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PubMedDate not supplied

[Is pre-operative treatment with ursodeoxycholic acid useful in reducing relapses in acute biliary pancreatitis?].

In the present paper, we evaluate the possible reduction in the rate of relapses in acute biliary pancreatitis through treatment with ursodeoxycholic acid (UCA), between the episode of pancreatitis and the moment of cholecystectomy. We studied 72 consecutive first episodes of acute biliary pancreatitis, in patients who had not yet undergone colecistectomy, followed up until surgery. The cases were divided into group A (n=30), treated with ursodeoxycholic acid 10 mg/kg/day, until surgery, and group B or control (n=42). We evaluated the differences between both groups, regarding patient characteristics, pancreatitis severity, characteristics of the lithiasis and delay until surgery. We analysed pancreatitis relapses in both groups, with and without UCA. In the UCA group we compared the duration of treatment between patients with and without pancreatitis relapse. The two groups did not show significant differences regarding any of the studied parameters. We registered 7/30 (23.3%) relapses in UCA group, versus 9/42 (21.4%) relapses in the control group (p = 0.85). In UCA group, treatment duration was similar between relapsed cases: 4.9+/-4.5 months and those without relapse: 4.4+/-1.9 months (p = 0.78). In our experience, the use of UCA until the moment of cholecystectomy does not reduce relapse incidence in patients following the first episode of acute biliary pancreatitis. UCA treatment duration did not seem to be related with the occurrence of pancreatitis relapse.

Acute Disease↗

PubMed2001

Bone marrow leukemic progenitor cell content in pediatric T-lineage acute lymphoblastic leukemia patients with an isolated extramedullary first relapse.

Isolated extramedullary relapse in childhood acute lymphoblastic leukemia (ALL) is associated frequently with the T-lineage immunophenotype and may be accompanied by occult bone marrow disease. We employed highly sensitive multiparameter flow cytometry and blast colony assays to quantify the leukemic progenitor cell (LPC) burden in the pretreatment bone marrows of 15 pediatric T-lineage ALL patients with an isolated extramedullary first relapse. Sites of extramedullary relapse were CNS (11 patients), testes (3 patients), and both CNS and testes (1 patient). Bone marrow LPC were detectable in 8 patients (53%) and undetectable in 7 patients (47%) at day 0 of post-relapse induction therapy, with LPC counts ranging from 0/10(6) mononuclear cells (MNC) to 518/10(6) MNC (mean +/- SEM, 50+/-34/10(6) MNC). Five of 9 patients with an early relapse (< 18 months after achieving a first complete remission [CR1]) and 3 of 6 patients with a late relapse (> or = 18 months from CR1) had detectable bone marrow LPC at day 0. Five of 8 patients with NCI-defined poor risk ALL and 3 of 7 patients with NCI-defined standard risk ALL had detectable LPC at day 0. Following post-relapse induction chemotherapy. LPC counts were detectable in bone marrows of 4 of 6 evaluated patients. Thus, approximately half of the extramedullary relapse T-lineage ALL patients studied had substantial occult involvement of the bone marrow. These findings may partly explain the previously observed poor prognosis of T-lineage patients following a CNS relapse.

Adolescent↗

PubMed2000

Autologous stem-cell transplantation for poor-risk and relapsed intermediate- and high-grade non-Hodgkin's lymphoma.

