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PubMed2002

Arsenic trioxide therapy for relapsed acute promyelocytic leukemia: a bridge to transplantation.

BACKGROUND AND OBJECTIVES: Arsenic trioxide (ATO) has been reported to be a safe and effective treatment for relapsed acute promyelocytic leukemia (APL). The aim of this study was to evaluate the efficacy and toxicity as well as the eligibility to stem cell transplantation (SCT) in a series of 7 patients with relapsing APL, managed with ATO. DESIGN AND METHODS: Seven patients with relapsing APL while on maintenance treatment with all-trans-retinoic acid (ATRA) or who were ATRA refractory-received ATO at a dose of 10 mg daily by 2-hour intravenous infusion until complete remission (CR). After consolidation chemotherapy, patients were programmed to receive autologous or allogeneic stem cell transplantation (SCT) according to donor availability. The median age of the patients was 55 (21-71) years: 2 patients presented with concomitant extramedullary relapse. RESULTS: Six patients (86%) achieved CR after a median of 35 ATO doses (20-49) with negligible toxicity; one patient died from pneumonia. After consolidation with a four-day course of cytarabine at 1 g/m2 and mitoxantrone 6 mg/m2, two patients underwent allogeneic SCT, two received PML/RARa negative autologous peripheral blood stem cells collected after consolidation plus granulocyte colony-stimulating factor, one failed mobilization and received a second consolidation course. One elderly patient refused further treatment and relapsed 6 months later. After a median follow-up of 15 months from CR2 achievement, 5 patients are alive in continuous CR. INTERPRETATION AND CONCLUSIONS: The high CR rate and the mild toxicity confirm that ATO represents a valid alternative to salvage chemotherapy for patients relapsing while on ATRA treatment or who are ATRA-refractory. Allogeneic or autologous SCT after ATO-induced CR is feasible in the majority of patients.

Adult↗
PubMed2004

Benefit-risk assessment of interferon-beta therapy for relapsing multiple sclerosis.

IFN-beta therapy has a central place in the management of relapsing multiple sclerosis, as demonstrated by the pivotal studies of three IFN-beta treatment regimens. However, questions remain concerning the optimal choice of preparation and dose regimen. The benefit-risk ratio for a given preparation is an important consideration in optimising treatment for an individual patient. Of the three IFN-beta preparations currently available, all have shown benefit on activity measures (relapses and active lesions apparent on magnetic resonance imaging), while benefit on progression measures (disability and total lesion burden) has been less consistent. Available data across studies suggest that dose and/or dose frequency are important determinants of efficacy, a finding supported by direct comparative data on different IFN-beta preparations. The added benefit of high-dose, high-frequency IFN-beta therapy is not achieved at the cost of compromised safety or tolerability, indicating that three-times-weekly treatment offers a superior benefit-risk ratio to once-weekly treatment. The potential advantages of IFN-beta therapy may be enhanced by regular monitoring of efficacy and safety in order to maintain patients on therapy beyond the first few months when side effects are most apparent.

Antibody Formation↗
PubMed1998

Management of acute promyelocytic leukemia relapse in the ATRA era.

BACKGROUND AND OBJECTIVE: The use of all-trans retinoic acid (ATRA) has changed the natural course of acute promyelocytic leukemia (APL), increasing the percentage of lasting complete remissions. However, management of the few relapses remains undefined. The purpose of the present study was to evaluate the different behavior of APL patients relapsed after induction chemotherapy which had or had not included ATRA. DESIGN AND METHODS: We retrospectively studied 8 patients (3 male and 5 female) who had relapsed after a clinical and molecular complete remission (CR). Five patients relapsed after conventional chemotherapy including anthracyclines, without ATRA which was not available at the onset (group A), 3 relapsed after induction treatment according to AIDA protocol (Idarubicin + ATRA) (group B). Seven patients had both molecular and clinical relapses, 1 (group B) had only a molecular relapse. The median first CR duration was 33 months (range 8-63). To induce a second CR all patients were treated with ATRA 45 mg/m2/day given orally until CR, combined with mitoxantrone 6 mg/m2/day for 6 days and cytarabine 1 g/m2/day for 6 days. RESULTS: Seven out of 8 patients (87.5%) achieved second CR, 1 (group A) did not respond and died within two months. Second CR duration was 21, 43+, 56+, 62+ months in group A and 5, 10, 12+ (with molecular relapse) months in group B. Therefore, only one patient relapsed in group A, while all the group B patients relapsed. INTERPRETATION AND CONCLUSIONS: ATRA combined with chemotherapy is an effective approach to treating APL relapse. It produces a high incidence of second CR with an acceptable toxicity. The duration of the second CR seems, however, to be longer in patients never treated with ATRA before than in patients who relapsed after the AIDA protocol. Therefore, it might be appropriate to adopt more aggressive protocols in this latter subset of patients.

