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PubMed1986

Prediction and prevention of relapse of acute lymphoblastic leukaemia after bone marrow transplantation.

Results of bone marrow transplantation (BMT) in 63 adults and children with ALL transplanted in the 5-year period 1979-83 were analysed. Twenty-one patients (33%) relapsed, 25% of the group died in relapse and 19% died from complications of BMT. The actuarial disease-free survival at 6 years was 38%. Relapse after BMT could be predicted by standard prognostic diagnostic features such as age, sex, cell type and presenting blast cell count. Patients transplanted in first remission selected for their poor prognosis had a lower relapse risk than a similar group of poor prognosis patients transplanted in second or subsequent remission (P less than 0.05). Relapse following second and subsequent remission BMT was predicted by a score based on standard prognostic features or by the pace of the disease: patients with an interval of less than 2 years between diagnosis and first relapse having a 15% actuarial disease-free survival, compared with 81% for patients with an interval greater than 2 years (P less than 0.001). These results emphasize that ALL is a heterogeneous disease and establishes the importance of determining relapse risk when selecting BMT and other treatment schedules for ALL patients.

Acute Disease↗

PubMed1988

Relapse after allogeneic bone marrow transplantation for acute leukaemia: a survey by the E.B.M.T. of 117 cases.

A multi-centre retrospective analysis on 117 patients relapsing after bone marrow transplantation (BMT) for acute leukaemia was carried out by the Leukaemia Working Party of the European Group for Bone Marrow Transplantation (E.B.M.T.). Forty-one patients had acute myeloid leukaemia (AML) and 76 had acute lymphoblastic leukaemia (ALL). Relapse occurred between 3 and 30 months after BMT and where investigated the leukaemia was found to have relapsed in recipient cells. In 10 cases the relapse was associated with new cytogenetic abnormalities. 74 patients received further treatment for leukaemia. Of these 21 out of 50 with ALL and 11 out of 24 with AML achieved a complete remission and had a median survival of 12 months compared with a median survival of 4 months for untreated patients or patients not achieving complete remission (P less than 0.001). Factors predictive for successful remission induction were a long interval between bone marrow transplant and relapse in ALL patients; and isolated extramedullary relapse. Presenting blast count, karyotype and remission status and number at the time of BMT were not predictive. Donor bone marrow was shown to be responsible for haemopoietic recovery occurring in the 21 out of 31 patients tested who achieved remission using donor karyotype or red blood cell antigens as markers. Nine patients received a second bone marrow transplant but only one became a long-term survivor. The results show that chemotherapy can usually prolong survival in selected patients with acute leukaemia relapsing after BMT but further BMT has a poor outlook.

Adolescent↗

PubMed2005

The gene expression signature of relapse in paediatric acute lymphoblastic leukaemia: implications for mechanisms of therapy failure.

Despite significant improvements in the treatment of childhood acute lymphoblastic leukaemia (ALL), the prognosis for relapsing patients remains poor. The aim of this study was to generate a transcriptional profile of relapsed ALL to increase our understanding of the mechanisms involved in therapy failure. RNA was extracted from 11 pairs of cryopreserved pre-B ALL bone marrow specimens taken from the same patients at diagnosis and relapse, and analysed using HG-U133A microarrays. Relapse specimens overexpressed genes that are involved with cell growth and proliferation, in keeping with their aggressive phenotype. When tested in 72 independent specimens of pre-B ALL and T-ALL, the identified genes could successfully differentiate between diagnosis and relapse in either lineage, indicating the existence of relapse mechanisms common to both. These genes have functions relevant for oncogenesis, drug resistance and metastasis, but are not related to classical multidrug-resistance pathways. Increased expression of the top-ranked gene (BSG) at diagnosis was significantly associated with adverse outcome. Several chromosomal loci, including 19p13, were identified as potential hotspots for aberrant gene expression in relapsed ALL. Our results provide evidence for a link between drug resistance and the microenvironment that has previously only been considered in the context of solid tumour biology.

Adolescent↗

PubMed1990

DQA2 U allele: a genetic marker for relapse of Graves' disease.

