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Survival analysis of patients with clinical stages I or II Hodgkin's disease who have relapsed after initial treatment with radiotherapy alone.

To aid treatment choice in early stage of Hodgkin's disease, we analysed patients registered in the IDHD Database with clinical stages I or II Hodgkin's disease who were not staged with laparotomy and whose initial treatment was with radiotherapy alone. The factors analysed for outcome after first relapse included initial stage, age, sex, histology, number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, alkaline phosphatase, serum albumin and haemoglobin. As well as presentation variables, we analysed the disease-free interval after initial radiotherapy and the extent of disease at relapse. A total of 1364 patients with clinical stage I or II Hodgkin's disease were treated with initial radiotherapy, of whom 473 relapsed. The probability of survival 10 years after relapse was 63%. For cause-specific survival (CSS), both multivariate and univariate analysis identified the importance of age at presentation and histological subtypes. When all causes of death were considered, the multivariate analysis identified age as the only significant factor. The length of initial disease-free interval had no influence on prognosis after relapse, but the 169 patients with nodal relapse had a higher cause-specific survival than those with an extranodal component of relapse (74% versus 51% at 10 years, P < 0.005). Thus, the important factors for outcome after initial treatment with radiotherapy are those factors predicting the risk of relapse after initial treatment together with those predicting outcome after relapse, namely age, histologic subtype and extent of disease at relapse.

Adult↗

Mechanisms of relapse in acute leukaemia: involvement of p53 mutated subclones in disease progression in acute lymphoblastic leukaemia.

Mutations of the p53 tumour suppressor gene are infrequent at presentation of both acute myeloblastic leukaemia (AML) and acute lymphoblastic leukaemia (ALL), being found in between 5-10% of AML and 2-3% of ALL. Here we have studied the frequency of detection of p53 mutations at relapse of both AML and B-precursor ALL. In those patients with detectable mutations at relapse we investigated whether the mutation was detectable at presentation and was thus an early initiating event or whether it had arisen as a late event associated with relapse. Bone marrow samples from 55 adults and children with relapsed AML (n = 41) or ALL (n = 14) were analysed for p53 gene alterations by direct sequencing of exons 5-9. For samples where a p53 mutation was found at relapse, analysis of presentation samples was carried out by direct sequencing of the exon involved, or by allele-specific polymerase chain reaction (PCR) if the mutation could not be detected using direct sequencing. A p53 mutated gene was found at relapse in seven out of 55 cases. The frequency was higher in relapsed ALL (four out of 14 cases; 28.6%) compared to AML (three out of 41 cases; 7.3%). In five out of the seven cases presentation samples were available to study for the presence of the mutation. In two out of two AML patients the p53 mutation was detectable in the presentation sample by direct sequencing. In three ALL patients analysis of presentation material by direct sequencing showed a small mutant peak in one case, the other two being negative despite the sample analysed containing > 90% blast cells. However in both of these patients, the presence of p53 mutation was confirmed in the presentation sample using allele-specific PCR. In one of these patients the emergence of a subclone at relapse was confirmed by clonality analysis using IgH fingerprinting. Our results confirm that in ALL p53 mutations are present in a proportion of patients at relapse. Furthermore cells carrying the mutation are detectable at presentation in a minor clone suggesting that p53 mutations in ALL may be a mechanism contributing to disease relapse.

Adolescent↗

Allogeneic bone marrow transplantation for relapsed and refractory Hodgkin's disease and non-Hodgkin's lymphoma.

