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PubMed2000

Cryptogenic organizing pneumonia. Characteristics of relapses in a series of 48 patients. The Groupe d'Etudes et de Recherche sur les Maladles "Orphelines" Pulmonaires (GERM"O"P).

Cryptogenic organizing pneumonia (COP) is a clinicopathologic syndrome characterized by rapid resolution with corticosteroids, but frequent relapses when treatment is tapered or stopped. We retrospectively studied relapses in 48 cases of biopsy-proven COP. One or more relapses (mean 2.4 +/- 2.2) occurred in 58%. At first relapse, 68% of patients were still under treatment for the initial episode. Compared with the no-relapse group, nine patients with multiple (>/= 3) relapses had longer delays between first symptoms and treatment onset (22 +/- 17 versus 11 +/- 8 wk, p = 0.02), and elevated gamma-glutamyltransferase (124 +/- 98 versus 29 +/- 13 IU/L, p = 0.001) and alkaline phosphatase (190 +/- 124 versus 110 +/- 68 IU/L, p = 0.04) levels. Relapses did not adversely affect outcome. Corticosteroid treatment side effects occurred in 25% of patients. Standardized treatment in 14 patients allowed a reduction of prednisone cumulated doses (p < 0.05) without affecting outcome or relapse rate. We conclude that: (1) delayed treatment increases the risk of relapses; (2) mild cholestasis identifies a subgroup of patients with multiple relapses; (3) relapses do not affect outcome, and prolonged therapy to suppress relapses appears unnecessary; (4) a standardized treatment allows a reduction in steroid doses.

Adult↗

PubMed1987

Long-term evaluation of a CNS prophylaxis trial--treatment comparisons and outcome after CNS relapse in childhood ALL: a report from the Childrens Cancer Study Group.

The current status of children with acute lymphoblastic leukemia (ALL) who had developed CNS disease while being treated on protocol CCG-101 was investigated. Seven hundred thirty-six eligible patients were entered into the study between June 1972 and July 1974. All children who were greater than 18 months of age were eligible for randomization to a CNS prophylaxis trial for which one regimen gave only a short course of intrathecal methotrexate (IT MTX) as prophylaxis. All other regimens included radiation therapy as prophylaxis. Current follow-up (median, greater than 10 years) shows no significant difference by standard life-table analysis for ultimate survival, although a substantial excess of CNS episodes occurred on the IT MTX regimen. Of the 675 patients who completed induction therapy and achieved remission in the study, 100 (14.8%) developed CNS disease as the first evidence of relapse. Fifty-five of these 100 had no subsequent CNS episodes. Only 17 of these 55 patients are surviving without further relapses since the CNS episode. The median time to isolated CNS relapse was 457 days. Time to the initial CNS relapse was found to be the most important factor for predicting outcome. Thirty-five of the 55 patients with isolated relapse subsequently relapsed in the bone marrow, and of these, 32 have died. Twenty patients of the 100 with CNS disease as the first evidence of relapse developed two episodes of CNS involvement and 17 of these 20 patients subsequently relapsed in the bone marrow; only one patient survived. Twenty-five patients of the 100 have shown a pattern of chronic CNS disease with multiple CNS relapses. The overall disease-free survival for the 100 patients who developed one or more relapse was only 16%. These data demonstrate that the occurrence of a CNS relapse is an indicator of poor subsequent outcome. Comparison of results of groups receiving different CNS prophylaxis required careful consideration of the entire pattern of relapses and mortality.

Adolescent↗

PubMed1998

Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial.

