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PubMed2004

An update on the management of relapsed and primary refractory Hodgkin's disease.

With the use of combined modality therapy for early stage disease and a risk-adapted approach for advanced stage disease, nearly 90% of patients with Hodgkin's lymphoma are cured with initial therapy. However, in patients who have primary refractory or relapsed disease, high-dose therapy and autologous stem cell transplantation is the best curative option. The use of peripheral blood progenitor cells has decreased transplant related mortality to less than 3%; but long-term progression-free survival as increased minimally. Although prognostic factors have been used to tailor therapy in de novo Hodgkin's lymphoma their utility in the relapsed-refractory setting has not been exploited. This update will discuss these important prognostic factors and try to guide oncologists in treatment decisions in this setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Management of Relapsed and Refractory Hodgkin's Disease.

Hodgkin's disease remains highly curable after relapse or even after an ineffective initial therapy. The likelihood of attaining a lasting second remission is particularly high for patients who failed to respond to a primary program of radiation therapy (RT) alone. The preferred treatment for these patients is with a doxorubicin-containing chemotherapy and additional RT (if feasible). The prospect for a "second cure" after failure to respond to initial chemotherapy is smaller and for most cases a program of high-dose therapy followed by stem-cell transplantation is required. Advances in using this modality over the last 15 years have resulted in a disease-free survival of approximately 40% with a follow-up that extends up to 10 years. Most important, a recent dramatic decrease in treatment-related mortality of high-dose therapy as well as a reduction in cost have been documented. Analysis of prognostic factors allows better selection of patients and a sounder choice of salvage options. Although it appears that further dose escalation of chemotherapy is limited by nonhematologic toxicity, the benefit from incorporation of RT into high-dose programs has only recently been recognized. Because of the availability of hematopoietic growth factors and easier mobilization and collection of peripheral blood stem cells, these have become the preferred source for hematopoietic support. The use of peripheral blood stem cells and growth factors was shown to correlate with more rapid recovery of granulocytes and platelets and a shorter hospitalization period. Still, many patients remain refractory to salvage despite intensive therapy. These patients can be identified by their response to re-induction chemotherapy before transplant and should be considered for alternative approaches such as allogeneic bone marrow transplantation, sequential bone marrow transplant, and other experimental programs. This article reviews standard-dose salvage as well as current development in high-dose therapy with particular attention to the role of RT.

Journal Article↗
PubMed2005

Biology and management of relapsed acute myeloid leukaemia.

Disease relapse remains the major cause of treatment failure in adults with acute myeloid leukaemia (AML). This reflects both the failure of current salvage regimens and the absence of effective strategies to secure long-term disease-free survival in those patients who achieve a second remission. Recent progress in understanding the pathogenesis of relapsed disease has enabled the identification of a variety of dysregulated molecular pathways and these now provide a rational basis for the design of novel targeted therapies. At the same time, advances in allogeneic stem-cell transplantation have permitted the extension of the curative potential of allografting to patients in whom it was previously contraindicated. As a result, a range of novel drug and transplant therapies has become available in patients with relapsed AML, and it is realistic to anticipate that a co-ordinated assessment of their clinical and biological impact will provide the basis for the design of future, more effective treatments in relapsed disease.

Acute Disease↗
PubMed1987

Continuation ECT in the management of relapses of major affective episodes.

Three cases are reported describing the use of continuation ECT. Continuation ECT consisted of six to twelve treatments for about 3 to 6 months after recovery from the index affective episode. Continuation ECT may be indicated in patients with a severe episode of illness, optimal acute response to ECT, and negative response to continuation drug therapy. In such patients, the mostly theoretical risks associated with the procedure may be outweighed by the dangers associated with early relapse.

Adult↗
PubMed2006

[Management of relapses in smoking dehabituation].

Due to the recurrent chronic nature of tobacco dependence, health care professionals should know the most common reasons for relapses and offer smokers who have stopped smoking a preventive treatment. In our setting, some authors state that the main causes for which smokers relapse are the negative emotional states and social pressures. Among the prevention strategies of relapse are providing the patient information, reinforcing his/her decision to stop smoking and helping the patient identify and face the danger situations for the maintenance of abstinence.

