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PubMed1997

Cerebrospinal fluid analysis differentiates between relapsing-remitting and secondary progressive multiple sclerosis.

OBJECTIVES: To find whether CSF analysis may differentiate between relapsing-remitting and secondary progressive multiple sclerosis. METHODS: In 17 patients with relapsing-remitting and 16 patients with secondary progressive multiple sclerosis, all without current or recent relapses, albumin CSF: peripheral blood ratio, mononuclear cell number, CD4+, CD8+, and B1+ subsets, CD4+:CD8+ ratio, IgG, IgG index, IgM, IgM index, complement components C3 and C4, and C3 and C4 indices, myelin basic protein, neuron specific enolase, S100, and lactate were determined. For each measure the statistical distance measure D2 was calculated. For computation of a discriminant score variables with a P value< or =0.15 were included (two sided univariate t test). These were albumin CSF: peripheral blood ratio, mononuclear cell number, IgM, IgM index, C3, C4, neuron specific enolase, S100, and lactate. Simultaneous distributions of the variables were compared between both groups (multivariate t test) and a discriminant score was computed (linear discriminant analysis). RESULTS: The discriminant score allocated all 14 relapsing-remitting patients to the relapsing-remitting group (positive score) and 12 of 13 secondary progressive patients to the secondary progressive group (negative score). One secondary progressive patient was allocated to the relapsing-remitting group. CONCLUSIONS: Patients with relapsing-remitting or secondary progressive multiple sclerosis differ in CSF profile and CSF analysis may help to differentiate between relapsing-remitting and secondary progressive multiple sclerosis.

Adult↗

PubMed1998

Molecular detection of acute lymphoblastic leukaemia in boys with testicular relapse.

AIMS: To determine the role of polymerase chain reaction (PCR) based minimal residual disease (MRD) detection of leukaemia specific DNA in testicular relapse in childhood acute lymphoblastic leukaemia. METHODS: DNA was obtained from archival testicular and bone marrow samples from boys with acute lymphoblastic leukaemia who relapsed in the testes. Overlapping DJH clone specific primers derived from clonal immunoglobulin heavy chain (IgH) gene rearrangement in each case were used to analyse testicular or bone marrow DNA. RESULTS: Histologically normal end of treatment testicular biopsies in the five patients in longterm remission were all MRD negative, but MRD positive in three of six boys with subsequent testicular relapse. Histologically normal bone marrow samples taken at the end of treatment were MRD negative in five of seven cases, but MRD positive in all cases at the time of isolated testicular relapse. Three boys with unilateral testicular relapse underwent unilateral orchidectomy, rather than bilateral testicular irradiation, as part of their treatment. Two of these boys were MRD positive in the histologically uninvolved testes, and both had subsequent relapses either in the testes or the bone marrow, while the MRD negative patient has not had a testicular relapse. CONCLUSIONS: The presence of MRD in testicular tissue can be assayed with a PCR based method to detect clone specific antigen receptor gene rearrangements. In this setting, PCR is more sensitive than conventional testicular histology for predicting clinical outcomes. MRD assays might be useful in the management of boys at the time of isolated testicular relapse, to confirm the presence of unilateral testicular disease.

Bone Marrow↗

PubMed2004

Identification of serum amyloid a protein as a potentially useful biomarker to monitor relapse of nasopharyngeal cancer by serum proteomic profiling.