PURPOSE: The purpose of this study was to investigate the prognostic value of time to relapse in 188 adult patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) included on the Parma trial at the time of their first relapse. PATIENTS AND METHODS: The median follow-up of these patients is 102 months after registration onto the Parma study. Time to relapse was calculated from initial diagnosis, and a cutoff of 12 months was used to separate 77 patients defined as early relapse from 111 patients defined as late relapse. RESULTS: Patients with early and late relapses had significantly different overall response rates to salvage therapy with two courses of dexamethasone, high-dose cytarabine, and cisplatin (DHAP; 40% v 69%; P=.00007) and different 8-year survival rates (13% v 29%; P=.00001). Features at relapse with a negative prognostic value in univariate analysis were higher than normal lactic dehydrogenase (LDH) levels, tumor size greater than 5 cm, Ann Arbor stages III to IV, and Karnofsky score less than 80%. Therefore, multivariate analyses were performed. Time to relapse (P=.001) and LDH levels at relapse (P=.003) had independent prognostic value, whereas tumor size did not reach statistical significance in the logistic model that predicted overall response after two courses of DHAP. The study of prognostic factors for overall survival (OS) and progression-free survival (PFS) confirmed the prognostic value of time to relapse (P < .0001 for OS and P=.005 for PFS) independent of response or treatment after two courses of DHAP. CONCLUSION: Time to relapse may be used to stratify patients at time of first relapse of intermediate to high-grade non-Hodgkin's lymphoma.

Adult↗

PubMed2006

Pathways through relapses and deaths of children with acute lymphoblastic leukemia: role of allogeneic stem-cell transplantation in Nordic data.

PURPOSE: Our focus was on patients with pediatric acute lymphoblastic leukemia (ALL) who experienced relapse or died without becoming transplantation candidates. The purpose was to outline measures needed to improve the outcome. PATIENTS AND METHODS: We analyzed our population-based 20-year data on 3,385 Nordic children with ALL treated on Nordic Society for Pediatric Hematology and Oncology ALL protocols, and described the flow of these patients through relapses, remissions, and deaths as a result of toxicity, demonstrating where major patient losses occurred. RESULTS: In total, 854 patients (25%) had a first and 274 patients (8%) had a second ALL relapse. P for survival after the first relapse was .35 +/- .02. The induction mortality (2.2%, primary; 10.3%, first relapse; 26.3%, second relapse) and remission mortality (1%, first complete remission [1CR]; 19%, second CR [2CR]) were significant; transplantation-related mortality (TRM) only represented 15% (69 of 459) of the deaths as a result of toxicity. Of the 766 patients entering 2CR, 29% underwent transplantation (P for survival, .46 +/- .04), whereas 71% continued receiving chemotherapy (P for survival, .39 +/- .02). Children with stem-cell transplantation indications in 2CR, if they did not undergo transplantation, generally died or had a second relapse. The patient groups that underwent transplantation in 1CR (n = 84), 2CR (n = 220), and > or = 3CR (n = 62) represented different risk profiles. Those with allogeneic stem-cell transplantation (allo-SCT) in > or = 3CR (P for survival, .37 +/- .07) had an ALL and first relapse with favorable features. CONCLUSION: Major patient losses occurred through mortality as a result of toxicity and resistant disease during the pathways before allo-SCT. After relapse, more patients were lost to mortality as a result of toxicity during conventional chemotherapy compared with TRM. After second relapse, the chance for rescue by allo-SCT in 3CR was minimal. The question of whether transplantation is recommended after ALL relapse should be carefully addressed, and more efficient relapse protocols should be launched.

Adolescent↗

PubMed1986

Antibiotic-associated colitis caused by Clostridium difficile: relapse and risk factors.

