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PubMed1990

Coping responses and relapse among adolescent substance abusers.

The present study investigates self-generated coping strategies and efficacy ratings in high risk for relapse situations of 50 adolescents treated for drug and alcohol abuse. Coping responses and self-efficacy assessments were elicited for self-generated high risk for relapse situations in which all teens successfully abstained and for responses generally used in such situations. Abstainers and relapsers were predicted to generate similar responses for successful abstinence situations, while relapsers were expected to generate fewer coping strategies and lower self-efficacy for high risk relapse situations in general. Teens with the poorest drug use outcome reported use of significantly fewer problem solving coping strategies and less self-efficacy in general high risk relapse situations. Results are discussed in relation to the cognitive behavioral theory of relapse and to previous findings on the process of relapse in teen substance abusers.

Adaptation, Psychological↗

PubMed1990

Factors contributing to skeletal relapse after surgical correlation of mandibular prognathism.

Postoperative follow-up and multiple regression analysis of skeletal relapse following mandibular setback were carried out to clarify the timing and causes of the relapse. The subjects were 24 mandibular prognathism patients. All patients underwent intraoral oblique sagittal splitting osteotomy with circumferential wiring and intermaxillary fixation for 8 weeks. Occlusal splints were not used. Postoperative positional changes of segments were evaluated by lateral cephalograms taken at appropriate intervals. Horizontal relapse was most evident within six months after surgery; vertical relapse seldom occurred. Multiple regression analysis revealed little association between preoperative morphological patterns and postoperative relapse. Although spatial changes of the proximal segment at operation and age of the patient were the best predictors for postoperative horizontal relapse, analysis indicated unsatisfactory prediction of vertical relapse because of its rare occurrence. Based on these results, the aetiology of relapse is discussed and two proposals are suggested for its prevention.

Adolescent↗

PubMed2006

Remission and relapse in psychosis: operational definitions based on case-note data.

BACKGROUND: In psychosis, the prime indicator of outcome has been relapse, but hospital readmission can no longer be used for this purpose. Researchers now require methods for assessing relapse that are objective, blind, reliable and valid. We describe the reliability and validity of such a technique using case-notes. METHOD: Information from routine clinical notes of participants in the Lambeth Early Onset (LEO) study (less all references that would unblind the assessor) were recorded on a form divided into 1-month sections. Operational definitions of remission and relapse enabled clinicians to identify remissions and relapses blindly from the summary information. We calculated reliability regarding both the fact and the timing of remission and relapse. PANSS ratings at 6 and 18 months provided a measure of validity. RESULTS: The kappa value for the identification of remission by individuals ranged from 0.64 to 0.82, while that for consensus between paired raters was 0.56. The corresponding values for relapse were 0.57-0.59 and 0.71. Intra-class correlations for time to remission and to relapse were very high. Raters guessed correctly whether the participants came from the intervention or control group on 60-75% of occasions. Independent PANSS ratings were strongly related to the remission/relapse status of participants. CONCLUSIONS: The reliability of the technique described here was moderate to good, its validity was good, and it provides a useful and timely addition to methods of evaluating remission and relapse in psychosis. On the basis of our experience, we recommend consensus rather than individual ratings.

Data Collection↗

PubMed2004

Cost-effectiveness analysis of a complementary health intervention: the case of smoking relapse prevention.

OBJECTIVES: We assess the cost-effectiveness of smoking relapse prevention interventions designed to keep quitters from resuming the use of cigarettes. Because relapse prevention is complementary to smoking cessation efforts, the appropriate test of its cost-effectiveness is whether it reduces the incremental cost-effectiveness ratio (ICER) of smoking cessation. The major goal of the study is to carry out such a test. METHODS: Data from a randomized trial that ascertained the effectiveness of alternative modes of smoking relapse prevention are combined with ICER estimates of smoking cessation to assess whether relapse prevention is cost-effective. RESULTS: The trial produced convincing evidence that relapse prevention yields statistically significant reductions in the proportion of quitters who are smoking at 24 months postquit. The intervention effects are substantial enough to raise the denominator terms of the smoking cessation ICER and, thereby, offset the amount relapse prevention adds to cost numerator terms. In this sense, smoking relapse prevention tends to pay for itself. CONCLUSIONS: Smoking relapse prevention is a highly cost-effective addition to current efforts to curb cigarette consumption. Complementary health interventions of this sort should be assessed by different methods than those commonly found in the cost-effectiveness literature.