The association of HLA-DR3 with Graves' disease in Caucasoids is well established but its significance is unclear and its clinical value as a predictive parameter for relapse after a course of antithyroid drug therapy is controversial. We have further investigated the predictive value at the genomic level in 51 patients with Graves' disease who were treated with a 6-month course of carbimazole and followed up for 2 years. Using DNA-restriction fragment length polymorphism (DNA-RFLP) allogenotyping, (i) complete concordance of HLA-DR assignment was observed between serological and DNA-RFLP analysis of all but one of 51 patients with Graves' disease; (ii) the DR beta 17(1)-DQ alpha 2-DQ beta 2a (a DNA-RFLP allogenotype of the classical Northern European haplotype of HLA-B8 DR3) was significantly (corrected P = Pcorr less than 0.02) associated with Graves' disease particularly in patients who relapsed (Pcorr less than 0.005); (iii) HLA-DR3 was highly associated with DQA2 U allele (chi 2 = 18.53, d.f.2, P less than 0.0005); (iv) a strong correlation between the DQA2 U allele and the outcome of the disease was observed. Relapse occurred in 91% (10/11) of the patients who were homozygous for the DQA2 U allele whilst only 65% (15/23) and 41% (7/17) of patients who were hetero or homo-zygous for the DQA2 L allele (DQA2 U/L and DQA2 L/L) relapsed within the same period of follow-up (chi 2 = 7.18, d.f.2, P less than 0.05). Though the relapse rate in patients with the DQA2 U/U genotype was not significantly higher than the relapse rate in patients with the DQA2 U/L genotype, it was significantly higher than the relapse rate in patients with DQA2 L/L genotype (P less than 0.0001) with a relative risk of 14.3.

Alleles↗

PubMed2005

Efficacy of lamivudine re-treatment for relapsed patients after an initial lamivudine therapy in HBeAg-positive chronic hepatitis B.

The efficacy of lamivudine re-treatment in chronic hepatitis B (CHB) patients who relapse after HBeAg seroconversion with lamivudine has not been investigated. The aim of this study was to evaluate the efficacy of lamivudine re-treatment in relapsed patients. Among 192 patients who had achieved HBeAg seroconversion with lamivudine at a dose of 100 mg/day, 121 patients discontinued lamivudine. Relapse occurred in 49 patients (40.5%). Thirty-three relapsed patients received lamivudine re-treatment for at least 6 months. The mean duration of lamivudine re-treatment was 16 months and the follow-up period was 8.9 months. HBeAg seroconversion was achieved in 23 patients (69.7%). The cumulative HBeAg seroconversion rates at 5, 9, and 12 months were 60, 64, and 67%, respectively. The mean time to HBeAg seroconversion in lamivudine re-treatment was shorter than that in the initial therapy (4.7 months vs. 9.7 months). Viral breakthrough occurred in six (18.2%) patients. All patients with viral breakthrough were accompanied by elevation of serum alanine aminotransferase (ALT) levels. Among 15 patients who discontinued lamivudine re-treatment after HBeAg seroconversion, relapse occurred in six patients (40%). All relapses occurred within 9 months after the discontinuation of lamivudine re-treatment. In conclusion, lamivudine re-treatment in relapsed patients after initial lamivudine therapy had a higher response rate and shorter duration to HBeAg seroconversion than during the initial therapy. However, HBeAg seroconversion induced by lamivudine re-treatment was not durable.

Adult↗

PubMed2005

Oral refeeding in patients with mild acute pancreatitis: prevalence and risk factors of relapsing abdominal pain.

BACKGROUND AND AIM: In acute pancreatitis (AP), oral refeeding may stimulate pancreatic secretion, increasing the inflammation of the glandular tissue causing relapse of abdominal pain or even exacerbation of the disease. This study aimed to assess the prevalence and risk factors of abdominal pain relapse over oral refeeding in patients convalescing with AP as well as the impact of pain recurrence on the hospital stay. METHODS: Inclusion criteria were AP confirmed by biochemical and/or radiological data in the absence of severe disease or extensive necrosis. The same diet was offered to all patients during oral refeeding. Demographic, clinical, biochemical and radiological data were prospectively recorded and analyzed. RESULTS: A total of 130 patients were included. During the oral refeeding period, 32 (24.6%) patients had pain relapse, which was more common on days 1 (68.8%) and 2 (28.1%). Pain relapse was related to higher serum levels of lipase on the day before refeeding, higher serum levels of C-reactive protein on the fourth day, and presence of peripancreatic fluid collections (P < 0.01). Pain relapse significantly increased total hospital stay (P < 0.01). CONCLUSIONS: In patients with mild AP, pain relapse during oral refeeding was relatively high (24.6%), particularly on the first or second day. Their risk appeared be associated with more intense or persistent pancreatic inflammation on the day before refeeding, and presence of peripancreatic fluid collections. Pain relapse increased hospital stay, and likely overall costs on disease treatment.

