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Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission after intensive primary and relapse therapy according to the BFM- and CoALL-protocols: results of the German Cooperative Study.

Fifty-one children between 26 and 214 months of age (median, 100 months) with acute lymphoblastic leukemia (ALL) were grafted in second remission from HLA-identical sibling donors (except for two patients who were grafted with a marrow with 1 antigen-mismatch). Initial treatment and relapse therapy were similar in all patients according to the BFM- and CoALL-protocols (front line: 38 patients according to BFM-protocols and 13 patients according to CoALL-protocols; relapse: 12 patients in study ALL-REZ-BFM 83, 17 in ALL-REZ-BFM 85, 20 in ALL-REZ-BFM 87, and two in ALL-REZ-BFM 90). The conditioning regimens were different, consisting of cyclophosphamide (CY) total body irradiation (TBI) plus (n = 27), VP-16-TBI (n = 23), and CY-TBI and ARA-C (n = 1). Three patients had a second graft after conditioning with CY-TBI for the first transplantation. The second ablative regimen consisted of CY plus VP-16 in the first patient and CY plus busulfan in the two other patients, one of whom relapsed again. All patients but three had bone marrow (BM), either isolated or combined, relapses. Twenty-nine of the patients are in continuous complete remission (CCR), ranging from 1 to 67 months after transplantation with a median time of 30 months. One patient was lost to follow-up in continuous remission. Nine patients died from treatment-related complications (infections and graft-versus-host disease) and 12 patients suffered a leukemic relapse; three of them received a second graft and two are in CCR. Kaplan-Meier analysis yields an event-free survival (EFS) of 0.52 +/- 0.08. The probability of a 7-year relapse-free interval (RFI) is 0.68 +/- 0.08. EFS for patients with late relapses is 0.47 +/- 0.12 and for patients with early relapses 0.56 +/- 0.1. The RFI for patients with late relapses is 0.65 +/- 0.12 and for patients with early relapses 0.69 +/- 0.11. There is a nonsignificant trend towards superior results for patients grafted after conditioning with VP-16 plus TBI. When all patients who are not in CCR at day +125 (which is the median interval between relapse diagnosis and BM transplantation [BMT]) are excluded from the chemotherapy results, there is no significant difference between the results of BMT and chemotherapy for late relapses. On the other hand, there is a significant advantage between chemotherapy and BMT for early relapses over chemotherapy (P less than or equal to .01).

Adolescent

[Relapse of Wegener's granulomatosis. Retrospective study of 18 cases].

During a mean therapeutic follow-up of 4 years, 25 out of 61 patients with Wegener's granulomatosis had one or several relapses. As in 7 of them the initial diagnosis had proved erroneous, this study concerns the remaining 18 patients who together totalled 31 relapses after the correct diagnosis was made. Twenty relapses occurred early on, within 4 months of a change in treatment, and they corresponded to recurrent activity of the disease. Ten relapses occurred later on, after treatment had been discontinued or kept at maintenance dose level. The relapses appeared as early as the first year in 41 percent of the cases. The ENT region was affected in 61 percent of the patients. Nine relapses occurred in the absence of treatment, including 6 which took place 1 to 8 years after treatment. Three relapses occurred less than 3 months after a prednisone and oral cyclophosphamide therapy was initiated. Compared with the group of patients without relapse, those in the relapse group were younger, more often treated with azathioprine and cyclophosphamide administered intravenously, and followed up for a longer period; their probability of survival was also higher. In case of early relapse after withdrawal of treatment the mean duration of that treatment had been shorter than in the absence of relapse. None of the patients whose treatment had been stopped more than 20 months after its onset had an early relapse. These data prompted us to make the following proposals: initially, cyclophosphamide should be administered as bolus injections (the time required to obtain results is then shorter than with the oral route), and maintenance therapy should last at least 20 months. Azathioprine should be used only when cyclophosphamide is contra-indicated. The relative indications for intravenous and oral cyclophosphamide remain to be determined. Discontinuing all treatments is a difficult decision to make, but even then the patients should be under close supervision in view of the possibility of late relapses.

