +/- 0.07 for very early relapsed patients. Sixty five patients are in complete remission (CR), 61 patients relapsed, 5 died from therapy related complications, 2 patients in CR were lost to follow-up and one patient developed a second malignancy. For patients who had undergone BMT, EFS at 5 years was 0.36 +/- 0.10 without significant difference between autologous BMT (8 of 14 in CR, 6 relapsed) and allogeneic BMT (6 of 17 in CR, 4 died of acute toxicity, and 7 relapsed).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Sucralfate in the prevention of duodenal ulcer relapse and factors influencing the relapse rate.

Forty three subjects with DU confirmed at endoscopy and healed after eight weeks of sucralfate therapy were subjected to a randomized double-blind controlled trial for six months. Twenty one subjects received sucralfate (1 g one hour before breakfast and dinner). Twenty two subjects received placebo. Symptoms were evaluated every month. The subjects were endoscoped at the end of the trial or earlier in case symptoms recurred. Sucralfate was found to be significantly more effective than placebo (6/21 vs. 17/22, p < 0.005) in preventing DU relapse. Age at presentation, age at onset, duration of illness, sex, periodicity, smoking, gastric stasis like symptoms, associated irritable bowel syndrome, degree of deformity of the bulb and initial presence of duodenitis were the factors examined for their effect upon the relapse. In the placebo group relapsers had significantly shorter mean duration of illness indicating that DU may relapse more frequently in earlier part of its natural course. Other factors did not influence the relapse rate. In the sucralfate group, higher ages at onset and at presentation were associated with significantly higher relapse rate. Sucralfate may be less effective in preventing relapse in elderly and late onset DU patients.

Adult↗

PubMed2001

Predictive value of lesions for relapses in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Recent studies have suggested that enhancing lesions on contrast-enhanced T1-weighted MR images are predictive of impending exacerbations in cases of relapsing-remitting multiple sclerosis. We examined whether enhancing lesions, new enhancing lesions, and new hypointense lesions ("black holes") could accurately predict exacerbations in a cohort of 50 patients with relapsing-remitting multiple sclerosis within a time frame of up to 6 months. METHODS: Data were obtained from 50 patients with relapsing-remitting disease. All patients underwent monthly MR imaging and clinical examinations for a period of 12 months. Putative predictors of clinical relapse were defined from enhancing lesions, new enhancing lesions, and new black hole outcomes, and their operating characteristics were studied. RESULTS: Overall, the positive predictive values (PV+) of enhancing lesions, new enhancing lesions, or new black holes for an exacerbation did not exceed 0.25 and the negative predictive values (PV-) were all near 0.9. The best predictor for new enhancing lesions was the occurrence of new enhancing lesions in each of the previous 3 months (PV+: 0.79 [95% confidence interval, 0.651-0.900]; PV-: 0.83 [95% confidence interval, 0.751-0.887]). Similarly, new black holes were predicted best by the occurrence of new black holes in each of the previous 2 months (PV+: 0.54 [95% confidence interval: 0.372-0.697]; PV-: 0.85 [95% confidence interval, 0.790-0.896]). CONCLUSION: None of the MR markers could predict an impending relapse with any reasonable degree of precision. Rather, the absence of MR markers is associated with a more favorable clinical course (ie, fewer relapses).

Adult↗

PubMed2005

Glucocorticoids and relapse of major depression (dexamethasone/corticotropin-releasing hormone test in relation to relapse of major depression).

BACKGROUND: Knowledge of pathogenic mechanisms and predictors of relapse in major depressive disorder is still limited. Hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation is thought to be related to the development and course of depression. METHODS: We investigated whether dexamethasone/corticotropin-releasing hormone (DEX/CRH) test parameters were related to the occurrence of relapse in 45 outpatients with clinically remitted major depression. The DEX/CRH test was administered before and after 8 weeks of antidepressant treatment. RESULTS: Posttreatment maximal adrenocorticotropic hormone (ACTH) and maximal cortisol levels, as well as delta ACTH and delta cortisol levels, were significantly higher (all p < .05) among patients who relapsed (n = 22) compared with patients in whom no relapse occurred (n = 23). Higher posttreatment maximal cortisol response on the DEX/CRH test was associated with shorter "relapse-free survival" (p = .05). CONCLUSIONS: In outpatients with clinically remitted major depression, higher posttreatment maximal cortisol levels on the DEX/CRH test were associated with relapse of major depression.

Adolescent↗

PubMed2003

Challenges in preventing relapse in major depression. Report of a National Institute of Mental Health Workshop on state of the science of relapse prevention in major depression.

On 21 and 22 May 2001, the National Institute of Mental Health convened a workshop to explore imminent scientific opportunities and encourage new research on preventing relapse in major depression, as a part of a larger effort to find treatments capable of producing durable long-term recovery from major depression. Participants considered definitional and developmental perspectives on depression relapse, the prophylactic potential of current treatments and their cost effectiveness and the neurobiological and psychological risk factors for episode return. It was recommended that the definition of the relapse construct be expanded to capture salient features of incomplete recovery or partial response to treatment that are associated with significant functional impairment. This information is often overlooked by the categorical criteria currently in use. With respect to interventions, there was support for sequencing pharmacological remission with psychological prophylaxis. Provision of focal, short-term treatments that embed relapse prevention skills augment the routes to effective prevention available to patients, beyond that afforded by continuation pharmacotherapy. The challenge will be to identify those subgroups of patients for whom each treatment algorithm is indicated. Finally, the link between basic science findings of biological and psychological markers of relapse vulnerability and treatment design needs to be strengthened. This could be accomplished by assessing patients in clinical prevention trials for the presence of, and changes in, relapse vulnerability markers, thereby providing direct, outcome-based data to gauge the protective value of different treatments that modify these markers.

Algorithms↗