Humans↗
PubMed2005

Diffuse large B-cell lymphoma: risk stratification and management of relapsed disease.

The clinical factors described by the International Prognostic Index (IPI) provide a model for risk stratification in diffuse large B-cell lymphomas (DLBCLs). However, there is variability in outcome within IPI risk groups, indicating the biological and clinical heterogeneity of these diseases. Studies of gene expression profiling (GEP) in DLBCL are uncovering biological heterogeneity with prognostic significance. Various gene expression signatures with predictive value independent of the IPI are now recognized. Immunophenotypic features of DLBCL have also been shown to have prognostic value. The use of fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning may provide additional predictive information when used at diagnosis or soon after initiation of treatment. Future prognostic models in DLBCL are likely to incorporate functional imaging, immunophenotype and GEPs as well as clinical data in risk stratification and choice of treatment. Treatment of relapsed DLBCL remains a major problem. High-dose therapy (HDT) and stem cell transplantation (SCT) has been shown to produce superior overall survival (OS) compared with conventional dose salvage therapy in patients with relapsed, chemosensitive DLBCL. However, only 20% to 30% of patients are cured by this approach, and the effectiveness of HDT and SCT in patients treated with rituximab-based combinations as first-line therapy is unknown. Although new transplant techniques including non-myeloablative allogeneic SCT are being investigated, their role is unclear. New treatment strategies are needed for these patients. The use of molecular techniques such as GEP is identifying many potential new therapeutic targets in DLBCL including histone deacetylase, HLA-DR, bcl-2, bcl-6, mTOR and TRAIL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Diagnosis and management of relapse in acute lymphoblastic leukemia.

Although the results are steadily improving, the treatment of the child with lymphoblastic leukemia in relapse remains unsatisfactory. Owing to the very nature of relapse, it is highly unlikely that future chemotherapy protocols will provide curative treatment for the majority of patients with recurrent disease. Therefore, the greatest possible emphasis must be given to further improvements and refinements in front-line (initial) therapy so as to prevent relapse from ever occurring. Our goal should be to put the relapse leukemia specialist "out of business."

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Experience with an LHRH analogue in the management of relapsed progressive prostatic cancer.

Seventeen patients with advanced progressive prostatic cancer who had relapsed or failed to respond to conventional endocrine therapy with oestrogens, orchiectomy or antiandrogens were treated with the LHRH analogue, ICI 118630. No significant objective tumour responses were seen, though 11 of 15 patients who presented with symptomatic metastatic bone pain had rapid short-term pain relief. The lack of objective clinical response seen in this study indicates no justification for the use of LHRH analogues in this group of patients. Though a significant subjective response was seen there was no added advantage over regular analgesics.

Acid Phosphatase↗
PubMed1995

The management of relapsed Wilms tumor.

Relapsed Wilms tumor is often very responsive to re-treatment, and cures are possible in many cases. Recurrent Wilms tumor forms a heterogeneous group because initial therapies vary widely. Given the complexity of the problem, there is a great need for an organized clinical investigative approach. Ideally, the treatment of initial relapse should be specified by the primary treatment protocol in order to better evaluate overall survival as an end-point for new primary therapy strategies. This is especially appropriate for Wilms tumor, because the investigations of this tumor over the last 20 years have attempted to determine the minimal therapy necessary for cure. Thus, survival rather than relapse-free survival is the most appropriate criterion for the success of a primary retreatment regimen. This investigative approach would also allow evaluation of treatment strategies tailored to a specific patient population. Important questions remain for those who treat recurrent Wilms tumor. Defining the role of high-dose therapy, defining the role of total body irradiation in high-dose therapy regimens, and defining the benefit and toxicity of cyclophosphamide compared with ifosfamide are three current questions under investigation. Developing new agents and regimens effective against Wilms tumor, especially against anaplastic tumors, RTK, and CCSK, is extremely important if progress is to be made in treating these tumors after relapse. Finally, there is a strong need to develop biologic information about tumors that recur, so not only will we better understand why patients relapse but also we can develop therapy tailored specifically to the biology of the recurrent tumor.

