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[The incidence and treatment of the first relapse in children with Hodgkin's disease].

From January 1988, to December 1997, among 447 children with Hodgkin's disease (HD) who underwent initial treatment in seven centres of the Polish Paediatric Leukaemia/Lymphoma Study Group, 442 patients obtained a complete remission (CR). The initial treatment consisted of multidrug chemotherapy (B-DOPA and MVPP) combined with local radiotherapy. Relapses occurred in 35 cases (7,9%). Two patients from other centres were also included in this analysis. Four patients were lost to follow-up; 33 patients with relapses were analysed. Early relapses (first complete remission (CR) shorter than 12 months) occurred in 17 cases. Treatment of the first relapse consisted of different types of multidrug chemotherapy. Six patients underwent high-dose chemotherapy and peripheral blood stem cells transplantation. Radiotherapy was used in 19 children. Second CR was achieved in 28 patients (85%). In 10 children (36%) second relapse occurred after 4 to 21 months (median = 10). In 17 cases the second CR lasted 12-14 (median=54) months. The probability of the 7-year freedom from second relapse was 64%. Eleven patients died; one of them in second CR due to toxic liver damage. Results of treatment in children with early relapses were significantly worse. In 17 patients with early relapse, and 16 children with late relapse, the second CR was achieved in 70% and 100% of cases, respectively. The probability of the 7-year overall survival, freedom from second relapse and event-free survival in children with early and late relapse was: 42, 58, 40%, and 94, 69, and 66%, respectively. The therapeutic results in the subgroups of children with relapses treated with different methods were not comparable because of the small number of children in each group. The use of multidrug chemotherapy with or without radiotherapy allows to achieve a long lasting second CR in more than 50% of children with HD who relapsed after initial combined modality treatment. The optimal treatment of relapsed HD in patients initially treated with multidrug chemotherapy with or without of radiotherapy, is currently unknown.

Adolescent↗

[Clinical studies on endocrine therapy for prostatic carcinoma (5): Analyses of relapse from endocrine therapy].

Prostate carcinomas are well known to be initially responsive to endocrine therapy. However, a significant number of the patients experience a relapse from endocrine therapy during the follow-up period. We clinically analyzed various aspects of the relapse which indicate a limitation in the effectiveness of endocrine therapy for prostate carcinoma. In a total of 372 patients, 117 (31.5%) had some evidence of local relapse such as regrowth of the primary lesion, or a generalized relapse such as re-elevation of total acid phosphatase, reactivation of previously present metastasis or the new appearance of metastasis, during endocrine therapy. Of these, one-fourth had local relapse alone and the remainder showed generalized relapse. The interval from the start of the treatment to the time of relapse tended to become shorter; 45.9 months (mean) in stage B, 36.8 in stage C and 29.3 in stage D, according to the stage progression. As to the non-relapse rate of the primary lesion, no differences were found among the stage, with the rate being approximately 90% at the fifth year in each stage. However, the generalized relapse-rate tended to increase with the stage progression. In the generalized relapse, the patients of stage C or D showed a non-relapse rate of 71.7% or 67.4%, respectively. Most of the generalized relapse appeared within five years following start of endocrine therapy in these advanced stages. The interval from relapse to prostate carcinoma-related death in patients with the generalized relapse was 9 approximately 21 months, and those in stage D tended to show a a poorer prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Premature chromosome condensation studies in human leukemia: 5. Prediction of early relapse.