Relapse is a common sequel of antibiotic-associated colitis due to Clostridium difficile. It has been suggested that Cl. difficile may persist in the stools in spite of the resolution of symptoms after treatment and this may cause the relapse. Our study was designed to define the factors that predispose to relapse and to determine if prolonging treatment to clear Cl. difficile from the stools might prevent relapse. Of 60 consecutive patients, 36 with more severe disease required treatment. Treatment with either vancomycin or bacitracin was continued until the results of the examination of stools for cytotoxin became negative and Cl. difficile could no longer be cultured (sensitivity of culture was 10-100 organisms/mL). This was achieved in 35 patients who were then followed for one month. Symptoms reappeared in 10 (28.6%) of the treated patients while Cl. difficile reappeared in the stools of an additional seven patients (20%) without the recurrence of diarrhoea. On comparing those who relapsed with those who did not, the age (67.3 +/- 5.5 years in those who relapsed compared with 51.6 +/- 4.4 years; P less than 0.025, means +/- SE) and a history of recent abdominal surgery (59% of those who relapsed compared with 17%; P less than 0.05) were significantly different. Although those who relapsed had received therapy with multiple antibiotic agents more often, this was not statistically significant. Disease was not more severe in patients who relapsed, nor was it more difficult to clear the pathogen from these patients. The 24 untreated patients did not suffer symptomatic relapse. Continuation of treatment until Cl. difficile apparently is absent from the stools is expensive and does not prevent relapse. Elderly patients and those who have recently undergone abdominal surgery are more likely to suffer a relapse.

Aged↗

PubMedDate not supplied

Relapsed non-Hodgkin's lymphoma: detection and treatment.

PURPOSE: To evaluate the optimal management strategy during clinical remission and after relapse in patients with non-Hodgkin's lymphoma (NHL). METHODS: Sixty-six patients with relapse of NHL from a state of clinical remission between 1987 and 1997 were analyzed retrospectively. The pattern of relapses, diagnostic methods used for relapses, and clinical outcome of salvage treatment were analyzed with attention to time after the achievement of clinical remission. RESULTS: Thirty-three relapses (50%) occurred within 12 months, and the remainder occurred gradually from 12-48 months after the first remission. Diagnosis of relapse in 61 of the 66 patients (93%) was made at unscheduled evaluations prompted by symptoms, on physical examinations, or because of high LDH levels. The 1- and 5-year cause-specific survival rates after relapse were 56.7% and 39.4%, respectively. The 1- and 5-year relapse-free survival rates were 50.1% and 35.0%, respectively. The 5-year relapse-free survival rate in patients with late relapse (49.5%) was significantly better than in those with early relapse (21.2%) (p<0.01). CONCLUSION: Time to relapse may be a useful factor to determine optimal management strategy in NHL patients.

Adult↗

PubMed2002

CEA and relapse after the operation of colorectal carcinoma.

BACKGROUND: Relapses have an important meaning in relation to the curative surgical intervention. In RO resections according to UICC classification, the local relapses were classified as the most important factor for survival. Without any doubts the most important of these tumor-biological prognostic factors in patients with colorectal carcinoma is the carcino-embryonal antigen. Up to now, the unquestionable importance of the determination of serum levels of CEA for the detection of relapses is most often described. MATERIAL AND METHODS: This study is retrospective, not randomized. Analyzed were medical records and data of patients, who underwent the surgery of colorectal carcinoma at IInd Department of Surgery, University Hospital, Faculty of Medicine, Comenius University, Bratislava, in period from January 1st, 1986 to December 31st, 1995. In our analysis we evaluate the age and gender of patients, date of the surgery and type of the surgery from the point of acuteness, as well as radicality, staging of the disease, levels of the serum CEA. Serum levels of carcino-embryonal antigen before operation were determined and evaluated. In patients, who remaind in the monitoring at our department we examine CEA in regular intervals. RESULTS: From our group of patients, in 28 patients the relapse of the disease was determined here. Before the first operation, the preoperative level of CEA was examined in 15 patients and in 13 patients it was not. From 15 patients with examined CEA level, 7 patients (46.7%) had increased and 9 patients (53.3%) normal level. In twenty-seven patients CEA level was examined to reveal a relapse. One patient was diagnosed during the acute surgery and CEA was not determined prior this operation. From the remaining 27 patients, CEA level was positive in 20 patients (74.1%) and 7 patients had normal levels (25.9%). From these 7 patients with normal CEA level, in 5 cases it was locoregional relapse and 2 patients have distant metastases. From all patients, in whom the relapse was determined at our department, in 13 patients locoregional relapse was detected and in 15 patients distant metastases were diagnosed. CONCLUSION: Due to the sensitivity of serum level of CEA for detection of relapses, which is higher compared to the primary tumor and also to found lead time 4 months we think the postoperative regular determination of CEA in patients after the curative resection is appropriate. Earlier determination of less progressive relapse is definitely important, although the current long-term survival after the surgery for relapses is not optimistic. Development of surgical procedures as well as alternative treatment can bring better results in less developed relapse of the disease. (Ref. 28.).

