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PubMed2002

Relapse predictors of patients with bulimia nervosa who achieved abstinence through cognitive behavioral therapy.

BACKGROUND: Little information exists on relapse in patients with bulimia nervosa who responded with complete abstinence from binge eating and purging to cognitive behavioral therapy. Identification of relapse predictors may be useful to design effective early intervention strategies for relapse of susceptible patients with bulimia nervosa. METHODS: This multisite study examined relapse in 48 patients with bulimia nervosa who had responded to cognitive behavioral therapy with complete abstinence from binge eating and purging. Structured interviews and questionnaires were used to assess patients before and after treatment and at 4 months after treatment. RESULTS: Four months after treatment, 44% of the patients had relapsed. Those who relapsed had a higher level of preoccupation and ritualization of eating and less motivation for change, and had maintained abstinence for a shorter time during the treatment period. CONCLUSIONS: The predictors of relapse found in this study can be readily determined by clinicians. The effectiveness of early additional treatment interventions needs to be determined with well-designed studies of large samples.

Adolescent↗

PubMed2005

Neural activation patterns of methamphetamine-dependent subjects during decision making predict relapse.

CONTEXT: Relapse is a common clinical problem in individuals with substance dependence. Previous studies have implicated a multifactorial process underlying relapse; however, the contribution of specific neural substrates has not yet been examined. OBJECTIVE: To determine whether results from functional magnetic resonance imaging (fMRI) shortly after drug cessation could predict relapse in stimulant-dependent individuals. PARTICIPANTS AND DESIGN: Treatment-seeking methamphetamine-dependent males (N = 46) underwent fMRI 3 to 4 weeks after cessation of drug use. Of the 40 subjects who were followed up a median of 370 days, 18 relapsed and 22 did not. MAIN OUTCOME MEASURE: Blood oxygen level-dependent fMRI activation during a simple 2-choice prediction task. RESULTS: The fMRI activation patterns in right insular, posterior cingulate, and temporal cortex obtained early in recovery correctly predicted 20 of 22 subjects who did not relapse and 17 of 18 subjects who did. A Cox regression analysis revealed that the combination of right middle frontal gyrus, middle temporal gyrus, and posterior cingulate activation best predicted the time to relapse. CONCLUSION: To our knowledge, this is the first investigation to show that fMRI can be used to predict relapse in substance-dependent individuals.

Adult↗

PubMed2000

Hypofractionated moderate dose radiation, intrathecal chemotherapy, and repetitive reinduction/reconsolidation systemic therapy for central nervous system relapse of acute lymphoblastic leukemia in children.

BACKGROUND: We assessed efficacy and morbidity of chemotherapy and 1, 800 cGy of hypofractionated craniospinal irradiation (CSI) in children with central nervous system (CNS) relapse following first remisssion of acute lymphoblastic leukemia (ALL). PROCEDURE: Nineteen patients with isolated CNS relapse and 4 with combined CNS/marrow or CNS/testicular relapse received treatment according to Children's Hospital of Philadelphia (CHOP) protocols CHP-449 and CHP-497. CNS treatment included intrathecal methotrexate, cytarabine, and hydrocortisone and 1,800 cGy CSI in 16 fractions over 12 months. Systemic therapy consisted of reinductions with vincristine, prednisone, and daunorubicin and reconsolidations with cytarabine, etoposide, and L-asparaginase every 56 days for 2 years. Outcome measures were event-free survival (EFS), survival, growth, and neuropsychologic assessment or school performance. RESULTS: Follow-up of survivors from first relapse ranges from 52 to 133 months(median 91 months). Actuarial survival and EFSat 10 years are 58% (CI95 = 38-78%) and 54% (CI95 = 32-76%). Events include 2 second CNS, 4 marrow, 1 testicular, and 2 testicular/marrow relapses and 1 secondary leukemia. EFS is 100% (CI95 = 93-100%) in 9 patients with recurrence more than 26 months from diagnosis. Three patients have significant treatment-related reduction in stature. Median full-scale IQs of 6 patients tested were 112 pretreatment and 111 posttreatment among surviving patients. All 17 survivors attend regular school, but 2 receive supplementary special services. CONCLUSIONS: Lower dose, hypofractionated CSI, intrathecal chemotherapy, and moderately intensive systemic chemotherapy provide excellent disease control for patients with late isolated CNS or combined marrow and CNS relapse. Children with brief first remissions remain at substantial risk of subsequent relapse with this therapy, especially in the marrow and testes.