Adolescent

Orthodontic relapse in subjects with varying degrees of anteroposterior and vertical dysplasia.

Fifty seemingly well-treated orthodontic cases were studied by means of pretreatment, posttreatment, and postretention dental casts, lateral cephalograms, and other orthodontic records. The sample was restricted to cases exhibiting anteroposterior and/or vertical dysplasia as revealed by pretreatment dental casts. The sample was divided into a stable group and a relapse group. Each group contained twenty-five cases. A double-blind design was used. The raw data were analyzed by the stepwise discriminant analysis and by the multivariate analysis of variance. On the basis of the results obtained from this study, the following conclusions can be drawn: 1. In seemingly well-treated orthodontic cases, relapse or stability can neither be predicted nor judged from one set of records alone. 2. Relapse or stability of an orthodontic case can be predicted by comparing the posttreatment variables with the pretreatment variables. 3. Relapse or stability of an orthodontic case can be judged by comparing the postretention variables to the posttreatment variables. 4. The PP-GoGn angle and the mandibular intercanine width are the two most important variables associated with orthodontic relapse. 5. Changing the PP-GoGn angle, either by treatment or by growth, was associated with relapse. In other words, changes in the PP-GoGn angle tended to be unstable. This suggests that decreasing the PP-GoGn angle should be avoided. 6. In both the stable and the relapse groups, the mandibular intercanine width decreased postretention. This decrease was associated more with the relapse group than with the stable group. 7. The mandibular intercanine width tended to relapse toward its original pretreatment value. This suggests that, at the end of active treatment, the mandibular intercanine width should be maintained as originally presented. 8. There was no significant interaction between orthodontic relapse (or stability) and Angle Class I and II cases. 9. There was no significant interaction between relapse (or stability), of an orthodontic case, and the sex of the patient. 10. There was no significant interaction between orthodontic relapse (or stability) and whether or not extraction was included as a part of the mechanotherapy. Thus, the pretreatment deep overbite is not necessarily a contraindication to extraction.

Analysis of Variance

Genomic and transcriptomic features of relapsed small cell lung cancer.

BACKGROUND: Relapsed small cell lung cancer is characterized by treatment resistance and poor outcomes. Genomic and transcriptomic alterations in relapsed SCLC have not been characterized well. We comprehensively profiled relapsed SCLC samples along with patient-matched treatment-naive samples, when available, using whole-exome (WES), whole-genome (WGS), and RNA-sequencing (RNA-seq) to describe the molecular landscape of relapsed SCLC. Our goal is to identify potential novel pathways for additional functional validation and eventually novel therapeutic options. METHODS: We analyzed 54 relapsed and 27 treatment-naive SCLC samples using WES (with 26 patient-matched paired samples). A subset of the samples was also analyzed by WGS (n=28) and RNA-seq (n=31). Differences in mutational signatures, gene expression, structural variants, splicing, and neoantigen profiles at diagnosis and relapse were investigated. RESULTS: Relapsed SCLC samples demonstrated mutation signatures characteristic of platinum and APOBEC mutagenesis. Furthermore, these samples were characterized by MYC, MYCL and MYCN amplifications. Both treatment-naive and relapsed SCLC samples showed high prevalence of mutation-associated neoantigens (median= 86 in treatment-naive and 90 in relapsed SCLC; p=0.8) and TP53 was the most frequently altered gene to result in a neoantigen (48% of analyzed samples). Potential mechanisms of immune evasion, including amplification of CD24, overexpression of IDO1, increased M2 macrophage presence, and upregulation of HLA-E were also observed in relapse samples. Differences in alternative splicing patterns were observed between treatment-naive and relapsed small cell samples. Retained intron events were significantly enriched in treatment-naive samples and affected genes involved in DNA repair, metabolism, and WNT and MYC pathways. CONCLUSIONS: This study highlights the genomic and transcriptomic features of relapsed SCLC. These samples were characterized by genomic instability, WNT and MYC dysregulation, and splicing aberrations. Additional studies targeting the splicing machinery, WNT signaling, and immune evasion pathways could identify novel therapeutic vulnerabilities in SCLC.

