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PubMed2003

Intraocular relapse of childhood acute lymphoblastic leukaemia.

Relapse of childhood acute lymphoblastic leukaemia (ALL) involving the eye is a rare but challenging problem. Twenty cases occurred in patients treated on the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia XI and ALL97 trials between 1991 and 2001, representing 2.2% of ALL relapses. Seventeen occurred as a first relapse, either in isolation or combined with relapse at another site, and three occurred as a second relapse. All patients with intraocular disease at first relapse were treated with both chemotherapy and radiotherapy, but the doses and protocols used varied. Eleven of these 17 patients are alive and in complete remission with a median follow up of 4 years 2 months from relapse. All 11 children that were treated with a full chemotherapy relapse protocol, together with local radiotherapy have survived. Patients treated with chemotherapy of shorter duration and intensity, despite radiotherapy and/or bone marrow transplantation, did poorly with only one survivor, currently in chronic relapse. Consequently, we suggest that children with eye relapse of ALL be treated with an intensive relapse chemotherapy protocol with local ocular radiotherapy, whether the relapse occurs in isolation or in combination with relapse at another site.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

The effect of radiotherapy treatment changes on sites of relapse in stage I testicular seminoma.

AIM: To evaluate relapse patterns in stage I testicular seminoma related to changes in radiotherapy practice. METHOD: Four hundred and six patients with stage I testicular seminoma were treated with adjuvant radiotherapy following orchidectomy: 338 patients received para-aortic radiotherapy only and 68 patients with added risk factors had radiotherapy extended to include the pelvis. Computed tomograms of relapsed patients were reviewed and sites of relapse were documented with correlation to the radiotherapy field. RESULTS: Thirteen relapses were identified; 10 occurring in the para-aortic radiotherapy group (3.0% relapse rate) and three in the extended radiotherapy field group (4.4% relapse rate). Sites of relapse were; five pelvis, three mediastinum, one lung, one scapula, one scrotum, while one patient had multiple relapse sites including the pelvis and one had a tumour marker relapse with no site identified. All the pelvic relapses occurred in the para-aortic radiotherapy group. CONCLUSION: Pelvic relapse only occurred when radiotherapy had been confined to the para-aortic region. Since para-aortic radiotherapy achieves equivalent outcome to wider field radiotherapy with reduced toxicity, it is likely to become standard practice in stage I seminoma and pelvic relapses will therefore increase in frequency. It is therefore important to include pelvic imaging when relapse is suspected.

Adult↗

PubMed2001

Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis.

BACKGROUND & AIMS: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. We aimed to assess whether clinical, biological, and histologic parameters in quiescent UC predict time to clinical relapse. METHODS: Seventy-four patients with clinically and endoscopically determined inactive UC were followed up for 1 year or for a shorter period if they had a relapse. Serum erythrocyte sedimentation rate; C-reactive protein, interleukin (IL)-1beta, IL-6, and IL-15 values; anti-neutrophil cytoplasmic antibody titers; and rectal biopsy specimens were obtained at baseline, at 6 and 12 months, and/or at relapse. Multivariate survival analysis was performed to determine independent predictors of clinical relapse. RESULTS: Twenty-seven patients relapsed (19/42 women; 8/32 men). Multivariate Cox regression analysis retained younger age (P = 0.003; hazard ratio, 0.4 per decade), greater number of prior relapses in women (P < 0.001; hazard ratio, 1.6 per prior relapse), and basal plasmacytosis (P = 0.003; hazard ratio, 4.5) on rectal biopsy specimens as predictors of shorter time to clinical relapse. Kaplan-Meier survival curves showed the 20-30-year-old age group and women with more than 5 prior relapses to be groups with shorter times to relapse. CONCLUSIONS: Younger age, multiple previous relapses (for women), and basal plasmacytosis on rectal biopsy specimens were independent predictors of earlier relapse. These findings may help identify patients with inactive UC who will require optimal maintenance medical therapy.

Adult↗

PubMedDate not supplied

The prognosis and survival of childhood acute lymphoblastic leukemia with central nervous system relapse.

