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PubMed2002

Down-regulation of antihost alloreactivity after bone marrow transplant permits relapse of hematological malignancy.

Relapse of leukemia remains a common event after allogeneic bone marrow transplantation, despite potential donor antihost alloreactivity present in most transplants. This work examined posttransplant relapse of the DBA/2 P815 mastocytoma in a murine model of MHC-matched, minor histocompatibility antigen (mHAg)-mismatched bone marrow transplantation (BALB/c donors into DBA/2 recipients). Antihost alloreactivity was associated with reduction of posttransplant tumor burden and prolongation of survival, but posttransplant relapse commonly occurred. No evidence of acquired resistance to immune control was found in 12 relapse reisolates. Relapse tumors remained sensitive to donor antihost CTLs in vitro, suggesting continued expression of mHAgs. Reisolates also continued to express Fas. However, loss of posttransplant alloreactivity was observed at 3 weeks. This was temporally associated with the time of relapse. Antihost alloreactivity could be reactivated in stable graft-versus-host disease-free recipients by immunization with host cells. The results of this study suggest that one mechanism for relapse after bone marrow transplant is acquired tolerance of allogeneic minor histocompatibility antigens and that posttransplant immunotherapy directed against mHAgs may induce antitumor activity.

Animals↗

PubMed2002

DNA methylation patterns at relapse in adult acute lymphocytic leukemia.

PURPOSE: Aberrant DNA methylation of promoter-associated CpG islands is an epigenetic DNA modification observed in acute leukemias that in certain cases has been associated with a poor prognosis and increased relapse rates. To study the role of DNA methylation in relapse mechanisms in acute lymphocytic leukemia (ALL), we have compared the methylation status of five genes at the time of initial presentation and at first relapse in 25 adult patients with ALL. EXPERIMENTAL DESIGN: Genes studied included the estrogen receptor (ER), multidrug resistance gene 1 (MDR1), p73, p15, and p16. DNA was extracted from paraffin-embedded bone marrow biopsies. DNA methylation was analyzed using PCR of bisulfite-modified DNA. RESULTS: Results indicate that methylation at the time of relapse was stable in 92% of patients for p73, 88% for ER, 80% for p16, 72% for MDR1, and 60% for p15. Only one case had p16 methylation at initial presentation, whereas 6 patients (P = 0.0001) had methylation at relapse. Three cases had concomitant methylation of p15 and p16 at relapse. The degree of MDR1 methylation inversely correlated with the presence of MDR1 expression as detected by immunohistochemistry. Eighteen patients (72%) had acquired no or one methylation change, whereas the rest (28%) had methylation changes in two or three genes. No clinical-biological correlations were found between methylation of any particular gene or pattern. CONCLUSIONS: In summary, DNA methylation patterns are stable in a majority of patients with relapsed ALL, but a subset of patients acquire new methylation changes, in particular affecting cell cycle regulatory genes.

Adolescent↗

PubMed2002

[Treatment of acute myeloid leukemias in the adult in relapse].

Main chemotherapy regimens used to treat adult patients with acute myeloid leukemia (AML) in first or further relapse were reviewed. In retrospective study, second complete remission rates ranged from 30% to 64%, while they ranged from 8% to 89% in prospective trials. The second complete remission rates were closely associated with age and duration of first complete remission. Combination therapies resulted in higher complete remission rates but were associated with higher toxicity. Median duration of second complete remission was < 14 months and overall median survival was < 12 months. The probability of 3-year survival ranged from 8% to 29%. The inhomogeneity of these studies, the differences in dosages and schedules, and the frequent absence of randomisation make it difficult to select the best salvage therapy. No reinduction regimen has so far clearly proven superior. Only stem cell transplantation provided durable remissions for the majority of AML patients after a first relapse. Considering the poor outcomes of patients with AML in first relapse, improved therapies need to be developed. A number of novel agents that include several differentiation agents, enzyme inhibitors, and monoclonal antibodies have been studied to provide improved outcomes for patients with AML who have relapsed. This is the same for acute promyelocytic leukaemia (APL). Arsenic trioxide has shown great promise for the induction, consolidation, and maintenance of complete remission in relapsed patients with APL. Within this context autologous and allogeneic bone marrow transplantations are also considered in second or subsequent relapse. Molecular monitoring for the PML-RARalpha fusion protein permits prompt intervention for early molecular relapse ultimately improving chances of prolonged remission.