Adolescent↗

PubMed2001

Premenopausal status accelerates relapse in node positive breast cancer: hypothesis links angiogenesis, screening controversy.

Much attention has been given to determining the benefit of mammographic screening to reduce breast cancer mortality. Eight randomized clinical trials have been conducted in four countries: the US, Canada, Scotland and Sweden. Trials report an early and stable 30% reduction in breast cancer mortality for women aged 50-59. For women under 50, unexpectedly, the early years of screening produce a disadvantage to the screened population. Only in later years does an advantage appear. To help understand this, we studied relapse patterns using a breast cancer database of 1,173 pre- and postmenopausal, node negative and positive patients treated with surgery only and having 16-20 years of follow-up. This approach is relevant since at least five of the eight screening trials began before the widespread use of adjuvant chemotherapy in the 1980s. Surgical cure rates were independent of menopausal status. However, a major difference in early relapse rate was found. In premenopausal and node positive patients, 27% of all distant relapses occurred within the first 10 months following resection. This is twice the early relapse frequency of any other clinical group. Using computer simulation, we interpret that these early relapses probably result from a disadvantage induced at surgery. A disinhibition or surgery/wounding induced angiogenic surge might be responsible. Disinhibition is known to occur in animal models such as Lewis lung where lung metastases are avascular and dormant until the primary is removed. Sudden outgrowth of tumor after wounding has been observed for a century. According to the simulation, in breast cancer this induction apparently accelerates inevitable relapses by a median of two years. This is offset in later years with a balancing reduction in relapses. These data suggest that the angiogenic switch may be upregulated more frequently among premenopausal women, perhaps depending upon the sex hormones. The acceleration would cause 0.11 deaths per 1,000 screened aged 40-49 subjects in years 2-3, a value comparable to the early year excess mortality in trials of a significant 0.15 deaths per 1,000 subjects. Equal screening advantage is predicted for node negative (but not node positive) pre- and postmenopausal patients. The acceleration of relapse after surgery may explain the paradoxical effect of mammographic screening for women under 50.

Adult↗

PubMed2002

Influence of Helicobacter pylori infection on healing and relapse of acetic acid ulcers in Mongolian gerbils.

Both Helicobacter pylori and NSAIDs play important roles in the healing and relapse of peptic ulcers in man. We examined how H. pylori infection, indomethacin, and their combination affects the healing of gastric ulcers and whether or not such factors provoke a relapse of healed gastric ulcers in Mongolian gerbils. Gastric ulcers were induced by serosal application of an acetic acid solution. H. pylori (ATCC43504) was orally administered once into animals with active and healed ulcers. Ulcers healed within eight weeks and remained healed for the following six months. H. pylori infection significantly delayed ulcer healing four weeks following infection. Indomethacin treatment showed a tendency to delay ulcer healing. Ulcer healing in H. pylori-infected Mongolian gerbils was significantly delayed by indomethacin. H. pylori infection resulted in a relapse of healed ulcers from one to six months after infection, with a gradual increase in size. By the fourth month following a relapse, the serum gastrin level had significantly increased. H. pylori-induced ulcers in the posterior wall coexisted with relapsed ulcers in the anterior wall five and six months later. Omeprazole markedly prevented the ulcer relapse caused by H. pylori infection. It is concluded that, in Mongolian gerbils, H. pylori infection delayed the healing of preexisting gastric ulcers and resulted in the relapse of healed ulcers, yet indomethacin had little or no effect on ulcer healing or relapse.

Acetic Acid↗

PubMed2003

Histological features associated with relapse after corticosteroid withdrawal in type 1 autoimmune hepatitis.

