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PubMed2004

Interferon-beta-1b: a review of its use in relapsing-remitting and secondary progressive multiple sclerosis.

Interferon-beta-1b (Betaseron, Betaferon) is a non-glycosylated recombinant human interferon-beta approved for high-frequency, subcutaneous (SC) administration in the treatment of multiple sclerosis (MS). Its mechanism of action is unknown, but may involve modulation of the autoimmune pathogenic processes of MS. In a randomised, double-blind trial in patients with relapsing-remitting MS (RRMS), SC interferon-beta-1b 250 micro g (8 million International Units [MIU]) every other day reduced the annual relapse rate and increased the proportion of relapse-free patients compared with placebo. It also reduced relapse severity, hospitalisations, and disease activity assessed by magnetic resonance imaging (MRI), and increased the time to first relapse. Progression of disability showed a trend towards reduction relative to placebo and baseline, but did not reach statistical significance. SC interferon-beta-1b 250 micro g every other day was shown in a randomised trial to be superior to intramuscular (IM) interferon-beta-1a 30 micro g (6 MIU) once weekly with respect to reductions in relapse-related parameters, disability progression and MRI-assessed disease activity. In patients with secondary progressive MS (SPMS), SC interferon-beta-1b 250 micro g every other day slowed progression of the disease relative to placebo in one randomised, double-blind trial, but not in another. In both studies, interferon-beta-1b 250 micro g recipients had fewer relapses and less MRI-assessed disease activity than placebo recipients. The difference in primary outcome may reflect differences in patient entry criteria. Interferon-beta-1b is generally well tolerated and the common adverse events (e.g. injection site reactions, asthenia and an influenza-like symptom complex) are clinically manageable. In a randomised trial, the tolerability of SC interferon-beta-1b 250 micro g every other day was generally similar to that of IM interferon-beta-1a 30 micro g once weekly, except for higher incidences of injection site reactions and neutralising anti-interferon-beta antibodies with SC interferon-beta-1b. In conclusion, SC interferon-beta-1b 250 micro g every other day reduces the frequency and severity of relapses and MRI measures of disease activity and may delay the progression of disability in RRMS. The drug appeared to be more effective than, and as well tolerated as, IM interferon-beta-1a 30 micro g once weekly. Interferon-beta-1b also has positive effects on relapse rates and disease activity in patients with SPMS, although its effects on disease progression remain uncertain. The drug is generally well tolerated, and the common adverse events are clinically manageable. Thus, interferon-beta-1b is a valuable first-line therapy for patients with RRMS and a potentially useful option in those with SPMS.

Age Factors↗

PubMed2004

Spotlight on Interferon-beta-1b in relapsing-remitting and secondary progressive multiple sclerosis.

Interferon-beta-1b (Betaseron, Betaferon) is a non-glycosylated recombinant human interferon-beta approved for high-frequency, subcutaneous (SC) administration in the treatment of multiple sclerosis (MS). Its mechanism of action is unknown, but may involve modulation of the autoimmune pathogenic processes of MS. In a randomized, double-blind trial in patients with relapsing-remitting MS (RRMS), SC interferon-beta-1b 250 micro g (8 million International Units [MIU]) every other day reduced the annual relapse rate and increased the proportion of relapse-free patients compared with placebo. It also reduced relapse severity, hospitalizations, and disease activity assessed by magnetic resonance imaging (MRI), and increased the time to first relapse. Progression of disability showed a trend towards reduction relative to placebo and baseline, but did not reach statistical significance. SC interferon-beta-1b 250 micro g every other day was shown in a randomized trial to be superior to intramuscular (IM) interferon-beta-1a 30 micro g (6 MIU) once weekly with respect to reductions in relapse-related parameters, disability progression and MRI-assessed disease activity. In patients with secondary progressive MS (SPMS), SC interferon-beta-1b 250 micro g every other day slowed progression of the disease relative to placebo in one randomized, double-blind trial, but not in another. In both studies, interferon-beta-1b 250 micro g recipients had fewer relapses and less MRI-assessed disease activity than placebo recipients. The difference in primary outcome may reflect differences in patient entry criteria. Interferon-beta-1b is generally well tolerated and the common adverse events (e.g. injection site reactions, asthenia and an influenza-like symptom complex) are clinically manageable. In a randomized trial, the tolerability of SC interferon-beta-1b 250 micro g every other day was generally similar to that of IM interferon-beta-1a 30 micro g once weekly, except for higher incidences of injection site reactions and neutralizing anti-interferon-beta antibodies with SC interferon-beta-1b. In conclusion, SC interferon-beta-1b 250 micro g every other day reduces the frequency and severity of relapses and MRI measures of disease activity and may delay the progression of disability in RRMS. The drug appeared to be more effective than, and as well tolerated as, IM interferon-beta-1a 30 micro g once weekly. Interferon-beta-1b also has positive effects on relapse rates and disease activity in patients with SPMS, although its effects on disease progression remain uncertain. The drug is generally well tolerated, and the common adverse events are clinically manageable. Thus, interferon-beta-1b is a valuable first-line therapy for patients with RRMS and a potentially useful option in those with SPMS.

