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PubMed1995

Case-control analysis of allogeneic bone marrow transplantation versus maintenance chemotherapy for relapsed ALL in children.

In a retrospective study, the results of maintenance chemotherapy and allogeneic bone marrow transplantation (BMT) for children who reached a second complete remission (CR2) of their acute lymphoblastic leukemia (ALL) were compared. Case-control analysis was performed comparing 25 allogeneic transplant patients (cases) with 97 patients treated with maintenance chemotherapy (controls), who were matched for site of relapse, duration of CR1 and leukemia-free interval from onset of CR2. Until the first relapse, the children were treated according to standard protocols. The majority of patients suffered from a bone marrow relapse, mostly occurring more than 24 months after the onset of CR1. Remission reinduction treatment was heterogeneous. Patients treated with allogeneic BMT received high-dose chemotherapy and total body irradiation prior to BMT. Maintenance chemotherapy in controls was given for approximately 2 years. Following BMT, relapse rate was lower but the treatment-related mortality was higher compared with maintenance chemotherapy, resulting in leukemia-free survival rates at 4 years of 44% and 24%, respectively (not significant, NS). Case-control analysis of leukemia-free survival showed a hazard ratio of 0.756 in favor of BMT compared with chemotherapy (NS). If bone marrow relapses and central nervous system relapses were analyzed separately, a tendency to better leukemia-free survival was present after BMT compared with maintenance chemotherapy for patients with a relapse in the central nervous system, but for an isolated bone marrow relapse, no differences in leukemia-free survival were seen between the two groups of patients.

Antineoplastic Agents↗

PubMed1993

Relapses in patients with a systemic vasculitis.

Treatment with cyclophosphamide and steroids has greatly improved survival in patients with systemic necrotizing vasculitis but does not always provide a complete cure. There are as yet few data on the incidence, pattern and outcome of relapses in these diseases. We studied relapses in 150 consecutive patients with an idiopathic necrotizing vasculitis: 12 with classical polyarteritis (CPAN); 95 with microscopic polyarteritis (MPA); 28 with Wegener's granulomatosis (WG); and 15 with limited Wegener's granulomatosis (LWG). The relapse rates and median time to relapse in months were: CPAN, 41.7%/33; MPA, 25.4%/24; WG, 44%/42; LWG, 52%/18. The clinical features of relapse were similar to or more aggressive than those of the original presentation in CPAN and LWG and included renal disease for the first time, but in MPA and WG, relapse involved less renal involvement in the majority of cases. Laboratory tests, although often positive at relapse, were unhelpful in its prediction. The considerable accumulative non-fatal relapse rate contrasts with the very good long-term survival rates, and confirms the importance of long-term follow-up in systemic vasculitis.

Adult↗

PubMed1994

Persistence of the same viral strain in early and late relapses of Epstein-Barr virus-associated Hodgkin's disease.

Twelve cases of relapsing Hodgkin's disease were investigated for the presence of Epstein-Barr virus (EBV). Of these, 7 cases contained EBV gene products (LMP1, EBER RNA) in the diagnostic Reed-Sternberg cells and variants at first presentation and at relapse(s), whereas 5 cases were negative at both first diagnosis and relapse. Among the 7 EBV-positive cases, material for DNA extraction was available in 2 cases at both diagnosis and relapse(s). Ig and T-cell receptor gene rearrangements displayed a germline configuration in the 2 cases. However, Southern blot analysis of the terminal repeats (TR) of EBV genome showed that, in 1 of the 2 cases, the fragment was of the same size at diagnosis and in the subsequent two relapses (1 early and 1 late). The second case contained monoclonal EBV genome at diagnosis, but the Southern analysis of the TR was negative at relapse. The latent membrane protein (LMP1) sequence analysis confirmed the persistence of a distinctive viral strain in each of the 2 cases with individual abnormalities within the carboxy terminal region (5 point mutations and a 30-bp deletion for the first case and 6 point mutations for the second case). The persistence of a given strain in early and late relapses is evidence towards the view that in Hodgkin's disease such relapses are related to a single residual tumor cell clone.

Adult↗

PubMed1993

Resistance to all-trans retinoic acid (ATRA) therapy in relapsing acute promyelocytic leukemia: study of in vitro ATRA sensitivity and cellular retinoic acid binding protein levels in leukemic cells.