Abdominal Pain↗

PubMed1984

Testicular relapse in childhood acute lymphoblastic leukaemia in Malaysia, 1967-82.

From 1967-82, 9 children with testicular relapse (TR) of acute lymphoblastic leukaemia (ALL) were diagnosed out of 99 boys treated, an incidence of 9.1%. The median time from the onset of ALL until diagnosis was 28 months (range 3-41 months). All were asymptomatic; six were detected on routine examination while three were diagnosed only on biopsy. Routine biopsy prior to stopping chemotherapy is useful in detecting occult TR. Biopsies should be done on both the testes regardless of the clinical findings. The age, leucocyte count and hepatosplenomegaly at diagnosis of ALL were not found to be significant factors in influencing relapse. Eight children were in bone marrow remission at the time of TR, but three had preceding or concurrent meningeal leukaemia while in the other five the testis was the first and only site of relapse. Radiotherapy was effective in local disease control but failed to prevent bone marrow relapse in all except two patients despite continuation of chemotherapy. The median time from onset of TR until bone marrow relapse was 7 months (range 3-13 months) and the median time until death, was 11 months (range 6-18 months). The frequency of testicular relapse may be related to the intensity of either the initial induction therapy or the consolidation chemotherapy. Further studies are required to determine whether the incidence of testicular relapse will decline with more intensive early treatment.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Persistent hypercholesterolaemia in frequently relapsing steroid-responsive nephrotic syndrome.

OBJECTIVE: To investigate long-term changes of serum cholesterol levels in children with frequently relapsing steroid-responsive nephrotic syndrome (NS). METHODOLOGY: Serum cholesterol values just before and during or immediately after 'relapse' were reviewed and the incidence of hypercholesterolaemia (> or = 200 mg/dL) was determined in eight patients (M:F, 6:2). RESULTS: The patients with frequently relapsing NS usually showed hypercholesterolaemia (mean incidence, 81%) just before 'relapse' during clinical remission, as well as in relapse (mean incidence, 96%). A high incidence of steroid therapy was also found in each case (mean, 89%) just before relapse. CONCLUSIONS: Our results demonstrate that children with frequently relapsing NS have prolonged periods of hypercholesterolaemia, even during clinical remission. It is suggested that serum lipid profiles be monitored carefully in such patients.

Adolescent↗

PubMed1991

Extramedullary relapse in childhood leukemia.

As long-term survival of children with leukemia is increasing, the prophylaxis of extramedullary leukemia has become a more important part of treatment. We studied the pattern of occurrence of extramedullary leukemia in a retrospective review. This review included a total of 2,317 childhood leukemia patients aged 15 years or less who had been treated at 38 institutes in Japan between 1976 and 1985. Extramedullary leukemia developed in 386 of 1,724 ALL patients (22.4%) and 63 of 544 patients with ANLL (16.3%). Among the ALL patients, CNS-L was the most common form and was observed in 315 cases (81.6%), followed by testicular leukemia in 89 (23.0%). In the case of ANLL, the most common form of extramedullary leukemia was CNS-L (45 cases, 71.4%), followed by cutaneous leukemia in 10 cases (15.9%). In addition, leukemia of the lymph nodes, ovaries, bones, kidneys and eyes was observed in 7, 5, 5, 4 and 4 cases, respectively. The survival rate of ALL patients with CNS-L was 40.1% for isolated relapse and 2.7% for bone marrow relapse, and no more deaths occurred after 6 years from relapse. The survival rate of patients with testicular leukemia was 40.1% for isolated relapse and 5.9% for complicating bone marrow relapse, and no deaths occurred after 7 years from relapse. Cutaneous leukemia tended to occur late in older children with ALL and early in infants with ANLL, and all these patients died. Infiltration into the kidney was observed in 4 patients, all of whom died. More than 75% of patients died after isolated relapse of leukemia of the bones, ovaries, lymph nodes and eyes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2005

Clinical study of six cases showing late relapse of germ cell tumors.