The primary objective of this study was to evaluate the outcome of patients treated with high-dose chemo-/radiotherapy or high-dose chemotherapy and autologous stem-cell transplant (ASCT) for relapsed, refractory, or poor-risk intermediate-grade (IG) and high-grade (HG) non-Hodgkin's lymphoma (NHL). The secondary objectives were to determine prognostic factors for relapse and survival. Between February 1987 and August 1998, 264 patients, 169 (64%) IG and 95 (36%) HG, underwent high-dose therapy and ASCT at City of Hope National Medical Center (COHNMC). There were 157 (59%) males and 107 (41%) females with a median age of 44 years (range, 5-69 years). The median number of prior chemotherapy regimens was 2 (range, 1-4), and 71 (27%) had received prior radiation as part of induction or as salvage therapy. The median time from diagnosis to ASCT was 10.8 months (range, 3-158 months). Ninety-four patients (36%) underwent transplantation in first complete/partial remission (CR/PR), 40 (15%) in induction failure, and 130 (49%) in relapse or subsequent remission. Two preparative regimens were used: total body irradiation/high-dose etoposide/cyclophosphamide (TBI/VP/CY) in 208 patients (79%) and carmustine/etoposide/cyclophosphamide (BCNU/VP/CY) in 56 patients (21%). One hundred sixty-three patients (62%) received peripheral blood stem cells (PBSC) and 101 (38%) received bone marrow (BM) alone or BM plus PBSC. At a median follow-up of 4.43 years for surviving patients (range, 1-12.8 years), the 5-year Kaplan-Meier estimates of probability of overall survival (OS), progression-free survival (PFS), and relapse for all patients are 55% (95% confidence interval [CI]: 49%-61%), 47% (95% CI: 40%-53%), and 47% (95% CI: 40%-54%), respectively. There were 27 deaths (10%) from nonrelapse mortality, including seven (3%) patients who developed second malignancies (five with myelodysplasia/acute myelogenous leukemia and two with solid tumors). By stepwise Cox regression analysis, disease status at ASCT was the only prognostic factor that predicted for both relapse and survival. The 5-year probability of PFS for patients transplanted in first CR/PR was 73% (95% CI: 62%-81%) as compared to 30% (95% CI: 16%-45%) for induction failure and 34% (95% CI: 26%-42%) for relapsed patients. Our results further support the role of high-dose therapy and ASCT during first CR/PR for patients with poor-risk intermediate- and high-grade NHL. Early transplant is recommended for patients failing initial induction therapy or relapsing after chemotherapy-induced remission. Relapse continues to be the most common cause of treatment failure. An alternative approach to prevent relapse, the incorporation of radioimmunotherapy into the high-dose regimen, is being investigated. The development of a second malignancy is a serious complication of high-dose therapy, which requires close surveillance.

Adolescent↗

PubMed2000

Pathologic role and temporal appearance of newly emerging autoepitopes in relapsing experimental autoimmune encephalomyelitis.

Relapsing experimental autoimmune encephalomyelitis (R-EAE) is a CD4+ T cell-mediated demyelinating disease model for multiple sclerosis. Myelin destruction during the initial relapsing phase of R-EAE in SJL mice initiated by immunization with the proteolipid protein (PLP) epitope PLP139-151 is associated with activation of T cells specific for the endogenous, non-cross-reactive PLP178-191 epitope (intramolecular epitope spreading), while relapses in R-EAE induced with the myelin basic protein (MBP) epitope MBP84-104 are associated with PLP139-151-specific responses (intermolecular epitope spreading). Here, we demonstrate that T cells specific for endogenous myelin epitopes play the major pathologic role in mediating clinical relapses. T cells specific for relapse-associated epitopes can serially transfer disease to naive recipients and are demonstrable in the CNS of mice with chronic R-EAE. More importantly, induction of myelin-specific tolerance to relapse-associated epitopes, by i.v. injection of ethylene carbodiimide-fixed peptide-pulsed APCs, either before disease initiation or during remission from acute disease effectively blocks the expression of the initial disease relapse. Further, blockade of B7-1-mediated costimulation with anti-B7-1 F(ab) during disease remission from acute PLP139-151-induced disease prevents clinical relapses by inhibiting activation of PLP178-191-specific T cells. The protective effects of anti-B7-1 F(ab) treatment are long-lasting and highly effective even when administered following the initial relapsing episode wherein spreading to a MBP epitope (MBP84-104) is inhibited. Collectively, these data indicate that epitope spreading is B7-1 dependent, plays a major pathologic role in disease progression, and follows a hierarchical order associated with the relative encephalitogenic dominance of the myelin epitopes (PLP139-151 > PLP178-191 > MBP84-104).

Adoptive Transfer↗

PubMed1999

Reboxetine, a unique selective NRI, prevents relapse and recurrence in long-term treatment of major depressive disorder.