Central nervous system (CNS) relapse in childhood acute lymphoblastic leukemia (ALL) has been overcome by sensitive therapeutic approachs. This study was planned to present the development of CNS relapse and survival in newly diagnosed 190 ALL patients whose cases were followed in the authors' unit between March 1991 and May 2002. St. Jude Study XI protocol was given to the patients who applied between March 1991 and March 1997 (group A) (n = 122), and St. Jude Study XIII protocol was given to the patients who applied between March 1997 and May 2002 (group B) (n = 68). The patients having isolated CNS relapse in group A received craniospinal irradiation (CSI) median 3.5 months after CNS relapse (range 2-6 months), a short time after reinduction, and 2 cures of consolidation. In group B, patients having isolated CNS relapse received IT once a month and a high-dose methotrexate treatment once every 8 weeks and 3 or 4, cures later therapy CSI median 7 months after CNS relapse (range 6-8 months) was given. When the overall survival rates of the 2 groups are compared, a statistically significant higher survival rate at 5 years was determined in group B than in group A (respectively, 82.3%, 58.4%) (p < .05). When subgroups of the patients (that is, those with no relapse, isolated CNS or BM relapse, or CNS + BM relapse) were compared in both groups, it was found that survival was much higher for the ones with no relapse and with isolated CNS relapse (respectively, 87.9%, 72.7%) compared to isolated BM or CNS + BM relapse groups (respectively, 10%, 13.3%) (p < .05). In a conclusion, for children with acute lymphoblastic leukemia and an isolated CNS relapse, with delayed definitive craniospinal irradiation allowing more intensive systemic and intrathecal chemotherapy results in better overall survival than has been previously reported.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Sensitive thyrotropin and thyrotropin-receptor antibody determinations one month after discontinuation of antithyroid drug treatment as predictors of relapse in Graves' disease.

OBJECTIVE: After primary successful antithyroid drug treatment (ATDT), Graves' disease has a relapse rate of 30% to 50%. Previous studies have evaluated age, gender, goiter volume, smoking habits, and the presence of thyrotropin-receptor antibodies (TRAb) as predictive markers to facilitate an individualized patient management. Despite higher sensitivity and specificity of the new second generation human TSH-receptor assay, the predictive value of TRAb for relapse of hyperthyroidism is still controversial. In a recent prospective multicenter study we have previously shown that suppressed or low TSH values predict both early (persistence) and late relapse of Graves' disease. We now present a more detailed analysis of the predictive value of TSH and TRAb for recurrent hyperthyroidism. METHODS: Four weeks after withdrawal of ATDT, 96 patients were available for thyroid function tests, including a sensitive third-generation TSH assay and a second-generation recombinant TSH receptor assay. Relapse of Graves' disease was evaluated for a total follow-up of 2 years. RESULTS: Within 2 years, 47 of 96 patients (49%) developed relapse of hyperthyroidism. Nine patients relapsed within the first 4 weeks after withdrawal of ATDT and were thus considered to have persistent Graves' disease. Ten of 15 other patients with TSH levels below 0.3 mU/L without overt hyperthyroidism relapsed within 2 years. Twenty-five of 65 patients with normal TSH (0.3-3.0 mU/L) and 3 of 4 patients with TSH values above 3 mU/L also had recurrent hyperthyroidism. After ATDT cessation, TSH had a positive predictive value of 70% and a negative predictive value of 62% (specificity 85%) for relapse of Graves 'disease. Mean TRAb levels in the group of patients with relapse were significantly higher (11.1 IU/L +/- 0.17) than TRAb values in the remission group (4.5 IU/L +/- 0.6), p < 0.001. Using a cutoff value of 1.5 IU/L, TRAb had low positive and negative predictive values of 49% and 54%, respectively (specificity, 14%), but with a cutoff level of 10 IU/L, predictive values improved to 83% and 62%, respectively (specificity, 92%). Combination of TSH and TRAb determinations did not further improve prediction of relapse. Other factors such as gender, age, goiter volume, smoking habits, presence of thyroid-associated ophthalmopathy, and urinary iodine excretion did not show a significant influence on relapse rate. CONCLUSION: Low TSH values 4 weeks after ATDT withdrawal predict relapse of Graves' disease, both early (persistence) and, to a lesser extend, within 2 years of follow-up. Also, TRAb above 10 IU/L found in a small subset of patients, correlated with a higher relapse rate.