Drug Administration Schedule↗

PubMedDate not supplied

[Erythema annulare centrifugum and relapsing polychondritis].

BACKGROUND: Relapsing polychondritis is a rare systemic disease. Skin involvement occurs in 20 to 50 % of cases. Cutaneous signs are most often related to a leukocytoclastic vasculitis. Association of relapsing polychondritis with neutrophilic dermatosis have also been reported. We report the first case of an erythema annulare centrifugum-like dermatosis associated with relapsing polychondritis, with a two years delay between both conditions. CASE REPORT: A 74 year-old man was seen for papulo-erythematous centrifugal annular lesions that appeared 18 months earlier in a context of bad general conditions. Biological tests were normal. Several skin biopsies were performed, showing at the beginning features of drug reaction and then of lupus-lichen. Treatment with hydroxychloroquine, topical corticosteroids, dapsone and thalidomide were unsuccessful. In the following months, the patient developed fever and relapsing bronchitis. Suddenly, a chondritis of the ears appeared, leading to the diagnosis of relapsing polychondritis. All the cutaneous, chondritic and respiratory signs disappeared with oral steroid therapy. Two years after the diagnosis of relapsing polychondritis the patient developed refractory anemia. DISCUSSION: Cutaneous signs of relapsing polychondritis are frequent and may occur several months or years before the chondritis. They are polymorphous, but to the best of our knowledge, a clinical aspect of erythema annulare centrifugum has never been described. Our observation recalls the sometimes long delay between the cutaneous and the chondritic signs of relapsing polychondritis and the high frequency of dysmyelopoiesis in relapsing polychondritis with cutaneous involvement.

Aged↗

PubMedDate not supplied

[West African tick-borne relapsing fever].

West African tick-borne relapsing fever is an endemic disease due to Borrelia crocidurae. The tick Alectorobius sonrai is the only known vector of this bacterium. Several species of rodents and insectivores may be reservoir for this spirochete. The geographic distribution of Borrelia crocidurae is not well known. The zone where the presence of the vector has been recorded is situated in Sahelian regions, from Mauritania and northern Senegal up to Chad. In Senegal, it has been shown that the persistence of drought is responsible for a considerable spread of tick-borne relapsing fever to the south. Few epidemiological data are available about West African tick-borne relapsing fever. In Senegal, epidemiological investigations indicate that Borrelia crocidurae is a major cause of morbidity (annual incidence rate of 5.1%). The relapsing nature of tick-borne borreliosis depends on Borrelia's antigenic variability. Except relapsing febrile episodes, this illness presents no pathognomonic signs. Borrelia crocidurae relapsing fever is generally benignant but neurologic or ocular complications can occur. The diagnosis of tick-borne relapsing fever is made by demonstrating the presence of Borrelia in peripheral blood in thick smear, by intraperitoneal inoculation of mice or more recently with quantitative buffy coat method (QBC test). The best treatment for relapsing fever is tetracycline or doxycycline. When tetracyclines are contraindicated, the alternative is erythromycin. In neurologic complications, the effective treatment is intravenous penicillin G or ceftriaxone. West African tick-borne relapsing fever must be systematically mentioned in case of fever in a patient returning from the endemic area.

Africa, Western↗

PubMedDate not supplied

Relapse of depression in primary care. Rate and clinical predictors.