BACKGROUND: The long-term efficacy and tolerability of the antidepressant reboxetine, a unique selective norepinephrine reuptake inhibitor (selective NRI), were assessed in an international study. METHOD: Two hundred eighty-three patients with recurrent DSM-III-R major depression who responded to 6 weeks of reboxetine treatment (> or =50% decrease in Hamilton Rating Scale for Depression [HAM-D] total score) were randomly assigned to receive reboxetine or placebo for 46 weeks in a double-blind phase. Relapse (> or =50% increase in HAM-D total score and/or a HAM-D total score > or =18) rate was the principal assessment criterion and included patients who experienced relapse or recurrence. Only patients who remained relapse-free at the end of the first 6-month treatment period were included in the relapse rate assessment at the end of the second 6-month treatment period. RESULTS: Reboxetine was associated with a markedly lower relapse rate than placebo (22% vs. 56%; p<.001) and a greater cumulative probability of a maintained response (p = .0001) during long-term treatment. Patients in remission (HAM-D total score < or =10) at the time of random assignment were less likely to relapse (16% reboxetine, 48% placebo; p<.001). The proportion of patients who were relapse-free and therefore remained in the study was significantly (p< or =.001) higher among those on reboxetine treatment than on placebo at the end of the first (61% vs. 40%) and second (88% vs. 59%) 6 months of treatment. Additional efficacy measures supported these findings. The incidence of adverse events with reboxetine was low and comparable with that for placebo. Discontinuation due to adverse events occurred infrequently. CONCLUSION: Reboxetine treatment over 1 year is more effective than placebo in the prevention of relapse in patients with recurrent depression. The low relapse rates at the end of the second 6 months of treatment further suggest that reboxetine effectively prevents recurrence of depressive symptoms following episode resolution. Reboxetine is well tolerated in long-term treatment of depression, a finding that bodes well for long-term patient compliance.

Adrenergic Uptake Inhibitors↗

PubMed1990

A study of relapse in paucibacillary leprosy in a multidrug therapy project, Baroda District, India.

In order to judge the value of therapeutic regimens in paucibacillary leprosy, knowledge of incubation time of relapses is essential, as this will define the length of time patients have to be followed up after treatment has been stopped. The prospective study of relapse includes paucibacillary cases of leprosy belonging to a non-lepromatous group consisting of tuberculoid, neuritic and indeterminate. Data are presented on the incubation time of 21 relapses after multidrug therapy in Baroda district; 76.19% of relapses occur during the first 2 years. This figure is most important in the analysis of results of drug trials in paucibacillary leprosy. This figure should also be relevant to regimens including drugs that are more bacteriocidal than dapsone, since the bacteriocidal activity has a bearing on the minimal necessary duration of treatment, but not on the incubation time of relapses. With the introduction of bactericidal drugs e.g. rifampicin in multidrug therapy, the incidence of relapse are very low, hence relapse rates fall down to a very low level after multidrug therapy. Our study shows a mean relapse rate of 0.19% after multidrug therapy. Factors associated with the occurrence of relapse are discussed.

Adolescent↗

PubMed2026

RAG-mediated structural variation and its impact on relapse risk in acute lymphoblastic leukemia.

Relapse during treatment of B-cell acute lymphoblastic leukemia (B-ALL) is a harbinger of poor outcomes. Identifying biomarkers for subsequent relapse risk which are detectable at B-ALL diagnosis remains a priority. Off-target recombination-activating gene (RAG)-mediated structural variants (SVs) generate genomic instability that drives leukemogenesis and may underlie treatment resistance. Leveraging sequencing data in 1,496 pediatric B-ALL patients enriched for relapse status (relapse n=532; non-relapse n=964), we characterized RAG-mediated SVs across B-ALL molecular subtypes and examined their association with patient characteristics and their impact on clinical outcomes. Off-target RAG-mediated SVs were overall frequent, particularly in ETV6::RUNX1, ETV6::RUNX1-like, and Ph-like B-ALL subtypes, while increasing age-at-diagnosis was positively associated with burden of off-target RAG-mediated SVs (P<.001). Off-target RAG-mediated SVs with a recombination signal sequence (RSS) at one breakpoint, a hallmark of off-target RAG activity, were significantly more frequent at diagnosis in patients who subsequently relapsed (P=.001). This association remained significant in multivariable regression analysis (per SV odds ratio [OR]:1.08, 95%CI:1.04-1.12), in minimal residual disease (MRD)-negative patients (OR:1.09, 95%CI:1.04-1.14) and across subtypes. Excluding deletions, MRD-negative ETV6::RUNX1 patients with ≥3 off-target RAG-mediated SVs had a >3-fold risk of relapse (hazard ratio:3.47, 95% CI:1.86-6.49). RAG-mediated SVs were also associated with relapse risk in T-cell ALL patients. Off-target RAG-mediated SV burden at diagnosis is a risk factor of relapse in pediatric ALL across molecular subtypes and independent of MRD status.