Adult↗

PubMed2003

Relapse of neonatal herpes simplex virus infection.

BACKGROUND: Neonatal herpes simplex virus (HSV) infection is a severe disease with high mortality and morbidity. Recurrence of skin vesicles is common. OBJECTIVE: To determine the features of relapse and identify the factors related to relapse. DESIGN: Thirty two surviving patients with neonatal herpes virus infections were enrolled. All patients received acyclovir treatment. Clinical and virological data were analysed and compared between relapsed and non-relapsed cases. RESULTS: Thirteen (41%) had either local skin or central nervous system relapse between 4 and 63 days after completing the initial antiviral treatment. Nine patients exhibited local skin relapses, and four developed central nervous system relapses. In one skin and two central nervous system relapse cases, neurological impairment later developed. Type 2 virus infection was significantly related to relapse (odds ratio 10.4, 95% confidence interval 1.1 to 99.0). Patients with relapse had worse outcomes than those without relapse. CONCLUSION: Neonates with HSV type 2 infections have a greater risk of relapse. Relapsed patients have poorer prognoses.

Acyclovir↗

PubMed1997

Detection of relapse in early-stage Hodgkin's disease: role of routine follow-up studies.

PURPOSE: To examine the costs and benefits of routine follow-up evaluation in patients treated with radiation therapy for early-stage Hodgkin's disease. PATIENTS AND METHODS: We retrospectively examined patterns of follow-up evaluation and methods of relapse detection among 709 patients with stage I and II Hodgkin's disease treated with primary radiotherapy between 1969 and 1994. We determined the probability of relapse detection for seven routine follow-up procedures, compared their relative costs, and determined the impact of each procedure on the likelihood of survival following salvage therapy. RESULTS: Relapse has occurred in 157 patients (22%) at a median 1.9 years (range, 0 to 13 years) posttreatment. Relapse was suspected primarily by history (Hx) in 55% of patients, physical examination (PE) in 14%, chest x-ray (CXR) in 23%, and abdominal x-ray (KUB) in 7%. Only one relapse (1%) was identified by a routine laboratory study. The rate of relapse detection was highest for a combination of Hx and PE (78 of 10,000 examinations) followed by CXR (26 of 10,000 examinations). The projected charges (1995 dollars) per relapse detected by routine follow-up Hx and PE were $11,000 compared with $68,000 for CXR and $142,000 for KUB. The 10-year actuarial survival rate following salvage therapy was 65% overall, 65% for patients in whom relapse was detected by Hx or PE, and 69% for patients in whom relapse was detected by radiographs (P = not significant). CONCLUSION: The majority of relapses occurred within 5 years of treatment and were identified by Hx and PE. CXR was useful during the first 3 years of follow-up evaluation. KUB, CBC, and laboratory studies accounted for nearly half of all follow-up charges and rarely led to the detection of relapse. Their routine use as a method of relapse detection is questionable. In general, the method of relapse detection did not have a significant impact on the likelihood of successful salvage therapy.

California↗

PubMed2001

Surveillance neuroimaging to detect relapse in childhood brain tumors: a Pediatric Oncology Group study.

