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[Relapses after multibacillary leprosy treatment].

Leprosy relapses are mainly due to bacillary persistence and diamino-diphenyl-sulphone (DDS) monotherapy. Case histories were examined for 33 patients with lepromatous leprosy (LL), diagnosed 7-48 years before the relapse and treated only with DDS during 4 to 38 years. Twenty-eight patients received irregular non-supervised polychemotherapy (PCT) since 1983. Five patients received only DDS, and presented relapses 13-20 years after the treatment was stopped. Relapses were diagnosed by clinical methods, including the reappearance of lesions or presence of new anesthetic areas. All cases were confirmed by bacilloscopy, and a subset of 20 cases by skin biopsy. Four patients presented indeterminate leprosy (IL) and one patient borderline tuberculoid leprosy (BT) in the biopsy. The latter 5 demonstrated presence of intraneural bacilli; the remainder were LL. Two patients relapsed even with PCT treatment. The others were cured with supervised PCT. Predisposing factors for relapses were as follows: DDS monotherapy, irregular PCT with inadequate dosage, unsupervised treatment, treatment uncompliance, and inadequate relationship between the patient and the health staff. Inspections for relapse in leprosy is recommended for in all multibacillary patients that were treated with DDS. The clinical appearance of new lesions or new anesthetic zones, the bacilloscopy and skin biopsy, used together, are effective in establishing the presence of relapses.

Adult↗

Risk factors for relapse in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis: tools for treatment decisions?

Current treatment based on the use of cyclophosphamide and corticosteroids has changed anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides from highly fatal into more chronic relapsing diseases. Relapses are a major problem in these diseases and cause increased morbidity and mortality. Current clinical research mainly focuses on achieving control of active disease while minimizing treatment-related toxicity. Risks for longterm relapse and their sequelae have been less thoroughly studied. It is noteworthy that, besides treatment, several other factors have been associated with the occurrence of relapses. Thus, compared to MPO-ANCA positive patients, patients with PR3-ANCA associated vasculitis run a significantly increased risk of experiencing relapses. ANCA-status during follow-up, levels of T cell activation, genetic background, and infectious and other exogenous factors have been linked to relapse as well. With a few exceptions, these associations are merely descriptive and not pathophysiologically proven. Furthermore, data on adapting treatment in accordance with risk factors for relapse are scarce. We review here the risk factors for relapse in ANCA-associated vasculitis, their potential pathogenic implications, and their possible role in preventive strategies and adaptations of current treatment policies.

Antibodies, Antineutrophil Cytoplasmic↗

[Relation between the expression of sIL-2R and the relapse in patients with acute lymphoblastic leukemia].

OBJECTIVE: To explore the relation of the serum level of sIL-2R in relapse patients with acute lymphoblastic leukemia (ALL). METHODS: With ELISA, we determined the levels of sIL-2R of 48 patients with ALL after their first diagnoses, complete remission 1 and relapse. The levels of sIL-2R of 30 patients from complete remission 1 to relapse were monitored. RESULTS: The levels of sIL-2R were higher in the relapse group and first diagnosed group than in the control. The levels of sIL-2R were higher in the relapse group and first diagnosed group than in the complete remission 1 group. However, the difference between the complete remission 1 and the control had no statistical significance. When we determined the levels of sIL-2R dynamically, we found that after complete remission, the levels of sIL-2R decreased, however, before one month of hematological relapse, the levels of sIL-2R increased. CONCLUSION: Monitor of the level of sIL-2R can predict impending relapse of patients with ALL and is helpful to early diagnosis of relapse.

Adult↗

Study of the characteristics and causes of relapse amongst leprosy cases in an urban area (Calcutta).