Previous reports have suggested that the technique of premature chromosome condensation (PCC) is useful for predicting relapse in patients with acute leukemia. However, these studies involved patients had been in complete remission (CR) for various periods of time and had heterogeneous expectations for relapse. The purpose of this study was to further determine the value of PCC in predicting relapse by examining the PCC characteristics of bone marrow specimens from patients with acute leukemia on a common therapeutic regimen after similar periods in CR. The remission durations after the PCC determinations were compared between patients with high or low proliferative potential indices (PPI, or the fraction of G1 cells in late G1 phase). Of 60 patients studied between two and eight weeks after achieving CR, 14 of the 16 patients exhibiting high PPI values (greater than or equal to 35) have relapsed. The mean time from PCC measurement to relapse was 23 weeks. In contrast, only 19 of the 44 patients exhibiting low PPI values have relapsed, with an estimated mean time to relapse of 68+ weeks. Likewise, of 38 patients studied between nine and 15 weeks of CR, nine of the ten patients exhibiting high PPI values have relapsed (mean time to relapse, 23 weeks), while only 16 of 28 patients with low PPI values have relapsed (estimated mean time to relapse, 54+ weeks). The predictive value of the PCC technique was found to be independent of other prognostic factors for the duration of CR, and it identified those patients within the poor prognostic category with a high likelihood of imminent relapse. While similar trends were observed at later time intervals in CR, the differences in relapse rate between patients with high or low PPI values is not significant. These results confirm the usefulness of the PCC technique in predicting relapse in acute leukemia and could aid in the identification of patients who might benefit by an alteration of therapeutic strategy.

Aminoacridines↗

Relapse after non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: early transplantation, use of an unrelated donor, and chronic graft-versus-host disease are protective.

We analyzed the incidence of posttransplant chronic myelogenous leukemia (CML) relapse in 283 consecutive related-donor (n = 177) and unrelated-donor (n = 106) allogeneic transplant recipients. Twenty-two of 165 related-donor recipients with stable or advanced disease at the time of transplant had hematologic relapse of CML following transplant (5-year Kaplan-Meier estimate of relapse, 20%; 95% confidence interval [CI], 11 to 30%). One of 12 patients transplanted in second stable phase following blast crisis also relapsed. Fifteen related-donor transplant recipients relapsed within 5 years of transplant; however, seven relapsed between 5 and 9 years after transplant. Factors independently associated with an increased risk of posttransplant relapse for related-donor recipients included prolonged interval between diagnosis and transplant (relative risk, [RR], 3.81; P = .009) and bone marrow basophilia (RR, 5.62; P = .01). Related-donor recipients with posttransplant chronic graft-versus-host disease (CGVHD) had a decreased risk of relapse (RR, 0.24; P = .005). Only two of 106 unrelated-donor transplant recipients relapsed following transplant (5-year Kaplan-Meier estimate of relapse, 3%; 95% CI, 0% to 7%). When both related- and unrelated-donor recipients were considered, the use of an unrelated donor was independently associated with a decreased risk of relapse (RR, 0.24; P = .07). Twelve of 16 relapsing patients who received further therapy (nine of 13 who underwent second transplant and three of three who received donor leukocyte infusions) remain alive. This analysis shows that relapse, sometimes occurring long after transplant, is an important adverse outcome in allogeneic transplantation for CML. Early transplant, posttransplant CGVHD, and use of an unrelated donor are associated with a reduced incidence of relapse, perhaps due to allogeneic disparities enhancing the graft-versus-leukemia effect.

Adolescent↗

Patterns of relapse and response to retreatment in patients with metastatic melanoma or renal cell carcinoma who responded to interleukin-2-based immunotherapy.