PURPOSE: To investigate the prognostic significance of surveillance neuroimaging for detection of relapse among children with malignant brain tumors. PATIENTS AND METHODS: A historical cohort study examined all children who experienced relapse from 1985 to 1999 on one of 10 Pediatric Oncology Group trials for malignant glioma, medulloblastoma, or ependymoma. RESULTS: For all 291 patients (median age at diagnosis, 8.2 years), median time to first relapse was 8.8 months (range, 0.6 to 115.6 months). Ninety-nine relapses were radiographic, and 192, clinical; median time to relapse was 15.7 versus 6.6 months, respectively (P = .0001). When stratified by pathology, radiographic and clinical groups showed differences in median time to relapse for malignant glioma (7.8 v 4.3 months, respectively; P = .041) and medulloblastoma (23.6 v 8.9 months, respectively; P = .0006) but not ependymoma (19.5 v 13.3 months, respectively; P = .19). When stratified by early (< 8.8 months) or late (> or = 8.8 months) time to relapse, 115 early relapses were clinical, and 32, radiographic; for late relapses, 77 were clinical, and 67, radiographic (P = .001). Overall survival (OS) from relapse was significantly longer for radiographic compared with clinical detection (median, 10.8 months; 1-year OS, 46% v median, 5.5 months; 1-year OS, 33%; P = .002), but this trend did not retain significance when analyzed by pathology subgroups. CONCLUSION: Surveillance neuroimaging detects a proportion of asymptomatic relapses, particularly late relapses, and may provide lead time for other therapies on investigational trials. During the first year after diagnosis, radiographic detection of asymptomatic relapse was infrequent. A prospective study is needed to formulate a rational surveillance schedule based on the biologic behavior of these tumors.

Adolescent↗

PubMed1991

Histoplasmosis relapse in patients with AIDS: detection using Histoplasma capsulatum variety capsulatum antigen levels.

OBJECTIVE: To assess the accuracy of Histoplasma capsulatum variety capsulatum polysaccharide antigen testing for the identification of histoplasmosis relapse in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective study using stored specimens. SETTING: A referral center and several private hospitals. PATIENTS: Twenty episodes of histoplasmosis relapse were evaluated in 17 patients with AIDS from November 1987 to August 1990. Controls included 30 patients with AIDS and histoplasmosis who did not have a relapse during maintenance therapy and who were initially tested during the same week as the patients with relapse. A second control group included seven patients with AIDS and histoplasmosis who were evaluated for relapse on 23 occasions; relapse, however, was excluded on each occasion. MEASUREMENTS: To avoid interassay variability, specimens were tested for H.c. var. capsulatum polysaccharide antigen with the same radioimmunoassay. MAIN OUTCOME MEASURE: The change in the H.c. var. capsulatum polysaccharide antigen level during successful as opposed to unsuccessful maintenance therapy for the prevention of histoplasmosis relapse. MAIN RESULTS: For the 20 episodes of relapse (17 patients), H.c. var. capsulatum antigen levels increased by at least 2 radioimmunoassay units in 12 of 14 serum specimens tested (85.7%; 95% Cl, 57.2% to 98.2%) and in 17 of 18 urine specimens tested (94.4%; Cl, 72.7% to 99.9%). Antigen levels increased in the urine or serum in 1 of 83 specimens (1.2%; CI, 0.03% to 6.6%) obtained on 56 occasions (1.8%; CI, 0.04% to 9.6%) from controls (specificity, 98.2%; CI, 90.4% to 99.96%). In three cases of relapse, antigen levels increased before clinical relapse, antigen levels increased before clinical relapse was suspected. Complement fixation titers increased by at least 2 dilutions in 4 of 11 cases (36.4%; CI, 10.9% to 69.2%) but in 0 of 9 control patients (CI, 0% to 28.3%). CONCLUSION: An increase in H.c. var. capsulatum polysaccharide antigen levels of 2 units or more strongly suggests histoplasmosis relapse. The presence of increasing titers of anti-H.c. var. capsulatum antibodies by complement fixation is less accurate for the diagnosis of relapse.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission after intensive primary and relapse therapy according to the BFM- and CoALL-protocols: results of the German Cooperative Study.