Acute Disease↗

PubMed2002

Surveillance in stage I testicular seminoma - risk of late relapse.

INTRODUCTION: Surveillance is an alternative to adjuvant radiotherapy for stage I testicular seminoma. We present the long-term results of seminoma surveillance, with emphasis on quantifying the risk of late relapse beyond 5 years. METHODS: From 1981 to 1993, of 431 men with stage I testicular seminoma, 203 were managed by surveillance following radical orchidectomy. The surveillance protocol comprised a combination of clinical examination, CT scans of abdomen and pelvis, chest x-rays and serum markers, at defined intervals. RESULTS: At a median follow-up of 9.2 years, 35 men have relapsed. Five of the relapses occurred more than 5 years after orchidectomy (at 5.1, 6.9, 7.3, 7.3, and 9.0 years). The actuarial risk of relapse at 5 and 10 years was 15% (standard error [SE] 1.1%) and 18% (SE 1.8%) respectively. One hundred sixty one men were free of relapse at 5 years, and have been followed beyond this point for a median of 4.3 years. The actuarial risk of relapse between 5 and 10 years was 4% (SE 0.5%). CONCLUSIONS: These results demonstrate that there is a small but clinically significant risk of relapse more than 5 years after orchidectomy for stage I seminoma. These data support the need for long term surveillance.

Adult↗

PubMed2000

Smoking Relapse During Postpartum.

PURPOSE: While many women quit smoking when learning of their pregnancy, the majority relapses within one year of giving birth. This paper provides an integrative review of studies that assess the contributing factors to maternal smoking relapse within the first year of giving birth. The framework for this review is the relapse prevention model, which seeks to uncover the contributing factors, or high-risk situations, that lead to relapse. Additionally, this paper examines existing practice interventions aimed at reducing postpartum relapse and provides recommendations for best practice. CONCLUSIONS: Research evidence to date shows that two main factors are associated with smoking relapse among postpartum women: (1) their association with other smokers and (2) their choosing not to breastfeed. Since maternal smoking results in poor health outcomes for both mothers and children, relapse prevention is a health issue worthy of examination. Nurses can use this information in planning, implementing, and evaluating smoking prevention and cessation programs for pregnant and postpartum women.

Journal Article↗

PubMed2003

Angiogenesis as determined by computerised image analysis and the risk of early relapse in women with invasive ductal breast carcinoma.

The purpose of this study was to define the value of angiogenesis as a prognostic factor indicating early relapse. We assessed the relationship between parameters of angiogenesis (microvessel count--MVC, microvessel area--MVA and microvessel perimeter--MVP) and relapse-free survival at 50 months in 226 women with invasive ductal breast carcinoma. Anti CD31 antibody was used as a marker of endothelial cells. Microvessel density was measured according to Weidner et al. using a computerised image analysis. The mean parameters of angiogenesis were significantly higher in women with relapse than in those without recurrence within 50 months after surgery. In node negative patients relapse did not occur if MVC was below 38.7. In node-negative subgroup with grade II carcinomas parameters of angiogenesis in the primary tumour differed significantly depending on the presence or absence of relapse. Univariate and multivariate analysis showed the prognostic value of angiogenesis parameters in all study groups with respect to 50-month relapse-free survival. In node negative subgroup only 62.5% of women with tumors with high MVC and as much as 94.9% with low MVC survived 50 months without recurrence. In the Cox analysis of node-negative subgroup only MVC, MVP and MVA were the independent prognostic factors. In women with node-negative disease the evaluation of angiogenesis can identify a subgroup of patients with high risk of relapse, hence it may help in decisions concerning adjuvant therapy. Computerised image analysis is a good and objective technique for evaluating the intensity of angiogenesis in breast cancer.