OBJECTIVE: To determine the clinical predictors and rate of relapse for major depression in primary care. DESIGN: A cohort study of subjects in 2 randomized trials of depressed patients diagnosed and prescribed antidepressant medicine by primary care physicians. Baseline, 7-month, and 19-month assessments were conducted. SETTING: A large primary care clinic of a staff-model health maintenance organization. PATIENTS: Two hundred fifty-one primary care patients who did not satisfy Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria for major depression at 7 months. MAIN OUTCOME MEASURES: Relapse was defined as (1) satisfying DSM-III-R criteria for major depression at 19 months, or (2) reporting an interval episode of 2 weeks or more of depressed mood and symptoms between 7 and 19 months. Predictors examined included demographic characteristics, medical comorbidity, disability, and psychological symptoms. Depressive symptoms were measured by Inventory of Depressive Symptoms and Hopkins Symptoms Checklist. RESULTS: Of the patients, 37.1% reported relapse of depression in the 12-month relapse-risk period. The 2 major risk factors associated with relapse were (1) persistence of subthreshold depressive symptoms 7 months after the initiation of antidepressant therapy (odds ratio, 3.3; 95% confidence interval, 2.74-3.93) and (2) history of 2 or more episodes of major depression, or chronic mood symptoms for 2 years (odds ratio, 2.1; 95% confidence interval, 1.41-2.76). Patients with both risk factors were approximately 3 times more likely to relapse than patients with neither. CONCLUSIONS: The relapse rate among primary care patients treated for depression approached that of specialty samples, with more than one third reporting relapse in 1 year. Clinical characteristics can help target high-risk patients for relapse prevention efforts.

Adult↗

PubMed2006

Stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses are predictive of cocaine relapse outcomes.

BACKGROUND: Cocaine dependence is associated with high rates of relapse. Stress and drug cue exposure are known to increase cocaine craving and stress arousal, but the association between these responses and cocaine relapse has not been previously studied. OBJECTIVE: To examine whether stress-induced and drug cue-induced cocaine craving and hypothalamic-pituitary-adrenal axis responses evoked in the laboratory are associated with subsequent cocaine relapse. DESIGN: Prospective study design assessing cocaine relapse and drug use during a 90-day follow-up period after discharge from inpatient treatment and research. Data were analyzed by Cox proportional hazards regression and multiple regression. SETTING: Inpatient treatment and research unit in a community mental health center. PATIENTS: Forty-nine treatment-seeking cocaine-dependent individuals. MAIN OUTCOME MEASURES: Time to cocaine relapse, number of days of cocaine use, and amount of cocaine used per occasion in the follow-up phase. RESULTS: Greater stress-induced, but not drug cue-induced, cocaine craving was associated with a shorter time to cocaine relapse. Stress-induced corticotropin and cortisol responses predicted higher amounts of cocaine use per occasion in the 90-day follow-up. CONCLUSIONS: These results demonstrate that stress-related increases in cocaine craving and hypothalamic-pituitary-adrenal axis responses are each associated with specific cocaine relapse outcomes. The findings support the use of stress-induced drug craving and associated hypothalamic-pituitary-adrenal axis responses to evaluate cocaine relapse propensity. Furthermore, treatments that address stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses could be of benefit in improving relapse outcomes in cocaine dependence.

Adrenocorticotropic Hormone↗

PubMed2006

Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment.

CONTEXT: Pregnancy has historically been described as a time of emotional well-being, providing "protection" against psychiatric disorder. However, systematic delineation of risk of relapse in women who maintain or discontinue pharmacological treatment during pregnancy is necessary. OBJECTIVE: To describe risk of relapse in pregnant women who discontinued antidepressant medication proximate to conception compared with those who maintained treatment with these medications. DESIGN, SETTING, AND PATIENTS: A prospective naturalistic investigation using longitudinal psychiatric assessments on a monthly basis across pregnancy; a survival analysis was conducted to determine time to relapse of depression during pregnancy. A total of 201 pregnant women were enrolled between March 1999 and April 2003 from 3 centers with specific expertise in the treatment of psychiatric illness during pregnancy. The cohort of women was recruited from (1) within the hospital clinics, (2) self-referral via advertisements and community outreach detailing the study, and (3) direct referrals from the community. Participants were considered eligible if they (1) had a history of major depression prior to pregnancy, (2) were less than 16 weeks' gestation, (3) were euthymic for at least 3 months prior to their last menstrual period, and (4) were currently or recently (<12 weeks prior to last menstrual period) receiving antidepressant treatment. Of the 201 participants, 13 miscarried, 5 electively terminated their pregnancy, 12 were lost to follow-up prior to completion of pregnancy, and 8 chose to discontinue participation in the study. MAIN OUTCOME MEASURE: Relapse of major depression defined as fulfilling Structured Clinical Interview for DSM-IV [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition] Diagnosis (SCID) criteria. RESULTS: Among the 201 women in the sample, 86 (43%) experienced a relapse of major depression during pregnancy. Among the 82 women who maintained their medication throughout their pregnancy, 21 (26%) relapsed compared with 44 (68%) of the 65 women who discontinued medication. Women who discontinued medication relapsed significantly more frequently over the course of their pregnancy compared with women who maintained their medication (hazard ratio, 5.0; 95% confidence interval, 2.8-9.1; P<.001). CONCLUSIONS: Pregnancy is not "protective" with respect to risk of relapse of major depression. Women with histories of depression who are euthymic in the context of ongoing antidepressant therapy should be aware of the association of depressive relapse during pregnancy with antidepressant discontinuation.