Journal Article

Acute myeloid leukaemia relapsing following interleukin-2 treatment expresses the alpha chain of the interleukin-2 receptor.

Immunotherapy with recombinant human Interleukin-2 (rhIL-2) was given to nine patients in first complete remission from acute myeloid leukaemia (AML). Five patients relapsed. The median time to relapse after commencing rhIL-2 was 26 weeks (range 2-44). Four patients were studied at relapse. The morphological and cytochemical features at relapse and presentation were similar. Cytogenetic analysis at relapse in patients 1 and 3 showed a normal karyotype. At relapse, patient 4 had the abnormality 46,XY, t(2;3). Patient 2 had the chromosomal abnormality t(8;21) at presentation and relapse. Patients 3 and 4 with M5 AML relapsed rapidly at 2 and 9 weeks after starting rhIL-2 treatment. Relapse leukaemia cells had features normally associated with lymphoid development. Patient 3 was TdT positive, with rearranged immunoglobulin genes, and a proportion of cells expressing the CD7 antigen; patient 4 also expressed the CD7 antigen. Relapse leukaemic cells from three of four patients expressed the alpha chain of the IL-2 receptor as assessed by flow cytometry. After overnight incubation and removal of T-lymphocytes the proportion of cells from these patients expressing the alpha chain increased from 15% to 61% (P less than 0.01). Using tritiated thymidine uptake to assess cell proliferation, two of three patients who expressed the IL-2 receptor alpha chain proliferated in response to 1000 u/ml of rhIL-2 in vitro, with a stimulation index greater than 1.95 (P less than 0.05). Following rhIL-2 immunotherapy for AML, relapse cells may express an inducible form of the alpha chain of the IL-2 receptor, which can mediate a proliferative response. It is possible that rhIL-2 when administered to AML patients in remission, may induce relapse. This may be a particular risk in patients with the M5 subtype.

Adult

Relapse in Burkitt's lymphoma.

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

Abdominal Neoplasms

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

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

Child

Preventing relapse in the treatment of nicotine addiction: current issues and future directions.

Although smoking-cessation rates have continued to increase, the vast majority of smokers who quit eventually relapse. Between 1974 and 1985, over 1.3 million smokers quit during each of those years. However, 75% to 80% of those individuals resumed smoking within six months. This article describes the dynamic phenomenon of smoking relapse within the context of cyclical episodes of smoking and quitting during an individual's lifetime. Theories of the determinants of smoking relapse are reviewed and methods designed to prevent relapse are described. Smoking relapse is discussed in terms of three aspects of tobacco addiction: (1) biological-addiction mechanisms, (2) conditioning processes, and (3) cognitive-social learning factors. The major determinants of smoking relapse are reviewed, including nicotine withdrawal, stress, weight gain, social influences, conditioning factors, causal attributions, and environmental variables. A transtheoretical-developmental model is explored in the longitudinal investigation of the natural history of slips (lapses) and relapse episodes. Relapse prevention interventions are described that emphasize self-awareness, self-regulation, self-efficacy, affect regulation, social support, and lifestyle balance. Recent developments in pharmacological adjuncts to treatment are also examined. It is concluded that innovative relapse prevention methods need to be designed for hard-core smokers with histories of cessation failures, substance abuse and/or psychiatric impairment. These and other recommendations for future research on smoking relapse and relapse prevention are discussed.

Humans

Value of routine bone marrow examination for detection of bone marrow relapse in children with standard risk acute lymphoblastic leukemia.