All-trans retinoic acid (ATRA) induces leukemic cell differentiation and complete remission (CR) in a high proportion of patients with acute promyelocytic leukemia (AML3 subtype). However, relapses occur when ATRA is prescribed as maintenance therapy, and resistance to a second ATRA-induction therapy is frequently observed. An induced hypercatabolism of ATRA has been suggested as a possible mechanism leading to reduced ATRA sensitivity and resistance. CRABPII, an RA cytoplasmic binding protein linked to RA's metabolization pathway, is induced by ATRA in different cell systems. To investigate whether specific features of the AML3 cells at relapse could explain the in vivo resistance observed, we studied the CRABP levels and in vitro sensitivity to ATRA of AML3 cells before and at relapse from ATRA. Relapse-AML3 cells (n = 12) showed reduced differentiation induction when compared with "virgin"-AML3 cells (n = 31; P < .05). Dose-response studies were performed in 2 cases at relapse and showed decreased sensitivity to low ATRA concentrations. CRABPII levels and in vitro differentiation characteristics of AML3 cells before and at relapse from ATRA therapy were studied concomittantly in 4 patients. High levels of CRABPII (median, 20 fmol/mg of protein) were detected in the cells of the 4 patients at relapse but were not detected before ATRA therapy. Three of these patients showed a decrease in differentiation induction of their leukemic cells, and a failure to achieve CR with a second induction therapy of ATRA 45 mg/m2/day was noted in all patients treated (n = 3). Results from this study provide evidence to support the hypothesis of induced-ATRA metabolism as one of the major mechanisms responsible for ATRA resistance. Monitoring CRABPII levels after ATRA withdrawal may help to determine when to administer ATRA in the maintenance or relapse therapy of AML3 patients.

Adult↗

PubMed1993

[Three cases of chronic relapsing thrombotic thrombocytopenic purpura].

We experienced three cases of thrombotic thrombocytopenic purpura (TTP) with repeated relapse and remission, in which the relapse was improved by plasma infusion. One case has continued remission after one relapse. The second case went into remission after several relapses, which were induced by viral infection and pregnancy. The third case has shown repeated chronic relapses over 7 years without any inducing factors. The course of TTP relapse commenced with thrombocytopenia accompanied by microangiopathic hemolytic anemia and neurological disturbances developed over 1-4 weeks. The volume plasma needed for recovery gradually increased with time from the start of relapse. These relapses were unable to be prevented by oral administration of antiplatelet agents (aspirin and dipyridamole).

Adult↗

PubMed1995

Allogeneic cell therapy for relapsed leukemia after bone marrow transplantation with donor peripheral blood lymphocytes.

Allogeneic bone marrow transplantation (BMT) is the treatment of choice for hematologic malignancies resistant to conventional chemotherapy and for patients who are at high risk for relapse. Until recently, no cure could be offered to patients relapsing following allogeneic BMT. We present our long-term observations of the first patient with remission reinduced by allogeneic cell therapy (allo-CT) using donor peripheral blood lymphocytes (PBL). In addition, we review the cumulative international experience with allo-CT used to treat 163 patients, 105 with CML and 58 with other hematologic diseases, who relapsed following allogeneic BMT. The first patient treated by allo-CT was diagnosed with acute resistant pre-B lymphoblastic leukemia (ALL) in extensive third hematologic and extramedullary relapse shortly after BMT. He was given infusions of donor (sister) PBL in multiple increments. Subsequently, he developed mild, reversible graft-vs-host disease (GVHD) in parallel with regression of all hematologic and cytogenetic disease manifestations. More than 8 years after allo-CT, he is disease-free with Karnofsky score 100% and no evidence of residual male cells by PCR. International data show that relapse after BMT was successfully reversed by donor PBL treatment in 97 of 158 evaluable patients; 72/100 (72%) with chronic myeloid leukemia (CML) and 25/58 (44.8%) with other malignant hematologic diseases including acute leukemia, lymphoma, and myelodysplastic syndrome. T cell depletion (TCD) for prevention of GVHD was performed for 60/105 (57%) patients with CML and 31/58 (53.4%) patients with other hematologic malignancies. Complete response after allo-CT was obtained in recipients of both TCD-BMT and unmodified BMT. GVHD due to allo-CT developed in 86/158 (54.4%) of the patients, 63/100 (63.0%) with CML and 23/58 (39.6%) with other hematologic diseases. alpha-interferon (IFN-alpha) was given to 67.9% of patients with CML and 28.1% of patients with other diseases. The cumulative experience shows that allo-CT can successfully reverse chemoradiotherapy-resistant relapse of acute leukemia and even more effectively of chronic leukemia independently of alpha-interferon therapy. Although GVHD was frequent among responders, accompanied occasionally by transient or irreversible marrow aplasia, remissions were also obtained in patients with no GVHD. Allo-CT should therefore be considered as treatment of choice for overt relapse or de novo minimal residual disease post-BMT. Administration of donor peripheral blood lymphocytes in graded increments at an early stage of relapse may be the best approach for combining optimal timing at the stage of minimal disease while controlling and minimizing the risk of GVHD on an individual basis.