Adult↗

PubMed1978

Patterns of relapse in advanced Hodgkin's disease treated with combination chemotherapy.

One hundred sixty-one patients with advanced Hodgkin's disease achieved complete remission after combination chemotherapy. Of these, 52 (32%) have subsequently relapsed and the patterns of relapse have been studied. The probability of relapse increases with increasing stage and particularly with the presence of systemic symptoms. Patients with Nodular Sclerosis histology are more likely to relapse than those with other histologies. Patients relapse primarily (92%) in sites of previous disease and particularly in nodal sites (75%). Nodal sites most frequently involved at relapse are the central nodal areas and the left supraclavicular area. When patients relapse in new sites they tend to be either adjacent to sites of previous disease which relapse or to be contiguous with previously involved sites of disease. In the small number of patients who received prophylactic radiation therapy to sites of nodal disease after complete remission, the pattern of relapse was not significantly altered.

Adolescent↗

PubMed1982

Pelvic and ovarian extramedullary leukemic relapse in young girls: a report of four cases and review of the literature.

Currently attention is focused on the testicle as a site of leukemic relapse. Leukemic involvement of the ovary has been described in several autopsy series with an incidence of 11-50% in patients with bone marrow relapse, but has rarely been reported during the clinical course of leukemia. In this report, four girls with childhood acute lymphocyte leukemia (ALL) who relapsed with a pelvic mass are presented. Three had marked ovarian infiltrates and the fourth had a presacral mass without ovarian disease. Involvement was also present in abdominal and pelvic lymph nodes, mesentery, omentum, and serosal surfaces. Two patients had infiltrates of the fallopian tubes and one had uterine involvement. Two patients had central nervous system disease and one patient has renal involvement at the time of relapse. Relapse occurred late in the course of disease. All patients had been in complete continuous remission prior to relapse. Retreatment was instituted in all patients and follow-up ranges from 18-135 months from the time of pelvic relapse. All patients have maintained continuous bone marrow remission from the time of initial diagnosis, and one patient died 18 months after ovarian relapse with significant extramedullary disease but no marrow involvement. This represents the first series of pelvic extramedullary leukemic relapse in females, an area of involvement that may be encountered more frequently in the future.

Adult↗

PubMed1993

Wide-field radiation therapy with or without chemotherapy for patients with Hodgkin disease in relapse after initial combination chemotherapy.

BACKGROUND: Patients with Hodgkin disease who have relapses after initial chemotherapy (CT) appear to have a poor prognosis, especially if the duration of the first complete remission (CR) was short. The authors performed a retrospective analysis of patients with Hodgkin disease whose relapse after combination CT was limited to nodal sites; their aim was to study the prognosis of this selected subgroup of patients. METHODS: In 28 patients with Hodgkin disease who had relapses in nodal sites after combination CT alone, the disease was restaged carefully to rule out simultaneous extranodal recurrences. Then the patients were treated with wide-field, high-dose radiation therapy (RT) with or without additional CT with curative intent between 1971 and 1987 at the Joint Center for Radiation Therapy. Fourteen patients were in first relapse and were treated with combination CT followed by RT. The remaining 14 patients (8 who were in first relapse and 6 who were in second relapse) were treated with RT alone. RT techniques were similar to those recommended for early-stage disease. RESULTS: The 7-year actuarial freedom from relapse and survival rates for the patients retreated with CT and RT were 93% and 85%, respectively, as compared with 36% and 36% for patients retreated with RT alone. There was a significant difference for freedom from relapse (P = 0.002) and survival (P = 0.03), favoring patients retreated with both CT and RT. CONCLUSIONS: This retrospective study demonstrates that RT combined with second-line CT can result in a high percentage of durable remissions in patients who have relapses primarily in nodal sites after original treatment with combination CT alone. These durable remissions are seen even in patients who have only a brief CR after initial CT.