The value of routine bone marrow examination (RBME) in children during and after treatment for standard risk acute lymphoblastic leukemia (SR-ALL) was investigated. The clinical symptoms and peripheral blood findings at the time of bone marrow relapse of 28 children were reviewed and compared with those of 28 matched controls in continuous complete remission. Five (45%) children with bone marrow relapse during maintenance therapy and six (35%) after cessation of cytostatic treatment were asymptomatic at the time of relapse. Signs indicative of relapse during treatment were lymphoblast cells in the peripheral blood, thrombocytopenia, hepatomegaly, anemia, or leukopenia in decreasing order of frequency. After cessation of treatment these signs were lymphoblasts in the peripheral blood, hepatomegaly, splenomegaly, thrombocytopenia, or leukocytosis. Except for one case with thrombocytopenia, no signs suspicious for relapse were found in the control groups. When each sign was evaluated separately only the presence of lymphoblasts in peripheral blood and hepatomegaly were significant symptoms for relapse after cessation of treatment. The mean percentage of lymphoblasts in the bone marrow at the time of relapse was significantly lower for patients with an unpredicted relapse (46.8%) than patients with clinical and/or laboratory evidence of relapse (79.5%). When lymphoblasts were present in the peripheral blood the percentage of lymphoblasts in the bone marrow was always more than 40%, both during and after cessation of treatment. These data suggest a relation between clinical and laboratory symptoms and progression of the disease. It is concluded that 46% of relapses are detected by RBME in the absence of clinical or laboratory symptoms. This early detection may have a positive prognostic influence with more effective treatment for relapsed ALL.

Adolescent

Treatment of testicular relapse in childhood acute lymphoblastic leukemia.

The experience of rescue therapy for 6 patients of childhood acute lymphoblastic leukemia (ALL) with testicular relapse is reported. In two patients, testicular relapse occurred 1 and 4 years off therapy, respectively. Two patients had testicular relapse on therapy. The remaining 2 patients had testicular relapse after premature discontinuation of therapy by the parents. Isolated testicular relapse was found in 2 patients. The rest of the testicular relapses were concurrent with either bone marrow (BM) or central nervous system (CNS) relapses. The rescue therapy included bilateral testicular irradiation 24 Gy, and systemic reinduction chemotherapy, followed by maintenance therapy as that of TCL 821 or TCL 842 protocol for high risk patients of ALL. CNS prophylaxis, which included intrathecal medication and/or cranial irradiation 18 Gy (if not given before), was also given. After testicular relapse, one had subsequent BM and CNS relapses and received more aggressive chemotherapy. Another one had subsequent CNS relapse 4 months after another premature withdrawal of treatment. One patient, who presented with CNS leukemia at diagnosis, had concurrent testicular and CNS relapses and died of CNS leukemia 3 months later. The remaining 5 patients remained in continuous complete remission for 26 to 95 months with a median duration of 54 months.

Child

Clinical, biologic, and histologic features of late relapses in diffuse large cell lymphoma.

After completing chemotherapy and achieving a complete remission (CR), patients with diffuse intermediate-grade lymphoma and immunoblastic lymphoma are usually considered cured if they are able to maintain that remission continuously for 24 months. Recently, we observed a number of patients with these disorders who relapsed after a continuous CR of greater than or equal to 30 months from the beginning of therapy or 24 months from completing chemotherapy. This finding led us to examine 503 consecutive cases to determine the risk of late relapse and their clinical and biologic features. We found that the overall risk of late relapse of those who attained CR was 6.8%, but several features at presentation were associated with a high risk: (1) the presence of a divergent histology; (2) a sclerosing large cell lymphoma; (3) a diagnosis based on an extranodal site with no nodal tissue available for examination. When none of these features were present, the risk of late relapse was minimal (only 3%). When any of these features was present, the risk was 14%. Most striking was the 43% late relapse rate of patients with divergent histology. All but one of the eight B-cell tumors studied at relapse showed kappa light chain restriction. Five of these eight has a low S phase at the time of relapse, suggesting chemotherapeutic selection of a clone of cells with a low proliferative potential that could have given rise to the late relapse. Nucleic acid flow cytometry and immunophenotypic studies on three tumors at initial diagnosis and after relapse failed to support the hypothesis of a second de novo lymphoma and were consistent with a true recurrence of the original tumor. The results of salvage chemotherapy in this group of late relapses showed a high CR rate (57%) but no evidence of a trend for cure in the time to treatment failure curve. In contrast to the experience with Hodgkin's disease, retreatment with the same or a similar regimen used for the original induction was not associated with durable response. Clinicians should be aware of the potential for a late relapse in cases with divergent histology and the need for new treatment strategies for such cases.