Adolescent↗

PubMed1996

Kinetics of increasing BCR-ABL transcript numbers in chronic myeloid leukemia patients who relapse after bone marrow transplantation.

We prospectively studied 98 chronic myeloid leukemia (CML) patients after bone marrow transplantation by competitive polymerase chain reaction to detect and quantify leukemia-specific BCR-ABL mRNA. Of 69 patients who had persistently undetectable, decreasing, or low BCR-ABL levels ( < 50 transcripts/microgram RNA) on sequential analysis, one (1%) subsequently relapsed. Of 29 patients who had increasing or persistently high BCR-ABL (> 50 transcripts/microgram RNA) on sequential analysis, 21 (72%) have relapsed (P < .00001). In 19 patients studied sequentially, a constant logarithmic increase in the number of BCR-ABL transcripts was found before relapse, indicating a constant BCR-ABL transcript doubling time. The doubling time for patients relapsing cytogenetically or into chronic phase (median, 24.7 days) was significantly longer than that of patients relapsing into advanced phases (median, 14.7 days; P = .005). Eight patients were treated for relapse by donor leukocyte transfusions. The doubling time of responders was significantly longer than that of nonresponders (P = .017). We conclude that quantification of BCR-ABL transcripts after bone marrow transplantation (BMT) is valuable in predicting relapse: a more rapid BCR-ABL transcript doubling time before relapse might indicate a more aggressive disease.

Biomarkers, Tumor↗

PubMed1995

Two-year trial of maintenance neuroleptic dose reduction in schizophrenic out-patients: predictors of relapse.

Low dose maintenance therapy has been proposed as a pharmacological strategy for reducing exposure to neuroleptic drugs in schizophrenia. However, reliable predictors of post-dose reduction relapse, which could guide clinicians in selecting patients suitable for this type of treatment, have not yet been determined. In this study, 41 schizophrenic out-patients were assigned, on the basis of their previously clinically determined dosages, to one of two reduced maintenance fluphenazine decanoate regimes (35 mg/4 wks. or 10 mg/4 wks.) and were assessed, subsequently, for a 2-year period. Demographic, clinical and treatment characteristics of relapsers (22 patients) and non-relapsers (18 patients) were compared using univariate and multivariate tests. Four parameters: age, course of illness, duration of illness and duration since last psychiatric hospitalization, suggested, in univariate tests, significant discrimination between relapsers and non-relapsers. Stepwise discriminant function analyses defined a highly significant function (p < .01) which included only 3 predictors of relapse. In order of importance, these predictors were: (1) a history of chronic psychosis (2) male sex, and (3) an illness of short duration. Parameters such as age, baseline rating scales scores, magnitude of dose reduction and baseline maintenance dose failed to improve the ability to discriminate between relapsers and non-relapsers. Implications of these findings for clinical practice are discussed.

Adult↗

PubMed1996

Effectiveness of intensified rotational combination chemotherapy for late hematologic relapse of childhood acute lymphoblastic leukemia.