Journal Article↗

PubMed2000

Application of a quality of life measure, the life situation survey (LSS), to alcohol-dependent subjects in relapse and remission.

BACKGROUND: Recent studies have shown that quality of life (QOL) is improved significantly when subjects do not relapse to heavy drinking, and QOL deteriorates significantly on prolonged relapse. This article further investigates these relationships using a QOL index, the Life Situation Survey (LSS). METHODS: Eighty-two DSM-IV alcohol-dependent subjects admitted for alcohol detoxification were studied at baseline and 12 week follow-up. Sociodemographic data were collected, and severity of alcohol dependence (SADQ) and General Health Questionnaire (GHQ-12) were baseline indices only. The main outcome measure, the LSS, was administered at both time points. RESULTS: Two subjects were lost to follow-up and one died during the study period. Thus, the relapse/ nonrelapse analysis related to 79 subjects. Fifty subjects (63%) had relapsed to heavy drinking at 3 months follow-up. There was a significant correlation between LSS and GHQ-12 scores. Significant changes occurred in total LSS scores as a result of relapse and nonrelapse. The improvement in LSS scores associated with nonrelapse was larger than the deterioration that accompanied relapse. In those subjects who did not relapse to heavy drinking, the mean follow-up score remained in the poor/borderline LSS range. Remission from heavy drinking was accompanied by significant improvements in appetite, sleep, and self-esteem. Relapse to heavy drinking coincided with a significant deterioration in mood/affect, public support, and work/life role scores. CONCLUSION: QOL as assessed by the LSS in recently detoxified alcoholics is impaired significantly. In the nonrelapse group, there was a significant improvement in LSS scores after 3 months. Relapse was accompanied by a smaller deterioration in LSS scores. The LSS can play an important role in monitoring the clinical care and progress of alcohol-dependent subjects.

Alcoholism↗

PubMed2001

Risk-assessment in diffuse large cell lymphoma at first relapse. A study by the Italian Intergroup for Lymphomas.

BACKGROUND AND OBJECTIVES: Our aim was to identify risk factors in adults with diffuse large cell lymphoma at first relapse. DESIGN AND METHODS: We studied 474 patients observed at 45 centers in Italy. Median time from diagnosis to relapse was 395 days, median age at relapse was 55 years and median follow-up from relapse was 3.3 years. Salvage therapy consisted of polychemotherapy in 79% of patients, monochemotherapy and/or radiotherapy and/or surgery alone in 16%, and palliative therapy in 5%. Salvage treatment was intensified with high-dose chemotherapy + stem cell transplant in 20% of patients. OS and PFS were compared by sex, International Prognostic Index at diagnosis, histology, B/T phenotype, initial treatment, salvage therapy, and features at relapse: time from diagnosis, LDH, stage, performance status and bone marrow involvement. Cox models, adjusted for salvage therapy, were performed with factors related to overall survival (OS) and progression-free survival (PFS). RESULTS: Overall response (complete + partial) was 63%, OS at 3 years 35% and PFS at 3 years 26%. Relapse within 12 months from diagnosis, elevated serum lactic dehydrogenase (LDH), advanced stage and poor performance status were independent adverse factors for OS and PFS. The cumulative number of adverse factors is proposed as prognostic index for DLCL at first relapse since it identifies risk groups (p<0.0001) and has been validated (p=0.01). Moreover, it predicts OS and PFS in the selected group of patients with a responsive relapse (p<0.0001). INTERPRETATION AND CONCLUSION: Delay from initial diagnosis, LDH, stage and performance status at relapse should be balanced in comparative studies of salvage therapy of adults with DLCL. Patients with more than 2 adverse factors are one third of all cases and deserve more effective salvage treatments.

Adult↗

PubMed2001

Shifts in expression of immunological cell markers in relapsed acute leukemia.