Late relapse of germ cell tumors has been considered rare. We report six patients treated at our institution with relapses of germ cell tumors more than 2 years after first successful management. Median time to late relapse for pure seminomas and non-seminomatous germ cell tumors was 30.0 and 75.5 months, respectively. The sites of the late relapses in two cases of pure seminoma were located out of the fields of irradiation. After systematic chemotherapy, both these patients remain disease free. Two patients with non-seminomatous germ cell tumors received salvage chemotherapy at the time of late relapse, but tumor markers did not normalize in either case. A complete resection of relapsed masses was performed in three cases of non-seminomatous germ cell tumors. All three patients are without evidence of disease. The incidence of late relapse in patients with pure seminomas and non-seminomas was 2.4% and 3.3%, respectively, which suggests the necessity for long-term follow up.

Adult↗

PubMed2001

Family transactions and relapse in bipolar disorder.

This study examined whether patient symptoms and relatives' affective behavior, when expressed during directly observed family interactions, are associated with the short-term course of bipolar disorder. Twenty-seven bipolar patients and their relatives participated in two 10-minute family interactions when patients were discharged after a manic episode. Results indicated that patients who showed high levels of odd and grandiose thinking during the interactions were more likely to relapse during a 9-month followup period than patients who did not show these symptoms during the family discussions. Relapse was also associated with high rates of harshly critical and directly supportive statements by relatives. Patients' odd thinking and relatives' harsh criticism were significantly more likely to be correlated when patients relapsed (r = .53) than when they did not relapse (r = .12). Results suggest that bipolar patients who show increased signs of residual symptomatology during family transactions during the post-hospital period are at increased relapse risk. The data also suggest that relatives of relapsing patients cope with these symptoms by increasing both positive and negative affective behaviors. Moreover, a bidirectional, interactional relationship between patients' symptoms and relatives' coping style seems to capture best the role of the family in predicting relapse in bipolar disorder.

Adaptation, Psychological↗

PubMed2004

Factors predicting relapse and poor outcome in type I autoimmune hepatitis: role of cirrhosis development, patterns of transaminases during remission and plasma cell activity in the liver biopsy.

AIM: To determine factors predicting relapse and poor outcome in patients with type I autoimmune hepatitis (AIH). METHODS: Patients with AIH were retrospectively recruited. Definitions-remission: AST/ALT < 2 ULN; relapse: AST/ALT > or = 2 ULN; poor outcome: cirrhosis complications, transplantation (OLTx), and death; abnormal transaminases: AST/ALT > ULN but within the remission range; abnormal transaminases index (ATI): number of occasions AST/ALT abnormal/years of remission. Liver biopsies were assessed by Ishak system, and additional score given for portal and parenchymal plasma cells. Data are presented as median (range). RESULTS: Seventy-one patients were identified. Twenty (28%) had cirrhosis at presentation, 14 (20%) developed it during follow-up of 52 months (18-336). Of the 14, four had histological confirmation, and the remainder had clinical/radiological evidence of cirrhosis. Factors independently associated with cirrhosis development were inability to have consistently normal transaminases during remission, OR 19.3 (95% CI 2.2-40), p = 0.002. Treatment was discontinued in 40/69 patients of whom 30 (75%) relapsed within 2 months (1-23), culminating in one death. Factors independently associated with relapse were: time to initial remission, OR 5.5, 95% CI 1.3-22, p = 0.01; failure to have consistently normal transaminases during remission OR 11.8, 95% CI 1.3-100, p = 0.02; and portal plasma cell score (PPCS) OR 10.6 (95% CI 1.0-107), p = 0.04. Time to remission > or = 5 months, PPCS > or = 3 and ATI > or = 2 was associated with > 90% probability of relapse (PPV 100%). Fifteen percent had a poor outcome. Independent predictors of poor outcome were: globulins at onset OR 3.4 (95% CI 1.1-10.1), p = 0.02 and cirrhosis development, OR 23 (95% CI 1.7-307), p = 0. CONCLUSIONS: Seventy percent of patients with AIH relapse upon drug cessation. Time to remission > or = 5 months, ATI > or = 2 and PPCS > or = 3 were associated with > 90% probability of relapse. Factors predicting poor outcome were globulins at onset and cirrhosis development.