PURPOSE: Nasopharyngeal cancer (NPC) is a common cancer in Hong Kong, and relapse can occur frequently. Using protein chip profiling analysis, we aimed to identify serum biomarkers that were useful in the diagnosis of relapse in NPC. EXPERIMENTAL DESIGN: Profiling analysis was performed on 704 sera collected from 42 NPC patients, 39 lung cancer patients, 30 patients with the benign metabolic disorder thyrotoxicosis (TX), and 35 normal individuals (NM). Protein profile in each NPC patient during clinical follow up was correlated with the relapse status. RESULTS: Profiling analysis identified two biomarkers with molecular masses of 11.6 and 11.8 kDa, which were significantly elevated in 22 of 31 (71%) and 21 of 31 (68%) NPC patients, respectively, at the time of relapse (RP) as compared with 11 patients in complete remission (CR; RP versus CR, P = 0.009), 30 TX (RP versus TX, P < 0.001), or 35 NM (RP versus NM, P < 0.001). The markers were also elevated in 16 of 39 (41%) lung cancer patients at initial diagnosis. By tryptic digestion, followed by tandem mass spectrometry fragmentation, the markers were identified as two isoforms of serum amyloid A (SAA) protein. Monitoring the patients longitudinally for SAA level both by protein chip and immunoassay showed a dramatic SAA increase, which correlated with relapse and a drastic fall correlated with response to salvage chemotherapy. Serum SAA findings were compared with those of serum Epstein-Barr virus DNA in three relapsed patients showing a similar correlation with relapse and chemo-response. CONCLUSIONS: SAA could be a useful biomarker to monitor relapse of NPC.

Adult↗

PubMed1998

Relapses of onychomycosis after successful treatment with systemic antifungals: a three-year follow-up.

BACKGROUND: Data about relapses of onychomycosis after treatment with the new systemic antifungals vary among the different studies, with figures ranging from 3 to 20% for terbinafine and from 21 to 27% for itraconazole, depending on the follow-up duration. OBJECTIVE: To determine the prevalence of relapses of onychomycosis cured by terbinafine compared with that of onychomycosis cured by itraconazole. METHODS: We followed up 47 patients whose toenail onychomycosis had been mycologically cured in an open randomized study comparing intermittent itraconazole treatment with continuous terbinafine treatment and intermittent terbinafine therapy. Patients were examined every 3 months for up to 3 years after the end of therapy. At each visit clinical and mycologic (direct microscopy and cultures) evaluations were performed. RESULTS: Eight of the 36 patients (22.2%) who completed the study had a relapse of onychomycosis during the follow-up period, including 2 patients of the terbinafine 250 mg group, 2 patients of the terbinafine 500 mg group and 4 patients in the itraconazole 400 mg group. As the original infection, the relapse was caused in all cases by Trichophyton rubrum. CONCLUSIONS: This study shows that 22.2% of patients with onychomycosis successfully treated with systemic antifungals experienced a relapse. The relapse rate increased from 8. 3% at month 12 to 19.4% at month 24 and to 22.2% at month 36. Relapses were more common in patients treated with pulse itraconazole (4/11) than in patients treated with continuous (2/12) or intermittent (2/13) terbinafine. Statistical analysis did not reveal any significant difference between relapse rates in the three groups.

Antifungal Agents↗

PubMedDate not supplied

Treatment approaches to major depressive disorder relapse. Part 2: reinitiation of antidepressant treatment.

BACKGROUND: Anecdotal reports concerning mood disorder patients suggest restarting drug treatment in patients who prematurely discontinue it may be associated with a diminished chance of response upon rechallenge. We evaluated the likelihood of response to reinitiation of fluoxetine treatment in patients relapsing after switching to placebo during a long-term efficacy study of two different dosing regimens of fluoxetine. METHOD: Patients who met the DSM-IV major depressive disorder criteria with modified HAMD17 scores > or =18 and CGI-Severity scores > or =4 were treated with open-label 20 mg/day fluoxetine for 13 weeks in a multicenter US study. Responders (n = 501) were randomized to placebo, 20 mg fluoxetine daily, or 90 mg enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. Patients relapsing during the continuation phase were offered 25 weeks of double-blind rescue treatment during which the study medication dose was increased as follows: (1) patients on placebo had treatment with fluoxetine 20 mg/ day reinitiated; (2) patients on fluoxetine 20 mg/day had their dose increased to 40 mg/day, and (3) patients on a 90-mg weekly dose had their dose increased to 90 mg twice a week. Only the results of the rescue phase for the group who relapsed while on continuation treatment with placebo are reported here. Analyses included percentage of responders (50% reduction of modified HAMD17 and CGI-Severity < or =2) and assessments of change from baseline to endpoint (HAMD, CGI-Severity). Safety measures included assessment of vital signs, laboratory measures, and treatment-emergent adverse events. RESULTS: Of 122 patients assigned to placebo, 57 (47%) relapsed during continuation treatment. Fifty-five (96%) of these elected to enter double-blind rescue treatment. Overall, patients who relapsed upon switching to placebo responded well to reinitiation of fluoxetine (62%). The mean modified HAMD17 score decreased from 20 to less than 9 and was maintained for up to 6 months. Thirty-eight percent of patients either did not respond or initially responded but again relapsed after reinitiation of medication. CONCLUSION: This study suggests that patients who, after an initial response to fluoxetine, relapse upon switching to placebo have a relatively high probability of responding to the reinitiation of fluoxetine treatment. These results challenge the view that the efficacy of an agent prematurely discontinued is diminished when such an agent is restarted. They also generally support reinitiation of the same antidepressant as a 'first-line' treatment strategy in patients who relapsed after stopping a previously effective antidepressant.