The immunophenotypic features of leukemia blast cells were analyzed in a group of 156 patients with different immunological subtypes of acute leukemia, both lymphoblastic and myeloblastic. Of the 58 patients for whom immunologic studies were performed at relapse, 42 (72%) showed changes in the expression of immunologic markers. The minor shifts in B-ALL were observed most frequently and concerned of the loss of CD34 antigen in 17 cases and the loss of cALLA (CD10) in 7 cases of B-ALL at the first relapse. The acquisition of cell markers was not frequently observed, only in four cases could be seen. HLA-DR molecules remained relatively constant from diagnosis to relapse. In 2 from 3 T-ALL cases the loss of CD1 and CD2 markers, respectively, was noticed at relapse. CD5 and CD7 markers were relatively stable. In AML cases at relapse the acquisition of CD13 marker (in 4 from 7 cases) was often observed. It was interesting that comparing to the B-ALL cases, the loss of CD34 marker in AML cases was stray. In one case the acquisition of this antigen at relapse was actually observed. The major interlineage shift was detected in one case of B-ALL, that was newly diagnosed at relapse as AML M4 and presented different cytogenetic features. This case provides strong connection with the treatment, as more recently epipodophyllotoxins (vumon in our patient) have been linked to the development of secondary AML associated with a shorter latency period. The immunophenotypic changes frequently occur at relapse in all acute leukemia types. The shifts (loss or acquisition) in expression of individual markers at relapse are bound with the first diagnosis and may have a relationship to the treatment and are important for correct assessment of minimal residual disease.

Adult↗

PubMed2002

Central nervous system mechanisms in alcohol relapse.

BACKGROUND: Alcohol relapse is a major problem in the treatment of alcohol abuse and alcoholism. Understanding the long-term neuronal alterations that promote relapse of alcohol drinking is critical for the development of pharmacotherapies to treat alcoholism and alcohol abuse. The major objectives of this workshop were to present recent findings, by using rodent models, on behavioral and neurobiological factors that may underlie alcohol relapse and the results of clinical and pharmacological treatment strategies for preventing relapse. METHODS: Prolonged ethanol drinking and repeated periods of alcohol deprivation were studied in nonselected rats and in rats selectively bred for high alcohol preference (P rat). The expression of a robust alcohol deprivation effect (ADE) was used as a model for alcohol relapse in rodents. Operant techniques were used to examine responding for ethanol after deprivation in both rats and C57BL/6J mice. Environmental cues and stress were used to assess their effects on reinstatement of alcohol responding. Microdialysis and [14C]-2-deoxyglucose techniques were used to examine neuronal alterations associated with alcohol relapse. RESULTS: Prolonged free-choice ethanol drinking followed by deprivation produced an ADE in both stock and P rats. These rats demonstrated loss of control on reinstatement after chronic drinking and after prolonged deprivation. Acamprosate and naltrexone effectively reduced the ADE in stock rats. Stress reinstated operant responding for alcohol, and rats trained to associate a cue with ethanol presentation increased responding on the ethanol-associated lever in the absence of ethanol. After repeated deprivations, P rats shifted their preference toward drinking higher concentrations of ethanol, which increased the magnitude and duration of the ADE. Stock rats also shifted their preference toward solutions with higher ethanol concentrations and demonstrated a loss of control after prolonged ethanol drinking and deprivation. Long-lasting alterations in neuronal activity, serotonin-3 receptor function, and dopamine neurotransmission within the mesolimbic system were evident after chronic drinking that followed a prolonged deprivation period. CONCLUSIONS: The ADE is a useful model for studying alcohol relapse in both rats and mice. The potential validity of this model is supported by the findings that acamprosate and naltrexone are effective in preventing the ADE in rodents, and both compounds have gained recognition for their therapeutic effects in clinical populations. Genetics, stress, and environmental cues are all important factors that influence alcohol relapse. Long-term alterations in neuronal activity within the mesolimbic system, which possibly involve dopamine and serotonin, may underlie alcohol relapse.

Acamprosate↗

PubMed2002

[Retreatment with interferon plus ribavirin in chronic hepatitis C patients with genotype 1 who had no response or a relapse with a previous interferon treatment. Long term follow-up].