Fifty-one children between 26 and 214 months of age (median, 100 months) with acute lymphoblastic leukemia (ALL) were grafted in second remission from HLA-identical sibling donors (except for two patients who were grafted with a marrow with 1 antigen-mismatch). Initial treatment and relapse therapy were similar in all patients according to the BFM- and CoALL-protocols (front line: 38 patients according to BFM-protocols and 13 patients according to CoALL-protocols; relapse: 12 patients in study ALL-REZ-BFM 83, 17 in ALL-REZ-BFM 85, 20 in ALL-REZ-BFM 87, and two in ALL-REZ-BFM 90). The conditioning regimens were different, consisting of cyclophosphamide (CY) total body irradiation (TBI) plus (n = 27), VP-16-TBI (n = 23), and CY-TBI and ARA-C (n = 1). Three patients had a second graft after conditioning with CY-TBI for the first transplantation. The second ablative regimen consisted of CY plus VP-16 in the first patient and CY plus busulfan in the two other patients, one of whom relapsed again. All patients but three had bone marrow (BM), either isolated or combined, relapses. Twenty-nine of the patients are in continuous complete remission (CCR), ranging from 1 to 67 months after transplantation with a median time of 30 months. One patient was lost to follow-up in continuous remission. Nine patients died from treatment-related complications (infections and graft-versus-host disease) and 12 patients suffered a leukemic relapse; three of them received a second graft and two are in CCR. Kaplan-Meier analysis yields an event-free survival (EFS) of 0.52 +/- 0.08. The probability of a 7-year relapse-free interval (RFI) is 0.68 +/- 0.08. EFS for patients with late relapses is 0.47 +/- 0.12 and for patients with early relapses 0.56 +/- 0.1. The RFI for patients with late relapses is 0.65 +/- 0.12 and for patients with early relapses 0.69 +/- 0.11. There is a nonsignificant trend towards superior results for patients grafted after conditioning with VP-16 plus TBI. When all patients who are not in CCR at day +125 (which is the median interval between relapse diagnosis and BM transplantation [BMT]) are excluded from the chemotherapy results, there is no significant difference between the results of BMT and chemotherapy for late relapses. On the other hand, there is a significant advantage between chemotherapy and BMT for early relapses over chemotherapy (P less than or equal to .01).

Adolescent↗

PubMed1991

[Relapse of Wegener's granulomatosis. Retrospective study of 18 cases].

During a mean therapeutic follow-up of 4 years, 25 out of 61 patients with Wegener's granulomatosis had one or several relapses. As in 7 of them the initial diagnosis had proved erroneous, this study concerns the remaining 18 patients who together totalled 31 relapses after the correct diagnosis was made. Twenty relapses occurred early on, within 4 months of a change in treatment, and they corresponded to recurrent activity of the disease. Ten relapses occurred later on, after treatment had been discontinued or kept at maintenance dose level. The relapses appeared as early as the first year in 41 percent of the cases. The ENT region was affected in 61 percent of the patients. Nine relapses occurred in the absence of treatment, including 6 which took place 1 to 8 years after treatment. Three relapses occurred less than 3 months after a prednisone and oral cyclophosphamide therapy was initiated. Compared with the group of patients without relapse, those in the relapse group were younger, more often treated with azathioprine and cyclophosphamide administered intravenously, and followed up for a longer period; their probability of survival was also higher. In case of early relapse after withdrawal of treatment the mean duration of that treatment had been shorter than in the absence of relapse. None of the patients whose treatment had been stopped more than 20 months after its onset had an early relapse. These data prompted us to make the following proposals: initially, cyclophosphamide should be administered as bolus injections (the time required to obtain results is then shorter than with the oral route), and maintenance therapy should last at least 20 months. Azathioprine should be used only when cyclophosphamide is contra-indicated. The relative indications for intravenous and oral cyclophosphamide remain to be determined. Discontinuing all treatments is a difficult decision to make, but even then the patients should be under close supervision in view of the possibility of late relapses.

Adolescent↗

PubMed1997

Late relapse after treatment for clinical stage I and II Hodgkin's disease.