Adolescent↗

PubMed1993

Interferon plus glucocorticoids as intensified maintenance therapy prolongs tumor control in relapsed myeloma.

Interferon-alpha-2b (IFN) has been demonstrated to prolong remission duration and survival in responding multiple myeloma (MM) patients. The aim of this study was to intensity maintenance therapy adding glucocorticoids (GLU) to the standard IFN therapy. Twenty-eight relapsed MMs with stable disease or response after conventional chemotherapy received IFN+GLU. The treatment included 3 megaunits of IFN 3 times a week continuously until relapse, plus 4 days pulsed high-dose dexamethasone (40 mg/day for 4 days every 28 days for 6 consecutive months every 12 months) in patients < 70 years, or oral prednisone (PDN, 50 mg 3 times a week) in patients > 70 years, both until relapse. Conventional chemotherapy induced a response in 12/28 MMs. For all patients the actuarial median progression-free survival from relapse was 24 months and the survival from relapse 42 months with no difference between responding and nonresponding patients. The first duration of tumor control, i.e. the interval from diagnosis to first relapse, was shorter than the period between first and second relapse in 11/28 patients (40%). Toxicity was mild and oral PDN significantly increased the subjective tolerability of IFN. These findings indicate that IFN+GLU after induction chemotherapy may prolong the duration of tumor control in relapsed MM.

Aged↗

PubMed1976

Relapse in pulmonary tuberculosis.

Five hundred forty-three patients with bacteriologically confirmed pulmonary tuberculosis who successfully completed treatment were followed for 5 years to determine relapse rates and to see whether any factors could be said to predispose to relapse. Practically the entire treatment of these patients had been carried out in their homes. The cumulative relapse rate during a 5-year period was 11.60 per cent. Relapse rates were low during the first 2 years of follow-up. Of the various factors considered in the analysis, age, sex, initial extent of disease or cavitation, and presence of initial or emergent drug-resistant bacilli did not influence the relapse rate. Patients who achieved complete radiographic clearing at the time treatment was stopped and those who were regular in treatment had comparatively low relapse rates. Cured patients included in the study were asked to report at least once annually for a checkup, and immediately if they developed any symptoms suggestive of relapse. Only one fourth of the cases of relapse were detected during routine annual checkup; in the remaining cases, the patients attended ahead of the next due visit because of symptoms. This casts doubt on the utility of keeping cured patients under prolonged routine surveillance.

Adult↗

PubMed2006

Lack of weight gain and relapse risk in a large tuberculosis treatment trial.