The aims of this study were twofold: i) to evaluate the sustained response rate at 6 months, at 12 months and at the end of the follow-up [(46.39 +/- 9.74 months) (range: 6-60 months)] in patients with chronic hepatitis C retreated with interferon-a (IFN-a) plus ribavirin for 6 months (group A), 12 months (group B), in patients with relapse and those with no response to a previous course of monotherapy with IFN-a; and ii) to evaluate changes in the histological liver lesion. One hundred and four patients (100 with genotype 1 and four without), 44 with relapse and 60 non-responders, were included. A total of 20.2% of the patients were excluded because of side effects. Fifty percent of the relapsing patients with genotype 1 showed a sustained response. The sustained response rate was higher in group B than in group A, whereas the rate for the relapsing patients was lower in group B than in group A (13/20 vs. 5/16; 7.2% vs. 61.5%; p <0.09 and p <0.009, respectively). However, 9.3% of the non-responding patients showed a sustained response (A/B: 2/2). The relapsing patients who had a genotype other than 1 showed a sustained response. The sustained response rate was constant throughout the follow-up, except in relapsing patients from group A (the late relapse rate was 28.6%). The viral load was not related to the response. The grade and stage of the histological lesion improved in patients with sustained response (n=20) and in one-third of the non-responding patients (n=45) (p <0.0001 and p <0.0001). IFN in combination with ribavirin was more effective in relapsing patients with genotype 1 at 12 months than in those at 6 months of treatment, whereas the effectiveness in non-responding patients was low. The sustained response evaluation at 6 months was reliable, except in relapsing patients with 6 months of treatment. The histological lesion improved significantly with combination antiviral therapy.

Adult↗

PubMed2003

An improved anti-leukemic effect achieved with donor progenitor cell infusion for relapse patients after allogeneic bone marrow transplantation.

OBJECTIVE: To observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization. METHODS: Twenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n = 11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n = 9). RESULTS: Five patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy. CONCLUSION: Donor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.

Adolescent↗

PubMed2004

Prognostic factors and therapeutic options for relapsed or refractory acute myeloid leukemia.

BACKGROUND AND OBJECTIVES: Considerable progress has been made in the treatment of acute myeloid leukemia (AML); however, current therapeutic results are still unsatisfactory in untreated patients and poorer in those with primary refractory or relapsed disease. The biological and clinical characteristics of relapsed AML are analyzed here. DESIGN AND METHODS: Most relevant literature in English language on relapsed AML from 1990 to 2004 was considered paying particular attention to the heterogeneity of the disease and prognostic factors at the time of relapse; therapeutic results in terms of second complete remission (CR) with conventional chemotherapy, stem cell transplantation and new agents are also summarized. RESULTS: Molecular relapse is a current indication for treatment of acute promyelocytic leukemia (APL); however, data are emerging for the treatment of molecular relapse in AML other than APL, such as AML with t(8;21) and AML with inv(16). Age, duration of first remission and cytogenetics are the most relevant prognostic factors in relapsed AML. Promising therapeutic results have been reported for the antiCD33 monoclonal antibody conjugated with calicheamicin and the new nucleoside analog clofarabine; preliminary studies indicate that FLT3, farnesyl-transferase and bcl-2 inhibitors are active in relapsed AML. CONCLUSIONS: All relapsed elderly patients and young adults with CR1 lasting for less than 12 months are ideal candidates for experimental therapies. Efficiently conducted phase II randomized trials are needed in order to achieve relevant information to be translated into phase III trials.

Acute Disease↗

PubMed2005

Relapse in a population based cohort of patients with polymyalgia rheumatica.

OBJECTIVE: To determine the incidence and the clinical, laboratory, and treatment related predictors of relapse in polymyalgia rheumatica (PMR). METHODS: Using the population based resources of the Rochester Epidemiology Project, we assembled an incidence cohort of subjects with PMR first diagnosed between January 1, 1970, and December 31, 1999. For inclusion, subjects were required to fulfill 3 criteria: (1) age > or = 50 years; (2) bilateral aching and morning stiffness in neck, shoulders, or hip girdle regions; and (3) erythrocyte sedimentation rate (ESR) > or = 40 mm/h. In subjects who fulfilled the first 2 criteria but had a normal ESR, a rapid response to low dose corticosteroids (CS) served as the third criterion. Patients were followed until permanent remission, migration, or a maximum of 5 years after their incidence date. Relapse was defined as an exacerbation of PMR symptoms requiring an adjustment of CS dose (> or = 5 mg) occurring at least 30 days after the incidence date. Time to relapse was modeled using the Kaplan-Meier method. CS treatment patterns were modeled using linear and nonlinear models. Cox regression models were used to evaluate predictors of time to first and subsequent relapses. RESULTS: The study population included 364 patients with a mean age of 73.4 years and 244 (67%) were women. Among the 284 patients treated with CS, a higher initial CS dose and faster CS tapering rate were significant predictors of future relapses, after adjusting for age, sex, ESR, giant cell arteritis at PMR diagnosis, and the intensity of rheumatologist care. Every 5 mg/day increase in initial CS dose was associated with a 7% increase in the risk of relapse [hazard ratio (HR) 1.07, 95% CI 1.02, 1.13]. The hazard of having a relapse was 4-fold higher when the CS tapering rate was fast (HR 4.27, 95% CI 2.84, 6.44), and 2-fold higher when the CS tapering rate was medium (HR 2.19, 95% CI 1.54, 3.11) compared to slow tapering. CONCLUSION: Higher initial CS doses and faster tapering are significant predictors of future relapses. Our results suggest that efforts should be made to minimize initial CS dose and taper CS slowly in order to avoid disease relapses.