BACKGROUND: Despite the excellent outcome for patients with early stage Hodgkin's disease, late relapses do occur. The recognition of the pattern and incidence of late relapse and subsequent outcome is more important to ensure the provision of optimal care of patients with early stage Hodgkin's disease. METHODS: A review of 731 patients with clinical stage (CS) I and II Hodgkin's disease treated at Princess Margaret Hospital over a 19-year period was undertaken to examine the characteristics of patients who relapsed more than 4 years after the commencement of initial therapy (late relapse). RESULTS: The actuarial survival for all patients was 76% at 10 years and disease free survival was 65%. There were 206 patients with relapse, and in 35 patients the relapse occurred late (4.0-15.3 years after initial therapy). From the time of relapse the 10-year survival was 46% after early relapse and 68% after late relapse. No prognostic factors predicting specifically for late relapse after treatment for CS I and II Hodgkin's disease were identified in this study, although by multivariate logistic regression analysis there was an increased proportion of large mediastinal masses in the late relapse group. CONCLUSIONS: Late relapse is associated with a better survival than relapse occurring within the first 4 years from the time of diagnosis.

Adolescent↗

PubMed1997

Central nervous system relapse in non-Hodgkin lymphoma. A single-center study of 532 patients.

OBJECTIVES: To define the cumulative risk of central nervous system (CNS) relapse in systemic non-Hodgkin lymphoma (NHL); to assess the risk factors of age, sex, malignancy grade, stage, localization, and response to initial therapy; and to evaluate the effect of CNS prophylaxis. PATIENTS AND METHODS: An unselected group of 532 patients with systemic NHL. A retrospective analysis. RESULTS: Eleven patients presented with systemic as well as CNS localization, whereas in 55 patients, CNS relapse occurred later. The cumulative risk of CNS relapse at 4 years for all 532 patients was 19%. High-grade NHL carried a 39% risk of CNS relapse, with the vast majority of relapses occurring in the first 14 months after the initial diagnosis. The cumulative risk in patients with intermediate-grade NHL was considerable (22%) and dispersed throughout a much longer period (6 years). Patients with low-grade NHL still carried a 7% risk of CNS relapse; in all these patients, low malignancy grade was transformed into a higher malignancy grade at that time. In a multivariate analysis, high- and intermediate-grade NHL and advanced stage were independent risk factors for CNS relapse. There was not any strong evidence for a beneficial role of CNS prophylaxis in patients with intermediate- and high-grade NHL, but a retrospective analysis cannot be conclusive with regard to the effect of therapy. Systemic relapse occurred rapidly after CNS relapse, resulting in a median survival time after CNS relapse of only 2 months. CONCLUSIONS: Patients with high- and intermediate-grade NHL carry a considerable risk of CNS relapse. Advanced stage is an additional independent risk factor. The role of CNS prophylaxis seems to be disappointing, but a retrospective analysis cannot be conclusive. Prognosis after CNS relapse is poor.

Adolescent↗

PubMed1982

Influence of chest radiotherapy in frequency and patterns of chest relapse in disseminated small cell lung carcinoma. A Southwest Oncology Group Study.

The value of radiotherapy to the chest (RC) in disseminated small cell lung carcinoma (SCLC) has been questioned. Two protocols for disseminated SCLC from the Southwest Oncology Group (SWOG) have been compared. They were developed four years apart. The first one included radiotherapy (RT), 3000 rad in two weeks, to the primary tumor, mediastinum and supraclavicular areas, while the second one deleted any RC. Multidrug chemotherapy (CT) and brain RT were used in both protocols. Nonresponders to CT were removed from the study. Our main findings are as follows: (1) Initial chest relapses (patients with no initial extrathoracic relapse) have increased from 24-55% when RC is not given (P = 0.0001). Overall chest relapse (adding those patients that relapsed simultaneously in the chest plus other sites) in the second protocol was 73%. (2) Amount of response to CT does not influence the chances for relapse. Even complete responders to CT have a high chance for chest relapse. (3) Sites of relapse without RC are mainly in the primary tumor, ipsilateral hilus and mediastinum. (4) With RC, relapses shift to the chest periphery, mostly to the lung outside the radiotherapy field and to the pleura. (5) The two very different CT regimens have produced similar percentages and duration of response. (6) CT schema with periodic reinductions prolongs duration of response and survival over schema with continuous maintenance. Hence, interruption of CT to allow RC does not seem to adversely influence CT efficacy. From our results and the review of the literature we conclude that: (1) patients with disseminated SCLC that respond to CT should be given RC to decrease chest relapses. (2) A dose of 3000 rad in two weeks seems to be enough to produce a low percentage of chest relapse in disseminated SCLC, as survival of these patients is short and many will die prior to developing chest relapse. However, according to the literature, 4000-4800 rad is probably a more effective dose. (3) More studies and guidelines are needed to outline proper boundaries of radiotherapy fields, to decrease chances of peripheral chest relapses. (4) Median survival might not be a good parameter to evaluate the impact of RC in disseminated SCLC. The study of long-term survivors seems to be more important.