Adult↗

PubMed2004

Outcome of very late relapse in children with acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: Few data are available on the long-term outcome of children who present with a very late relapse of acute lymphoblastic leukemia, so treatment of these patients remains controversial. The present study was aimed at investigating clinical features and treatment outcome of children with very late relapse, diagnosed and treated in Italy in the last 20 years. DESIGN AND METHODS: All children diagnosed in Italian centers with a first relapse of acute lymphoblastic leukemia occurring >or= 60 months after attainment of first complete remission were included in this study. These relapses were diagnosed between 1982 and 1997. RESULTS: Ninety-three patients (58 males, 62.4%) had a first very late relapse occurring at a median time of 6.1 years (range 5.8 - 13.7 years) after the initial diagnosis. At a median follow-up time of 9.1 years after relapse, the overall 5-year survival (SE) and event-free-survival (SE) were 55.6% (5.2) and 39.5% (5.1), respectively. In multivariate analysis the site of relapse was the only significant predictor of duration of the second complete remission. Patients with isolated bone marrow relapse fared worse than those with combined or isolated extramedullary relapse [5-year event-free survival (SE) 24.5% (5.9), 51.3% (11.1) and 68.4% (10.7), respectively; (p=0.004)]. All 7 patients who underwent an allogeneic bone marrow transplantation from a matched related donor are alive in second complete remission. INTERPRETATION AND CONCLUSIONS: In this evaluation patients with a very late relapse isolated to the bone marrow had a poor outcome while re-treatment of extramedullary or combined relapse was associated with better cure rate. Our data suggest that patients with very late isolated bone marrow relapse should be treated intensively; bone marrow transplantation from a matched related donor may be indicated.

Adolescent↗

PubMedDate not supplied

Primary resected meningiomas: relapses and proliferation markers.

UNLABELLED: Relapses of meningiomas are a well known phenomenon during follow-up. The significance of sex, age, surgical treatment and mitotic frequency with regard to relapses are still a matter of debate. PATIENTS AND METHODS: The study included 125 meningioma patients who underwent surgical intervention between 1986 and 1997 They were in follow-up for 3, 5, 10 and 15 years; they were grouped as "stable" or "relapsing" tumours. The follow-up was based on magnetic resonance image (MRI) and tomodensitometry (TDM). The labelling index for Ki67 and PCNA (proliferation markers) was scored at resection. Risk factors for relapse were reviewed using univariate analysis and Cox hazards model. RESULTS: One hundred and twenty-five patients were under medical control of whom 26 showed a relapse. Among them 25 arose from subtotal resected tumours and 1 was a recurrence. Relapses comprised 16 females and 10 males. Tumour relapses at 3,5,10 and 15 years were, respectively, 8.8%, 13.6%, 17.6% and 20.8%. Proliferation markers, at group level, were statistically significantly different to distinguish stable from relapsing and malignant from benign meningiomas. Factors significantly associated with tumour relapse in univariate analysis were incomplete resection, histopathology and proliferation markers. In multivariate analysis the proliferation markers and incomplete resection were the only significant risk factors (p<0.05) for relapse. CONCLUSION: To avoid relapses of meningiomas, total resection is recommended. The resection type and proliferation markers are predictive factors for tumour relapse. The proliferation markers cannot be applied at the individual level.

Adolescent↗

PubMed2005

Predictors of relapse in steroid-sensitive nephrotic syndrome.