PURPOSE: The purpose of this study was to examine the pattern of relapse and the treatment of relapse with either surgery or repeat immunotherapy in patients with metastatic melanoma or renal cell carcinoma who had previously responded to interleukin-2-based therapy. PATIENTS AND METHODS: Over a 10-year period 1051 patients with metastatic melanoma or renal cell carcinoma were treated with interleukin-2-based immunotherapy at a single institution. One hundred fifty-nine patients who relapsed after an initial partial response or complete response to interleukin-2-based immunotherapy formed the study population for this retrospective review. Medical records, physical examination forms, and relevant radiographs were reviewed to determine response, relapse site(s), and response to treatment for relapse. RESULTS: Relapse after an initial response to interleukin-2-based therapy occurred in 84 (80%) of 105 patients with metastatic melanoma and in 75 (70%) of 107 patients with metastatic renal cell carcinoma. Relapse after an initial partial response involved 71 (97%) of 73 patients with metastatic melanoma and 55 (86%) of 64 patients with metastatic renal cell carcinoma. The initial site(s) of relapse after a partial response involved a new site(s), old site(s), or both old and new sites with relatively even distribution. Relapse after an initial complete response occurred in 13 (41%) of 32 patients with metastatic melanoma and in 20 (47%) of 43 completely responding patients with metastatic renal cell carcinoma. Surprisingly, the initial site of relapse after a complete response involved only new sites of disease in 70% of patients. Retreatment of relapses with the same interleukin-2-based therapy originally used was effective in only one (2%) of 54 selected patients, but a different interleukin-2-based therapy in 35 patients resulted in five responders (a 14% secondary response rate). Most re-responders, however, responded to treatment with tumor-infiltrating lymphocytes and interleukin-2, and only one of 20 patients responded to retreatment with interleukin-2 alone. Surgical metastasectomy with therapeutic intent in 25 selected melanoma patients and in 31 selected renal cell cancer patients resulted in a 2-year progression-free survival of 18% in patients with metastatic melanoma and 37% in patients with metastatic renal cell carcinoma. DISCUSSION: In patients with metastatic melanoma or renal cell carcinoma, tumor relapse was common after a partial response to an interleukin-2-based therapy and included previously identified sites of disease in most patients. Relapse after a complete response was less frequent and involved only new sites in a majority of patients. In selected patients who relapsed, repeat treatment with the same interleukin-2-based therapy that provided the initial response was rarely effective. However, with a different interleukin-2-based therapy, usually using tumor-infiltrating lymphocytes, repeat treatment induced secondary responses in some patients. In addition, salvage metastasectomy resulted in durable progression-free survival in selected patients.

Carcinoma, Renal Cell↗

Relapse rates and enhancing lesions in a phase II trial of natalizumab in multiple sclerosis.

BACKGROUND: Natalizumab, a humanized monoclonal IgG4 antibody, is an alpha4-integrin antagonist, which inhibits the migration of inflammatory cells into the central nervous system, a key pathogenic mechanism in multiple sclerosis (MS). In a six month, phase II clinical trial of patients with relapsing MS, natalizumab significantly reduced the formation of new gadolinium-enhanced (Gd+) lesions and the number of clinical relapses. OBJECTIVE: To investigate the relationship of historical relapse rate and new Gd + lesion number with subsequent MS disease activity and natalizumab treatment in the phase II study. METHODS: Patients who participated in the phase II study were stratified into subgroups according to: (i) the number of relapses in the two years prior to entry into the study: 2 relapses (n = 108), 3 relapses (n =57), and >3 relapses (n =48); (ii) the number of new Gd + lesions at baseline (Month 0): 0 (n = 129), 1-2 (n =50), and >2 (n =33). Relapses and new Gd + lesions during the treatment phase of the trial were determined and compared for each subgroup. RESULTS: Both the prestudy relapse rate and number of new Gd + lesions at baseline were related to the subsequent risk of a relapse; baseline number of Gd + lesions was related to the likelihood of subsequent new Gd + lesion formation. There was a lower proportion of subjects with an on-study relapse and fewer new Gd + lesions in all natalizumab-treated subgroups when compared with their placebo counterpart; the difference was most apparent in the subgroups of patients with >3 relapses in the two years prior to study entry and >2 new Gd -- lesions at Month 0. CONCLUSIONS: There was a lower proportion of subjects with an on-study relapse in natalizumab-treated patients, particularly in those with a more active disease at study entry. Larger ongoing phase III studies will allow more definitive investigation of these preliminary subgroup findings.

Adult↗

Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder.