In this retrospective study of the 3737 cases of leprosy released from treatment and followed-up during 1975 to 1990, 63 had relapsed giving an overall relapse rate of 1.69%. The relapse rate was significantly higher in the immunologically unstable N?L (Borderline) cases (2.9%). It was also higher in those who had dapsone monotherapy (1.92%) compared to those who had multidrug therapy (1.01%). The relapse rate was higher in the 10 to 29 years age group and among those who became pregnant suggesting puberty and pregnancy could be risk factors. Males had a significantly higher relapse rate (2.1%) than females (1.1%). 45.2% of relapses in N (Non-lepromatous) cases occurred within 24 months and 71.4% within 36 months of stopping treatment. In those having monotherapy, 57.1% of relapses occurred within 24 months and 76.8% within 36 months. Regularity in treatment did not seem to have much influence on relapse rates.

Adolescent↗

Smoking relapse one year after delivery among women who quit smoking during pregnancy.

OBJECTIVES: The aim of the randomized trial was to evaluate the risk of smoking relapse one year after delivery among the women who quit smoking during pregnancy. MATERIALS AND METHODS: The study was carried out in 2002 and 2003 and included the collection of data on smoking relapse within one year after delivery among 175 women who participated in the randomized smoking cessation trial and quit smoking during pregnancy. RESULTS: About 50% of women who quit smoking during pregnancy relapsed into that habit within 12 months postpartum. The analysis of women who quit smoking before 14 weeks of pregnancy revealed a significantly higher risk of smoking relapse after delivery for women with the higher level of smoking addiction indicated by the Fagerström test (OR = 5.0; 95% CI: 1.5-16.2). Compared to the control group, spontaneous quitters who participated in intervention activities during pregnancy showed lower risk of smoking relapse within one year after giving birth (OR = 0.3; 95% CI: 0.1-0.9). In the group of women who quit smoking after 14 weeks of gestation, the risk of smoking relapse postpartum was significantly higher for those with the higher Fagerström test score (OR = 4.8; 95% CI: 1.6-14.1). The risk of smoking relapse 12 months after delivery was lower for spontaneous quitters who participated in the intervention during pregnancy and for women who quit smoking after participation in the intervention activities than for controls (OR = 0.03; 95% CI: 0.01-0.2, OR = 0.1; 95% CI: 0.03-0.6). CONCLUSIONS: Women who had higher score in the Fagerström test before quitting smoking had significantly higher risk of smoking relapse within 12 months after delivery. Anti-smoking intervention during pregnancy helps women to maintain smoking abstinence after delivery.

Adolescent↗

Influence of the relapse and remission periods on hearing status in children with minimal change nephrotic syndrome.

OBJECTIVE: Minimal change nephrotic syndrome (MCNS) is characterized by the onset of NS (Nephrotic Syndrome) without systemic disease, hypocomplementemia, or other serious signs of renal disease. Hearing status is not very well known in MCNS. Our objective was to address this question and to find out remission and relapse periods of the syndrome would affect the hearing of the patients. METHODS AND PATIENTS: Otologic status of 26 children with clinical MCNS was investigated in relapse and remission periods using audiometry and tympanometry. The pure tones that were obtained at the frequencies 250, 500, 1000, 2000, 4000 and 6000 Hz were noted. Pure tone averages (PTAs) were calculated at 500, 1000, 2000 and 4000 Hz frequencies. RESULTS: In both remission and relapse periods, PTA of the patients did not change and was 13 dB. The frequency specific pure tone results were not significantly different between the right and left ears of the patients as well as between the remission and relapse periods (p > 0.05). In the relapsing and remission periods, type A tympanogram was encountered in 86.4% and 92.3% of the ears, respectively. Type B tympanogram was encountered in 11.5% and 3.8% of the ears in the relapsing and remission periods, respectively. Type C tympanogram was encountered in 3.8% of the ears both in the relapsing and remission periods. Differences between the tympanometry results were not significant (p > 0.05). CONCLUSION: MCNS in childhood is not associated with an alteration in the hearing status, both in remission and relapse periods of the disease.

Acoustic Impedance Tests↗

Three cases of renal relapse after allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia.