BACKGROUND: Readily identified markers of tuberculosis relapse risk are needed, particularly in resource-limited settings. The association between weight gain or loss during antituberculosis therapy and relapse has not been well studied. METHODS: Subjects in the Tuberculosis Trials Consortium Study 22 were studied. Underweight was defined as 10% or more below ideal body weight at diagnosis. Weight change was assessed between (1) diagnosis and completion of induction phase therapy, (2) diagnosis and end of continuation phase therapy, and (3) completion of induction to completion of continuation phase therapy. RESULTS: A total of 857 subjects were monitored for 2 yr, and 61 of 857 (7.1%) relapsed. Relapse risk was high among persons who were underweight at diagnosis (19.1 vs. 4.8%; p < 0.001) or who had a body mass index of less than 18.5 kg/m(2) (19.5 vs. 5.8%; p < 0.001). Among persons who were underweight at diagnosis, weight gain of 5% or less between diagnosis and completion of 2-mo intensive phase therapy was moderately associated with an increased relapse risk (18.4 vs. 10.3%; relative risk, 1.79, 95% confidence interval, 0.96-3.32; p = 0.06). In a multivariate logistic regression model that was adjusted for other risk factors, a weight gain of 5% or less between diagnosis and completion of 2-mo intensive phase therapy among persons underweight at diagnosis was significantly associated with relapse risk (odds ratio, 2.4; p = 0.03). CONCLUSIONS: Among persons underweight at diagnosis, weight gain of 5% or less during the first 2 mo of treatment is associated with an increased relapse risk. Such high-risk patients can be easily identified, even in resource-poor settings. Additional studies are warranted to identify interventions to decrease risk of relapse in such patients.

Adult↗

PubMed2005

Substance abuse relapse in a ten-year prospective follow-up of clients with mental and substance use disorders.

OBJECTIVES: This study addressed the rate and predictors of substance abuse relapse among clients with severe mental illness who had attained full remission from substance abuse. METHODS: In a ten-year prospective follow-up study of clients with co-occurring severe mental and substance use disorders, 169 clients who had attained full remission, defined according to DSM-III-R as at least six months without evidence of abuse or dependence, were identified. The Kaplan-Meier survival curve was developed to show the pattern of relapse, and a discrete-time survival analysis was used to identify predictors of relapse. RESULTS: Approximately one-third of clients who were in full remission relapsed in the first year, and two-thirds relapsed over the full follow-up period. Predictors of relapse included male sex, less than a high school education, living independently, and lack of continued substance abuse treatment. CONCLUSIONS: After attaining full remission, clients with severe mental disorders continue to be at risk of substance abuse relapse for many years. Relapse prevention efforts should concentrate on helping clients to continue with substance abuse treatment as well as on developing housing programs that promote recovery.

Adult↗

PubMed2000

A delphi approach to characterising "relapse" as used in UK clinical practice.

BACKGROUND: 'Relapse' is a common outcome indicator in intervention studies in schizophrenia. In community studies it is frequently equated with hospitalisation and in psychopharmacological studies with predetermined symptom scores. Its clinical meaning, however, remains undefined. METHOD: Consensus on the defining features of 'relapse' in schizophrenia used by academic and clinical schizophrenia experts in the UK, was investigated using a four stage Delphi process. A two panel, four stage, Delphi based methodology was used to investigate the implicit meanings of 'relapse' in clinical practice. A multidisciplinary panel of twelve members each listed anonymously ten indicators of relapse. A second panel, of ten experienced psychiatrists, rated the 188 submitted indicators from essential-unimportant (1-5). This panel completed a one day workshop during the remaining Delphi rounds ending with a structured discussion of the results. RESULTS: Very strong consensus was achieved on the relative importance of potential relapse indicators. There was complete agreement about some aspects of a definition of relapse (such as recurrence of positive symptoms) and a number of the complex issues underlying the concept were clearly articulated. CONCLUSIONS: This four stage Delphi process achieved consensus on core features of relapse. The elucidation of the "softer" features at the threshold between normal fluctuations in functioning and the start of relapse require continuing investigations.

Delphi Technique↗

PubMedDate not supplied

The importance of providing smoking relapse counseling during the postpartum hospitalization.