UNLABELLED: Relapse of type 1 autoimmune hepatitis after drug withdrawal may relate to incomplete histological improvement during corticosteroid therapy and/or persistence of pathogenic mechanisms. AIM: Determine the histological features prior to drug withdrawal that are associated with relapse in patients satisfying pre-established clinical, laboratory, and histological criteria for remission and relapsing after corticosteroid withdrawal. METHODS: One hundred liver tissue samples obtained immediately prior to corticosteroid withdrawal from 88 patients who had previously satisfied criteria for histological remission were reviewed retrospectively. RESULTS: Histological findings in the patients who relapsed were similar to those in the patients who sustained remission in regard to histological activity index (1.7 +/- 0.1 versus 1.6 +/- 0.2, P = 0.6), fibrosis score (2.6 +/- 0.3 versus 2.3 +/- 0.4, P = 0.5), and frequencies of interface hepatitis (36% versus 20%, P = 0.2), cirrhosis (21% versus 17%, P = 0.8), and normal or near normal tissue (9% versus 7%, P > 0.9). Only the presence of portal plasma cells was associated with relapse (31% versus 7%, P = 0.01). The positive predictability of portal plasma cell infiltration for relapse was 92%, but its sensitivity was only 31%. CONCLUSIONS: Portal plasma cell infiltration is predictive of relapse after drug withdrawal in tissue specimens already satisfying criteria for remission. Portal plasma cell infiltration may be indicative of an active antibody-dependent pathogenic mechanism. Its low sensitivity for relapse indicates the need for other complementary predictors of outcome.

Adrenal Cortex Hormones↗

PubMed1989

Prediction of smoking relapse: analyses of temptations and transgressions after initial cessation.

Different types of "relapse crises" and associated coping responses were associated with the resumption of smoking using a prospective design. One hundred and two previously heavy smokers (M = 23.9 cigarettes a day) who achieved initial abstinence through a smoking cessation program were interviewed by telephone at 1, 2, and 3 months posttreatment. At each assessment, subjects described relapse crises, situations in which they were tempted to smoke or actually smoked but resumed abstinence (lapsed). Prospective analyses indicated that any smoking lapse is strongly related to subsequent relapse. Situational characteristics of relapse crises and the number of cognitive and behavioral coping responses reported during crises were only modestly consistent over time and were unrelated to later relapse. Confidence ratings and situational attributions about the relapse crises were also not prospectively associated with eventual relapse. Subanalyses suggested that lapses associated with urges and emotional (guilt) responses and lapses occurring in frequent situations are more likely to result in relapse.

Adaptation, Psychological↗

PubMedDate not supplied

Relapse prevention for alcohol and drug problems: that was Zen, this is Tao.

Relapse prevention, based on the cognitive-behavioral model of relapse, has become an adjunct to the treatment of numerous psychological problems, including (but not limited to) substance abuse, depression, sexual offending, and schizophrenia. This article provides an overview of the efficacy and effectiveness of relapse prevention in the treatment of addictive disorders, an update on recent empirical support for the elements of the cognitive-behavioral model of relapse, and a review of the criticisms of relapse prevention. In response to the criticisms, a reconceptualized cognitive-behavioral model of relapse that focuses on the dynamic interactions between multiple risk factors and situational determinants is proposed. Empirical support for this reconceptualization of relapse, the future of relapse prevention, and the limitations of the new model are discussed.

Alcoholism↗

PubMed1992

Different types of non-P-glycoprotein mediated multiple drug resistance in children with relapsed acute lymphoblastic leukaemia.

Although cellular drug resistance is considered to be an important cause of the poor prognosis of children with relapsed acute lymphoblastic leukaemia (ALL), the knowledge of drug resistance in these patients is very limited. Different aspects of drug resistance were studied in 17 children with relapsed ALL. The in vitro sensitivity profile was determined using the MTT assay. Cells from relapsed children were significantly more resistant to 6-thioguanine, prednisolone, cytosine arabinoside, daunorubicin (DNR), mustine-HCl and mafosfamide but not to L-asparaginase and vincristine (VCR) than cells from 41 children with ALL at initial diagnosis. Some relapsed patients showed a general drug resistance while others were resistant to only 1-3 drugs. The relevance of the multidrug resistance (MDR) model was analysed: In all DNR- and VCR resistant cases a co-resistance to drugs not involved in the MDR model was found. P-glycoprotein was not detected in any of 28 untreated and 14 relapsed samples tested. VCR- and DNR accumulation in the most resistant cells were not lower than in sensitive cells. Resistance modifiers did not potentiate the cytotoxicity of VCR and DNR. We conclude that resistance to anthracyclines and vinca alkaloids in childhood relapsed ALL is not due to P-glycoprotein mediated MDR. Different types of drug resistance varying from a resistance to only one drug to a general chemoresistance, can be detected in children with relapsed ALL. VCR and L-asparaginase seemed to be only infrequently involved in drug resistance. Knowledge of drug resistance might lead to more effective and less toxic therapies for children with relapsed ALL.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

A cannabinoid mechanism in relapse to cocaine seeking.