BACKGROUND: We examined relapse after response to a first episode of schizophrenia or schizoaffective disorder. METHODS: Patients with first-episode schizophrenia were assessed on measures of psychopathologic variables, cognition, social functioning, and biological variables and treated according to a standardized algorithm. The sample for the relapse analyses consisted of 104 patients who responded to treatment of their index episode and were at risk for relapse. RESULTS: Five years after initial recovery, the cumulative first relapse rate was 81.9% (95% confidence interval [CI], 70.6%-93.2%); the second relapse rate was 78.0% (95% CI, 46.5%-100.0%). By 4 years after recovery from a second relapse, the cumulative third relapse rate was 86.2% (95% CI, 61.5%-100.0%). Discontinuing antipsychotic drug therapy increased the risk of relapse by almost 5 times (hazard ratio for an initial relapse, 4.89 [99% CI, 2.49-9.60]; hazard ratio for a second relapse, 4.57 [99% CI, 1.49-14.02]). Subsequent analyses controlling for antipsychotic drug use showed that patients with poor premorbid adaptation to school and premorbid social withdrawal relapsed earlier. Sex, diagnosis, obstetric complications, duration of psychotic illness before treatment, baseline symptoms, neuroendocrine measures, methylphenidate hydrochloride challenge response, neuropsychologic and magnetic resonance imaging measures, time to response of the initial episode, adverse effects during treatment, and presence of residual symptoms after the initial episode were not significantly related to time to relapse. CONCLUSIONS: There is a high rate of relapse within 5 years of recovery from a first episode of schizophrenia and schizoaffective disorder. This risk is diminished by maintenance antipsychotic drug treatment.

Adolescent↗

Risk factors for relapse in health care professionals with substance use disorders.

CONTEXT: Substance use disorders among physicians are important and persistent problems. Considerable debate exists over whether use of major opioids, especially among anesthesiologists, is associated with a higher relapse rate compared with alcohol and nonopioids. Moreover, the risk factors for relapse with current treatment and monitoring strategies are unknown. OBJECTIVE: To test the hypothesis that chemically dependent health care professionals using a major opioid (eg, fentanyl, sufentanil, morphine, meperidine) as drug of choice are at higher risk of relapse. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 292 health care professionals enrolled in the Washington Physicians Health Program, an independent posttreatment monitoring program, followed up between January 1, 1991, and December 31, 2001. MAIN OUTCOME MEASURE: Factors associated with relapse, defined as the resumption of substance use after initial diagnosis and completion of primary treatment for chemical dependency. RESULTS: Twenty-five percent (74 of 292 individuals) had at least 1 relapse. A family history of a substance use disorder increased the risk of relapse (hazard ratio [HR], 2.29; 95% confidence interval [CI], 1.44-3.64). The use of a major opioid increased the risk of relapse significantly in the presence of a coexisting psychiatric disorder (HR, 5.79; 95% CI, 2.89-11.42) but not in the absence of a coexisting psychiatric disorder (HR, 0.85; 95% CI, 0.33-2.17). The presence of all 3 factors--major opioid use, dual diagnosis, and family history--markedly increased the risk of relapse (HR, 13.25; 95% CI, 5.22-33.59). The risk of subsequent relapses increased after the first relapse (HR, 1.69; 95% CI, 1.13-2.53). CONCLUSIONS: The risk of relapse with substance use was increased in health care professionals who used a major opioid or had a coexisting psychiatric illness or a family history of a substance use disorder. The presence of more than 1 of these risk factors and previous relapse further increased the likelihood of relapse. These observations should be considered in monitoring the recovery of health care professionals.

Adult↗

Adult acute lymphoblastic leukemia at relapse. Cytogenetic, immunophenotypic, and molecular changes.