The objective of this study was to identify predictors of relapse and determine the predictive score for relapse in steroid-sensitive nephrotic syndrome. Ninety-nine children with nephrotic syndrome visiting the pediatric nephrology outpatient clinic of Soetomo Hospital from 1983 to 2001 were studied. There were 63 children with relapses (50 infrequent relapses, 13 frequent relapses) and 36 children without a relapse for at least 1 year after beginning steroid treatment, which served as a control group. The selected variables were grouped into non-renal factors (age, sex, nutritional status, infection) and renal factors (histopathologic findings, hypertension, hematuria, azotemia, hypocomplementemia, rapidity of early steroid response, number of relapses within the first 6 months, time-interval between early steroid response and first relapse). Using the discriminant analysis function test, it was found that the statistically significant predictors of relapse were the time-interval between early steroid response and the first relapse, number of relapses within the first 6 months, infection during the first relapse, hematuria and sex. A prediction score can be determined using 3, 5 or 6 parameters by including the rapidity of early steroid response.

Child↗

PubMed2006

[Comparison of the immunophenotype of patients with B lineage acute lymphoblastic leukemia at diagnosis and relapse].

OBJECTIVE: To compare the leukemia-associated immunophenotypes (LAIP) in patients with B lineage acute lymphoblastic leukemia (B-ALL) at diagnosis and relapse, and investigate its implications for minimal residual disease (MRD) detection. METHODS: The immunophenotype of leukemia cells from 410 newly diagnosed and 6 relapsed patients with B-ALL were detected by four to six antibody combination, mainly CD34/CD10/CD45/CD19 of 4-color CD45/SSC gating flow cytometry (FCM). RESULTS: The proportion of CD45 under-expressed or negative in relapsed patients was much higher than that in newly diagnosed patients, being 69.2% and 37.8% respectively. Immunophenotypic changes occurred in 9 relapsed patients (including 8 hematological relapse and 1 central nerves system relapse) when analyzed by paired samples analysis at diagnosis vs at relapse: 4 cases showed CD45 down-modulation and 2 up-modulation; 4 CD34 down-modulation and 2 CD10 up-modulation, while the expression of CD19 remained no change. MRD was observed in all 7 cases of hematological relapse 2 - 4 months before relapse, and the immunophenotype of MRD cells was the same as that in relapse. CONCLUSION: A high frequency of immunophenotypic changes occurred at relapse and even in MRD before relapse, however the accuracy of MRD monitoring seemed not affected by the FCM strategy used in this investigation.

Adolescent↗

PubMedDate not supplied

Long-term relapses in breast cancer patients.

The authors examined 100 cases of long-term relapses of breast cancer arising more than 5 years after radical mastectomy and 100 cases of early relapses (within 3 years). Precautional radiotherapy or chemotherapy had not been performed during these intervals. Histologic type did not appear important. Long-term relapses were relatively less frequent than early relapses at the level of the locoregional lymph nodes (P less than 0.01). Other investigations were directed to the eventual importance of hormones on the incidence of long-term relapses. Since many of the cases were not recent and therefore no data were available as regards hormone receptors, it was impossible to base the study on the latter. The incidence of long-term relapses was considerably lower in postmenopausal than in premenopausal patients and lower than the incidence observed for early relapses (P less than 0.04). This finding could be attributed to a hormonal effect. Therapeutic oophorectomy determines relatively better results in cases with long-term relapses, but their survival does not appear to be significantly better than that of cases with early relapses. Among the patients with long-term relapses, the N - cases at the time of mastectomy were relatively more numerous than observed among cases with early relapses (P less than 0.04). This finding, which also explains the relatively minor frequency of long-term relapses in locoregional lymph nodes, reduces the prognostic importance of the histologic status of axillary lymph nodes, as is well known for patients with hormonal receptors.

Breast Neoplasms↗

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↗

PubMed2006

Relationship between stress and relapse in multiple sclerosis: Part I. Important features.