Aged↗

PubMed2005

Value of culture and nested polymerase chain reaction of blood in the prediction of relapses in patients co-infected with leishmania and human immunodeficiency virus.

The use of culture and a nested polymerase chain reaction (PCR) of blood in predicting the probability of relapse was evaluated in 20 patients co-infected with Leishmania and human immunodeficiency virus (HIV). Fourteen of 20 patients relapsed, with 24 clinical relapses diagnosed. During clinical relapse, the parasite was detected by culture in 21 of 24 blood samples and by nested PCR in 23 of 24 blood samples. After treatment and during asymptomatic periods, the parasite was detected by culture in 18 (19.1%) of 94 blood samples and by nested PCR in 58 (61.7%) of 94 blood samples. For positive blood cultures, the Kaplan-Meier probability estimates for relapse at 6, 12, 18, and 24 months were 44%, 68%, 76%, and 76%, respectively, while for positive nested PCRs, the estimates were 20%, 33%, 45%, and 50%, respectively. For negative blood cultures, relapse probabilities for the same time points were 7%, 12%, 12%, and 12%, while for negative nested PCRs, these probabilities were 8%, 14%, 21%, and 26%. Nested PCR-positive results in asymptomatic periods indicated presence of the parasite, but not necessarily relapse. However, the presence of viable parasites during post-treatment follow-up increased the probability of relapse and showed that culture positivity could be a good relapse marker.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

Chest wall relapse after mastectomy for ductal carcinoma in situ: a report of 10 cases with a review of the literature.

Local chest wall relapse following mastectomy for ductal carcinoma in situ (DCIS) is an unusual event. We report on 10 cases of patients treated with mastectomy for DCIS who subsequently experienced a chest wall relapse as the first site of recurrence. To our knowledge, this is the largest reported collection of postmastectomy chest wall relapses for DCIS. The tumor registry and medical records from Yale-New Haven Hospital of all patients treated for ductal carcinoma in situ were reviewed. Individual records and radiation therapy charts of those patients sustaining a chest wall relapse following mastectomy were reviewed in detail. All pathology from the original mastectomy, as well as from the chest wall relapse, was re-reviewed by the pathologist. All chest wall relapses were treated with radiation therapy, with or without adjuvant systemic therapy. Of the 10 cases, 9 patients remain alive without evidence of disease. Young patient age, multiquadrant disease, and the presence of residual normal breast tissue were common features among these chest wall relapses. Pathological features of the original mastectomies and chest wall relapses are presented and discussed. Postmastectomy chest wall relapses in patients with DCIS are an uncommon event. Patients treated aggressively with resection of the lesion followed by radiation therapy to the chest wall have a favorable prognosis.

Adult↗

PubMed1991

The current unsatisfactory state of relapse prevention in schizophrenic psychoses--suggestions for improvement.

The current state of relapse prevention in schizophrenic psychoses is very unsatisfactory. Although in the form of neuroleptics a very efficient means of relapse prevention has been available for almost 40 years, approximately 50% of the schizophrenic patients still suffer a relapse within the first year after their most recent episode. Seventy percent of the hospitalized schizophrenic patients are readmissions, and the noncompliance rate for neuroleptic relapse prevention is 75%. An important factor contributing to these high rates of noncompliance and relapse seems to be the fact that, 40 years after the introduction of neuroleptics, there is still no consensus on how these drugs are to be used in relapse prevention. An inquiry among Austrian and German psychiatrists revealed unacceptably high discrepancies concerning their recommendations for indication and duration of neuroleptic relapse prevention. To overcome this unsatisfactory situation, an international consensus meeting on guidelines for neuroleptic relapse prevention was organized by the author in April 1989. Precise guidelines on indication, duration, and dosage of neuroleptic for relapse prevention that resulted from that meeting are presented.

Antipsychotic Agents↗