BACKGROUND: There have been published reports on cytogenetic, immunophenotypic, and molecular changes at relapse in childhood acute lymphoblastic leukemia (ALL) including lineage switch and secondary leukemia. There are limited data, however, on the cytogenetic, immunophenotypic, and molecular parameters of adult ALL at relapse. Because, as in children, the cytogenetic and/or immunophenotypic changes observed in adult ALL at relapse may have prognostic significance, the authors investigated the significance of such changes. METHODS: Fifty-three patients with relapsed adult ALL for whom cytogenetic, immunophenotypic, and/or molecular analyses were performed at diagnosis and at relapse were studied. Changes in any of the parameters at relapse were correlated with total survival and survival from the time of relapse. RESULTS: Of the 32 patients for whom cytogenetic studies were performed at relapse, 21 (66%) showed clonal cytogenetic changes, 40% of which were clonal evolution. None of these cases, however, showed two entirely different abnormal karyotypes at diagnosis and at relapse. The immunophenotypes showed occasional gain or loss of one or two surface markers, and the molecular genetic configurations for JH, JK, and the T-cell receptor beta were stable throughout the evolution of the disease. Patients with clonal evolution had a shorter overall survival than the rest of the group (P = 0.02). This difference, however, was not significant with respect to survival measured from the time of relapse. CONCLUSIONS: The most frequent changes in the biologic profile of adult ALL at relapse are shifts in the karyotype, with or without clonal evolution. Clonal evolution detected at relapse is associated with a higher frequency of unfavorable karyotypes at diagnosis and with a worse overall prognosis. However, survival from the time of relapse is similar in patients with and without clonal evolution.

Adolescent↗

Relapse prevention interventions for smoking cessation.

BACKGROUND: Several treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. There are interventions designed to help prevent relapse. OBJECTIVES: To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction group trials register in September 2004 for studies mentioning relapse prevention or maintenance in title, abstracts or keywords. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of relapse prevention interventions with a minimum follow up of six months. We included smokers who quit on their own, or were undergoing enforced abstinence, or who were participating in treatment programmes. We included trials that compared relapse prevention interventions to a no intervention control, or that compared a cessation programme with additional relapse prevention components to a cessation programme alone. DATA COLLECTION AND ANALYSIS: Studies were screened and data extracted by one author and checked by a second. Disagreements were resolved by discussion or referral to a third author. MAIN RESULTS: Forty studies met inclusion criteria, but were heterogeneous in terms of populations and interventions. We considered studies that randomized abstainers separately from studies that randomized participants prior to their quit date. We detected no benefit of brief and 'skills-based' relapse prevention interventions for women who had quit smoking due to pregnancy, or for smokers undergoing a period of enforced abstinence. We also failed to detect significant effects in trials in other smokers who had quit on their own or with a formal programme. Amongst trials recruiting smokers and evaluating the effect of additional relapse prevention components we also found no evidence of benefit in any subgroup. We did not find that providing training in skills thought to be needed for relapse avoidance reduced relapse, but most studies did not use experimental designs best suited to the task, and had limited power to detect expected small differences between interventions. AUTHORS' CONCLUSIONS: At the moment there is insufficient evidence to support the use of any specific intervention for helping smokers who have successfully quit for a short time to avoid relapse. The verdict is strongest for interventions focusing on identifying and resolving tempting situations, as most studies were concerned with these. There is very little research available regarding other approaches. Until more evidence becomes available it may be more efficient to focus resources on supporting the initial cessation attempt rather than on additional relapse prevention efforts.

Behavior Therapy↗

Staphylococcal enterotoxin B and tumor-necrosis factor-alpha-induced relapses of experimental allergic encephalomyelitis: protection by transforming growth factor-beta and interleukin-10.