OBJECTIVE: The aim of this two-year prospective study was to examine the relationship between multiple aspects of life-event stress and relapse in multiple sclerosis (MS) patients. BACKGROUND: Few studies have defined the critical features of this life-event stress; for example, stressor duration, frequency, severity, disease-dependency, valency, or stressor constructs, such as the propensity to cause emotional distress/threat or the frustration of life goals. METHODS: 101 consecutive participants with MS were recruited from two MS clinics in Sydney, Australia. Stressful life events were assessed at study-entry and at three-monthly intervals for two years. Patient-reported relapses were recorded and corroborated by neurologists or evaluated against accepted relapse criteria. RESULTS: Acute events, but not chronic difficulties (CDs), predicted relapse occurrence: acute stressor frequency counts predicted greater relapse risk, along with low disability score (EDSS) and being male. We also confirmed the bi-directional stress-illness hypothesis: stressors predicted relapse, and relapse separately predicted stressors. CONCLUSIONS: Life-event stress impacts to a small degree on MS relapse. The number and not the severity of acute stressors are most important; chronic stressors do not predict later relapse. Males and those with early stage disease are also at greater risk of relapse. MS patients should be encouraged to reduce acute stressors during times of high stress, and feel reassured that disease-related chronic stressors do not increase their relapse risk.

Acute Disease↗

PubMed1976

Relapse in Burkitt's lymphoma.

Of 109 patients with histologically confirmed Burkitt's lymphoma who completed a course of chemotherapy, 86 (79%) achieved complete remission. Forty-five (52%) of patients with initial complete remission relapsed with tumour over an observation period ranging from 2 years to over 5 years. Relapse was more common in patients who initially presented with abdominal or central nervous system (CNS) involvement than in patients who presented with localized facial tumours (p less than 0.01). Anatomical distribution of tumour on relapse differed from that at presentation. Facial bones were much less frequently involved on relapse; on the other hand, the CNS, cranial nerves, orbits and skin were frequent sites of disease on relapse. CNS involvement occurred in 42% (19/45) of patients at the first relapse and in 73% (11/15) of patients with multiple relapses. Prognosis in these patients was poor. Two relapse types were clinically identifiable. Early relapse (remission duration less than 12 weeks) was associated with frequent involvement of the CNS, drug resistance and a generally unfavourable outcome. Patients with late relapse (remission duration greater than 12 weeks) responded much better to secondary treatment. Possible pathogenic mechanisms underlying these two relapse types are discussed.

Abdominal Neoplasms↗

PubMed2001

Molecular discrimination between relapsed and secondary acute lymphoblastic leukemia: proposal for an easy strategy.

BACKGROUND: Discrimination between late relapse of acute lymphoblastic leukemia (ALL) and secondary ALL might be clinically important, because the former might still respond favorably to chemotherapy and/or bone marrow transplantation, whereas secondary ALL is associated with poor prognosis. PROCEDURE: We present a pre-B-ALL patient in whom disease recurred 2 years after completion of treatment. Differences in cytomorphology and immunophenotyping raised a suspicion of secondary ALL. We performed detailed molecular studies of immunoglobulin and T-cell receptor genes for discrimination between relapsed and secondary ALL. RESULTS: Southern blot analysis showed an oligoclonal immunoglobulin heavy chain (IGH) gene configuration at diagnosis and a monoclonal configuration at relapse. The size of one of the rearranged bands at relapse was identical to one of the faint rearranged bands at diagnosis. However, heteroduplex PCR analysis demonstrated that none of the clonal IGH gene rearrangements at diagnosis and at relapse was fully identical. Sequencing of several clonal PCR products revealed an identical DH6-13<-->JH6b junction shared by two different rearrangements at diagnosis and one rearrangement at relapse, thereby proving the clonal relationship between diagnosis and late relapse in this patient. CONCLUSIONS: We propose a stepwise molecular approach for discrimination between relapsed and secondary ALL based on the rapid and cheap heteroduplex PCR technique, including mixing of clonal (homoduplex) PCR products identified at diagnosis and at relapse. Direct sequencing and comparative sequence analysis of IGH gene rearrangements at diagnosis and at relapse should be regarded as an ultimate standard, but can be limited to the rare cases, in which no identical clonal PCR products at diagnosis and at relapse were detected with the mixed heteroduplex PCR analyses.