Adolescent↗
PubMed2000

Narratives of smoking relapse: the stories of postpartum women.

Many women who stop smoking during pregnancy relapse soon after the birth of their infants. Using narrative research, experiences of smoking relapse were explored using interviews with 27 postpartum women. The stories of relapse were analyzed to identify important components, paying attention to commonalities, differences, and areas of emphasis. Five general story lines were identified: (1) controlling one's smoking (starting with a "puff" and consciously restricting the amount smoked); (2) being vulnerable to smoking(relapsing because of an inability to resist cigarettes); (3) nostalgia for one's former self(relapsing to recapture feelings of freedom and happier times); (4) smoking for relief(relapsing to manage emotions and stress); and (5) never really having quit (relapsing because they did not quit for themselves). The findings of this study provide support for the claim that the experiences of smoking cessation and relapse among postpartum women may be unique and, consequently, may require specialized intervention.

Adaptation, Psychological↗
PubMed2007

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

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

Adolescent↗
PubMed1980

Improved treatment results in the management of single and multiple relapses of acute lymphoblastic leukemia.

One hundred twenty-five hematologic relapses of acute lymphoblastic leukemia (ALL) were treated with a four-drug reinduction regimen consisting of L-asparaginase, vincristine, daunomycin, and prednisone (Asp-VDP). Complete remission was achieved in 114 of 125 (91%) treatment courses. The regimen also proved to be highly effective in the management of multiple subsequent relapses which occurred in patients who had previously attained complete remissions with this regimen. The rates of remission induction for second and third reinduction attempts were 89% and 90%, respectively. Ten patients received this regimen for the treatment of four or more consecutive relapses and achieved complete remissions on each occasion. Toxicities related to therapy were not excessive. Although myelosuppression was the most frequently encountered toxicity, documented infection complicated only 14% of the treatment courses. These results constitute a considerable improvement in the management of recurrent ALL.

Adolescent↗
PubMed1998

The cost effectiveness of acamprosate in the treatment of alcoholism in Germany. Economic evaluation of the Prevention of Relapse with Acamprosate in the Management of Alcoholism (PRAMA) Study.

Alcoholism places a considerable economic burden on society. The rate of relapse of previously weaned alcoholics has been shown to decrease following treatment with acamprosate. Therefore, this study investigated the cost effectiveness of acamprosate in the treatment of alcoholism in Germany from the perspective of the German healthcare system. In this retrospective analysis of clinical data, the additional direct medical costs per additional abstinent alcoholic incurred by adjuvant acamprosate therapy of previously weaned alcoholics were quantified. In the base-case analysis, average case-related direct costs were applied. The cost-effectiveness ratio was -2600 deutschmarks (DM) per additional abstinent patient. Thus, the administration of acamprosate is cost saving. The cost benefit of acamprosate was also shown in a sensitivity analysis. The variance of the target variable under 'real world' conditions was simulated and the impact of the model variables on the target variable was quantified using a deterministic model. The variance was broad and the rate of abstinence under acamprosate was the independent variable with the greatest impact on the target variable. From the perspective of both the German healthcare system (i.e. direct medical costs) and the Statutory Health Insurance expenses, adjuvant acamprosate therapy led to net savings, while at the same time improved the patient's state of health. Based on the naturalistic design of the underlying clinical trial and on this economic evaluation, it can be concluded that adjuvant acamprosate therapy leads to net savings under 'real world' conditions.