Adolescent↗

PubMed1985

Leukemia relapse in long-term survivors of acute leukemia.

Between 1964 and 1982, 862 patients with acute leukemia who were collected from medical institutions throughout the country had a survival of 5 years or longer. Their remission has been achieved mainly with a combination therapy of vincristine and prednisone in childhood acute leukemia and daunomycin, cytosine arabinoside, 6-mercaptopurine, prednisone (DCMP) regimen in adult acute leukemia. Among 320 relapsed patients, 88 (38.8%) of 227 children had a primary relapse in the marrow, 85 in the central nervous system (CNS), 37 in the testis/ovary, and 13 in a combined site. The large majority of adult relapsed patients relapsed in the marrow. Ninety-three patients who experienced only one relapse had a much longer prolongation of survival, not yet reaching a median over 14 years after diagnosis, compared to those experiencing two or more relapses. Survival curves in five groups of patients divided by length of maintained remission were investigated by the life table method. In children as well as adults, survival duration in patients on 5 or more years maintained remission was significantly longer than that in the other maintained groups. With respect to relation between frequency of CNS relapse and type of CNS prophylaxis, there was no statistically significant difference between patients who received CNS prophylaxis and patients who did not. However, a better survival was observed in patients who received CNS prophylaxis with cranial radiation plus intrathecal methotrexate. Thus, long-term clinical follow-up might provide important information for the therapeutic strategy against acute leukemia.

Actuarial Analysis↗

PubMed1987

Relapse-associated variables in stage I favorable histology Wilms' tumor. A report of the National Wilms' Tumor Study.

All 24 cases of confirmed and evaluable Stage I favorable histology (FH) Wilms' tumor (WT) relapsing to date on the Third National Wilms' Tumor Study (NWTS-3) were compared with 48 matched control subjects who had not relapsed for at least 2 years after diagnosis. Fifteen of the clinical and pathological variables studied, including patient age and tumor size, had no significant relationship to the outcome of this study. Four histologic features, all related to the degree of tumor extension within the "tumor-kidney unit" proved to be significantly associated with relapse. These were (1) invasion of the tumor capsule, (2) presence of an "inflammatory pseudocapsule," (3) renal sinus invasion, and (4) tumor in intrarenal vessels. One or more of these features was present in 100% of relapsed cases (excluding one for which two variables were unevaluable), but occurred in only 46% of controls (P less than 0.0002). Therefore, no relapses occurred in the NWTS-3 when all four variables were negative. This result was confirmed by a review of all Stage I cases in the NWTS-1 who had relapsed and who were treated by single-agent chemotherapy. Again, no relapses occurred when all four factors were negative. These results demonstrate the feasibility of "microsubstaging" and could serve as a basis for future refinements of therapy for Stage I favorable histology Wilms' tumor.

Child↗

PubMed1991

Remission induction and continuation therapy in children with their first relapse of acute lymphoid leukemia. A Pediatric Oncology Group study.

Between January 1979 and April 1983, 113 children undergoing their first relapse of acute lymphoid leukemia (ALL) at any site were registered in Pediatric Oncology Group study 7834; 98 were eligible and evaluable. In addition to radiotherapy administered to sites of local relapse, induction consisted of vincristine, doxorubicin, and prednisone (VAP) chemotherapy. Continuation therapy consisted of triple-drug intrathecal therapy and regimens of 6-thioguanine and cytarabine alternating with vincristine, prednisone, cyclophosphamide, and cytarabine. Randomization in continuation was between VAP pulses or no pulse, regardless of the site of relapse. This report provides long-term follow-up of these patients. Thirty-two of 39 children with bone marrow involvement achieved a complete response (CR). Only one of these is alive in an unmaintained remission, a child who did not have an initial CR. Thirty-four of 36 evaluable children with central nervous system involvement as the site of relapse achieved CR. Of these ten are alive; eight are in continuing CR. Nineteen of 20 boys with testicular relapse achieved CR. Of these, 14 are still alive and not receiving therapy, although only one half received treatment in compliance with the protocol described. These results illustrate the possibility of cure of patients who have relapsed with ALL when it is (1) confined to a meningeal or gonadal site and (2) treated vigorously with radiotherapy and a new regimen of systemic chemotherapy. The results reconfirm the need to prevent an initial relapse at any site.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