Treatment of cocaine addiction is hampered by high rates of relapse even after prolonged drug abstinence. This relapse to compulsive cocaine use can be triggered by re-exposure to cocaine, by re-exposure to stimuli previously associated with cocaine or by exposure to stress. In laboratory rats, similar events reinstate cocaine seeking after prolonged withdrawal periods, thus providing a model to study neuronal mechanisms underlying the relapse to cocaine. The endocannabinoid system has been implicated in a number of neuropsychiatric conditions, including drug addiction. The active ingredient of marijuana, Delta9-tetrahydrocannabinol, activates the mesolimbic dopamine (DA) reward system and has rewarding effects in preclinical models of drug abuse. We report here that the synthetic cannabinoid agonist, HU210 (ref. 13), provokes relapse to cocaine seeking after prolonged withdrawal periods. Furthermore, the selective CB1 receptor antagonist, SR141716A (ref. 14), attenuates relapse induced by re-exposure to cocaine-associated cues or cocaine itself, but not relapse induced by exposure to stress. These data reveal an important role of the cannabinoid system in the neuronal processes underlying relapse to cocaine seeking, and provide a rationale for the use of cannabinoid receptor antagonists for the prevention of relapse to cocaine use.

Animals↗

PubMed1999

Autologous stem cell transplantation for relapsed and primary refractory myeloma.

The aim of this study was to evaluate the effectiveness of autologous stem cell transplantation for patients with relapsed or primary chemotherapy-refractory myeloma. Seventy-five patients, 50 men and 25 women, ages 33-68 years (median, 53 years), who underwent transplantation for relapsed or primary refractory myeloma were studied. Patients underwent transplantation 5-88 months (median, 23 months) after diagnosis of myeloma. The time to transplantation was significantly shorter in patients with refractory disease than for those with relapsed myeloma (median, 8 and 32 months, respectively; P < 0.001). Patients with primary refractory myeloma had a significantly lower plasma cell labeling index than those with relapsed disease (P = 0.008). There were no differences in overall and complete response rates between patients with primary refractory and relapsed disease. The median survival of the entire cohort from diagnosis was 53 months. Overall survival from transplantation among patients with relapsed myeloma receiving therapy, relapsed myeloma off therapy, and primary refractory myeloma was significantly different (P = 0.04), with median times of 12, 21 and 30 months, respectively. Progression-free survival also was different (P < 0.001), with median times of 7, 13, and 26 months, respectively. We conclude that overall and progression-free survival in patients with primary refractory myeloma appear better than in patients with relapsed disease and need further study.

Adult↗

PubMed2000

Second allogeneic hematopoietic stem cell transplantation as treatment for leukemia relapsing following a first transplant.

We report 27 patients with relapsed acute or chronic leukemia who underwent a second hematopoietic stem cell transplant (HSCT) from a related or unrelated donor. Seventeen patients were diagnosed with acute myelogenous leukemia (AML), six with acute lymphocytic leukemia (ALL) and four with chronic myeloid leukemia (CML). Ages ranged from 22 to 49 years (median 37); 13 patients were female and 14 male. Relapse was diagnosed between 1 and 45 months after the first HSCT. Sixteen patients who relapsed had received an autologous transplant initially and 11 an allogeneic transplant. Ten patients relapsed within 6 months and 17 patients later than 6 months. Chemotherapy was used as reinduction for relapse after HSCT in 16 patients who had received an autologous transplant and in three who had received an allogeneic transplant, since the latter did not respond to reduction of immunosuppression to induce a graft-versus-leukemia (GVL) reaction. Five of these 19 patients (26%) achieved complete remission (CR), seven patients did not respond to chemotherapy and seven achieved a partial remission (PR). The stem cell source for the second HSCT included bone marrow (n = 12) and PBSC (n = 4) from genotypically identical unrelated donors, PBSC (n = 7) and bone marrow (n = 3) from related donors. Currently eight of the 27 patients are alive and disease-free after the second HSCT. One patient is alive and disease-free after two allogeneic transplants (day +1538), eight patients, who relapsed after an autologous transplant followed by an allogeneic transplant (days +248 to +1140), acute myeloid leukaemia (n = 6) and chronic myeloid leukemia (n = 2) are alive and disease-free. The overall disease-free survival is 30% (8/27). The overall disease-free survival of autologous transplant patients subsequently undergoing an allogeneic transplant is 43% (P = 0.049). It is suggested that a second HSCT is possible for patients with leukemia relapse following the first autologous transplant. A second transplant might also be offered to patients relapsing after the first allogeneic HSCT. Bone Marrow Transplantation (2000) 25, 41-45.