Relapsed acute lymphoblastic leukemia (ALL) usually carries a dire prognosis. We evaluated the effectiveness and long-term complications of intensive rotational combination chemotherapy for late hematologic relapse (median, 16 months after elective cessation of therapy) among 34 children and young adults (ages 4 to 23 years). Concurrent central nervous system (CNS) relapse was present in 3 cases and testicular relapse in 4. Secondary therapy comprised an intensive five-drug reinduction (6 weeks) followed by continuation treatment with four drug pairs, rotated weekly in 4-week cycles over 120 weeks. Intrathecal chemotherapy (methotrexate, hydrocortisone, cytarabine) was given three times during reinduction and every 8 weeks during continuation. Treatment was electively discontinued at week 120 in the absence of detectable disease. Thirty-three patients (97%) attained a second complete remission. At a median follow-up of 9.3 years (range, 4.5 to 11.4), estimates of 5-year second event-free and overall survival (+/- SE) are 65% +/- 8% and 79% +/- 7%, respectively. Eleven patients had a second relapse (9 marrow, 2 testicular) and one developed secondary myeloid leukemia. There have been no CNS relapses or deaths in remission. Treatment was well-tolerated and was given largely on an outpatient basis. Late effects are primarily endocrinologic; one child had a second malignant solid tumor (presumed related to initial radiation therapy) that was treated successfully. Intensive treatment with alternating non-cross-resistant drug pairs for late hematologic relapses of ALL is effective and well-tolerated, and produces results similar to those achieved in patients with newly diagnosed ALL. Event-free survival compares favorably with reports of other relapse regimens, including those incorporating bone marrow transplantation.

Adolescent↗

PubMed1995

Combination antiviral therapy with ribavirin and interferon alfa in interferon alfa relapsers and non-responders: Italian experience.

BACKGROUND/AIMS: A sustained biochemical and virologic response to standard interferon therapy for chronic hepatitis C is seen in no more than 25% of patients, and the efficacy of re-treatment or of higher doses in non-responders and relapsers has not been established. A more effective therapy for interferon alfa-resistant hepatitis C is needed. METHODS: A study of ribavirin plus interferon alfa combination therapy was conducted in 30 patients with chronic hepatitis C resistant to a previous standard course of interferon alfa (14 interferon non-responders, 16 interferon relapsers). Patients were randomly assigned to receive either ribavirin, 800 mg daily, and interferon alfa, 3 MU thrice weekly (n = 15), or interferon alfa alone, 3 MU thrice weekly (n = 15), for 6 months. RESULTS: At the end of treatment, normal alanine aminotransferase levels were observed in eight patients in the combination therapy group: one (14%) interferon non-responder and seven (87%) interferon relapsers (p = 0.01). Six months post-therapy, sustained normalization of alanine aminotransferase was achieved in seven (87%) interferon alfa relapsers, but not in any of the interferon alfa non-responders (p = 0.001). In the group of patients treated with interferon alfa alone, sustained normalization of alanine aminotransferase was observed in one interferon relapser only. Serum HCV RNA became negative in eight patients receiving combination therapy--two (28%) interferon non-responders and six (75%) interferon relapsers. Six months later, circulating HCV RNA remained negative in seven patients: one (14%) interferon non-responder and six (75%) interferon relapsers (p = 0.04). Sustained clearance of HCV RNA was not observed in patients re-treated with interferon alone. The sustained response to combination therapy was accompanied by reduced hepatic necroinflammatory activity on liver biopsy. Hepatitis C virus genotype was not significantly associated with response to combination therapy. Side effects were mild and well tolerated. CONCLUSIONS: Our experience indicates that combination therapy of ribavirin plus interferon alfa induces sustained biochemical, virologic, and histologic responses in most patients who are interferon relapsers.

Antiviral Agents↗

PubMed1996

Central nervous system relapse after bone marrow transplantation for acute leukemia in first remission.

Four hundred and eighty-seven patients undergoing allogeneic or autologous BMT for acute leukemia in first remission received no prophylactic intrathecal chemotherapy after BMT. The conditioning regimen included total body irradiation in 433 (89%). Patients with acute lymphoblastic leukemia received cranial irradiation if they had no central nervous system (CNS) disease and all patients with CNS disease received craniospinal irradiation. Eleven of 311 patients examined had CNS disease at presentation, but none had active CNS disease at the time of BMT. Lumbar punctures were performed in 93 patients 1-2229 days (median 98) after BMT because of suspected CNS infection, hemorrhage or relapse (n = 65), or after systemic relapse (n = 28). CNS disease was seen in seven patients at 217-1209 days (median 340), none of whom had CNS disease pre-transplant. Systemic relapse had preceded CNS relapse by 4-207 (median 128) days in all seven and no isolated CNS relapse was seen. The actuarial risk of CNS and systemic relapse at 5 years was 2.9 and 35.9%, respectively. We conclude that CNS relapse is uncommon after BMT for acute leukemia in first remission, and that isolated CNS relapse is likely to be extremely uncommon. Therefore, routine prophylactic intrathecal chemotherapy is not warranted after BMT for acute leukemia in first remission.