Isolated renal relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) in children with acute lymphoblastic leukemia (ALL) is a rare condition. Generally, in ALL, the sites most frequently affected by extramedullary relapse are the central nervous system (CNS) and the testicles. Here we report on three young boys with relapsed B-precursor ALL, who underwent alloHSCT from HLA-identical siblings and suffered a histopathologically proven isolated unilateral renal relapse (two patients) or a combined renal and testicular relapse (one patient) 6, 10 and 12 months post alloHSCT. In all patients at the time of relapse bone marrow showed complete remission with complete donor hematopoiesis. They all received total body irradiation with partial shielding of the kidneys as part of their conditioning therapy, such that renal shielding could be an explanation for the observed accumulation of renal relapses. Moreover, during the past few years so called immune privilege has been postulated for frequent relapse sites such as the CNS, the testicles and the anterior chamber of the eye. Impaired accessability of these organs by cytotoxic T-cells (CTLs) with a reduced graft-versus-leukemia (GvL) effect after alloHSCT is based on a number of different molecular and cellular mechanisms. Similar mechanisms have been shown to be effective in the tubulointerstitial space of the kidney, rendering the kidney a potentially immune privileged site. Due to these observations we advocate sufficient treatment of the kidneys during conditioning therapy.

Antineoplastic Combined Chemotherapy Protocols↗

Longer relapse-free period after sucralfate than after H2-blocker treatment of duodenal and gastric ulcers.

In a prospective investigation of 2,045 patients with recurrent peptic ulcer disease, the relapse-free period after acute treatment with sucralfate was evaluated over 1 year. This remission period was compared retrospectively with that achieved by previous treatment with a histamine-H2-blocker in the same patients. Only patients who had a symptomatic relapse within 1 year after H2-blocker therapy were included. Patients with no relapses within 1 year after sucralfate were assumed to have a relapse on day 366, in order to compare the two periods. In 73% of the evaluable 2,045 patients, remission after sucralfate was longer than after H2-blocker, and 23% of these patients had no symptomatic relapse at all within 1 year after sucralfate. The average relapse-free period after sucralfate was 212 days, as compared with 132 days after H2-blockers (difference = 80 days; p less than 0.0001). Elderly and nonsmoking patients and those experiencing their first recurrence, or who had a duodenal ulcer, benefited especially from acute treatment with sucralfate. It can be concluded that peptic ulcer patients with a relapse after treatment with an H2-blocker are suitable candidates for sucralfate therapy. There is a high probability that the relapse-free period after sucralfate is longer than after H2-blocker treatment in both gastric and duodenal ulcer patients.

Anti-Inflammatory Agents, Non-Steroidal↗

Intensive therapy for multiple myeloma in patients younger than 60 years. Long-term results focusing on the effect of the degree of response on survival and relapse pattern after transplantation.

BACKGROUND AND OBJECTIVES: From 1994 to 1997 we conducted a population-based, prospective study on intensive therapy in newly diagnosed symptomatic myeloma patients younger than 60 years, comparing their survival to that of a conventionally treated historic population. Long-term results are presented, including the impact of the degree of response on survival and relapse pattern after transplantation. DESIGN AND METHODS: The prospective population was formed of 397 patients and the historic population of 313 patients. Both populations were calculated to comprise more than 75% of the expected number of new cases. RESULTS: After a median follow-up of 7 years survival was longer in the prospective population than in the historic one (median 60 versus 39 months; p=0.0002). When comparing only patients eligible for intensive therapy the median survival was 63 versus 44 months (p<0.0001). Attaining a complete response was associated with prolonged event-free survival but not overall survival. The pattern of relapse after transplantation was heterogeneous but could be divided into four major groups; insidious, classical, plasmacytoma form and transformed disease. The median survival after relapse was 29 months. The relapse pattern and time to relapse predicted outcome. Patients relapsing with an insidious or classical form of disease with skeletal events only, or after a long lasting first response were likely to respond well to conventional salvage therapy. In contrast, relapse with multiple symptoms, transformed disease or a short duration of first response implied bad prognosis. INTERPRETATION AND CONCLUSIONS: The relapse pattern after autologous transplantation is heterogeneous and response to salvage therapy is variable. The degree of response and event-free survival after transplantation are not reliable surrogate markers for survival.