Testicular relapse in adult acute myelogenous leukemia.

Testicular relapse (TR) in adult acute myelogenous leukemia (AML) is uncommon, occurring in only 1-2% of patients with bone marrow relapse. TR in the absence of systemic relapse has been reported previously in 2 adults and 12 children, of which 67% were monocytic variants of AML. This article presents the case of a 29-year-old man with AML that relapsed in his testicle without evidence of bone marrow relapse. This patient and the two previously mentioned adults experienced bone marrow relapse within 2 months and died within 7 months of their TR. TR in adult myelogenous leukemia should be considered a harbinger of systemic relapse and suggests a need for aggressive local and systemic therapy.

Adult↗

PubMed1993

Prognostic factors for patients with Hodgkin disease in first relapse.

BACKGROUND: This study aims to identify factors that predict outcome after salvage therapy for patients with Hodgkin disease (HD) in first relapse. METHODS: Between 1969 and 1985, 627 patients with Pathologic Stage IA-IIIB HD were treated at the Joint Center for Radiation Therapy. With a median follow-up time for survivors of 135 months, 138 patients (22%) have experienced relapse. One hundred twenty-seven of these were retreated with curative intent and form the basis of this report. RESULTS: The complete response (CR) rate after retreatment was 79%. The 10-year actuarial freedom from second relapse (FSR) was 53%, and the 10-year survival rate from the time of first relapse was 57%. For patients experiencing relapse after initial radiation therapy (RT) alone (n = 110), the 10-year FSR and overall survival rates were 58% and 62%, respectively. Histologic type was the single most important prognostic factor for second CR rate, FSR, and survival. Patients with nodular sclerosis or lymphocyte predominant (NS/LP) histologic type had a 91% second CR rate, 67% 10-year FSR rate, and 75% 10-year survival rate, compared with 66%, 44%, and 43%, respectively, for patients with mixed cellularity or lymphocyte depleted (MC/LD) histologic type. For patients who experienced relapse after initial combined modality therapy (CMT; n = 17), the 10-year FSR and overall survival rates were 13% and 24%, respectively. CONCLUSION: This study demonstrates that patients who experience relapse after RT alone can be effectively salvaged with combination chemotherapy. The implications of these results for clinical decision making are discussed.

Adult↗

PubMed1990

Low-dose corticosteroid therapy after multiple relapses of severe HBsAg-negative chronic active hepatitis.

To evaluate the efficacy of low-dose corticosteroid therapy after multiple relapses of severe HBsAg-negative chronic active hepatitis, 22 patients who had relapsed on 3.4 +/- 0.4 occasions (range = two to seven relapses) were treated with the lowest dose of medication necessary to ameliorate symptoms and maintain serum AST activity below five-fold normal. Results were compared with those in 31 patients who had received conventional retreatments after 3.4 +/- 0.3 relapses (range = two to eight relapses). During 44 +/- 7 mo of low-dose therapy (range = 9 to 149 mo), one patient (5%) entered sustained remission, 16 patients (72%) continued treatment, two patients (9%) received liver transplantations, two patients (9%) died of liver-related complications and one patient (5%) died of a nonliver-related cause. Drug-related side effects improved in 11 of 13 patients who had acquired them during conventional therapy (85%). The median dose of prednisone was 7.5 mg daily (range = 1 to 17.5 mg) with and without azathioprine. Thirteen patients received long-term treatment consisting of 10 mg or less of prednisone only. Patients receiving conventional treatment entered remission more frequently than those on low-dose therapy (97% vs. 36%, p less than 0.001) but they relapsed after drug withdrawal (53% vs. 87%, p greater than 0.01), required continuous therapy (55% vs. 72%, p greater than 0.1) and died of liver-related complications (10% vs. 9%) as commonly as those receiving low-dose therapy. We conclude that low-dose corticosteroid therapy in patients who have experienced multiple relapses has similar efficacy and less morbidity than conventional retreatments.