Carcinoma, Small Cell↗

PubMed1996

Cumulative rate of relapse of lupus nephritis after successful treatment with cyclophosphamide.

OBJECTIVE: To determine the cumulative rate of relapse of lupus nephritis that has been treated successfully with cyclophosphamide (CYC), and to estimate the association between time to relapse and demographic, clinical, laboratory, and treatment variables. METHODS: This was an observational study of 48 systemic lupus erythematosus (SLE) patients who were treated successfully with CYC between 1979 and 1993 and followed up thereafter at 3 university hospitals. Demographic and clinical variables, laboratory data during the first month of nephritis, and therapy-related variables were recorded from charts. Renal biopsy specimens were retrieved and analyzed by a pathologist. Relapse of nephritis was the outcome of interest. Descriptive analysis of patients who did and those who did not have a relapse was performed by chi-square test, Fisher's exact test, and Wilcoxon 2-sample test. The cumulative rate of relapse was computed using the actuarial method. Univariate comparisons of time to relapse were computed by log-rank test. Proportional hazards modeling was used to assess the combined effect of patient characteristics that have been hypothesized to be prognostic factors. RESULTS: Nephritis relapsed in 11 patients. Previous hematologic disorder, arthritis or arthralgia, and the use of CYC in oral form were more frequent in patients who had a relapse. The cumulative rate of relapse was 25% and 46% at 5 years and 10 years, respectively. A significant univariate difference in time to relapse was found when patients were stratified by time from diagnosis to initiation of CYC treatment (< or = 5 months versus > 5 months; P = 0.02). By multivariate analysis, age < 29 years at nephritis onset (relative risk [RR] 6.29, 95% confidence interval [95% CI] 1.13-34.94, P = 0.03) and delay of > 5 months from onset of nephritis to initiation of CYC therapy (RR 3.66, 95% CI 1.06-12.63, P = 0.04) were independently associated with time to relapse. CONCLUSION: A selected population of SLE patients may have long-term remission of renal disease following successful CYC therapy. Patients in whom CYC treatment is delayed or who are young at the time of nephritis onset are at increased risk of relapse.

Administration, Oral↗

PubMed2003

Outcome after relapse in an unselected cohort of children and adolescents with Ewing sarcoma.

BACKGROUND: Survival after relapse in patients with Ewing sarcoma is very poor and this retrospective study attempts to identify of prognostic factors predicting survival after relapse. PROCEDURE: A total of 191 patients with localised Ewing sarcoma were registered in the ET-2 trial of the United Kingdom Children's Cancer Study Group (UKCCSG). All patients received standardised primary treatment with chemotherapy and surgery and or radiotherapy as local modality treatment. Sixty-four patients who relapsed are included in this report. Treatment at relapse was variable and included chemotherapy, surgery, radiotherapy and high dose therapy (HDT) or megatherapy with peripheral stem cell transplantation (PBSCT) or autologous bone marrow transplantation (ABMT) in various combinations. A subgroup of patients had only non-specific symptomatic treatment at relapse. Both univariate and multivariate methods were used to investigate variables affecting survival after relapse. RESULTS: The overall actuarial median survival from relapse for all patients was 14 months (95% CI 11-16 months). Univariate analysis showed that males had a longer survival (median, 16 months vs. 11 months); patients who relapsed while on treatment did worse (median, 3 months vs. 16 months) and patients who had a longer disease-free interval (DFI) prior to relapse had a better outcome (DFI <1 year, median survival = 3 months; DFI 1-2 years, survival = 8 months; DFI > 2 years, median survival = 24 months, P < 0.001). Multivariate analysis confirmed that duration of first remission was the only factor associated with longer survival after relapse. CONCLUSIONS: These data suggest that although aggressive therapy may delay disease progression after relapse for some children, the course of the disease after relapse is usually fatal. International co-operative studies are needed to evaluate new strategies.