Adolescent↗

PubMed2004

Early detection of relapse in panic disorder.

OBJECTIVE: To explore predictive models of relapsing based on change in symptoms at a time when panic disorder patients are still in remission following discontinuation of antidepressants. METHOD: Forty-seven subjects, who were randomized to double-blind placebo and who had valid data at four time points: pretreatment, randomization to placebo substitution, an assessment on placebo prior to the last assessment or relapse and their last assessment (relapsers n = 15, non-relapsers n = 32) were studied using descriptive, growth curve analysis and logistic regression methodologies. RESULTS: Measures of generalized anxiety, fearfulness and disability at work and at home were better predictors of relapse than measures of panic and anxiety sensitivity. Logistic regression models using any one of these four general variables and its linear change correctly predicted relapse for 78.7-84.4% of the study subjects. CONCLUSION: It is possible to gauge, with a fair degree of accuracy, the probability of relapsing in panic disorder patients who have discontinued serotonergic antidepressants 2 months prior to the return of panic.

Adult↗

PubMed1984

Central nervous system relapse surveillance by serial beta 2-microglobulin measurements in childhood acute lymphoblastic leukemia.

Beta 2-microglobulin (beta 2m) is synthesized particularly in lymphocytes. Its value for early detection of central nervous system (CNS) involvement in acute lymphoblastic leukemia in children was tested by serial determinations. Before 9 overt CNS relapses, the mean increase of the cerebrospinal fluid (CSF) beta 2m concentration was 588 micrograms/l/month (range: -50 to +2020), which was significantly higher than the steady levels during maintenance treatment. Although the absolute value of CSF beta 2m was increased to 1 430 micrograms/l in the group with overt CNS relapse, individual variations in CSF beta 2m before a relapse were so great that no difference was seen between samples from CSF with or without lymphoblasts. The ratio between beta 2m in the CSF and in serum did not increase in serial samples prior to overt relapse, but the ratio was higher in patients with CNS relapse compared with a control group on maintenance therapy. In 9 children without CNS leukemia, the beta 2m concentration in CSF and serum decreased to a nadir 4 weeks after the start of induction treatment. The subsequent increase of CSF beta 2m was similar to the increase before a CNS relapse. Mean values of CSF beta 2m changes differed between groups of children with and without CNS leukemia early in the induction phase and during the maintenance treatment, but the wide range in individual values made serial beta 2m determinations unsuitable for detecting a CNS relapse.

Adolescent↗

PubMed2005

Recurrent melioidosis in patients in northeast Thailand is frequently due to reinfection rather than relapse.

Human melioidosis is associated with a high rate of recurrent disease, despite adequate antimicrobial treatment. Here, we define the rate of relapse versus the rate of reinfection in 116 patients with 123 episodes of recurrent melioidosis who were treated at Sappasithiprasong Hospital in Northeast Thailand between 1986 and 2005. Pulsed-field gel electrophoresis was performed on all isolates; isolates from primary and recurrent disease for a given patient different by one or more bands were examined by a sequence-based approach based on multilocus sequence typing. Overall, 92 episodes (75%) of recurrent disease were caused by the same strain (relapse) and 31 episodes (25%) were due to infection with a new strain (reinfection). The interval to recurrence differed between patients with relapse and reinfection; those with relapses had a median time to relapse of 228 days (range, 15 to 3,757 days; interquartile range [IQR], 99.5 to 608 days), while those with reinfection had a median time to reinfection of 823 days (range, 17 to 2,931 days; IQR, 453 to 1,211 days) (P = 0.0001). A total of 64 episodes (52%) occurred within 12 months of the primary infection. Relapse was responsible for 57 of 64 (89%) episodes of recurrent infection within the first year after primary disease, whereas relapse was responsible for 35 of 59 (59%) episodes after 1 year (P < 0.0001). Our data indicate that in this setting of endemicity, reinfection is responsible for one-quarter of recurrent cases. This finding has important implications for the clinical management of melioidosis patients and for antibiotic treatment studies that use recurrent disease as a marker for treatment failure.