Adolescent↗

PubMed1994

Prostate specific antigen doubling time and disease relapse after radiotherapy for prostate cancer.

BACKGROUND: Serum prostate specific antigen (PSA) correlates with prostate tumor volume. Therefore, PSA-doubling time (PSA-DT) in patients with a rising PSA profile after radiotherapy should be predictive of the time to clinical disease relapse. The purpose of this study was to characterize the relationship between PSA-DT and the time to disease relapse after the onset of a rising PSA (PSA-TTR) in 427 men treated in the PSA-era with high dose radiotherapy for Stages T1-4 adenocarcinoma of the prostate. METHOD: There were 119 patients with a rising PSA profile after radiotherapy, and of these, there was sufficient information to calculate PSA-DT using nonlinear least squares regression in 100. There were 44 patients in this cohort who had documented disease relapse. The median patient follow-up was 38 months. RESULTS: The average PSA-DT was 13.5 plus or minus 11.6 mo (+/- standard deviation). PSA-DT values correlated with tumor grade, pretreatment PSA, and stage. PSA-DT was also strongly related to the outcome measures of local relapse, distant metastases, and any disease relapse. The shorter the PSA-DT, the greater the risk of disease relapse. The average PSA-TTR was 10.1 plus or minus 8.2. The only prognostic factor that correlated with PSA-TTR was tumor grade. A linear regression analysis of normalized PSA-DT and PSA-TTR revealed a significant correlation in which a PSA-DT of 11 months predicted for disease relapse 24 months later. Because several factors including physician and patient preferences could alter this relationship, a comparison was made between the actuarial PSA rise time for patients treated in the PSA-era and actuarial clinical disease relapse using a cohort of similarly treated men from the pre-PSA-era (n = 798). The results showed the lead time to be over 40 months in the majority of patients and that this lead time was much shorter in those with high grade tumors. CONCLUSIONS: PSA-DT is a strong prognostic factor for patients with biochemical evidence of failure after radiotherapy. A short PSA-DT predicts for more rapid progression to symptoms. The timing of the progression from a rising PSA to clinical disease relapse is probably longer than expected and is estimated to be 40 months on average.

Adenocarcinoma↗

PubMed1991

Therapeutic implications and sites of relapse predicted by elevated posttherapy erythrocyte sedimentation rate in early stage Hodgkin disease.

An analysis was performed of all 57 early relapses (ER) (within 18 months of therapy initiation) seen in a group of 301 patients treated on three successive European Organization for Research and Treatment of Cancer (EORTC) protocols from 1964 to 1981; to determine whether a posttherapy elevated erythrocyte sedimentation rate (ESR) (greater than or equal to 30 mm) could predict the type of relapse and the effect upon the relapse of different therapies received. Overall most ER occurred in extranodal (EN) (42%) or irradiated transdiaphragmatic nodal (TDN) (40%) sites. Compared to patients with normal posttherapy ESR (n = 12), patients with elevated posttherapy ESR (n = 45) had the same proportions of outfield and late relapses; more frequent multiple sites of ER (38% vs. 25%), increased proportions of early EN relapses (16% vs. 3%), TDN relapses (17% vs. 2%), and other ER (6% vs. 1%). ER were most frequently observed between 1964 and 1971, and "modern" radiotherapy (Rt) decreased ER overall from 27% to 13% and for elevated posttherapy ESR patients from 54% to 25%. When chemotherapy (Ct) was used as either adjuvant or initial therapy, ER were greatly reduced vs. Rt alone [overall (6% vs. 28%) and for patients with elevated posttherapy ESR (10% vs. 39%)]. Stepwise logistic regression showed Ct to be the most important factor "protecting" from EN relapse, but elevated posttherapy ESR was still significant. For early TDN relapse, elevated posttherapy ESR had the highest predictive value for relapse, greater than the types of radiation fields used and chemotherapy. An unexplained elevated posttherapy ESR, regardless of previous therapy, predicts for ER from aggressive HD, frequently in EN and irradiated areas, and warrants further early therapy.