Adolescent↗

PubMed2003

Chromosomal imbalances: a hallmark of tumour relapse in primary cutaneous CD30+ T-cell lymphoma.

Primary cutaneous CD30+ large T-cell lymphoma (CD30+ CTCL) is a subset of non-epidermotropic primary cutaneous T-cell lymphoma. Although frequent spontaneous regression may be observed, skin relapses occur frequently. Cytogenetic abnormalities that could play a role in CD30+ CTCL tumour pathogenesis and relapses remain unknown. The identification of recurrent cytogenetic abnormalities is hampered by difficulty in culturing tumours and the lack of CD30+ CTCL serial studies comparing genetic changes both at diagnosis and at relapse. The purpose of this study was to investigate the cytogenetic abnormalities present in a series of 13 CD30+ CTCL samples obtained from nine patients fulfilling both EORTC and WHO diagnostic criteria, by the use of comparative genomic hybridization (CGH). CGH analysis revealed a non-random distribution of genetic imbalances between relapsing and non-relapsing disease. In relapsing disease, chromosomal abnormalities were detected both in the primary tumour and in relapses. The mean number of changes in non-relapsing disease was 0.33 (range 0-1), compared with 6.29 (range 1-16) in relapsing disease. The recurrent chromosomes involved in relapsing disease were chromosomes 6 (86%), 9 (86%), and 18 (43%). While chromosome 9 was mostly affected by gain, chromosomes 6 and 18 mainly contained regions of loss, exclusively on 6q and 18p. The common regions of deletion were 6q21 and 18p11.3. In one patient, we successfully cultured tumour cells from a skin biopsy from a second relapse. The G-banded karyotype was concordant with both CGH and fluorescence in situ hybridization (FISH) results. Although further studies are required to strengthen these data, this CGH analysis demonstrates chromosomal imbalances that may be involved in the pathogenesis of relapsing CD30+ CTCL.

Adult↗

PubMed2004

The patterns of relapse in osteosarcoma: the Memorial Sloan-Kettering experience.

BACKGROUND: With the introduction of intensive high-dose chemotherapy for the treatment of osteosarcoma, changes in the pattern of metastases observed at relapse have been reported. To further investigate this hypothesis, the relapse patterns among groups receiving chemotherapy regimens of variable intensity at Memorial Sloan-Kettering Cancer Center were analyzed. PROCEDURE: All patients treated with the protocols T4, T5, T7, T10, and T12 were included. Patients were divided into two groups, one including those patients treated with less intense therapy (T4, T5, and T7) and the other, those treated with current regimens (T10 and T12). RESULTS: Of the 25 patients who relapsed on the earlier protocols, 76% relapsed to the lungs, 8% had local recurrences, and 16% distant metastases to the bone. The median time to first relapse was 12 months. Of the 69 patients who relapsed on the T10 and T12 protocols, 75% relapsed in the lungs, 9% had local recurrences, and 16% distant bone metastases. The median time to first relapse was 17 months. There was no statistically significant difference in the timing of relapse between the two groups studied, although a longer median time to relapse was observed for patients treated on the later protocols. The range of time to relapse was also wider in the later protocols. CONCLUSIONS: These data do not support the hypothesis that patterns of relapse are changing with alterations in osteosarcoma treatment. This limited single institutional experience can be explored further in the context of a multi-institutional effort.

Antineoplastic Combined Chemotherapy Protocols↗