Antineoplastic Agents↗
PubMed2002

Metastatic squamous cell carcinoma of the neck from an unknown primary: management options and patterns of relapse.

PURPOSE: Management of squamous cell carcinoma of undetermined primary tumors in the head and neck region is controversial. Here we report the Southern California Kaiser Permanente experience with these patients. METHODS AND MATERIALS: From January 1969 through December 1994, 106 patients were eligible for this retrospective analysis. Distribution of nodal staging was as follows: 14 N1, 27 N2A, 39 N2B, 2 N2C, and 24 N3. Initial treatment included excisional biopsy alone in 12, radical neck dissection alone in 29, radiotherapy alone in 24, excisional biopsy followed by radiotherapy in 15, and radical neck dissection plus postoperative radiation in 26 patients. RESULTS: Except for two patients, all patients have had a minimum follow-up of 5 years. Overall, 57 patients (54%) have had recurrences. Only two patients (3%) who had received radiotherapy as part of their initial treatment had an appearance of a potential primary site inside the irradiated field vs 13 patients (32%) who had not received radiotherapy (p =.006). Combined modality therapy resulted in fewer neck relapses, particularly in patients with advanced neck disease. Including salvage, surgery alone as the initial treatment resulted in 81% ultimate tumor control above the clavicle for patients with N1 and N2a disease without extracapsular extension. The 5-year survival for the entire population was 53%. Radiotherapy alone resulted in poor survival in patients with advanced/unresectable neck disease. No significant difference in survival based on the initial treatment was found. The statistically significant adverse factors in determining survival included advanced nodal stage and the presence of extracapsular extension. CONCLUSIONS: Radiotherapy is very effective in reducing the rate of appearance of a potential primary site. However, in the absence of advanced neck disease (N1 and N2A without extracapsular extension), radiotherapy can be reserved for salvage. Radiotherapy alone results in poor outcomes in patients with advanced/unresectable neck disease, and incorporation of concurrent chemotherapy and cytoprotective agents should be investigated.

Carcinoma, Squamous Cell↗
PubMed1991

Haemangiopericytoma--Queensland Radium Institute experience and a review of the literature.

We report the presenting clinical characteristics, management, relapse patterns and survival of 17 patients with haemangiopericytoma treated at the Queensland Radium Institute, Australia from 1962 to 1989. Twelve patients were referred at the time of first diagnosis and were treated with curative intent. Three patients were treated with palliative intent when referred following initial diagnosis, and the remaining two patients were referred at the time of relapse. Disease was metastatic at presentation in 4 patients. Radiotherapy was used as a component of primary treatment of disease in 11 patients, in both patients referred for management of local relapse of haemangiopericytoma, and for palliation of metastatic disease developing in 3 patients. One patient received chemotherapy as part of initial treatment. Nine patients have died with survival from first treatment ranging from 3 to 139 months. All 8 surviving patients remain free of disease at 6 to 94 months from first treatment.

Adolescent↗
PubMed2003

Cost of managing an episode of relapse in multiple sclerosis in the United States.

BACKGROUND: The purpose of this study was to determine the direct medical US cost of managing multiple sclerosis relapses. METHODS: Direct data analysis and cost modeling were employed to derive typical resource use profiles and costs in 2002 US dollars, from the perspective of a third-party payer responsible for comprehensive health-care. The location and scope of health care services provided over a 90-day period were used to define three levels of relapse management. Hospitalization and resulting subsequent care was defined as high intensity management. A medium level of intervention was defined as either use of the emergency room, an observational unit, or administration of acute treatments, such as intravenous methylprednisolone in an outpatient or home setting. The lowest intensity of care comprised physician office visits and symptom-related medications. Data were obtained from many sources including all payer inpatient, ambulatory and emergency room databases from several states, fee schedules, government reports, and literature. All charges were adjusted using cost-to-charge ratios. RESULTS: Average cost per person for high management level was 12,870 dollars, based on analysis of 4,634 hospital cases (mean age 48 years, 73% female). Hospital care comprised 71% of that cost. At discharge, 36% required inpatient sub-acute care, rehabilitation or home care. The typical cost per moderate episode was 1,847 dollars and mild episode 243 dollars. CONCLUSIONS: Management strategies leading to a reduction in the frequency and severity of a relapse, less reliance on inpatient care, or increased access to steroid infusions in the home, would have a substantial impact on the economic consequences of managing relapses.