Adult↗

PubMed2005

Defining remission and relapse in bulimia nervosa.

OBJECTIVE: The goals of the current study were to compare the relapse rates obtained when definitions of both remission and relapse were systematically varied and to propose some consensus definitions related to relapse in bulimia nervosa (BN). METHOD: This was an uncontrolled, prospective follow-up study based on 46 women who met criteria for BN (based on criteria in the 3rd Rev. ed. of the Diagnostic and Statistical Manual of Mental Disorders [Washington, DC: American Psychiatric Association]) before treatment and were abstinent or had low frequency symptoms after treatment. Assessments were conducted every 3 months for up to 19 months. Data were analyzed with Kaplan-Meier survival analysis. RESULTS: Relapse rates at 19 months ranged from 21% to 55% depending on the definitions of remission and relapse applied. DISCUSSION: Relapse rates are strongly influenced by definitions of remission and relapse. We propose that partial remission, defined as a maximum of two symptom episodes per month for 2 months, should constitute eligibility for relapse and relapse should be defined as meeting full diagnostic criteria for 3 months.

Adult↗

PubMed1996

Chronic relapsing experimental autoimmune encephalomyelitis (CREAE) in mice: enhancement by monoclonal antibodies against interferon-gamma.

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated inflammatory and demyelinating disorder of the central nervous system. Depending on the experimental conditions, it takes an acute monophasic or a chronic relapsing-remitting course. We have previously reported that the incidence and severity of acute EAE in mice are reduced by administration of interferon (IFN)-gamma and augmented by treatment with neutralizing antibodies against IFN-gamma. Here, we investigated the role of IFN-gamma in chronic relapsing models of EAE (CREAE) in SJL/J and Biozzi ABH mice. Spontaneous relapses in Biozzi mice as well as induced relapses in SJL/J mice were facilitated by administration of neutralizing monoclonal antibody (mAb) against IFN-gamma in the disease-free interval. The enhancing effect of anti-IFN-gamma mAb given before and during the primary attack did not carry over to the relapses. However, early administration of IFN-gamma in Biozzi mice, which developed spontaneous relapses in a high proportion, provided partial protection not only against the first attack, but also against subsequent relapses. Administration of exogenous IFN-gamma during the remission phase provided some protection against subsequent relapses. These results indicate that in both types of relapses, IFN-gamma is produced and does provide a certain degree of protection against disease progression.

Animals↗

PubMed2003

Role of splenectomy in patients with refractory or relapsed thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) was once uniformly fatal. Therapeutic plasma exchange in combination with immunosuppressive and anti-platelet agents, however, have resulted in improved survival rates of greater than 80% for patients with TTP. In spite of aggressive plasma exchange and adjuvant therapy, a number of TTP patients are refractory to treatment. In addition, up to 40% of TTP patients who initially respond to therapy eventually relapse. Alternative therapies such as splenectomy have been used with varying degrees of success in refractory and relapsing TTP patients. The usefulness of splenectomy in preventing relapse of TTP or treating those patients who are refractory to plasma exchange remains controversial. We present a single institution's experience with 14 patients who underwent splenectomy for refractory (six patients) or relapsed (eight patients) TTP since 1984. In both patient groups, splenectomy induced stable long-term remissions. Six of six (100%) patients who were refractory to plasma exchange, survived to be discharged from the hospital, apparently free of disease. Four of eight patients (50%) who had a splenectomy for relapsing TTP went into a complete remission and had no further relapses of their disease. Moreover, in relapsing patients who failed to experience long-term remission, the relapse rate after splenectomy was 0.3 events per patient year compared to 1.0 events per patient year prior to splenectomy. We conclude that splenectomy is a reasonable treatment option for TTP patients refractory to standard plasma exchange therapy or who have experienced multiple and/or complicated relapses. We believe this is the first series that demonstrates efficacy of splenectomy in plasma exchange-refractory TTP.

Adult↗

PubMed1981

Long-term survivors of acute lymphoblastic leukemia--risk of relapse after cessation of therapy.