A study was made of the ability of the superantigen staphylococcal enterotoxin B (SEB) to induce relapses of experimental allergic encephalomyelitis (EAE) in SJL mice that had partially or completely recovered from acute EAE. We find that a single injection of 0.05 mg SEB i.v. induces mild relapses in 50% of such mice. In addition, tumor necrosis factor (TNF)-alpha (0.2 micrograms, i.p.) also induces EAE relapses in 43% of SJL mice when injected 1-2 months after recovery. SEB does not induce a second relapse if reinjected when V beta 17a+T cells are still partially deleted. In these mice, however, TNF-alpha is equally effective in inducing relapses as in mice that did not receive SEB previously. We showed earlier that transforming growth factor (TGF)-beta and TNF-alpha have antagonistic effects on experimental autoimmune diseases; e.g., in spontaneously relapsing EAE, TGF-beta and anti-TNF were protective, while anti-TGF-beta caused disease exacerbation. Interleukin (IL)-10 is also known to counteract certain TNF effects. We now find that both human IL-10 and TGF-beta 2 lower the incidence of EAE relapses when given simultaneously with SEB or TNF-alpha. The protective effect of TGF-beta is significant only against relapses induced by SEB (reduced to 9%), and that of IL-10 only against relapses induced by TNF (reduced to 0%) with the treatment regimens employed. Neutralizing anti-TGF-beta does not increase the incidence of SEB-induced EAE relapses. In contrast, anti-IL-10 increases both the incidence and the severity of such relapses. We conclude that TNF production is probably important in causing EAE relapses, but that other aspects of the SEB-induced reactivation of myelin-specific T cells also contribute. Furthermore, endogenous IL-10 rather than TGF-beta production appears to limit the susceptibility to induction of EAE relapses in this model.

Animals↗

Prognostic factors for relapsed childhood acute lymphoblastic leukemia: impact of allogeneic stem cell transplantation--a report from the Kyushu-Yamaguchi Children's Cancer Study Group.

BACKGROUND: The treatment results of childhood acute lymphoblastic leukemia (ALL) with a first relapse were retrospectively analyzed to determine prognostic factors. In particular, an attempt was made to clarify whether stem cell transplantation (SCT) had any advantages over chemotherapy. PROCEDURES: Of the 407 children with ALL diagnosed between 1984 and 1996, 117 suffered from a relapse before December 1999. The patients were treated differently according to the protocols of each institution. The potential prognostic factors examined were: the time of initial diagnosis, gender, immunophenotype of leukemic blasts and the NCI-risk classification at initial diagnosis, the site of relapse, the time of relapse (early: within 18 months after diagnosis, intermediate: other than either early or late relapse, late: later than 6 months after the discontinuation of front-line chemotherapy), and the treatment after relapse (chemotherapy alone and SCT). RESULTS: A second complete remission (CR2) was achieved in 90 patients (77%) and thirty of them maintained CR2, thus resulting in an event-free survival rate (EFS) of 25.1% and an overall survival rate of 26.1%. The significant prognostic factors identified by a multivariate analysis included the time of relapse (EFS: early 16.2%, intermediate 23.9%, late 35.1%, P = 0.012) and the treatment after relapse (EFS: SCT 30.3%, chemotherapy 22.0%, P = 0.049). When patients with an isolated bone marrow relapse and continuous CR2 for more than 3 months were analyzed, the treatment in CR2 was the only independent prognostic factor (EFS: SCT 60.2%, chemotherapy 25.7%, P = 0.005). CONCLUSIONS: In children with ALL and a first relapse, the time of relapse and the treatment after relapse were found to be independent prognostic factors. Allogeneic SCT in CR2 showed significantly better results than chemotherapy in patients with an isolated bone marrow relapse.

Antineoplastic Combined Chemotherapy Protocols↗

Outcome after relapse in childhood acute lymphoblastic leukemia.

Among 157 children with acute lymphoblastic leukemia (ALL) who experienced relapse at 54 institutes participating in the Japan Association of Childhood Leukemia Study, we analyzed the outcomes after relapse in 103 and 30 eligible cases with bone marrow (BM) and central nervous system (CNS) relapse, respectively. Reinduction rates in BM and CNS relapse cases were 72.3% and 83.3%, respectively. High reinduction rates were observed in B-precursor (B-pre) phenotype ALL in both relapse groups and in late (more than 24 months from onset) BM-relapse patients. After BM relapse, the overall 5-year survival rate was superior in the allogeneic stem cell transplantation (SCT) group compared to the non-SCT group (41.9%+/-8.2% versus 13.6%+/-6.5%, P < .0001). In contrast, the 4-year overall survival rate was not significantly different between the SCT (allogeneic plus autologous) and non-SCT groups after CNS relapse (26.8%+/-14.2% versus 61.9%+/-12.3%, P = .252). The late BM-relapse patients showed a significantly higher survival rate than did early-relapse patients, and survival rates were similar between the allogeneic and autologous group when the patients underwent SCT during a second complete remission. Moreover, B-pre ALL patients classified in the standard-risk group according to National Cancer Institute/Rome's criteria at onset had a good prognosis after allogeneic SCT. Improving the cure rate in relapsed ALL patients requires more intensive reinduction therapy and efforts to succeed with SCT in early BM-relapse patients as well as the establishment of a treatment strategy including indications of SCT for CNS-relapse patients.