Azathioprine↗

PubMedDate not supplied

Lomustine, vindesine and bleomycin (LVB) used in the treatment of relapsed advanced Hodgkin's disease. A prospective study on behalf of the East of Scotland and Newcastle Lymphoma Group (ESNLG).

Sixty-three patients with relapsed advanced Hodgkin's disease were treated with lomustine (CCNU), vindesine and bleomycin (LVB). Age range was 17-72 years, with 38 males and 25 females. Thirty patients achieved complete remission (CR) with a median duration of 24+ months (range 3-55). Nineteen continue in unmaintained CR. CR rates were highest for those patients who relapsed greater than 6 months after first line treatment and for those at second or subsequent relapse. CR rates were higher in those with nodal only relapse. Twenty-seven patients were non-responders and six were partial responders. These 33 patients were subsequently changed to alternative chemotherapeutic regimes and 26 failed to respond to any therapy and have since died. Only one patient is in unmaintained complete remission. The regimen was well tolerated by patients, and easy to administer. It produced no serious episodes of toxicity. We conclude that LVB is of value in the management of relapsed advanced Hodgkin's disease especially in chronic relapsing patients, and where relapse occurs greater than 6 months after the first line treatment. We are presently unsure whether it offers any advantage over reintroduction of first line treatment in the latter group.

Adolescent↗

PubMed2005

Peptide vaccination after repeated resection of metastases can induce a prolonged relapse-free interval in melanoma patients.

This pilot study was carried out to gain a first insight into the effects of peptide vaccination in melanoma patients in the high-risk adjuvant disease setting. From the adjuvant peptide vaccination studies carried out in our institution since 1998, we identified all melanoma patients with a history of at least 3 completely resected metastases during the year preceding enrollment into the trial and describe the clinical and immunologic observations. Out of a total of 44 patients with resected cutaneous melanoma entered into adjuvant peptide vaccination trials, 9 patients were identified with more than 3 metastases in the year before vaccination. After initiation of vaccination, 2 patients remained relapse-free for 27 and 42+ months, 2 patients experienced single or several initial relapses and subsequent relapse-free intervals of 18 and 65+ months, whereas 5 patients progressed. In both patients with relapse after prolonged relapse-free intervals, the relapses were initially confined to the small intestine and could be resected. Induction or boosting of functional tyrosinase peptide-specific T cells was noted in 6 of 8 patients, including all 4 patients with prolonged relapse-free intervals. In conclusion, adjuvant peptide vaccination was associated with cessation of recurrences in 4 of 9 patients, of whom all 4 had an immunologic response to the vaccine.

Adjuvants, Immunologic↗

PubMed2004

Analysis of factors that predict alcohol relapse following liver transplantation.

Alcoholic liver disease has become a major indication for liver transplantation in the United States. Factors that predict alcohol relapse after liver transplantation are poorly defined. The aim of our study was to identify predictors of alcohol relapse in patients undergoing liver transplantation for alcoholic liver disease. One hundred and eleven patients undergoing liver transplantation for alcoholic liver disease between 1985 and 1999 were identified from our database. Patients were selected for liver transplantation if their risk of relapse was felt to be low by the transplant team. A chart review was conducted to determine if relapse had occurred, the presence or absence of factors that were thought to predict relapse, and survival. Demographic and psychosocial variables were analyzed using univariate and multivariate logistic regression to identify independent predictors of relapse. The median duration of abstinence before liver transplantation was 15 months (range: 1-120). Hepatitis C virus was present in 64% of patients. A family history of alcoholism in a first-degree relative was identified in 38%, and 78% received treatment for alcoholism before liver transplantation. The mean duration of follow-up was 44.1 +/- 3.7 months. There were 29 deaths (26%) overall. Seventeen patients (15%) returned to alcohol use. On multivariate analysis a family history of alcoholism was found to be an independent predictor of alcohol relapse (P=.03). Further prospective studies are needed to examine this association in greater detail to provide targeted treatment for alcoholism both before and after liver transplantation.