Adult↗

Relapsed gestational trophoblastic neoplasia: A 20-year experience.

OBJECTIVE: To review relapsed gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Patients who had relapsed GTN between 1978 and 2001 at Queen Mary Hospital were included in the study. Records were reviewed and data analyzed regarding treatment, follow-up and survival. RESULTS: Eighteen patients with relapsed GTN were identified. Patients' ages ranged from 21 to 56 years, with a median of 34. Eight were classified as low risk, 1 as medium risk and 9 as high risk at the time of diagnosis. Seven, 3 and 8 patients were treated with single-, dual- and multiple-agent chemotherapy, respectively. The median interval between remission and relapse was 6.5 months (range, 1-132). The time interval to relapse did not correlate with patient mortality (Mann-Whitney U test, p = 0.873). Four patients died of the disease, and all of them were classified and treated as low risk at the time of diagnosis. Three were lost to follow-up at some point. The remaining patient had relapsed choriocarcinoma and developed progressive disease despite intensive multiple-modality treatment. The overall survival rate for relapsed GTN was 77.8%. CONCLUSION: Patients with relapsed GTN are salvageable. Failure of treatment seems attributable to patients who defaulted treatment or follow-up and presented late with massive disease.

Adult↗

[The usefulness of systematic follow-up of tuberculosis for the diagnosis of relapse in French Polynesia between 1971 and 1984].

Standard chemotherapy for one year was proposed for the treatment of tuberculous patients in French Polynesia between 1971 and 1978, and for nine months with the addition of pyrazinamide from 1979 to 1984. After treatment, the patients were followed up systematically for a period of 5 years. The aim of this study was to evaluate the value of the follow up measures to detect relapses. Of 1,065 patients treated between 1971 and 1984 at the centre for the control of tuberculosis 35 (3%) presented with a relapse, of whom 30 were confirmed either by bacteriological examination or histological examination. The level of relapse seen was not linked to age, sex, nor type of treatment received (one year or nine months). However, the level of relapse in non compliant patients to the initial treatment (7%) was significantly greater than those observed in patients who were totally compliant (2%) (p less than 0.0001). Of the 35 relapses 9 (26%) were discovered during routine follow up visits, of whom 8 were detected during the first year. The median delay separating apparent recovery from relapse was 8 months. 28 patients (80%) presented with symptoms suggestive of a relapse. Over 5 years 5773 consultations were carried out, which meant 642 consultations to detect one relapse. The authors suggest that in French Polynesia a systematic follow up limited to one year after apparent cure should be adequate.

Adult↗

Comparison of relapse in bilateral sagittal split osteotomies for mandibular advancement: rigid internal fixation (screws) versus inferior border wiring with anterior skeletal fixation.

A retrospective study of 28 patients treated by bilateral sagittal split ramus osteotomies for mandibular advancement and stabilized by two different methods of fixation was performed. Fourteen patients received rigid fixation, and 14 patients had inferior border wiring with anterior skeletal fixation. The postoperative and long-term cephalograms (greater than 6 months) were analyzed in a horizontal and vertical direction for relapse. In the horizontal direction, the rigid group experienced a 1.5% relapse in point B and a 3.2% relapse in pogonion. In the vertical direction, the rigid group experienced a 4% relapse in point B and a 9% relapse in pogonion, while the wire osteosynthesis group had a 13% relapse in point B and a 6% relapse in pogonion. These results support the belief that rigid fixation is more stable than is wire osteosynthesis and that it helps prevent relapse in the long-term results.