Blotting, Southern↗

PubMed1995

Relapse after first cessation of therapy in childhood acute lymphoblastic leukemia: a 10-year follow-up study. Italian Association of Pediatric Hematology-Oncology (AIEOP).

The outcome of 171 children with ALL who relapsed for the first time after elective cessation of therapy (1-86 mo) and followed over 10 years (median 60 mo; range 1-232 mo) has been evaluated. One hundred and three patients relapsed in the bone marrow (BM), 29 in the testis (T), 21 in the central nervous system (CNS), 14 in the BM plus another site and 4 in other sites. Second remission was achieved in 97% of patients (97% BM, 100% T, 90% CNS, respectively) with reinduction schedules including three or more drugs. All but 4 out of 100 patients who relapsed in the BM received cranial reprophylaxis with intrathecal CT alone or CT plus radiotherapy. Seven patients in second CR underwent allogeneic bone marrow transplantation from an HLA matched sibling. The overall survival was 34% and disease-free survival (DFS) probability at 100 years was 22%. A second relapse was observed in 73% of patients. Forty children are alive in second continuous remission and 24 are alive after a second or subsequent relapse. Patients with isolated T relapse showed a significant better outcome than those with BM or CNS involvement. Most patients (62%) with isolated BM relapse showed a further disease recurrence in BM, and DFS was shorter when relapse occurred within 12 months from off-therapy. Eighty-two patients in second CR stopped the treatment a second time and showed a survival and DFS probabilities, respectively, of 69% and 43%. Thus, children with ALL who relapse after cessation of therapy still have a high risk of further late relapses and should be treated with intensive chemotherapy and CNS reprophylaxis. BMT must be considered for all patients relapsing in the BM within 12 months from off-therapy.

Adolescent↗

PubMed1992

Long-term, low-dose prednisolone therapy in frequently relapsing nephrotic syndrome.

The efficacy of daily administration of a small dose of prednisolone was examined in 21 patients with corticosteroid-responsive, frequently relapsing nephrotic syndrome (FRNS). After induction of remission of a third or subsequent relapse with a 6-week course of prednisolone (standard therapy with prednisolone, STP), this drug was continued in a single daily dose of 0.25 mg/kg body weight (low-dose prednisolone, LDP) for 18 months. Relapses occurring during this period were treated with STP, following which LDP therapy was resumed. The historical controls comprised 14 patients with FRNS in whom relapses were treated with STP and who were observed over a minimum period of 30 months. The two groups were comparable for age at the onset of nephrotic syndrome and sex. Twenty patients completed LDP therapy, during which 12 had no relapse, 6 had infrequent and 2 frequent relapses (1 patient became steroid dependent and was taken off LDP). Twelve patients were followed for 12-42 months after stoppage of LDP; during this period 7 had no relapse, 4 had infrequent relapses and 1 showed steroid dependence. The number of relapses during LDP therapy (0.5/patient per year) was significantly less (P less than 0.001) than in the preceding 12 months (3.62/patient per year), and continued to remain low during the following 12 months (0.6/patient per year). Whereas the frequency of relapses in the LDP group was similar to that in the historical control group in the 1st year of comparison, it was significantly less during LDP therapy (0.5/patient per year versus 2.25/patient per year). No side effects were observed in patients on the LDP regimen, at the end of which the height percentiles improved in 6 patients and remained unchanged in 14. Our observations indicate that long-term therapy with a small daily dose of prednisolone can significantly reduce the number of relapses in patients with FRNS, and that the beneficial effect may continue even after its stoppage.

Child↗