The relative benefit of allogeneic bone marrow transplantation (alloBMT) vs autologous BMT (autoBMT) for patients with relapsed or refractory Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) remains uncertain. Toxicity from graft-versus-host disease (GVHD) may diminish the potential benefits both of graft-versus-tumor activity and of receiving uncontaminated donor marrow stem cells. From 1987 to 1995, 27 adults (ages 18-60 years; median 36) underwent alloBMT for lymphoma after failure of standard chemotherapy. Twenty-one had NHL and six had HD (nodular sclerosis). Thirteen patients had primary refractory disease or chemotherapy-resistant relapses; two of these had relapsed after autoBMT. Three patients had untested relapses (one of them had relapsed after autoBMT), and 11 had chemotherapy-sensitive relapses. Twenty-four received HLA-matched bone marrow from a sibling (one twin); three received haploidentical marrow cells. Nine (33%) died from lymphoma. Eleven (41%) died of treatment-related causes. Opportunistic infections were a substantial problem leading to eight of these deaths (30%). Six patients (22%) survive free of lymphoma 17-70 months post-BMT (median, 56 months); four had had sensitive relapses, one had had a resistant relapse, and one had had nontested relapse. Three have chronic GVHD (limited in one; extensive in two). One HD patient who had relapsed after autoBMT remains in remission 19 months after alloBMT. No therapy-related myelodysplasia has been observed. We conclude that alloBMT has substantial morbidity in heavily pretreated lymphoma patients due to acute toxicity, infections and GVHD. However, 22% of our HD/NHL patients have had long-term disease-free survival.

Adolescent↗

Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients.

BACKGROUND: One of the most troublesome features of atopic dermatitis (AD) is its chronic relapsing nature, and there is a lack of published evidence on the best treatment strategy for long-term management of the disease. OBJECTIVE: To compare an intermittent dosing regimen of fluticasone propionate (FP) cream 0.05% (twice per week) with its vehicle base in reducing the risk of relapse when added to regular daily emollient in adult and paediatric subjects with stabilized AD. METHODS: Subjects (aged 3 months to 65 years) with moderate or severe AD were enrolled into an open-label Stabilization Phase of up to 4 weeks on daily emollients plus FP twice daily. Those subjects who achieved 'treatment success' (Global Assessment Score </= 2, erythema, pruritus, and papulation/induration/oedema scores </= 1) entered the double-blind Maintenance Phase. They continued with regular emollients and were randomized at a 2 : 1 ratio to either intermittent FP or vehicle, once daily 4 days per week for 4 weeks followed by once daily 2 days per week for 16 weeks. Subjects who relapsed on intermittent FP were discontinued from the study. Those who did not relapse continued for an additional 24 weeks on intermittent dosing for safety monitoring. RESULTS: A total of 372 (247 paediatric, 125 adult) subjects were enrolled into the Stabilization Phase. Of these, 348 (231 children, 117 adults) were randomized into the Maintenance Phase. Analysis of the primary efficacy parameter showed that subjects receiving intermittent FP cream (twice per week), in addition to regular daily emollients in the Maintenance Phase, were 7.7 times less likely to have an AD relapse than subjects receiving intermittent vehicle cream/emollients [Mantel-Haenszel (MH) estimate of the odds ratio, 95% confidence interval (CI) 4.6, 12.8; P < 0.001]. Paediatric subjects were 8.1 times less likely to have an AD relapse (95% CI 4.3, 15.2; P < 0.001) and adult subjects were 7.0 times less likely to have an AD relapse (95% CI 3.0, 16.7; P < 0.001). For subjects receiving intermittent FP cream/emollient, the median time to relapse could not be estimated as the majority remained controlled at 20 weeks. For those receiving intermittent vehicle/emollient, the median time to relapse was 4.7 weeks. For paediatric and adult groups, this was 5.1 and 4.1 weeks, respectively. Median exposure to FP for all subjects was 337 days. There was only one study drug-related adverse event (acne) and there were no reports of skin thinning or atrophy associated with the use of FP cream in paediatric or adult subjects. CONCLUSIONS: In paediatric and adult subjects, once stabilized with regular FP treatment, the risk of relapse of AD can be significantly reduced by extended intermittent dosing with FP cream in addition to regular emollient therapy.