Child↗

Prediction of subsequent relapse in children with steroid-sensitive nephrotic syndrome.

Among nephrotic children with frequent relapses at risk for cumulative steroid toxicity, identification of children who may be at high risk for subsequent relapse is very important in making the decision to introduce cytotoxic drugs. We examined the clinical course of 467 relapses in 121 steroid-sensitive nephrotic children to elucidate the risk factors for subsequent relapse, using the Cox proportional-hazards regression model. Gender, age at onset, duration of illness from onset, prednisolone dosage at the most-recent relapse, and regimens of initial steroid therapy at onset were not associated with risk. Relapse within the 1st year was a powerful independent predictor of subsequent relapse irrespective of the duration of illness. The hazard ratio of patients with more than one relapse within the 1st year increased to 1.72-2.12 compared with those without a relapse within the 1st year. The remission period just before the most-recent relapse was also a significant predictor. The risk for patients with a 1-year or longer remission period decreased to 0.57. Patients treated with cyclophosphamide for 12 weeks had a significantly longer remission than those treated with prednisolone alone. Our results suggest that early relapse after onset and/or a short remission period just before recent relapse are independent risk factors for subsequent relapse. Cytotoxic therapy has serious adverse effects and its effect may be limited. Our results may be helpful in deciding on the suitability of cytotoxic drugs.

Adolescent↗

An examination of the cocaine relapse process.

Although empirical studies of the relapse process have been done with alcoholics, smokers, and opiate addicts, comparatively little information is available on the relapse process in cocaine abusers. This paper presents data from the Cocaine Relapse Interview (CRI), a structured interview that assesses factors associated with the onset, course, and termination of cocaine relapse episodes. In a sample of 95 cocaine dependent patients, the experiences that occurred with the greatest frequency immediately prior to relapse were wanting drugs, being alone, having money, and feeling extremely bored and lonely. Following the onset of the relapse, the most frequent experience was unpleasant affect, although positive reactions were also relatively common. The factors perceived as most important in terminating relapse were painful internal states, help-seeking behaviors, and other coping responses. Three types of relapse experiences, or pathways, were identified: (a) unpleasant affect--painful internal states prior to and throughout the relapse; (b) positive affect--positive affect and pleasant social experiences prior to relapse coupled with a relatively unproblematic course; and (c) sensation seeking--sensation seeking and interpersonal problems prior to relapse coupled with mixed emotional reactions and antisocial behavior during the relapse, and interpersonal problems at relapse termination.

Adult↗

Treatment of relapsed acute leukemia after allogeneic transplantation: a single center experience.