Adult↗

PubMed2003

Assessment of clonal stability of minimal residual disease targets between 1st and 2nd relapse of childhood precursor B-cell acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements are excellent patient-specific targets for polymerase chain reaction (PCR)-based detection of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL). Nevertheless, instability of these targets during the course of the disease has important implications for PCR-based MRD monitoring and may lead to false negative results. DESIGN AND METHODS: Several studies have shown that Ig and TCR targets are reasonably stable in ALL between diagnosis and first relapse, but up to now, there are no data on the stability of these targets between first and second relapse. We, therefore, performed a PCR-study on bone marrow samples from 49 children with precursor B-ALL at first and second relapse. Homo-heteroduplex PCR analyses were used for identification of clonal IGH, IGK-Kde, TCRG and TCRD gene rearrangements. Clonal targets were studied by sequencing and/or comparative homo-heteroduplex analysis. RESULTS: In 52% (25/48) of the patients, all PCR targets identified at first relapse were preserved at second relapse; in 92% (44/48) of the patients at least one target and in 73% (35/48) at least two targets remained stable. Best stability was found for IGH and TCRG gene rearrangements. INTERPRETATION AND CONCLUSIONS: Based on these first data about clonal stability of Ig and TCR targets between first and second relapse of childhood precursor B-ALL, we developed a stepwise strategy for appropriate selection of stable PCR targets for MRD monitoring. This strategy was applicable in 84% of the relapsed patients and resulted in at least one stable MRD-PCR target per patient in 98% of these children.

Adolescent↗

PubMed2003

Chimerism status is a useful predictor of relapse after allogeneic stem cell transplantation for acute leukemia.

BACKGROUND AND OBJECTIVES: The role of hematopoietic chimerism after allogeneic stem cell transplantation (SCT) for acute leukemia remains controversial. We studied the relationship between hematopoietic chimerism and several prognostic variables on the outcome of SCT in patients with acute leukemia. DESIGN AND METHODS: Chimerism was determined by a semiquantitative method, based on polymerase chain reaction (PCR) amplification of variable number tandem repeat (VNTR) minisatellites, in 133 consecutive patients who underwent allogeneic SCT for acute leukemia (68 myeloid, 58 lymphoid and 7 biphenotypic), all receiving a myeloablative conditioning regimen. RESULTS: The median follow-up for the surviving patients was 44.8 months (range: 12.0-129.0). Recipient hematopoiesis (mixed chimerism, MC) was detected in 40 cases (30.1%). Two types of patients could be distinguished in this MC group: 29 with increasing MC and 9 with decreasing MC. The remaining 93 cases maintained complete donor chimerism (CC) over the whole follow-up period. Patients with increasing MC showed a significantly higher (p<0.001) rate of relapse (93.1%) and death (89.7%) in comparison to both those with CC (26.9% relapse, 44.1% dead) or decreasing MC (11.1% relapse, 44.4% dead). The detection of increasing MC preceded relapse by a median of 74 days (range: 5-434) and was significantly related with the absence of chronic graft-versus-host disease. Univariate and multivariate analysis confirmed that chimerism was the most significant variable involved in relapse, leukemia-free survival and overall survival after SCT. INTERPRETATION AND CONCLUSIONS: These results demonstrate that sequential determination of chimerism allows the prediction of relapse and death after SCT for acute leukemia. The interval between detection of increasing MC and relapse may permit timely implementation of therapeutic measures.

Acute Disease↗

PubMed1992

Continuous treatment with all-trans retinoic acid causes a progressive reduction in plasma drug concentrations: implications for relapse and retinoid "resistance" in patients with acute promyelocytic leukemia.

Although all-trans retinoic acid (RA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL), all groups have described clinical relapses despite continued RA treatment. This finding suggests that resistance to the cytodifferentiating effects of the retinoid had been acquired. To investigate potential mechanisms of clinical resistance to RA, we serially evaluated the clinical pharmacology of the drug in APL patients treated with this agent. Leukemic cells from patients relapsing from RA treatment were cultured in the presence of RA and examined for evidence of morphologic maturation. We also studied messenger RNA expression of the newly described gene product of the (15;17) translocation in APL, PML/RA receptor-alpha (PML/RAR-alpha). Serial pharmacokinetic studies showed that continuous daily RA treatment was associated with a marked decrease in plasma drug concentrations at the time of relapse compared with the initial day of therapy. Doubling the RA dose in six patients failed to reinduce response at the time of relapse and also failed to significantly augment plasma RA concentrations. However, leukemic cells obtained at the time of relapse from four patients retained in vitro sensitivity to the differentiating activity of RA (10(-6) mol/L). No change was observed in the pattern of PML/RAR-alpha expression assessed by Northern blot analysis at the time of relapse compared with pretreatment in two patients who were tested. These results indicate that clinical relapse and "resistance" to continuous treatment with all-trans RA in APL is associated with progressive reduction of plasma concentrations, potentially to levels below those that sustain differentiation of leukemic cells in vivo. Long-term success of this treatment will require the development of strategies that circumvent this pharmacologic phenomenon.