Administration, Topical↗

Total body irradiation-high-dose cytosine arabinoside and melphalan followed by allogeneic bone marrow transplantation from HLA-identical siblings in the treatment of children with acute lymphoblastic leukaemia after relapse while receiving chemotherapy: a Société Française de Greffe de Moelle study.

We investigated the use of a new conditioning regimen followed by allogeneic bone marrow transplantation (BMT) for treating children with acute lymphoblastic leukaemia (ALL) after relapse within 6 months of the completion of therapy. One hundred and sixteen children with acute lymphoblastic leukaemia in second or subsequent complete remission (CR) underwent allogeneic bone marrow transplantation from HLA-identical siblings after a preparative regimen comprising total body irradiation (TBI), high-dose cytosine arabinoside and melphalan (TAM regimen). The Kaplan-Meier product-limit estimate (mean +/- SE) of disease-free survival (DFS) at 7 years was 59.5 +/- 9% (95% confidence interval). The estimated chance of relapse was 22.5 +/- 15% with a median follow-up of 88.5 months (range 51-132). 26 patients (22.4%) died with no evidence of recurrent leukaemia, mainly from interstitial pneumonitis, veno-occlusive disease or acute graft-versus-host disease (GVHD). Three factors significantly affected DFS: acute GVHD. site of relapse and, for children in second remission after a marrow relapse, the disease status at the time of transplantation. The DFS were 59.02 +/- 12.6%, 37.5 +/- 19.8% and 774 +/- 15% among patients in CR2 after a marrow relapse, in CR3 or in untreated partial marrow relapse, and in CR2 after an isolated CNS relapse, respectively. The lowest DFS was seen in children with acute GVHD grades 3-4. Two significant factors were associated with relapse: the marrow status at the time of transplantation and chronic GVHD. The relapse rate was lower among children in CR2 or with chronic GVHD. We conclude that transplantation after the TAM regimen is an effective therapy for this population with acceptable toxicity, particularly for children in second remission after a very early marrow relapse, or those with early isolated CNS involvement.

Adolescent↗

Survival after relapse following tandem autotransplants in multiple myeloma patients: the University of Arkansas total therapy I experience.

Despite the superiority of high-dose (compared with standard) treatment in multiple myeloma, relapses still occur. We evaluated relapse patterns, salvage treatments employed and outcome in patients given tandem transplants on our total therapy I protocol. We focused on 146 patients (of 231 enrolled) who received tandem autotransplants < or =12 months apart and survived > or =2 months after the second transplant. With a median follow-up of 9 years after enrollment, 31 (21%) patients remain in complete or stable partial remission. Ninety-five (65%) patients received therapy for relapsing myeloma. The median time from the first transplant to relapse was 2.9 years. The median overall survival from relapse was 2.4 years. In one-quarter (23/95) of cases, the postrelapse interval exceeded the interval from the first transplant to relapse. On multivariate analysis, the presence of any cytogenetic abnormalities [P<0.001, Hazard Ratio (HR): 3.84] and beta-2 microglobulin levels >4 mg/l at relapse (P<0.001, HR: 2.87) were significant for poor survival after relapse. The median survival after relapse was 5.1, 1.3 and 0.7 years in patients with none (44%), one (46%) and two (10%) poor-risk factors, respectively. In conclusion, a sizeable fraction of myeloma patients relapsing after tandem autotransplants without poor-risk features enjoyed meaningful survival prolongation when appropriately treated.

Disease-Free Survival↗

Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease.