OBJECTIVES: To determine during the postpartum period (a) the most feasible time for addressing smoking relapse, (b) the reasons women relapse, (c) differences in relapse rates in women who receive a counseling intervention in the immediate postpartum period compared to those who do not, and (d) differences in self-reporting of tobacco use compared to cotinine analysis. DESIGN: Randomized clinical trial. SETTING: Medical center in the Northeast United States and two prenatal care sites. PARTICIPANTS: A nonprobability convenience sample of 62 pregnant women. INTERVENTION: A brief counseling session using empowerment techniques, motivational interviewing, identification of stressors and individual coping strategies, and educational materials. MAIN OUTCOMES MEASURE: Relapse to smoking measured by cotinine analysis and descriptive data collected during the antepartum, intrapartum, and postpartum periods. RESULTS: Fifty-two percent of women relapsed to smoking by the 2nd week postdelivery, identifying rest and relaxation and depression as main factors for relapsing. Chi-square analysis showed no significant difference between the two groups regarding the intervention provided. There was a 39% discrepancy rate between self-reporting of tobacco use and cotinine analysis during pregnancy and a 27% discrepancy rate after delivery. CONCLUSIONS: Because of the high occurrence of relapse in the first 2 weeks after delivery, it is imperative that nurses provide interventions to women before their postpartum hospital discharge to prevent smoking relapse. Nurses should also address smoking behaviors each trimester because women stopped smoking at different time intervals and self-reported data were unreliable.

Adult↗

PubMed1990

Prognostic factors for patients relapsing after radiotherapy for early-stage Hodgkin's disease.

Prognostic factors were analyzed retrospectively in 109 patients who relapsed after treatment with radiation only for Hodgkin's disease. Factors analyzed included initial stage, age, time to first relapse, histology, sex, extent of initial irradiation, sites of relapse, relapse stage (RS), average relative dose intensity (ARDI) of chemotherapy, and type of salvage therapy. Ninety-three percent of the patients received either standard or modified mechlorethamine, vincristine, procarbazine, and prednisone (MOPP). With a median follow-up of 8.3 years, the actuarial survival and freedom from second relapse (FF2ndR) was 57% at 10 years. The extent of disease at the time of relapse, or so-called RS was found to be the single most important prognostic factor. Nearly 90% of patients with RS IA or IEA (favorable group) were disease free, and nearly 60% of patients with RS IIA, IIEA, or IIIA (intermediate group) were disease free compared with only 34% of patients with B symptoms or stage IV disease (unfavorable group). In a subset analysis, the use of combined modality therapy (CMT) was associated with an improved FF2ndR and survival in patients from the intermediate and unfavorable relapse groups. Age greater than 50 years was associated with an increased risk of second relapse and a lower survival. The other factors analyzed appeared to be of no independent prognostic value.

Adolescent↗

PubMed1992

Conventional-dose salvage combination chemotherapy in patients relapsing with Hodgkin's disease after combination chemotherapy: the low probability for cure.

PURPOSE: The study was undertaken to evaluate clinical prognostic factors, probability of response to therapy, duration of response, and overall survival of patients with Hodgkin's disease relapsing from a chemotherapy-induced complete remission. PATIENTS AND METHODS: Study population comprised 107 patients with Hodgkin's disease treated with combination chemotherapy at the National Cancer Institute who relapsed after achieving a complete remission. RESULTS: Half of the relapses occurred within the first year of achieving complete remission; among patients in remission 5 years or longer, only 4% relapsed. The overall survival of the relapsed patients is projected to be 17% at 20 years, calculated from the date of relapse. Primary treatment regimen, presence of B symptoms, stage, sex, liver involvement, pleural involvement, marrow involvement, and histologic subtype did not affect the survival of relapsed patients. Only age at diagnosis (older or younger than 30 years) and length of initial remission (shorter or longer than 1 year) made a significant impact on survival. Patients whose initial remission was longer than 1 year had significantly higher complete response rates to salvage therapy, significantly more durable second remissions, and significantly longer survival than patients whose initial remission was shorter than 1 year. Survival beyond 11 years from relapse of patients with long initial remissions was 24%; for those with short initial remissions, 11% (P2 = .027). Despite the fact that with salvage therapy, patients with long initial remission had an 85% complete response rate to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) with a disease-free survival of 45% at 20 years, acute leukemia and other treatment-related complications combined to lower the survival rate of this more favorable subset. CONCLUSIONS: These data with conventional-dose salvage therapy provide results for comparison with novel salvage approaches including myeloablative therapy with autologous marrow or peripheral-blood stem-cell support.

Adolescent↗

PubMed1993

Patterns of relapse after autologous purged bone marrow transplantation for neuroblastoma: a Childrens Cancer Group pilot study.