Acamprosate↗
PubMed1998

Management of withdrawal syndromes and relapse prevention in drug and alcohol dependence.

The primary care physician is in a good position to diagnose, manage and intervene with patients who are undergoing the process of treatment and recovery from alcohol and drug disorders. Medications such as benzodiazepines are effective in the treatment of withdrawal syndromes, and naltrexone and disulfiram can be used to augment relapse prevention. Patients may also participate in psychosocial methods of addiction treatment that can reduce the risk of relapse and improve their psychosocial, health, legal and employment status.

Alcoholism↗
PubMed2003

[Preliminary outcome for patients with relapsed or resistant advanced non-Hodgkin's lymphoma treated by EPOCH regimen].

BACKGROUND & OBJECTIVE: In the management of relapsed or refractory non-Hodgkin's lymphoma(NHL), there is still no standard salvage chemotherapy regimen so far. Potentiation of effectiveness and reduction of toxicity for some anti-cancer agents through continuous intravenous infusion were shown in some pre-clinical and clinical studies. The purpose of this study was to evaluate the efficacy and toxicity of EPOCH regimen. METHODS: A prospective phase II study of EPOCH regimen (doxorubicin/epirubicin,vincristine,etoposide over 96 hours infusion with bolus cyclophosphamade and oral prednisone) was administered to 26 patients with relapsed or refractory/resistant aggressive NHL. There were 20 patients (84.7%) among them treated by over 2 kinds of chemotherapy regimen with median regimen types of 2 (range,1-6 types) and median chemotherapy cycles of 8 (range,3-16 cycles) given for all patients. Fifteen patients (65.7%) were chemo-resistant recurrence. RESULTS: All the 26 patients were assessable. The response rate for the whole group was 50.0% with complete remission (CR) rate of 19.2%. Among the 7 patients with T-cell lymphoma and the 19 patients with B-cell lymphoma, the response rates were 28.6% and 57.9%,respectively. Major toxicity was myelosuppression with 34.8% and 8.7%incidence of grade III-IV neutropenia and thrombocytopenia respectively in all 46 cycles of EPOCH. Other toxicities were mild. CONCLUSION: EPOCH was effective for the patients with relapsed or refractory/resistant aggressive non-Hodgkin's lymphoma. Continuous infusion schedules of several chemotherapeutic agents may partially reverse chemo-resistance and reduce toxicity. EPOCH can be used as standard salvage regimen. Further clinical study is warranted.

Adolescent↗
PubMed1998

Management of adults recovering from alcohol or other drug problems: relapse prevention in primary care.

Patients recovering from substance use disorders are commonly seen in the primary care setting, and relapse is a serious long-term problem for these patients. Extrapolating from therapeutic strategies effective in specialty addiction treatment settings, this article outlines a practical approach to relapse prevention in the primary care setting. Working within a supportive patient-physician relationship, the primary care physician can help recovering patients decrease their susceptibility to relapse, recognize and manage high-risk situations, and use available self-help, pharmacological, and specialty resources. Drawing on the therapeutic relationship and skills they already possess, primary care physicians can have an important, productive, and satisfying role in the long-term management of patients in recovery from alcohol or other drug problems.

Adult↗
PubMed1994

Psychotherapy and pharmacotherapy for ambulatory cocaine abusers.