Adult↗

PubMed1984

Peptichemio in neuroblastoma at relapse.

Peptichemio (PTC), a multipeptidic complex of m-L-phenyl-alanine mustard, was administered to 39 children with neuroblastoma at relapse. The compound was given in two 5-day cycles at dosages varying from 1.0-1.5 mg/kg/day. We were able to evaluate 29 of the initial 39 children for PTC effect; 21 of them had received PTC as first therapy following diagnosis. Ten patients underwent other chemotherapy for relapse before PTC. Three patients were off therapy when relapse occurred. Subjective improvement was observed in 18 cases (62%). Eleven patients (38%) experienced an objective regression, which was scored as complete response in three cases, partial response in two, mixed response in six. In ten children no significant disease change was observed; the remaining eight had a progression of their disease while receiving PTC. The incidence of responses has been higher in patients off therapy at moment of relapse, and lower in those pretreated for their relapse. Previous administration of PTC did not reduce the chance of response at relapse. Major toxic effects were transient, mostly moderate myelodepression and phlebosclerosis. Allergic reactions, nausea, and vomiting, occurred in a few patients. These data indicate that PTC may exert objective antitumor activity in approximately one-third of neuroblastoma patients at relapse.

Child↗

PubMed2004

Ex vivo drug resistance in childhood acute myeloid leukemia on relapse is not higher than at first diagnosis.

Relapsed pediatric patients with acute myeloid leukemia (AML) have a poor clinical prognosis. The aim of this study was the analysis of the ex vivo drug resistance profile on relapse in childhood AML in comparison to newly diagnosed AML. The results of 98 pediatric AML samples tested by the MTT assay were analyzed. Eighteen samples (18%) were excluded from the further analysis due to spontaneous apoptosis of blasts in 4-days culture, low percentage of myeloblasts in the sample either in the beginning or at the end of the assay, infection, or formation of clots in the sample. Finally, ex vivo drug resistance of 20 relapsed samples were compared with that of 60 de novo AML, including 9 matched pairs. Up to 18 drugs were tested for each patient. No significant differences between drug resistance at diagnosis and at relapse in AML was found, neither for the whole groups of patients, nor for matched pairs only. Possibly, relatively good sensitivity of myeloblasts on relapse was found against melphalan, thiotepa, 4-HOO-ifosfamide, and cladribine. In summary, cellular drug resistance in childhood AML at relapse is not higher than at first diagnosis. These observations suggest that other, than cellular drug resistance, factors play a key role in therapy failure of relapsed childhood AML.

Acute Disease↗

PubMed2004

Late relapse of osteosarcoma: implications for follow-up and screening.

Long-term disease-free survival in patients with localised osteosarcoma treated in large multicentre randomised trials is over 50%. Most relapses occur early, usually within 2-3 years. Relapse after 5 years is uncommon and has been infrequently described. Eight patients with osteosarcoma treated at The London Bone and Soft Tissue Tumour Service since 1986 developed recurrence of disease after 5 years, the latest 14 years after the initial diagnosis. Five patients developed pulmonary metastases, two patients isolated bone metastases and one patient intra-abdominal metastases. Although a second complete remission was achieved in six patients, four patients relapsed again, all with pulmonary metastases. Two patients had co-existent brain metastases. One of those with a second recurrence has achieved a further complete remission and remains well 50 months after the most recent treatment. A second patient is disease-free 24 months after complete excision of an isolated pulmonary metastasis and one further patient is disease-free 6 months after chemotherapy and pneumonectomy for pleural and pulmonary metastases. Five patients have died of disease with a median survival from the date of relapse of 17 months (2-68 months). Current data looking at long-term outcome of patients with osteosarcoma is limited. Reports of late relapse are rare as numbers are small, thus long-term surveillance of patients is essential. It is possible that sites of relapse are more unusual, and more extensive staging may be necessary when late relapse occurs.