PURPOSE: The goal of this investigation was to determine if comparing sites of neuroblastoma at relapse after myeloablative chemoradiotherapy and purged autologous bone marrow transplantation (ABMT) with sites of disease at diagnosis and before ABMT could provide insight to the reasons for treatment failure. PATIENTS AND METHODS: Ninety-nine patients with high-risk neuroblastoma underwent ABMT after induction chemotherapy, surgery +/- local radiation (RT) and then myeloablative therapy with teniposide (or etoposide), melphalan, doxorubicin, cisplatin, and total-body irradiation (TBI). RESULTS: Forty-one of 84 assessable patients (15 toxic deaths) developed progressive disease 1 to 44 months after ABMT. The overall probability of relapse 36 months after ABMT was 49%. Tumor recurred in primary (n = 22), bone (n = 20), bone marrow (n = 18), lung (n = 3), and other sites (n = 9). Eight patients relapsed in the primary site alone, 14 in primary and distant sites, and 19 in distant sites only. Of 41 patients with progressive disease, 33 have died, with a median interval from relapse to death of 4 months. Both bone and bone marrow involvement at diagnosis correlated with specific relapse in that site (P < .05). Bone marrow tumor content at harvest greater than 0.1% also correlated with bone marrow relapse (P = .001). There was an association between incomplete resection of the primary tumor at diagnosis and relapse in that site (P = .06). CONCLUSION: Neuroblastoma normally recurs in multiple sites after ABMT, particularly in areas of previous disease. More intensive treatment to known areas of disease (aggressive early surgery, effective myeloablative consolidation therapy) and post-ABMT therapy for minimal residual disease should be studied for their potential to decrease the frequency of relapse.

Adolescent↗

PubMed2001

Relapse of TEL-AML1--positive acute lymphoblastic leukemia in childhood: a matched-pair analysis.

PURPOSE: The aim of this study was to investigate whether, in relapsed childhood acute lymphoblastic leukemia (ALL), the frequent genetic feature of TEL-AML1 fusion resulting from the cryptic chromosomal translocation t(12;21)(p13;q22) is an independent risk factor. PATIENTS AND METHODS: A matched-pair analysis was performed within a homogeneous group of children with first relapse of BCR-ABL-negative B-cell precursor (BPC) ALL treated according to relapse trials ALL-Rezidiv (REZ) of the Berlin-Frankfurt-Münster Study Group. A total of 249 patients were eligible for this study: 53 (21%) were positive for TEL-AML1, and 196 (79%) were negative. Positive patients were matched for established most-significant prognostic determinants at relapse, time point, and site of relapse, as well as age and peripheral blast cell count at relapse. RESULTS: Fifty pairs matching the aforementioned criteria could be determined. The probabilities with SE of event-free survival and survival at 5 years for matched TEL-AML1 positives and negatives are 0.63 +/- 0.10 versus 0.38 +/- 0.10 (P =.09) and 0.82 +/- 0.09 versus 0.42 +/- 0.19 (P =.10), respectively. These results were confirmed by multivariate analysis, revealing an independent prognostic significance of time point and site of relapse (both P <.001) but not of TEL-AML1 expression (P =.09). CONCLUSION: TEL-AML1 expression does not constitute an independent risk factor in relapsed childhood BCP-ALL after matching for relevant prognostic parameters. It undoubtedly characterizes genetically an ALL entity associated with established favorable prognostic parameters. High-risk therapeutic procedures such as allogeneic SCT should be considered restrictively.

Adolescent↗

PubMed2005

Incidence of late-relapse germ cell tumor and outcome to salvage chemotherapy.