Actuarial Analysis↗

PubMed1996

Relapse of hairy cell leukemia after 2-chlorodeoxyadenosine: long-term follow-up of the Northwestern University experience.

Although 2-chlorodeoxyadenosine (2-CdA) is effective in inducing complete remissions (CRs) in the majority of patients with hairy cell leukemia (HCL), neither the actual relapse rate, the clinical factors that may predict relapse, the long-term outcome, nor the response rate to re-treatment at relapse has been clearly determined. Fifty-two consecutive patients with previously untreated or treated HCL were treated with 2-CdA at a dose of 0.1 mg/kg/d by continuous intravenous infusion for 7 days. Of 50 assessable patients, 40 (80%) achieved CR, and 9 (18%) achieved partial remission (PR). A total of 7 patients (14%) have relapsed, at a median duration of 24 months (range, 12 to 44). Of the 7 relapsed patients, 5 were re-treated with a second cycle of 2-CdA; 2 achieved a second CR and 3 attained a PR. The progression-free survival (PFS) rate is 72% at 4 years for all 52 patients and 83% for patients achieving CR. The overall survival (OS) rate is 86% at 4 years. Only prior therapy was predictive of relapse. The majority of patients achieve durable CRs with a single cycle of 2-CdA. The relapse rate is low and the long-term prognosis is excellent. The few patients who relapse can attain second remissions after re-treatment with 2-CdA.

Adult↗

PubMed1996

Breast cancer patients: long-term relapses.

The authors evaluated 200 cases of long-term relapses in patients subjected to mastectomy at least 8 years before and not given any hormonal or other therapy that would have significantly affected the course of the disease. A group of 200 mastectomy patients with early relapses (within 3 years) was used as a control. The following parameters were compared: histologic type, singularity or multiplicity of the relapses at the time of the diagnosis, the patient's age at the time of the mastectomy, the presence of metastatic lymphnodes at the axilla, the clinical course of the disease after the diagnosis of relapse, and the presence of estrogen receptors in the primary tumor. There was a significant higher incidence of lobular histologic type in the group of patients with long-term relapses (p < 0.001). The cases with long-term relapses showed a relatively lower number of relapses in local-region lymphnodes (p < 0.005) a higher number of cases with metastases to the axillary lymphnodes at the time of mastectomy (p < 0.001), a better clinical course (survival) after the diagnosis (mean 3 vs 2.6 years), and more cases with estrogen receptors (p < 0.001) than controls. Premenopausal or postmenopausal status at the time of mastectomy was not significant. After a review of the literature, the authors conclude that relapses that appear after 8 years from the mastectomy occur almost exclusively in patients with a cancer for which the hormonal factor is very important. They hypothesize that even the 18 cases of the series who were without estrogen receptors in reality had receptors saturated by circulating estrogens or receptors for other hormones.

Breast Neoplasms↗

PubMed1996

Assessment issues and domains in the prediction of relapse.

The present paper provides a brief overview of methodological issues involved in the process of assessment related to the classification and prediction of relapse. These include conceptual and operational definitions of relapse, retrospective versus prospective assessment, attributional biases in recalling relapse events, single versus multiple determinants of relapse, static versus dynamic assessment models, and the necessary level of specificity involved in the assessment of relapse categories. Additionally, general domains representing distal personal characteristics, intermediate background variables and factors proximal in time to relapse situations are reviewed. Potential variables appropriate for assessment within each of these domains are described. It is concluded that relapse is best understood as a complex process having multiple and interactive determinants that vary in their temporal proximity from and their relative influence on relapse. An adequate assessment model must be sufficiently comprehensive to include theoretically relevant variables from each of the multiple domains and different levels of potential predictors.

Alcoholism↗

PubMed1996

Taxonomy of high-risk situations for alcohol relapse: evolution and development of a cognitive-behavioral model.

The purpose of this paper is to provide an historical overview of the development of the taxonomy of high-risk situations for relapse in patients receiving abstinence-based treatment for alcoholism. Research conducted during the 1970s on determinants of relapse is briefly reviewed, beginning with a preliminary analysis of relapse patterns in alcoholics treated with aversion therapy. Theoretical foundations underlying the development of the taxonomy are then discussed with an emphasis on social-learning theory and its implications for cognitive-behavioral interventions for relapse prevention. Findings supporting the efficacy of coping-skills training for high-risk relapse situations, based on a prospective treatment outcome study for inpatient alcoholics, are also presented in support of the clinical validity of the relapse model. The paper concludes with a description of the refined and extended taxonomy of high-risk situations and the associated cognitive-behavioral model of relapse described in the Marlatt & Gordon (1985) text on relapse prevention.