Carrier Proteins↗

PubMed1992

[Immunohistochemical detection of carcinoembryonic antigen and P-glycoprotein in small cell lung cancer at diagnosis and relapse, with special reference to the tissue expression of CEA and response to chemotherapy].

Small cell lung cancer (SCLC) is one of the most sensitive tumors to drug therapy; however, the majority of patients eventually relapse within a few years. Emergence of drug resistance is thought to play a major role in the dismal course of this disease. However, the mechanism of drug resistance in SCLC still remains obscure. Based on the clinical observation that a significant proportion of patients with relapsing tumor show an elevated serum carcinoembryonic antigen (CEA) concentration while serum neuron-specific enolase (NSE) concentration remains normal, we attempted to determine whether the tissue of CEA is indicative of a clonal change in SCLC, in contrast with the tissue expression of NSE and P-glycoprotein (P-gp). We examined 22 SCLC patients with tumor specimens available both at diagnosis and at relapse. Of the 22 patients, two had CEA expression at diagnosis, and a further three patients showed CEA expression at relapse. It is of note that there were two patients whose tumors expressed NSE alone at diagnosis but expressed CEA alone at relapse. Serum CEA concentration was concordant with the tissue expression of CEA; however, serum NSE concentration was not concordant with the tissue expression of NSE. Tumors with CEA expression at relapse were generally resistant to salvage chemotherapy, while there was no close relationship between the tissue expression of P-gp and refractoriness to drugs at relapse. These findings indicate that the tissue expression of CEA in SCLC is a marker of a clonal change during chemotherapy, and such a clonal change would play a role in the emergence of drug resistance in SCLC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

Effect of drug therapy on the relapse of peptic ulcers. 1st communication: the effect of acute therapy.

The following study was conducted in order to investigate the effect of drug therapy on the relapse of peptic ulcers. Acute therapy with pirenzepine (Gastrozepin, CAS 28797-61-7) (100 mg/d) or cimetidine (CAS 51481-61-9) (800 mg/d) was given to 402 patients with peptic ulcers using the envelope method. Subsequently, 1-year maintenance therapy with pirenzepine (75 mg/d) or placebo was carried out in a double-blind study in 251 patients who had been cured within 3 months. During the study period, an endoscopic examination was repeated regularly to study the relapse of ulcers. When the results were stratified and analyzed by Cutler-Ederer's life table method to see changes in relapse over time, it was noted that the acute therapy for active ulcers did have an influence on the course of relapse after the ulcer lesions had been cured. Pirenzepine, a M1 antagonist, was superior to cimetidine, a H2 antagonist, in the prevention of relapse of ulcers after they had been cured. The results suggest that the prevention of relapse of peptic ulcers should be started at the stage of acute therapy for active ulcers and that care should be taken in selecting drugs. The results also suggest that the natural history of peptic ulcers with respect to their relapse can be modified to a certain extent by drug therapy although the period for such cannot be specified.

Cimetidine↗

PubMed2003

[Induction of aGVHD after allogeneic hematopoietic stem cell transplantation for refractory or relapsed acute leukemia].

BACKGROUND & OBJECTIVE: Patients with refractory or relapsed acute leukemia after allogeneic hematopoietic stem cell transplantation had a poor prognosis with high death rate due to relapse or transplant-related mortality (TRM). The purpose of this paper was to clarify the role of inducing acute graft-versus-host disease (aGVHD) during transplantation in preventing relapse. METHODS: Thirty adult patients with refractory or relapsed leukemia were acute lymphoblastic leukemia (n=16), acute myelogenous leukemia (n=10), and acute mixed leukemia (n=4). They were in first complete remission (n=4), second complete remission (n=9), partly remission (n=12), and non-response (n=5) at the time of transplantation. Patients underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from HLA-identical siblings (n=21), mismatched siblings donors (n=3), and allogeneic bone marrow transplantation (n=5) or allo-PBSCT (n=1) from unrelated HLA matched donors. All patients received myeloablative regimens for eliminating residual leukemic cell. For aGVHD prophylaxis the patients with HLA-identical siblings donors received cyclosporine (CSA) alone, and the patients with mismatched siblings or unrelated donors received CSA, methotrexate, mycophenolate mofetil, and low-dose ATG. For inducing aGVHD after transplantation, patients were scheduled to be quickly reduced the maintenance dose of CSA at 20% to 30% off every week or treated with pre-emptive donor leukocyte infusion if there was no appearance of aGVHD at +30 days to 60 days after transplantation. RESULTS: After a median follow-up of 18.1 months, there were 24/30 (80%) patients developed aGVHD (grade 3 or 4 had 4/30, 13.3%). There were 11/19 (57.9%) patients developed chronic GVHD (cGVHD), with 3/19 (15.8%) had extensive cGVHD. Eighteen patients are alive with disease-free survival (18/30, 60%) and 12 patients have died of relapse (5/28, 17.9%) and TRM (7/30, 23.3%). CONCLUSION: Induction of aGVHD after transplantation is feasible and effective to prevent relapse in patients with refractory or relapsed acute leukemia.