BACKGROUND: At present, there is no consensus regarding effective treatment for cocaine abuse or the most productive roles for the two major forms of treatment, pharmacotherapy and psychotherapy. We conducted the first randomized clinical trial evaluating psychotherapy and pharmacotherapy, alone and in combination, as treatment for ambulatory cocaine abusers. METHODS: One hundred thirty-nine subjects were assigned to one of four conditions offered over a 12-week abstinence initiation trial: relapse prevention plus desipramine hydrochloride, clinical management plus desipramine, relapse prevention plus placebo, and clinical management plus placebo. All treatments were manual-guided, delivered by experienced therapists, and monitored to promote the integrity of both forms of treatment. RESULTS: First, although all groups showed significant improvement, significant main effects for medication or psychotherapy, or their combination, were not found for treatment retention, reduction in cocaine use, or other outcomes at 12 weeks. Second, baseline severity of cocaine use interacted differently with psychotherapy and pharmacotherapy: higher-severity patients had significantly better outcome when treated with relapse prevention than with clinical management, while desipramine was associated with improved abstinence initiation among lower-severity subjects. Third, desipramine was significantly more effective than placebo in reducing cocaine use over 6, but not 12, weeks of treatment. Fourth, depressed subjects had greater reduction in cocaine use than nondepressed subjects and had better response to relapse prevention than to clinical management. CONCLUSION: These findings underscore the significance of heterogeneity among cocaine abusers and the need to develop specialized treatments for clinically distinct subgroups of cocaine abusers.

Adult↗
PubMed2004

Management of prostate-specific antigen relapse in prostate cancer: a European Consensus.

A European Consensus on the management of prostate-specific antigen (PSA) relapse in patients with prostate cancer has been formulated. The key recommendations proposed are that total PSA is the best detection tool for prostate cancer, with free and complexed PSA having a role in the PSA range 1-4 ng/ml. PSA relapse after radical prostatectomy (RP) has been defined as a value of 0.2 ng/ml with one subsequent rise, while the ASTRO definition should be used after radiotherapy. A PSA level of less than 0.4 ng/ml after hormonal therapy can be considered an indicator of a positive response. Continuous assessment using nomograms or artificial neural networks will help to determine whether progression after local therapy is distant or local, which is the basis for treatment decisions. Secondary treatment after local failure of RP should be initiated when PSA levels reach 1.0-1.5 ng/ml and salvage radiotherapy can be considered with or without hormonal therapy. Local failure after radiotherapy can be treated with a choice of high-intensity-focused ultrasound, salvage RP (only in highly selected patients), cryotherapy or external beam radiation. Treatment of distant failure involves hormonal manipulation, the type and the timing of which is based on both physician and patient preferences.

Antineoplastic Agents, Hormonal↗
PubMed2002

Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis.

PURPOSE: Several management options are available to patients with stage I seminoma, including adjuvant radiotherapy, surveillance, and adjuvant chemotherapy. We performed a pooled analysis of patients from the four largest surveillance studies to better delineate prognostic factors associated with disease progression. PATIENTS AND METHODS: Individual patient data were obtained from each center (Princess Margaret Hospital, Danish Testicular Cancer Study Group, Royal Marsden Hospital, and Royal London Hospital) for 638 patients. Tumor characteristics (size, histologic subtype, invasion of rete testis, and tumor invasion into small vessels [SVI]) as well as age at diagnosis were analyzed for prognostic importance for relapse. RESULTS: With a median follow-up of 7.0 years (range, 0.02 to 17.5 years), 121 relapses were observed for an actuarial 5-year relapse-free rate (RFR) of 82.3%. On univariate analysis, tumor size (RFR: 4 cm, 76%; P =.003), rete testis invasion (RFR: 86% [absent] v 77% [present], P =.003), and the presence of SVI (RFR: 86% [absent] v 77% [present], P =.038) were predictive of relapse. On multivariate analysis, tumor size ( 4 cm, hazard ratio 2.0; 95% confidence interval [CI], 1.3 to 3.2) and invasion of the rete testis (hazard ratio 1.7; 95% CI, 1.1 to 2.6) remained as important predictors for relapse. CONCLUSION: We have identified size of primary tumor and rete testis invasion as important prognostic factors for relapse in patients with stage I seminoma managed with surveillance. This information will allow patients and clinicians to choose management based on a more accurate assessment of an individual patient's risk of relapse. In addition, it will allow clinicians to tailor follow-up protocols based on risk of occult disease.

Adult↗
PubMed2003

[General practitioners' approach to relapsing multiple sclerosis].