Adolescent↗

PubMed2006

Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing tumors.

BACKGROUND: The prognosis of Ewing tumor (ET) patients has significantly improved to cure rates approximating 70%. The prognosis in relapse, however, is poor. Promising response rates have recently been reported for the combination of topotecan (TOPO) and cyclophosphamide (CYC) encouraging wider application of this combination in patients with relapsed ETs. This report summarizes the experience of patients treated with TOPO/CYC for recurrent or refractory disease within the German ET trials. PROCEDURE: Fifty-four patients aged 3.2-49.5 (median: 17.4) years received TOPO (0.75 mg/m2/day, days 1-5) and CYC (250 mg/m2/day, days 1-5) following first (40) or second (6) relapse or progression under first-line therapy (8). RESULTS: A median of 3 (range: 1-11) TOPO/CYC courses were given. Sixteen patients (32.6%) showed partial response (PR), 13/49 (26.5%) had stable disease (SD), 14/49 (28.6%) progressed, 2/49 (4.1%) showed a mixed response (MR). In 4 patients response was not documented, 5/54 patients with complete initial resection at the diagnosis of relapse were excluded from the response analysis. At completion of relapse therapy, 24/54 patients had entered complete (19) or partial (5) remission, 2 had SD, 26 showed progression, information was unavailable in 2 patients. Of the 19 relapse patients achieving complete response (CR), 10 maintained remission (52.6%). At the time of evaluation, after a median follow-up for survivors of 23.1 (range: 7.8-59.8) months from the event prompting TOPO/CYC treatment, 14/54 patients (25.9%) were in continuous complete (13) or partial (1) remission. Overall survival (OAS) after 1 year was 0.61 (95%-CI 0.47-0.74). CONCLUSION: TOPO/CYC is active in relapsed ETs and warrants further evaluation.

Adolescent↗

PubMed1988

The incubation time of relapses after treatment of multibacillary leprosy with rifampicin containing regimens.

In order to determine the duration of follow-up needed to evaluate the efficacy of short-course bactericidal regimens for multibacillary leprosy, information is needed on the incubation time of relapses after stopping treatment. Several groups of patients, who had been on rifampicin-containing regimens, were followed up for periods ranging from 4 to 10 years. Two groups of relapses were observed: early relapses occurring within 3.5 years after stopping treatment, with a median incubation time of 1 year and 10 months (upper limit of 95% confidence interval: 2 years); and late relapses occurring more than 3.5 years after stopping treatment, with a median incubation of 5 years. Early relapses are probably due to insufficient treatment, and late relapses to persisting bacilli or to reinfection. It is concluded that the efficacy of short-course RMP-containing therapeutic regimens can be evaluated by observing the occurrence of early relapses, 50% of which occur before 2 years after the end of therapy.

Drug Therapy, Combination↗

PubMed1993

Viral infections trigger multiple sclerosis relapses: a prospective seroepidemiological study.

A neurological surveillance was combined with prospective recording of upper respiratory and gastrointestinal infections and serological diagnosis of five common viral infections in 60 benign multiple sclerosis patients, with a mean follow-up of 31 months. During 4-week at risk (AR) periods encompassing common infections, a significant excess of MS relapses was found in the AR period, with a relative risk of 1.3. A seasonal variation of the MS relapse rate was found with a minimum in summer. There was a significant correlation between the number of AR relapses and the number of common infections per month explaining the periannual distribution of relapses. The non-AR relapses showed no seasonal variation. There was a significant correlation between adenovirus CF titre rises associated with upper respiratory infections and the occurrence of a major MS relapse in the AR period (n = 7), while influenza infections were not followed by a major MS relapse (n = 6). Linear homologies have been demonstrated between adenovirus and basic myelin protein. The epidemiological approach is essential to our understanding of systemic antigens triggering multiple sclerosis activity.

Adult↗