Acute Disease↗

PubMed2004

Frequency of visceral leishmaniasis relapses in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy.

There are contradictory data about whether highly active antiretroviral therapy (HAART) prevents visceral leishmaniasis (VL) relapses in human immunodeficiency virus type 1 (HIV-1)-infected patients. The aim of this study was to assess the frequency of VL relapses in individuals receiving HAART. Thirty-one patients who received HAART after developing VL were included in a retrospective cohort study. Ten of them received secondary chemoprophylaxis and the rest did not. Eight (38%) patients without secondary chemoprophylaxis showed a VL relapse. None of the seven subjects with VL relapses and 6 of 11 without recurrence (P = 0.038), in whom all scheduled data were available, showed an increase of more than 100 CD4+ cells/mm(3) during the follow-up. Patients with relapse showed higher levels of HIV RNA viral load at their last visit (P = 0.047). The frequency of VL relapses in patients receiving HAART is high. Relapses of VL are observed only in individuals with uncontrolled HIV replication and/or poor immunologic responses.

Adult↗

PubMed2004

[Second allogeneic transplant for leukemia relapsed after first allogeneic transplantation].

OBJECTIVE: To evaluate the efficacy of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of leukemia relapsed after first allo-HSCT. METHODS: Nine patients with relapsed acute leukemia (5 AML, 4 ALL) and one with chronic myelogenous leukemia (CML) who showed cytogenetic relapse after first allo-HSCT received second allo-HSCT. The median relapse time from the first allo-HSCT was 141 days. Conditioning regimens for second allo-HSCT were combination chemotherapy based on moderate-dose Ara-C (n = 5), Bu (n = 3), conventional-dose Ara-C (n = 1) and Flud/Mel (n = 1). Prophylaxis for acute graft-versus-host disease (aGVHD) were CsA alone (n = 2), CsA/MTX (n = 1), FK506 (n = 1), and no prophylaxis in 6. The median number of peripheral blood mononuclear cells transfused was 6.1 x 10(8)/kg. RESULTS: Eight cases were evaluable. All of them were engrafted and 7 developed aGVHD (grade I 4, grade II 3). The median time for absolute neutrophil count (ANC) > 0.5 x 10(9)/L and platelets > 20 x 10(9)/L were 11 and 12 days, respectively. Five cases developed localized chronic GVHD. Of all the 10 cases received second allo-HSCT, 8 died from interstitial pneumonia (n = 2), multiple-organ failure (n = 1), sepsis (n = 1), fungous pneumonia (n = 1), and leukemia relapse (n = 3), and 2 survived without leukemia for +986 and +1913 days, respectively. The leukemia free survival, transplantation related mortality and relapse rate at 2 year were 20%, 50% and 30%, respectively. CONCLUSION: Second allo-HSCT is a therapeutic alternative for selected patients with relapsed leukemia after first allo-HSCT.

Adult↗

PubMed1992

Prognostic significance of testicular relapse in boys with acute lymphoblastic leukemia.

Among 107 boys with acute lymphoblastic leukemia who achieved initial complete remission after treatment according to two therapeutic protocols for standard and high risk leukemias, respectively, in 14 (13%) testicular leukemia was observed. Isolated testicular involvement was noted in 4, and combined with medullary relapse in 10 patients. The prognosis was worse in children with high risk leukemias (mainly in those with more than 20 x 10(9)/l white blood cells and/or with less than 50 x 10(9)/l platelets). Prognosis depended also on the type of relapse. It was better in isolated as well as in late testicular relapse. It was worse in combined relapses as well as in early testicular involvement. Bilateral wedge biopsy of the testes was performed in 16 boys at the end of chemotherapy and leukemic infiltration was shown in none of them. Two to 13 months thereafter, in four boys testicular relapse developed, and in 2 boys bone marrow relapse followed 9 and 13 months later. Wedge biopsy of the testes in boys with leukemia does not seem to be of importance neither for diagnosis of testicular relapse nor for improving prognosis.