BACKGROUND & AIMS: Prediction of relapse of inflammatory bowel disease has important implications for therapeutic strategies. We assessed whether measurement of intestinal permeability and inflammation could predict relapse of inflammatory bowel disease (IBD). METHODS: Forty-three patients with Crohn's disease (CD) and 37 with ulcerative colitis (UC) in clinical remission provided a stool sample to be assayed for calprotectin (a neutrophil-specific marker), and patients with CD additionally underwent a small intestinal permeability test. Relapse was defined using clinical disease activity indices. RESULTS: Twenty-five (58%) patients with CD and 19 (51%) with UC had a relapse over the 12-month period. Median calprotectin levels in the relapse groups (122 mg/L for CD, 123 mg/L for UC; normal <10 mg/L) differed significantly (P<0.0001) from those of the nonrelapse groups (41.5 mg/L for CD, 29.0 mg/L for UC). At 50 mg/L, the sensitivity and specificity of calprotectin for predicting relapse in all patients with IBD were 90% and 83%, respectively. Permeability in the CD patients who relapsed (median, 0.075; normal <0.04) differed significantly (P = 0. 004) from that in the nonrelapse group (median, 0.038). At the level of 0.05, the sensitivity and specificity of permeability in predicting relapse were 84% and 61%, respectively. CONCLUSIONS: Fecal calprotectin predicts clinical relapse of disease activity in patients with CD and UC, whereas small intestinal permeability is a useful predictor of relapse in patients with small intestinal CD.

Adolescent↗

Increased rectal wall thickness may predict relapse in ulcerative colitis: a pilot follow-up study by ultrasonographic colonoscopy.

BACKGROUND AND STUDY AIMS: Ulcerative colitis is a chronic inflammatory bowel disease with repeated remission and relapse, although the occurrence of relapse is difficult to predict. We performed a prospective study to determine whether there is a relationship in ulcerative colitis between the inflammatory changes identified by endoscopic ultrasonography (EUS) and relapse. PATIENTS AND METHODS: Participants were 23 ulcerative colitis patients who had not suffered a relapse for 1 month, with a Seo activity index less-than-or-equal 150 and Baron grade 1 at colonoscopy. The thickness of the first to the third layer of the rectal wall in these patients was measured by EUS at the start of the study. They were subsequently followed up for 1 year to record any relapses, defined as having a Seo activity index > 150 and Baron grade greater-than-or-equal 2 at colonoscopy. RESULTS: Relapse occurred in eight patients. The mean activity index of the relapsed patients was 187.3 (95 % confidence interval (CI), 166.4 - 208.2) at the end of the study. The thickness of the first to the third layer of the rectal wall, as evaluated by EUS at the beginning of the study, was significantly larger in the relapse group (mean 2.73 mm, 95 % CI 2.13 - 3.33 mm) than in the non-relapse group (1.79 mm; 1.56 - 1.99 mm; P = 0.0001). CONCLUSIONS: Catheter probe-assisted endoluminal ultrasonography may predict the occurrence of relapse of ulcerative colitis.

Adult↗

Long-term results of conventional-dose salvage chemotherapy in patients with refractory and relapsed Hodgkin's disease (Croatian experience).

BACKGROUND: The aim of this study was to analyze outcome of patients with Hodgkin's disease (HD) in whom first-line chemotherapy with mustine/vincristine/procarbazine/prednisone (MOPP) had failed. PATIENTS AND METHODS: From January 1982 to December 1989 among 210 patients treated with MOPP and radiotherapy to initial bulky sites, 65 patients were primary refractory to or relapsed after initial treatment. RESULTS: Twenty-nine of 65 patients (44%) were primary refractory to initial chemotherapy, 20 relapsed within 12 months after complete remission (CR) and 16 relapsed after CR that lasted more than 12 months. Patients with primary refractory HD and early relapse (<12 months after CR) were treated with doxorubicin/bleomycin/vinblastine/darcarbazine. In patients with late relapse (>12 months after CR) MOPP was repeated. The median follow-up for all patients was 115 months. The overall response rate was 63%. Thirty-three patients (51%) achieved a second CR and eight patients (12%) partial response. Remission rate was greatest in patients with late relapse (CR >12 months) (75 versus 55% for early relapse versus 35% for primary refractory HD) (P <0.01). At 10 years, overall and failure-free survival rates were 21 and 16%, respectively. Patients who were in first remission longer than 12 months had a superior overall survival (37 versus 18% for early relapse) and failure-free survival (24 versus 10% for early relapse). No patient with primary refractory HD was alive beyond 52 months after initial treatment failure (P <0.01). Main prognostic factors were duration of the first remission and tumor bulk at relapse. CONCLUSIONS: Our results confirm previous observations that a significant proportion of patients with HD who experience induction treatment failure cannot be cured with conventional treatment and probably need more aggressive therapy.