The results of cessation of therapy (COT) in 64 long-term survivors (disease-free survival of five years or more) of acute lymphoblastic leukemia (ALL) were analyzed to determine the incidence of relapse off therapy. Thirty-seven of the patients had intermittent central nervous system (CNS) prophylaxis. Total follow-up from diagnosis varied from 5.75 to 27.75 years. The median time off therapy was three years (range, 8 months to 26 years). Eighty-six percent (55/64) of the patients continue in their initial remission. Eight patients had relapse, and one patient had a morphologically different leukemia at recurrence. All the relapses occurred between five to eight years from diagnosis and the cumulative rate of relapse for the period was 0.14. There was no significant difference in the rate of relapse for those receiving CNS prophylaxis (0.08) versus those not receiving CNS prophylaxis (0.19). The difference in the relapse rates for boys (0.24) versus girls (0.04) was statistically significant (P = 0.04). Isolated testicular relapse (ITR) was not seen in any of the 34 boys. The present study confirms the earlier observations by others that relapse is uncommon in ALL patients remaining in remission longer than seven to eight years. ALL patients treated with intermittent CNS prophylaxis administered throughout the period of maintenance chemotherapy appear to be at no greater risk for relapse off therapy than those treated with high-dose initial cranial irradiation and intrathecal methotrexate. The longer duration of therapy and the use of a repetitive reinduction regimen for maintenance seem to be associated with a decreased risk of ITR after discontinuation of therapy for boys and men. There appears to be a small but definite risk of "second" leukemia in the long-term survivors of leukemia.

Antineoplastic Agents↗

PubMed1990

Intracellular ribonucleotide pools of lymphoblastic leukemic cells in untreated and relapsed ALL children.

Intracellular ribonucleotide pools were analyzed by HPLC with leukemic blasts obtained from 20 children, including 13 untreated ALL, 5 relapsed ALL, and 2 lymphomas with hematological relapse. Nucleotide pools were, in general, found more expanded among relapsed cases. Also, the larger mono and diphosphate ribonucleotide levels found in relapsed cells, for instance adenine nucleotide pools, were significantly larger among the relapsed patients, as measured 216.97 +/- 53.30 nmol/10(8) cells, in contrast to 109.70 +/- 39.54 nmol/10(8) cells with untreated children (p less than 0.005). Furthermore, AMP and ADP occupied only 18% of the total adenine pool in untreated children, but 34% in relapsed children. The similar pattern of nucleotide pools was observed in guanine, cytidine, and uridine nucleotide pools. Inosine mono phosphates were measured 5.07 +/- 6.02 nmol/10(8) cells with untreated ALL, and 3.55 +/- 1.44 nmol/10(8) cells with relapsed ALL, but thymidine mono phosphates, as a key pyrimidine nucleotide of salvage pathway, were larger (p less than 0.01) among with relapsed patients measuring 31.47 +/- 8.11 nmol/10(8) cells as compared with that of untreated ALL, 11.19 +/- 12.84 nmol/10(8) cells. The present results may suggest that there is a difference in nucleotide metabolism between untreated and relapsed leukemic cells, and nucleotide profiles provide more accurate information of leukemia chemotherapy.

Adolescent↗

PubMed2005

Lack of benefit of early detection of relapse after completion of therapy for acute lymphoblastic leukemia.

BACKGROUND: Although most pediatric oncologists obtain routine blood counts in patients who have completed treatment for acute lymphoblastic leukemia (ALL), the value of this practice is unproven. We therefore sought to determine if detection of relapse by blood counts before the onset of symptoms provided any clinical benefit. PROCEDURES: We performed a retrospective review of 72 patients with ALL who suffered isolated or combined hematologic relapses after the completion of therapy. We compared attainment of second remission and survival after relapse among patients who were asymptomatic and diagnosed by routine blood count, those who had symptoms suggestive of relapse and were diagnosed at the time of a scheduled follow-up, and those whose relapse was diagnosed because of the appearance of symptoms. RESULTS: Only 11% of patients who suffered a relapse were asymptomatic at the time of relapse and diagnosed solely by routine blood counts. There were no significant differences in the survival distributions for the three groups of patients. CONCLUSIONS: In this cohort of patients with relapsed ALL, we found no evidence that detection of relapse by routine blood counts before the onset of symptoms leads to a better outcome.

Adolescent↗