Bacterial Typing Techniques↗

PubMed1983

Analgesic ingestion and other factors preceding relapse in ulcerative colitis.

To investigate factors which predispose to relapse in patients with ulcerative colitis, we conducted a survey to compare the events occurring in the four weeks preceding the clinic attendance of 62 outpatients in remission with those taking place in the same period before the onset of relapse in 21 patients attending with active disease. The only event which occurred significantly more often in patients who subsequently relapsed was ingestion of paracetamol and other inhibitors of prostaglandin synthesis (76% (16/21) relapse vs 39% (24/62) remission, p less than 0 . 01). Recent upper respiratory tract infection (38% vs 26%) was not significantly more common in patients in relapse than in remission, and emotional stress, atopic events, antibiotic treatment, dietary indiscretions, foreign travel, and gastroenteritis were relatively rare in both groups. The surprisingly high prevalence of analgesic ingestion before relapse itself requires confirmation but does lend indirect support to the theory that colonic mucosal prostaglandin deficiency induces relapse in some patients with ulcerative colitis.

Acetaminophen↗

PubMed1989

Comparison of relapse rates and of mucosal abnormalities after healing of duodenal ulceration and after one year's maintenance with cimetidine or sucralfate: a light and electron microscopy study.

Forty six patients with endoscopically diagnosed duodenal ulceration were randomly allocated to treatment with either sucralfate 1 g qds (n = 24) or cimetidine 200 mg tds and 400 mg nocte (n = 22). When the ulcers healed, a maintenance dose of sucralfate 1 g bd or cimetidine 400 mg nocte was given for one year (or until relapse if earlier). Biopsies of duodenal mucosa adjacent to ulcer sites for light and electron microscopy were obtained before and after healing and again after one year's maintenance if the ulcer remained healed. Duodenal biopsies were also taken from 20 age and sex matched controls. Rates of healing and relapse during maintenance did not differ between the two treatments, although relapses occurred earlier with cimetidine. In the three year post-maintenance follow up period 10/13 cimetidine patients relapsed compared with four of 11 sucralfate patients (p less than 0.05), the relapses occurring significantly earlier in the cimetidine treated patients (p less than 0.05). Mucosal biopsies from both treatment groups still showed considerable abnormalities after healing. During maintenance, however, the sucralfate scores fell significantly (p less than 0.02) to near control levels unlike the cimetidine scores which remained raised at pretreatment values. The histological and ultrastructural changes were not predictive of later relapse. These findings favour the use of sucralfate in preference to cimetidine for maintenance treatment in the prevention of relapse of healed duodenal ulcers.

Adolescent↗

PubMed1995

Changes in cytomorphology of childhood lymphoblastic leukaemia at the time of disease relapse. Childhood Leukaemia Working Party of the United Kingdom Medical Research Council.

AIMS: Children in a United Kingdom national trial for relapsed non-B lymphoblastic leukaemia (ALL) had their diagnostic and relapse marrow cytomorphology compared to see what changes occur during the evolution of the disease. METHODS: Each relapse slide was assessed blindly for French American British (FAB) type and other morphological features by a panel of three independent microscopists without reference to each other or any diagnostic material. Diagnostic slides had been assessed by the same panel on an earlier occasion. RESULTS: A total of 134 consecutive children was studied. Six (5%) were classified as FAB type L2 at diagnosis, compared with 18 (13%) at relapse (a difference of 9%). Twenty two (16%) changed their FAB type, 17 (13%) from L1 to L2 and five (4%) from L2 to L1. The FAB score fell at relapse in 34 children and rose in 14, a difference of 14%. Cell size was the commonest feature to change (increasing in 22 and diminishing in nine) followed by prominent nucleoli (appearing in 21 and disappearing in six). Forty four (33%) children had vacuolated blasts at diagnosis, compared with 48 (36%) at relapse. Twenty five changed their vacuole score substantially, 14 gaining > 10% and 11 falling < 10%. CONCLUSIONS: These findings reflect the variability of lymphoblast cytomorphology, but also show a trend for cells to have more prominent nucleoli and greater size at relapse. Factors controlling these features of the FAB type are unknown, but they may simply be related to the growth fraction of a particular disease and not to any lineage specific biological feature.

Adolescent↗