Adolescent↗

Early detection of relapse by whole-body positron emission tomography in the follow-up of patients with Hodgkin's disease.

BACKGROUND: Relapse after treatment of Hodgkin's disease (HD) is usually identified as a result of the investigation of symptoms. We undertook this study to examine the value of whole-body positron emission tomography (PET) for the detection of preclinical relapse. PATIENTS AND METHODS: Thirty-six patients underwent 2-[fluorine-18]fluoro-2-deoxy-D-glucose ((18)F-FDG) PET at the end of treatment and than every 4-6 months for 2-3 years after the end of polychemotherapy and/or radiotherapy. In those cases of abnormal (18)F-FDG accumulation a confirmatory study was performed 4-6 weeks later. RESULTS: One patient had residual tumor and four patients relapsed during a follow-up of 5-24 months. All five events were correctly identified early by (18)F-FDG PET. Residual tumor or relapse was never first diagnosed based on clinical examination, laboratory findings or computed tomography (CT) studies. Two patients presented B symptoms and the three others were asymptomatic at the time of residual disease or relapse. Confirmation of residual disease or relapse was obtained by biopsy in four patients 1, 1, 5 and 9 months after PET and by unequivocal clinical symptoms and CT studies in one patient 3 months after PET. False-positive (18)F-FDG PET studies incorrectly suggested possible relapse in six other patients, but the confirmatory PET was always negative. Our study also provides important information about physiological (18)F-FDG uptake in the thymus. CONCLUSIONS: Our data suggest the potential of (18)F-FDG PET to detect preclinical relapse in patients with HD. This could help identify patients requiring salvage chemotherapy at the time of minimal disease rather than at the time of clinically overt relapse. Further studies are warranted to determine the impact of PET on treatment management and outcome. In fact, the aim of follow-up procedures is not only to detect preclinical relapse but mainly to obtain better results by starting salvage treatment earlier. A cost-benefit analysis will also be necessary before (18)F-FDG PET can be used routinely in the follow-up of patients with HD.

Adolescent↗

What is relapse in schizophrenia?

Relapse can be defined as "the return of a disease after partial recovery". This definition is directly applicable to schizophrenic disorder. Relapse in this condition can be evaluated at the symptomatic, phenomenological and behavioural levels. Relapse impinges on inter-personal, social and occupational spheres of the patient's activity. In turn, relapse has wider implications for the family in general, for the provision of medical and social facilities and for health economics. There are no generally accepted criteria for relapse but outcomes such as violence or suicide, extreme psychotic behaviour and rehospitalization have been used. Less obvious criteria include major and minor symptom worsening and prodromata. Relapse is a relative term and must take into account the following factors: the patient's condition before the original onset of illness; his level of functioning before the present episode; the severity of the relapse in terms of symptom severity, duration and interference with personal functioning; the appearance of any new symptoms or behaviour patterns; the type of treatment given prior to relapse, and hence relatively ineffective; the type of treatment given during relapse, and its efficacy. Relapses often follow a pattern which may be fairly specific to each individual patient. Social factors may have predictive power but these need validation in different samples.

Confusion↗

Intestinal permeability and postheparin plasma diamine oxidase activity in the prediction of Crohn's disease relapse.