Adaptation, Psychological↗

PubMed1996

Looking forward and back to relapse: implications for research and practice.

In this commentary, the three principal investigators of the Relapse Replication and Extension Project (RREP) reflect on clinical and research implications of study findings from the three collaborating sites. A primary purpose of RREP was to study the reliability and validity of a taxonomy of relapse antecedents originally proposed by Marlatt two decades ago. Under the best of research conditions, with extensive training and practice, it was difficult to achieve reliability of coding with the original three-level system, although with only two levels of classification more reasonable albeit variable reliability was found. Modifications may improve the taxonomy's reliability, but RREP data indicate that a more appropriate strategy is to measure possible antecedents of relapse by continuous scales such as those provided by Annis, Heather and Litman. There is reasonably consistent evidence for two common antecedents of relapse: negative emotional states, and positive emotional states in a social context. Antecedents of relapse show only modest consistency within individuals from one occasion to the next. The causes to which clients attribute relapses may exert a significant effect on future drinking episodes. Stable and internal attributions, such as are commonly associated with a dispositional disease model, may serve to perpetuate relapse. From the RREP studies, the availability of coping skills appears to be a potent protective factor, and ineffective coping a consistent predictor of relapse. Implications for clinical research and practice are considered.

Adaptation, Psychological↗

PubMed1997

A trial of relapse prevention with severely dependent male problem drinkers.

Over the last two decades, relapse prevention has emerged as a major focus of the treatment of drug problems. Few studies have demonstrated any impact on generally high relapse rates. In this paper the outcome of a controlled trial of a relapse prevention programme with male problem drinkers (n = 60) attending an Alcohol Treatment Unit is reported. Subjects who met the inclusion criteria were allocated to a relapse prevention (n = 20) procedure or a discussion (n = 20) or no-additional treatment (n = 20) control procedure. Subjects were followed-up at 6 and 12 months by the first author. The relapse prevention programme was associated with significantly greater increases in pre- and post-treatment self-efficacy compared to the discussion control group and significantly greater probability of total abstinence than all controls over the first 6-month follow up. In addition, the relapse prevention programme was associated with significantly longer survival time to an initial lapse and relapse than the controls. At 12-month follow-up, treatment effects had been eroded. It was concluded that the relapse prevention programme was an effective treatment in the short term and that longer-term impact may require greater focus on maintenance factors, such as the individual's environment.

Adult↗

PubMed1997

Therapeutic activity of malononitrilamides (MNA 279 and MNA 715) on acute and chronic, relapsing, experimental, allergic encephalomyelitis (EAE).

Due to their immunosuppressive mode of action, we examined the therapeutic effects of the malononitrilamides MNA 279 and MNA 715 in acute EAE, and two models of chronic relapsing EAE in Lewis rats and Biozzi mice. In the first model, sensitization of adult Lewis rats with guinea pig spinal cords results in an acute clinical episode of severe EAE, and by day 15 all animals had died. Treatment of these sensitized rats with the MNAs was most effective in delaying and reducing the onset of clinical symptoms, and mortality of acute EAE was prevented in a dose-dependent manner. The protection afforded by the two MNAs was long-lasting and no subsequent relapse was observed. Similarly, in the chronic relapsing disease, aged Lewis rats were immunized with rabbit myelin basic protein, and all untreated animals developed a disease with up to three relapses. The second and third episodes were both milder and shorter in duration than the first. All animals treated with the MNAs survived the first attack, which also was delayed. Pathological signs were reduced and relapses did not occur. Inhibition of chronic relapsing EAE in aged Lewis rats was observed, even when the MNA-treatment was started after the first appearance of clinical symptoms. All treated animals recovered completely and mortality was prevented. Also in the second model of chronic relapsing EAE in Biozzi AB/H mice, MNA treated animals showed only one acute and delayed episode and no further relapses. All these results qualify both MNA 279 and MNA 715 as powerful immunosuppressants with therapeutic potential in human multiple sclerosis (MS).

Acute Disease↗