Biopsy↗

PubMed2004

[Intestinal Crohn disease: surgical aspects and predictive factors of risk of relapse. About 26 cases].

Crohn disease is an inflammatory bowel disease of which one cannot declare itself healed. It is a considerably invalidating disease, and surgery is necessary with more than 80% of patients during its long evolution. After a recent review of the literature, we wanted to contribute to the study of the predictive factors of risk of relapse among 26 patients operated for an intestinal Crohn disease during a period of 16 years, from 1986 till 2001. Sex ratio was 0.3 and average age was 33.9 years. Six patients only (23.1%) were known undergoing and treated for Crohn disease. Surgery was indicated urgently in 12 cases (46.2%). The gravity of urgently operated patients burdened the post-operative morbidity in 38.5% of cases of which 2 deaths. Six patients presented a post-operative relapse for an average delay of 40.8 months; among them 3 patients were operated. In our series, we noted that the relapse rate is more frequent with women that with men (42%/21%), and age does not intervene in the relapse contrary to smoking. The rate of relapses was so much more brought up that Crohn disease is former. The relapse was more frequent when the edge of section was sick (5/6). A post-operative medical treatment in the severe forms reduces the rate of relapses until 24%.

Adolescent↗

PubMed2005

Gram stain as a relapse predictor of bacterial vaginosis after metronidazole treatment.

Bacterial vaginosis is the most prevalent disease of the female genital tract. In spite of various effective antibiotics in the treatment of bacterial vaginosis, its high relapse rate is a common problem. Bacterial species causing bacterial vaginosis are generally unable to be cultured by conventional methods. It is impractical and inadequate to use culture methods to guide initial treatment. Gram stain of vaginal secretion is a practical tool to establish the diagnosis of bacterial vaginosis. We enrolled 78 cases of Gram stain-proven bacterial vaginosis and tried to use Gram stain as a predictor of relapse after 1 week of treatment with metronidazole. Possible predictive factors for relapse in Gram stain were analyzed, including absence of large Gram-positive rods, presence of small Gram-negative rods, small Gram-variable rods, curved Gram-variable rods, or Gram-positive cocci. Gram stain was repeated immediately after treatment, and at 1 month and 3 months after treatment. All cases showed beneficial clinical effect after metronidazole treatment. Eighteen cases (23.1%) relapsed during the follow-up period. All 16 cases with significant Gram-positive cocci in pretreatment smears relapsed after metronidazole treatment. Presence of small Gram-negative rods, small Gram-variable rods, and curved Gram-variable rods, or absence of large Gram-positive rods did not predict relapse. Gram-positive cocci in pretreatment smear was a good predictor of relapse after metronidazole treatment.

Anti-Infective Agents↗

PubMed2005

Predictors of relapse among pulmonary tuberculosis patients treated in a DOTS programme in South India.

OBJECTIVE: To identify risk factors associated with relapse among cured tuberculosis (TB) patients in a DOTS programme in South India. DESIGN: Sputum samples collected from a cohort of TB patients registered between April 2000 and December 2001 were examined by fluorescence microscopy for acid-fast bacilli and by culture for Mycobacterium tuberculosis at 6, 12 and 18 months after treatment completion. RESULTS: Of the 534 cured patients, 503 (94%) were followed up for 18 months after treatment completion. Of these, 62 (12%) relapsed during the 18-month period; 48 (77%) of the 62 relapses occurred during the first 6 months of follow-up. Patients who took treatment irregularly were twice more likely to have a relapse than adherent patients (20% vs. 9%; adjusted odds ratio [aOR] 2.5; 95% CI 1.4-4.6). Other independent predictors of relapse were initial drug resistance to isoniazid and/or rifampicin (aOR 4.8; 95% CI 2.0-11.6) and smoking (aOR 3.1; 95% CI 1.6-6.0). The relapse rate among non-smoking, treatment adherent patients with drug-sensitive organisms was 4.8%. CONCLUSIONS: The relapse rate under the DOTS programme may be reduced by ensuring that patients take their treatment regularly and are counselled effectively about quitting smoking.

Adult↗