A method of detecting presymptomatic relapse of Crohn's disease could allow for the selective use of maintenance or intensified medical therapy in those with an increased risk of relapse. The aim of this study was to evaluate three potential laboratory markers of relapse: intestinal and gastroduodenal permeability and plasma diamine oxidase activity. Intestinal permeability (lactulose/mannitol test), gastroduodenal permeability (urinary sucrose excretion), and postheparin plasma diamine oxidase activity were serially measured in 61 adults with Crohn's disease in remission (CDAI <150) for at least 30 days. Subjects were followed periodically for clinical relapse (CDAI >150 and increased by at least 100 points or the need for steroids or surgery). Fourteen patients (23%) relapsed. A cut-off of 0.030 for the lactulose/mannitol ratio was defined. Those with ratios above the cutoff had a 7.0 times greater risk of relapse (p<0.001). Three subjects who went from a normal ratio to an abnormal ratio relapsed, whereas none of 32 subjects with a repeatedly normal ratio relapsed. Sucrose excretion and plasma diamine oxidase activity did not predict relapse. Serial testing of intestinal permeability, but not of gastroduodenal permeability or plasma diamine oxidase activity, was useful in predicting relapse in asymptomatic patients.

Adult↗

Ultrasensitive serum prostate specific antigen nadir accurately predicts the risk of early relapse after radical prostatectomy.

PURPOSE: Ultrasensitive prostate specific antigen (PSA) assays allow a lower limit of detection (less than 0.01 ng/ml) than standard PSA assays. In this study we examined the ability of ultrasensitive PSA nadir to predict relapse after radical prostatectomy (RP). MATERIALS AND METHODS: A total of 906 men treated with RP were followed with PSA measurements at 3, 6 and 12 months, and yearly thereafter. Of the 906 men 545 (60%) with a PSA nadir of less than 0.01 ng/ml or at least 3 followup ultrasensitive PSA measurements underwent analysis and stratification by PSA nadir. Biochemical relapse was defined as 2 consecutive increasing post-nadir PSA measurements of 0.1 ng/ml or greater. The ability of ultrasensitive PSA nadir to predict relapse was assessed by univariate and multivariate analysis. RESULTS: At a mean followup of 3.1 years 54 of 545 men (9.9%) experienced biochemical relapse with a mean time to relapse of 25.2 months. Relapse rates in men with a PSA nadir of less than 0.01 (423), 0.01 (75), 0.02 (19) and 0.04 or greater ng/ml (28) were 4%, 12%, 16% and 89%, respectively. Men with a nadir of less than 0.01 ng/ml had a significantly lower relapse rate than men with a nadir of 0.01 (p <0.01), 0.02 (p <0.025) or 0.04 or greater ng/ml (p <0.01). Multivariate logistic regression analysis showed that a nadir of 0.01 (p <0.05), 0.02 (p <0.05) and 0.04 or greater ng/ml (p <0.01) independently predicted an increased risk of biochemical relapse compared to a nadir of less than 0.01 ng/ml. CONCLUSIONS: Ultrasensitive PSA nadir accurately predicts the risk of early biochemical relapse following RP. Men who achieve a nadir of less than 0.01 ng/ml have a low likelihood of early relapse. Higher nadir points may identify candidates for early adjuvant or salvage therapies.

Follow-Up Studies↗

Late relapse of testicular germ cell neoplasms: a descriptive analysis of 122 cases.