Relapsed acute leukemia after allogeneic transplantation has a poor prognosis and most reports have focused on the role of second transplantations in relapsed patients. We report our single-institution experience on the management of relapsed acute leukemia after allogeneic transplantation. We aimed to describe the outcome of relapsed acute leukemia after allogeneic transplantation at our institution and investigate whether maneuvers intended to augment donor T cell allogeneic reactivity were associated with durable graft-versus-leukemia effects. We analyzed 310 patients with acute leukemia who received allogeneic hematopoietic progenitor cell transplants from HLA-matched donors between 1982 and 2005 (229 with acute myelogenous leukemia, 81 with acute lymphoblastic leukemia). Mean post-transplant follow-up was 5 years (range, 0.5-22 years). Factors associated with relapse incidence, therapy for relapse, response to treatment, and post-relapse survival were assessed. One hundred of 310 patients (32%) with acute leukemia relapsed after transplantation, including 28 of 81 patients (35%) with acute lymphoblastic leukemia and 72 of 229 (31%) with acute myelogenous leukemia at a median of 136 days after transplantation. Median post-relapse survival periods were 51 days for the 69 patients who received chemotherapy/supportive care, 84 days for 11 recipients of donor lymphocyte infusions, 303 days for 13 recipients of second transplants, and 442 days for 7 patients treated with interferon-alpha and granulocyte-macrophage colony-stimulating factor. A multivariable Cox regression analysis indicated that a longer time to relapse after transplantation, peripheral blood as source of stem cells, and initial post-relapse therapy with cytokines, donor lymphocyte infusions, or second transplants were associated with improved post-relapse survival (P <.001, <.001, and .025). The outlook for patients with post-transplant relapse of acute leukemia is extremely poor; currently, no single therapy consistently results in durable remissions. Our study highlights the need for clinical trials in this area. Therapy with granulocyte-macrophage colony stimulating factor and interferon-alpha-2b is promising and will be pursued in a prospective trial at our center.

Adolescent↗

Conceptual, methodological, and analytical issues in the study of relapse.

This article examines conceptual, methodological, and analytic issues in research on relapse to alcohol and other drug use. The review notes the continued move in relapse research from a primary reliance on retrospective assessment of factors surrounding the onset of relapse episodes to an increased focus on the use of new technologies to obtain "near real time" data on proximal factors in relapses. Recent advances in neurobiology have yielded important gains in our understanding of vulnerability to relapse in alcohol and other drug abusers. New statistical techniques are also available to analyze data on relapse. From a theoretical standpoint, there has been an increasing appreciation for the complicated and dynamic interplay of distal and proximal factors in the relapse process. At this point, the strongest and most detailed data on factors in the onset and course of relapse have been generated by studies of smoking relapses that have made use of Ecological Momentary Assessment (EMA) technology. However, there is still limited "near real" time data on proximal factors in alcohol and other drug relapses, and no such data on factors that influence the course of these relapses, once they have begun. Nevertheless, important methodological advances have been and continue to be made in the study of relapse, and our knowledge about the nature and process of relapse has increased considerably over the past 10 years.

Alcoholism↗

Late relapse of germ cell tumors after cisplatin-based chemotherapy.

BACKGROUND: Sparse data are available with regard to the incidence, clinical characteristics, therapeutic management and prognosis of male patients with germ cell tumors, who relapse more than two years after completion of cisplatin-based chemotherapy. PATIENTS AND METHODS: A review of 530 patients treated at two institutions from 1978 to April 1994 was conducted. Twenty-five cases of late relapse were identified. Cumulative risk of late relapse was calculated according to the Kaplan-Meier method. RESULTS: 418 of 523 patients (80%) who received their first-line treatment at our institutions were relapse-free at two years. Among these 418 patients 18 cases (4.3%) developed a late relapse. The cumulative risk of late relapse was 1.1% at five years and 4.0% at ten years excluding patients with prior early relapses who carried risks of 9.4% and 29%, respectively (P < 0.0001). No case of late relapse was observed among patients receiving adjuvant chemotherapy. The risk of late relapse was lower in patients with good-risk non-seminomatous germ cell tumors than in poor-risk patients according to Medical Research Council criteria (P < 0.01). Seven further patients were referred from other institutions for treatment of late relapse. At a median follow-up of 38 months (range, 3 to 121) after treatment of late relapse 9 of 25 patients (36%) are continuously disease-free. Six of these nine patients had surgical resection of carcinoma or teratoma as a component of their therapy. CONCLUSION: The incidence of late relapse after cisplatin-based chemotherapy of germ cell tumors is related to initial tumor burden and is somewhat higher than previously expected. Chemotherapy seems to have only minor curative potential, but localized resectable disease can be cured by surgery. Annual follow-up evaluations allow to detect the majority of late relapses at an asymptomatic stage and should be extended throughout the patient's life.

Adult↗