Antineoplastic Combined Chemotherapy Protocols

Initial relapses in previously treated Hodgkin's disease. I. Results of second treatment.

Two hundred forty-three consecutive patients with Hodgkin's disease who relapsed after an initial course of treatment at the Stanford University Division of Radiation Therapy underwent subsequent systematic evaluation and retreatment. An analysis of the influence of numerous parameters, including sex, histopathology, original stage, relapse site, and original and second therapy, on actuarial survival and on relapse-free survival was undertaken. Most relapses (87%) occurred within 3 years of the initial treatment course. The 5-year relapse-free survival measured from the time of second treatment increased from 14% before to 39% after the introduction of multiple agent chemotherapy (MOPP) for relapsing disease. Patients treated with MOPP chemotherapy for nodal relapses showed increased subsequent relapse-free survival (61%) when compared with patients treated only with radiotherapy for nodal relapses. Based on the combined findings of this analysis, recommendations are made regarding the management of patients with Hodgkin's disease who have suffered a relapse.

Female

Ovarian tumors in relapsing acute lymphoblastic leukemia: a review of 23 cases.

Five cases of relapsing acute lymphocytic leukemia (ALL) presenting as an ovarian tumor have been treated at this institution, representing the largest reported series. In a review of the literature we identified 18 additional cases of ovarian leukemic relapse. Together, these 23 patients form the basis for this report. Abdominal pain is the most common presenting symptom of ovarian leukemia. An abdominal mass is usually palpable, and at least four patients had hydronephrosis. Nine patients had documented bilateral ovarian involvement; however, bilateral disease was not a poor prognostic sign. Most ovarian relapses occurred more than 36 months after the original diagnosis of ALL, with these "late'h relapsers responding more favorably to treatment than "early" relapsers. Definitive statements can not be made from a retrospective review of 23 case reports; however, salpingooophorectomy had no obvious advantage over simple biopsy, and there was no obvious advantage to the routine use of radiation therapy. Most failures in treating ovarian leukemia occurred within 2 years. Most failures were systemic rather than local, illustrating the need for aggressive multiagent systemic chemotherapy. Survival after ovarian leukemic relapse is possible, with eight of the 23 patients alive and in complete continuous remission following the ovarian relapse (median follow-up since relapse, 42 months; range, 2 to 135+ months). With the use of more intensive chemotherapy in recent protocols, the frequency of ovarian leukemic relapses appears to be decreasing. At this institution, no child with ALL diagnosed in the 1980s has subsequently developed an ovarian relapse.

Adolescent

Lifetime history of relapse from exercise.

Most research on relapse from exercise has investigated one relapse episode following a structured program. The present study examined the patterns and determinants of the lifetime history of relapse from exercise in a community population. Subjects were 1.811 randomly selected residents of San Diego, California who completed an extensive mailed survey. Subjects reported the number of times over their lifetime that they had exercised vigorously for at least six months and then stopped exercising for at least three months. Approximately 60% of subjects reported zero relapses, 20% reported one or two relapses, and 20% reported three or more relapses. Relapse histories of current exercisers and current nonexercisers were virtually identical. The most commonly reported reason for the last relapse was injuries for both nonexecisers and exercisers. Multiple regression analyses were used to identify correlates of exercise relapse history. These data indicate that cross-sectional surveys of exercise behavior are inadequate to characterize exercise behavior in a population, and injuries are probably a major cause of relapse.

California

Impact of local tumor relapse on patient survival after cobalt 60 plaque radiotherapy.

The authors investigated the impact of local intraocular tumor relapse on survival in a matched-group comparison study of patients with primary choroidal or ciliary body melanoma managed with cobalt 60 plaque radiotherapy. Sixty-two patients with local relapse were matched with an equal number of relapse-free patients in terms of known clinical prognostic factors for both melanoma-specific mortality (largest linear tumor dimension, location of anterior tumor margin, age) and local tumor relapse (location of posterior tumor margin). The follow-up of every relapse-free patient equaled or exceeded the interval to relapse for each matched patient with local relapse. The estimated 5-year survival (Kaplan-Meier) in the relapse-free patients was 87% (standard error = 4%), while that in the local relapse group was 58% (standard error = 6%). This difference is statistically significant (P less than 0.0001, log rank test). These results support the hypothesis that local tumor relapse after cobalt 60 plaque radiotherapy is an important post-treatment clinical indicator of the tumor's greater malignant potential and the patient's increased risk of melanoma-specific mortality.