PURPOSE: The problem of late relapse of testicular germ cell tumor (GCT) is poorly understood. No more than approximately 300 cases have been reported to date. It appears that late relapse (L/R) of GCT involves a more aggressive biology than virginal GCT. In the present study we increased the understanding of L/R by analyzing these events in a large patient sample. MATERIALS AND METHODS: Late relapse was defined as recurrence of disease more than 2 years after completion of primary treatment. A total of 122 patients (50 with pure seminoma and 72 with nonseminoma) were retrospectively studied. Several parameters were analyzed including age, clinical stage, treatment at primary presentation, occurrence of prior early relapse, interval to L/R, tumor markers, site of relapse, and mode and outcome of L/R treatment. Possible effects of various clinical parameters on treatment results were studied by multivariate statistical analysis. RESULTS: Median age at first presentation was 34 years and 26.5 years in patients with seminoma and nonseminoma, respectively. The intervals to L/R were 42 months (range 25 to 276) in seminoma and 64.5 months (range 28 to 216) in nonseminoma. A total of 75% of nonseminomas but only 20% of seminomas had disseminated disease at first presentation, while 51 patients with nonseminoma had initially received chemotherapy. alpha-Fetoprotein was increased in 45 patients (of 59 eligible) with nonseminoma at L/R, human chorionic gonadotropin in 12 cases. alpha-Fetoprotein levels greater than 100 U/l indicated poor prognosis. Topographically relapses were mainly confined to lymph nodes of the abdomen, chest and neck. Of 72 patients with nonseminoma cure failed in 37 in contrast to only 6 patients with seminoma (of 48 eligible). Inclusion of surgery increased the chance of cure (RR 4.0, 95% confidence interval 0.9-18.5). CONCLUSIONS: Late relapses of GCT are biologically and clinically distinct from virginal GCT. These events occur in nonseminoma and seminoma, but clinical features are quite different in the 2 groups. Increase of alpha-fetoprotein is typical in late relapsing nonseminoma and levels of more than 100 U/l appear to indicate poor prognosis. Anatomically L/R presents as lymphadenopathy of abdomen, chest or neck. Treatment should include surgery in nonseminoma. Seminomas and otherwise chemotherapy naive cases might respond to chemotherapy only. Particular risk groups for late relapse are nonseminoma with prior early relapse, patients receiving chemotherapy for disseminated disease at first presentation and those with pure teratoma. These latter subgroups should be followed with annual health examinations for at least 10 years.

Adolescent↗

Effect on disability outcomes of a depression relapse prevention program.

OBJECTIVE: This report evaluates the effects of a depression relapse prevention program on disability outcomes among patients treated for depression at high risk for relapse. MATERIALS AND METHODS: Primary care patients initiating antidepressant treatment for depression were assessed 6 to 8 weeks after the initial prescription. Patients responding to initial treatment but at high risk for relapse were randomized to usual care or a relapse prevention intervention (N= 386). The 12-month relapse prevention program included systematic patient education, two psycho-educational visits with a depression prevention specialist, shared decision-making regarding maintenance pharmacotherapy, and ongoing monitoring of medication adherence and depressive symptoms via telephone and mail. Disability outcomes were assessed via blinded telephone assessments at 3, 6, 9, and 12 months using SF-36 and Sheehan Disability scales. RESULTS: Usual care patients and relapse prevention program patients had high rates of use of maintenance pharmacotherapy. Both relapse prevention and usual care patients showed improved functioning over the 12-month follow-up period. One of the three disability measures (the SF-36 Social Function scale) showed a significant intervention effect because of continuing improvement at 9 and 12 month follow-up, whereas the Sheehan Disability Scale showed a nonsignificant trend toward greater improvements in disability among relapse prevention patients than among usual care controls. CONCLUSIONS: Moderate effects of a relapse prevention intervention on depressive symptoms were associated with modest and variable effects on disability outcomes. Inconsistent effects of the intervention for disability outcomes may be because of the high rates of maintenance pharmacotherapy among usual care patients, relatively mild levels of depressive symptoms among both intervention and control patients at baseline, the absence of a specific relapse prevention effect of the intervention, and the resultant modest differences in depressive symptoms between intervention and control patients in this trial.

Adult↗

PCR assessment of bone marrow status in 'isolated' extramedullary relapse of childhood B-precursor acute lymphoblastic leukaemia.