Bone Screws↗

Alterations in immunoglobulin or T cell receptor gene rearrangement at relapse: involvement of 11q23 and changes in immunophenotype.

We studied the organization of immunoglobulin (Ig) genes and the beta-chain gene of the T cell receptor (TCR) along with the clinical features, immunophenotypes, and karyotypes of 14 children with acute leukemia at diagnosis and relapse. The median time to relapse was 23 months. Eleven children had identical gene rearrangement patterns at diagnosis and relapse. All three patients whose blast cells showed variations in gene rearrangement patterns between diagnosis and relapase also demonstrated a change in the immunophenotype: one from cALLA+ to cALLA- B precursor cell ALL; one from T-ALL to AML; and one showed a marked increase in myeloid characteristics at relapse. Blast cells from these three patients at relapse showed the presence of chromosomal translocations involving 11q23; for two patients, this involved replacement of the original karyotype. We conclude that while most relapses are the result of reemergence of the original clone, new clones that differ in immunophenotype, karyotype, and gene rearrangement are occasionally present at relapse. Relapses may also occur in which the original clone has undergone major changes in gene expression and arrangement of the Ig heavy chain genes in the absence of karyotypic replacement.

Acute Disease↗

Spontaneous remissions in frequently relapsing and steroid dependent idiopathic nephrotic syndrome.

We studied retrospectively the clinical course of 32 steroid sensitive nephrotic children with frequent relapses with or without steroid dependency associated with minimal glomerular lesions. Six hundred twenty-seven relapses were traced during a mean observation period of 7 years per patient. The median period between the beginning of significant proteinuria and the start of prednisone therapy was 5 days (range 0-194 days). At least one spontaneous remission occurred in 10 of the 15 frequent relapsers and in 11 of the 17 steroid dependent patients. Twenty-three percent of the relapses in frequent relapsers and 10% of the relapses in steroid dependent patients remitted spontaneously. The disappearance of proteinuria was documented in 79% of these relapses between day 4 and day 14 after onset. A delay of up to 10 days in starting prednisone therapy did not influence the further course of this or the subsequent relapse. Our results suggest that this delay is justified in the absence of progressive clinical signs and may, by the occurrence of spontaneous remissions, contribute to reduce the total amount of steroids needed.

Adolescent↗

Factors associated with prognosis in human breast cancer. I. Predictors for rate of evolution and relapse.

The associations of several clinical factors with general survival, percentage of relapse and survival in the group of patients who relapsed were analyzed in a series of 399 Stage II breast cancer patients operated and irradiated at the Institute of Oncology and Radiobiology in Havana. In another series of 187 patients these associations were studied in regard to the presence of estradiol receptors in the tumors. Factors related to the presence of estrogen receptors were unrelated to the percentage of relapse in long term follow-up. Age and menstrual status were related to the presence of estradiol receptors and to survival inside the group of patients who relapsed but were unrelated to the percentage of relapses. Lymph node status was mainly associated with the percentage of relapses but not related to the presence of estradiol receptors. Other factors (parity and age at first childbirth), related to the presence of receptors, did not clearly influence prognosis. Lactation influenced positively survival inside the relapse group without any clear association with hormone receptors. Results are discussed in terms of a model considering particular host--tumor interaction: The probability of relapse and the speed of evolution of the systemic disease, mutually independent, but determining the prognosis.

Adult↗

Relapse after long-term follow up of multibacillary patients treated by WHO multidrug regimen. Marchoux Chemotherapy Study Group.