Management of multiple sclerosis depends on close multidisciplinary collaboration but general practitioners play a particularly important role, especially in case of relapse, due to their close relationship with the patient. The purpose of this work was to conduct a survey of general practitioners' knowledge of relapsing multiple sclerosis and ascertain their main difficulties in patient management. One hundred seventy-seven practitioners answered a written questionnaire with two headings, diagnostic criteria for relapse and therapeutic approaches. Analysis of the results showed that this common event is under recognized. While 55.9 p.cent of the general practitioners stated they diagnosed relapse by themselves, only 2.8 p.cent knew its exact definition. Differential diagnosis accounted for a large number of mistakes. Our survey also underlined the use of certain therapeutic options (low-dose oral corticosteroid therapy) for which the effectiveness has not been demonstrated. It would be important to propose specific education on relapsing multiple sclerosis for general practitioners and improve cooperation with specialists. An integrated care network might be useful.

Adrenal Cortex Hormones↗
PubMed2000

Purine nucleoside analogs in indolent non-Hodgkin's lymphoma.

This article details both the contribution of the purine nucleoside analogs to the current management of relapsed indolent non-Hodgkin's lymphoma (NHL) and the role of pentostatin (Nipent) in that management. Of the three purine nucleoside analogs, pentostatin has received the least attention with regard to the management of indolent NHL. Although data in the literature appear to indicate that fludarabine (Fludara) and 2-chlorodeoxyadenosine (cladribine [Leustatin]) are more active in NHL, this conclusion could be flawed because many of the studies investigating pentostatin in indolent NHL have contained a large number of patients previously treated with the other purine analogs. As these agents are most likely cross-resistant, it is unfair to conclude that pentostatin is less active. Recently, there has been interest in using a new, more protracted schedule of 2 mg/m2/d of pentostatin for 5 days. Although the schedule used in the trials conducted in indolent NHL might not be optimal, pentostatin has nevertheless shown significant activity in these disorders.

Adenosine Deaminase Inhibitors↗
PubMed1989

Juvenile myoclonic epilepsy: long-term response to therapy.

Data from 50 patients with juvenile myoclonic epilepsy (JME) were analyzed retrospectively to assess the response to drug therapy--long-term seizure control, relapse rates, and confounding factors in seizure recurrence. Valproate is the only available antiepileptic drug that has been shown to be effective in controlling the generalized seizure components of JME--myoclonic, tonic--clonic, and absence seizures--without significant side effects. Data were collected using the EpiMonitor software and represented case follow-up from 2 months to 9 years. Forty-three patients (86%) were seizure free for at least 1 year; 25 patients (50%) relapsed at some point during follow-up. Relapses were precipitated most frequently by fatigue, noncompliance, stress, sleep deprivation, and alcohol consumption. With accurate diagnosis and appropriate therapy, seizures in JME can be adequately controlled, although JME is a chronic disorder that may require lifelong therapy. To minimize relapse, patient management must also focus on patient lifestyle to eliminate or control lifestyle-associated precipitants of seizure relapse.

Adolescent↗
PubMed1981

Relapse rate and long-term management of plaque psoriasis after treatment with photochemotherapy and dithranol.

The relapse rate of plaque psoriasis after initial clearing with the "Ingram" dithranol regimen or photochemotherapy was comparable when no maintenance treatment was given. It was estimated that psoriasis recurs to half of its pretreatment extent after about six months in half the patients. Maintenance treatment with photochemotherapy once a week or once every three weeks was useful in reducing the relapse rate. This study failed to show any statistical difference in relapse rates between these two maintenance schedules. If this finding turns out to be true over longer periods of study the maintenance schedule entailing treatment once every three weeks with its lower cumulative dose of long-wave ultraviolet light will clearly be preferable. The psoriasis in most patients was under better overall control with maintenance treatment than with intermittant clearing courses given when the extent of the psoriasis had become unacceptable to them. There was, however, a group of roughly one-fifth of patients who remained in satisfactory remission for over 16 months after initial clearing. Regular maintenance treatment was unnecessary in them. Much more information is needed on response to treatment in subgroups of patients to permit recognition from the start of which patients are likely to have long remission and which are not.

Adult↗