Approximately one-third of first relapses of childhood ALL occur at an extramedullary site without morphological evidence of bone marrow disease. However, the high incidence of subsequent medullary relapse in these cases strongly suggests that leukaemia is present at submicroscopic levels at the time of 'isolated' relapse. PCR analysis of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements now allows detection of leukaemia at levels as low as 0.001%. We have therefore used this technique to reassess bone marrow status at morphologically isolated relapse in 13 children with B-lineage ALL (11 with off-treatment relapses, two on treatment). In 12 of these 13 patients marrow disease was detectable by PCR at the time of this relapse--in all cases at levels below the threshold of light microscopy. Where relapse occurred off-therapy this indicated re-emergence of disease. since MRD has never been detected by PCR at this stage in patients remaining in long-term remission. In both patients who relapsed on-therapy the level of MRD at the time of relapse represented an increase on that seen in their previous marrow sample. We conclude that re-emerging bone marrow disease can be detected in most cases of 'isolated' relapse when investigated by this highly sensitive technique. Our findings at a molecular level confirm a long-held clinical suspicion and indicate that full systemic re-induction as well as local therapy is obligatory for these children.

Adolescent↗

Outcomes of patients with acute leukaemia who relapsed after reduced-intensity stem cell transplantation from HLA-identical or one antigen-mismatched related donors.

The characteristics of relapse following reduced-intensity stem-cell transplantation (RIST) remain to be clarified. We reviewed the medical records of 19 patients with acute leukaemia [acute myeloid leukaemia (AML), 16; acute lymphoblastic leukaemia (ALL), 3] who relapsed after RIST from related donors using purine-analogue-based regimens. Their median age was 55 years (range, 29-65 years). Median interval between RIST and relapse was 4.9 months (range, 1.8-24.9 months). Three chose not to receive interventions. The remaining 16 patients received withdrawal of immunosuppression (n = 3), chemotherapy (n = 2), donor lymphocyte infusion (n = 10) and second transplantation (n = 7), alone (n = 9) or in combination (n = 7). Four are alive with a median follow-up of 27.6 months (range, 16.0-28.9 months); three in remission and one in relapse. The 2-year overall survival after relapse was 28.9%. Causes of death in 15 patients included progressive disease (n = 7), graft-versus-host disease (n = 5) and infections (n = 3). Cumulative incidences of relapse-related and non-relapse-related deaths at 2 years after relapse were 37% and 32% respectively. Two prognostic factors were identified on univariate analysis: age [P = 0.017; hazard ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.32], and ALL as underlying disease (P = 0.011; HR, 10.4; 95% CI, 1.73-62.4). Some AML patients who relapse after RIST achieve durable remission with allogeneic immunotherapy-based interventions; however they carry a significant risk of non-relapse mortality.

Acute Disease↗

Relapse antecedents for methamphetamine use and related factors in Taiwanese adolescents.

The purpose of the present study was to identify the relapse antecedents for methamphetamine (MAMP) use in Taiwanese youth, and to examine the relationships between attribution of these antecedents, demographic variables, psychiatric disorders, characteristics of MAMP use, attitudes toward MAMP use, and personality. A total of 60 Taiwanese adolescents who had previously experienced MAMP relapse were studied. Their relapse antecedents for MAMP use were evaluated using the Questionnaire for Relapse Antecedents of Methamphetamine Use. Their psychiatric disorders were also assessed. The relationships among the relapse antecedents of MAMP use, demographic variables, MAMP-use characteristics, psychiatric disorders, attitudes toward MAMP use and personality were analyzed. The results of the analysis reveal that social pressure to use MAMP was the leading antecedent of relapse. Social adaptation, emotional stability, and education level were the factors that influenced adolescents' attributions of relapse antecedents for MAMP use. However, psychiatric disorder status and attitudes toward MAMP use were not related to any of the relapse antecedents. The results indicate that multiple factors influenced adolescents' attributions of relapse antecedents for MAMP use, and may serve as a basis for construction of models for teaching adolescents to manage the antecedents and reduce the risk of relapse of MAMP use.

Adolescent↗