Adult

Period of freedom from relapse as an indication of cure in minimal change nephrotic syndrome in adults.

17 adult-onset nephrotic patients with minimal-change glomerular lesions experienced 39 relapses in all. The relationship between the remission period t (expressed in months) preceding each relapse and the rate of relapse (relapse rate) F (t) was proven to correspond closely to Weibull's distribution function as follows (chi 2 = 1.72, 0.5 less than p less than 0.75): In In (formula - see text) From the equation, the time when 99% of relapsing patients have relapsed is 39.3 months. This means that adult-relapsing nephrotic patients with minimal-change lesions will experience a relapse within 39.3 months of remission. They should be free from relapse and considered cured with a 99% reliability when remission has continued longer than 39.3 months, i.e. beyond the 'period of freedom from relapse'.

Adolescent

Relapses in multibacillary leprosy patients after stopping treatment with rifampin-containing combined regimens. Marchoux Chemotherapy Study Group.

During the decade between the mid 1970s and the mid-1980s, 12 rifampin (RMP)-containing combined regimens were tested among lepromatous leprosy patients in the Institut Marchoux. The 384 patients who were seen at least once during the period beginning 12 months after completion of treatment were considered eligible for analysis of the relapse rate. By the end of May 1991, relapse, manifested by a significant increase of the bacterial index (BI) and the appearance of new lesions with a BI greater than that of preexisting lesions, had been observed in 68 (17.7%) of these patients. Relapse was confirmed by the presence of viable Mycobacterium leprae in skin biopsy specimens obtained from 54 of the first 61 cases; virtually all of the isolated strains remained susceptible to RMP. The relapses occurred late, about 5 +/- 2 years after stopping treatment; the shorter the duration of RMP administration, the earlier the appearance of the relapse. The variations of the relapse rate among regimens were considerable: total relapse rate ranged from 2.9% to 27.8%, and the relapse rate per 100 patient-years of observation ranged from 0.8 to 6.9. Among the 12 regimens, only the WHO/MDT yielded an acceptable relapse rate (defined as a rate lower than 1.0 per 100 patient-years). However, because the mean duration of follow up was shortest among the patients treated with WHO/MDT, the relative low relapse rate among these patients must be interpreted with great caution.

Drug Therapy, Combination

Relapses in leprosy patients after release from dapsone monotherapy; experience in the leprosy control program of the all Africa Leprosy and Rehabilitation Training Center (ALERT) in Ethiopia.

Before implementation of multidrug therapy (MDT), leprosy patients who were clinically inactive, skin-smear negative and had been treated with dapsone monotherapy for at least 5 years (paucibacillary patients) or for at least 10 years (multibacillary patients) were released from treatment. An analysis was made of self-reporting relapses in 1081 paucibacillary (PB) patients and 1123 multibacillary (MB) patients who had been released in Addis Ababa and two rural districts of the leprosy control program of the All Africa Leprosy and Rehabilitation Training Center (ALERT). During an average period of 6.6 years after stopping dapsone, 44 relapses were diagnosed among the PB patients and 148 relapses among the MB patients. The overall relapse rate was 4.1% or 7.2 per 1000 patient-years after release from treatment for PB patients and 13.2% and 24.8, respectively, for MB patients. The annual relapse rate in PB patients did not differ significantly from year to year. However the relapse rate for MB patients was significantly lower during the fifth to seventh years after stopping treatment compared with the first 4 years. Based on clinical findings there was a strong suspicion of relapse with dapsone-resistant bacilli in 40.4% of MB relapses. It is concluded that the relapse rate for PB patients is acceptable. However, the relapse rate for MB patients is considered too high. It is strongly recommended to administer to all MB patients, including those who have been on long-term treatment with dapsone and have become clinically and bacteriologically inactive, a 2-year course of MDT.

Adolescent