PURPOSE: To define the incidence, clinical features, and outcome to salvage chemotherapy in patients with late-relapse germ cell tumor (GCT) after a complete response to first-line chemotherapy. PATIENTS AND METHODS: Two patient populations were examined. First, retrospective analysis of 246 patients treated on a clinical trial with salvage chemotherapy was performed; 29 patients with late-relapse GCT were identified and evaluated for treatment outcome and survival. Salvage regimens included paclitaxel, ifosfamide, and cisplatin, single agents, or a high-dose chemotherapy program. Second, the incidence of late relapse was assessed by retrospective analysis of 551 patients after a complete response (CR) to first-line chemotherapy. RESULTS: Twenty-nine patients received salvage chemotherapy on a clinical trial for late relapse GCT. The median survival was 23.9 months. At a median follow-up of 50.6 months, there were nine survivors. The chemotherapy regimens varied, but the only CRs were observed in patients treated with paclitaxel, ifosfamide, and cisplatin. Seven (50%) of 14 patients treated with paclitaxel, ifosfamide, and cisplatin achieved a continuous CR. Among the second population of 551 patients who had previously achieved a CR to a first-line chemotherapy trial, 17 were identified as having a late relapse (3%). The median time to relapse for these 17 patients was 7.8 years. CONCLUSION: Late-relapse GCT is uncommon and is associated with a poor prognosis resulting from a high degree of resistance to chemotherapy. Chemotherapy with paclitaxel, ifosfamide, and cisplatin followed by surgery may be effective in patients with late-relapse GCT who are not considered candidates for primary surgery.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Abnormalities of p51, p53, FLT3 and N-ras genes and their prognostic value in relapsed acute myeloid leukemia.

To clarify the role of the genetic mutations in the clinical course of acute myeloid leukemias (AML), we analyzed for p51, p53, FLT3 and N-ras gene mutations and the expression of the p51 gene in relapsed AML. Paired samples obtained from patients with AML at both stages of diagnosis and first relapse were analyzed. Twenty-four patients with relapsed AML survived for 6 to 81 months (median 24 months) from diagnosis. In one patient, no point mutation of the p51 gene was detected, but loss of the p51 gene expression was observed at both stages. Point mutations of the p53 gene were positive at both stages (+/+) in two patients and negative at diagnosis and positive at relapse (-/+) in two patients. Tandem duplication of the FLT3 gene was detected in five patients at both stages (+/+). N-ras gene mutations at both stages (+/+) were detected in three patients. Mutant p53 at relapse was associated with short survival in patients with relapsed AML (P<0.014). Our findings show that p53 mutations were, at least in part, associated with the mechanism of relapse in AML, while new p51, FLT3 and N-ras gene alterations did not occur at relapse. Loss of the p51 gene expression in de novo AML has not been reported yet.

Adult↗

PubMed2005

Asthma in remission: can relapse in early adulthood be predicted at 18 years of age?

STUDY OBJECTIVE: To determine the frequency of relapse of asthma in young adults in remission at 18 years of age, during a follow-up period of 8 years, and to identify possible prognostic markers for relapse. DESIGN: Longitudinal study of birth cohort (n = 1,037) born in New Zealand in 1972-1973. SETTING: University hospital research clinic. MEASUREMENTS: Participants were assessed at 9, 11, 13, 15, 18, 21, and 26 years of age using a respiratory questionnaire (all ages), spirometry (all ages), bronchodilator response (18 years and 26 years of age), methacholine challenge (9, 11, 13, 15, and 21 years of age), and allergen skin-prick testing (13 years and 21 years of age). RESULTS: Approximately one third of study members (35%) with asthma in remission at 18 years of age relapsed by 21 years or 26 years of age. Atopy and lower FEV(1)/FVC ratio at 18 years of age were significant independent prognostic factors for relapse in multiple logistic regression analyses. Increased responsiveness to methacholine (provocative concentration < 8 mg/mL) or bronchodilator (improvement in FEV(1) >/= 10%) at 21 years of age were more common among those with relapse, but the positive and negative predictive values for a previous positive methacholine challenge test result at 15 years of age were low. Asthma after relapse was generally mild (mean FEV(1) 97.1% predicted). Totally new adult asthma developed by 26 years of age in 9% of study members who had no asthma or wheezing at any time up to 18 years of age. CONCLUSIONS: Subsequent relapse of previously diagnosed asthma in remission at 18 years of age occurs in one in three young adults. Such relapse is not easily predicted, especially by measurements of airway responsiveness. A history of asthma currently in remission should not be used to prejudice employment opportunities for young adults.

Adolescent↗