Thirty-five multibacillary (MB) leprosy patients were treated with 2 years of multidrug therapy (MDT) and followed up regularly for relapse. Relapse was defined as: a) an increase of the bacterial index (BI) by 2+ over the previous value from any single site of old lesions and b) the occurrence of definite new skin lesion(s) which demonstrated a higher BI than any pre-existing lesion. After a mean duration of 72.7 +/- 17.3 months of follow up per patient, seven relapses were diagnosed; the mean incubation period of relapse was 62.7 +/- 18.7 months. The overall relapse rate was 20.0% (or 3.3 per 100 patient-years), very significantly higher than the figures obtained from the same group of patients analyzed 2 1/2 years earlier, indicating that relapses occurred late (at least 5 +/- 2 years) after stopping MDT. Further analysis indicated that the relapse rate was closely correlated with the bacterial load of the patient, occurring far more frequently among patients with a BI of > or = 4.0 before MDT or with a BI of > or = 3.0 at the end of MDT. To avoid the alarmingly high relapse rate, it is proposed that the duration of MDT be doubled to 4 years in patients with an average BI of > or = 4.0 before MDT.

Adolescent↗

Epidemiological aspects of relapses in leprosy.

Life table methods in which the cumulative probability of relapse in successive periods is calculated are preferable to the presentation of overall relapse rates. Their use facilitates the comparison of relapse rates and trends from different studies independent of duration of follow-up. Results from various studies including data from Malawi indicate that, (1) unlike after dapsone monotherapy, the cumulative probability of relapse in multibacillary patients is near to zero after WHO/MDT if strict definitions of relapse are used and, (2) the cumulative probability of relapse may approach 5% in paucibacillary patients 10 years after completion of WHO/MDT. On the whole, the epidemiological relevance of relapses is insignificant and future treatment regimens should be evaluated concerning their efficacy in preventing disabilities rather than relapses.

Humans↗

Immunophenotypic changes between diagnosis and relapse in childhood acute lymphoblastic leukemia.

To get more insight into the phenotypic changes of childhood acute lymphoblastic leukemia (ALL) at relapse, a detailed morphological and immunophenotypic study in 40 childhood ALL cases (32 precursor B-ALL and 8 T-ALL) was performed. Expression patterns of non-lineage specific markers (terminal deoxynucleotidyl transferase (TdT), CD34, and HLA-DR), B-lineage markers (CD10, CD19, CD20, and CD22), T-lineage markers (CD1, CD2, CD3, CD4, CD5, CD7, and CD8), and cross-lineage myeloid markers (CD14, CD15, and CD33) were compared at diagnosis and relapse. In case of low blast counts (< or = 70%) at relapse, double labeling for membrane markers and TdT was used in order to define the precise immunophenotype of the TdT+ leukemic cells. An immunological marker-shift was defined as either a conversion from positive to negative and vice versa or a difference in positivity of > or = 50%. Morphological differences between diagnosis and relapse were detected in 34% of precursor B-ALL and 14% of T-ALL. Differences in immunological marker expression were found in 72% of precursor B-ALL and in 75% of T-ALL, and generally concerned minor shifts with loss or acquisition of a few markers. The morphological shifts and immunophenotypic shifts were not correlated. Immunophenotypic shifts were found for all markers tested in precursor B-ALL, except for HLA-DR. Shifts in CD10 expression (16% of cases) were only observed in relapses occurring 30 months or more after diagnosis. In four precursor B-ALL an intra-lineage shift was found at relapse (one common ALL to null ALL and three pre-B-ALL to common ALL or null ALL) and two precursor B-ALL cases were diagnosed as acute non-lymphocytic leukemia at relapse based on morphology and immunophenotype. In T-ALL, neither intra-lineage nor inter-lineage shifts were observed, although shifts were detected in all T cell markers tested, except for the lineage specific CD3 and T cell receptor (TcR) markers. In conclusion, immunophenotypic shifts at relapse frequently occur in precursor B-ALL and T-ALL, in a small percentage leading to an intra-lineage shift (10%) or inter-lineage shift (5%). Therefore immunophenotypic monitoring of minimal residual disease in ALL patients should be based on multiple marker combinations, preferably together with polymerase chain reaction analysis of rearranged immunoglobulin and/or TcR genes or chromosome aberrations.

Adolescent↗