Adult↗
PubMed2000

Patterns of relapse and subsequent management following high-dose chemotherapy with autologous haematopoietic support in relapsed or refractory Hodgkin's lymphoma: a two centre study.

BACKGROUND: High-dose chemotherapy has an established role in recurrent or refractory Hodgkin's lymphoma (HL) although a significant proportion of patients subsequently relapse. This manuscript describes the clinical characteristics of such patients and documents their further management at two major UK cancer centres. PATIENTS AND METHODS: Between 1987 and 1996 one hundred patients with recurrent or refractory HL received high-dose chemotherapy (HDCT) with autologous haematopoietic rescue. All had recurred within 12 months of initial therapy or had two or more recurrences. RESULTS: With a median follow-up of 2 years, 56 patients are currently progression-free. There were six treatment-related deaths. One patient died of pneumonia in remission. Thirty-seven patients have relapsed, intrapulmonary disease being seen for the first time in 53% and recurrence at previous sites of disease in 81%. Following recurrence, therapy was determined by circumstances: either one agent at a time was used (single sequential approach) or multiagent chemotherapy was chosen. There was a survival advantage for those who achieved a symptomatic response (13 vs. 4 months median, P = 0.0001). A trend towards longer survival was seen for those whose disease recurred beyond six months following high-dose chemotherapy and in those who received combination chemotherapy. CONCLUSIONS: These results confirm that HDCT with autologous haematopoietic support is inadequate for about half the patients who receive it for high-risk HL. Relapse in the site of prior disease is the most likely pattern with intrapulmonary disease for the first time occurring frequently. It is possible to administer further chemotherapy after failure of HDCT, and both objective as well as subjective benefit can be achieved. A few patients appear to get long-term benefit from further treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Relapse signatures and insight: implications for CPNs.

Schizophrenia is, largely, an episodic illness with periods of remission and relapse. Early warning signs (EWS) strategies provide a guide to patients, their carer and mental health worker, to collaboratively manage relapse by identifying each individual's EWS of relapse, and agree a plan of action should EWS occur. Although there is evidence to suggest these strategies can reduce hospitalization, the psycho-educational component is likely to impact on the patient's insight. Rapid increases in insight have been associated with low mood. Consequently the clinician using this strategy risks unintended negative consequences. This paper argues that the flexible and broad community psychiatric nurse role means they are in an ideal position to address this possible pitfall, whilst maximizing the benefits of the strategy.

Awareness↗
PubMed1999

Response to plasma exchange and steroids as combined therapy for patients with thrombotic thrombocytopenic purpura.

We describe our experience in the management of 11 consecutive patients with thrombotic thrombocytopenic purpura (TTP) treated with a combined therapy of plasma exchange (PE) and steroids. Nine patients (82%) achieved complete remission (CR) after a median of 6 rounds of PE (range 2-22). There were 3 early relapses managed in the same way as the initial episode. One patient relapsed 23 months after diagnosis achieving CR with standard therapy; another patient suffered several relapses, and splenectomy was performed after the last one. Three patients died, 2 of them with resistant disease 9 and 38 days after diagnosis, and the remaining one died due to AIDS-related complications while he was in CR. Eight patients are alive in CR with a median follow-up of 38 months (range 8-74). The combination of PE and steroids is a well-tolerated and effective treatment of TTP, but improvements in therapy are needed to manage refractory patients.

Adult↗