Acute Disease↗

PubMed2003

Bone marrow vs extramedullary relapse of acute leukemia after allogeneic hematopoietic cell transplantation: risk factors and clinical course.

A total of 118 consecutive adult patients with acute leukemia (78 AML, 36 ALL, and four acute mixed lineage leukemia) underwent allogeneic hematopoietic cell transplantation (HCT) after conditioning with BuCy (n=113) or a nonmyeloablative regimen of busulfan-fludarabine (n=5). After a median follow-up of 35.8 months (range, 6.4-91.0), 34 patients experienced at least one episode of leukemia relapse. Of 34 initial episodes, 14 (41%) occurred in extramedullary sites, with (n=8) or without (n=6) concomitant bone marrow involvement. The median time to relapse in the extramedullary sites was longer than that of relapse in bone marrow only (13.5 vs 6.1 months, P=0.046). Acute leukemia subtype and disease status at HCT showed an independent predictive value for overall relapse, as well as for extramedullary relapse with or without bone marrow involvement (Philadelphia chromosome positive acute leukemia vs low-risk AML, relative risk 22.68 (95% CI, 2.18-235.64); other than first CR vs first CR, relative risk 5.61 (95% CI, 1.80-17.51)), but not for bone marrow relapse. Our study suggests that there may be different pathogenetic mechanisms for bone marrow vs extramedullary relapse of acute leukemia after allogeneic HCT. The mode of relapse needs to be investigated in future reports of acute leukemia treated with allogeneic HCT.

Acute Disease↗

PubMed2006

Elevated serum insulin-like growth factor binding protein-2 is associated with a high relapse risk after hematopoietic stem cell transplantation in childhood AML.

Insulin-like growth factor binding protein (IGFBP)-2 has mitogenic effects in normal and neoplastic cells. The purpose of this study is to examine the diagnostic and prognostic significance of elevated IGFBP-2 levels in children with AML after hematopoietic stem cell transplantation (HSCT) at relapse and continuous complete remission (CCR). In 27 children with AML (mean age 13.6+/-5.3 years; patients in remission n=15 with relapse n=12) serum parameters of IGFBP-2, IGFBP-3, IGF-I and IGF-II were analyzed up to 18 months after HSCT by RIA. AML-patients with evidence of relapse demonstrated a continuous increase of IGFBP-2 levels during the follow-up. At day 100 after HSCT, IGFBP-2 concentrations were significantly higher in patients with relapse than in children without relapse (7.4+/-4.0 standard deviation score (SDS) vs 3.9+/-1.7 SDS; P=0.01). Serum IGFBP-2 was identified as an independent factor for the prediction of relapse. Furthermore, the probability of relapse-free survival (RFS) in patients with IGFBP-2 >4.5 SDS at day 100 after HSCT was 31% compared to patients with IGFBP-2 <4.5 SDS was 72% (P=0.004). Patients with IGFBP-2 concentration up to 4.5 SDS more likely developed a relapse and had a poorer outcome. Identification of these patients allows a more individualized and aggressive adjuvant treatment and follow-up.

Adolescent↗

PubMed1997

Immunophenotype of adult and childhood acute lymphoblastic leukemia: changes at first relapse and clinico-prognostic implications.

The immunologic features of leukemic cells at the time of 1st hematologic relapse were compared to those obtained at initial diagnosis in 128 patients (69 children and 59 adults) with acute lymphoblastic leukemia (ALL) treated at a single institution. An immunophenotypic change was observed in 59 cases (46%), more frequently in T (20/25) than in B (39/103) lineage ALL (80 vs 38%, P=0.0008), but with a similar incidence in adults and children. Of these cases, 34 (24 B- and 10 T-ALL) changed at relapse their intralineage subgroup affiliation, although no complete shift from B to T lineage ALL, or vice versa, was observed. The myeloid antigens CD13 and/or CD33 were frequently lost (2/5 cases) or acquired (12/123 cases) at relapse. In 21 cases, the immunophenotype at relapse was more undifferentiated than at diagnosis, while it was more differentiated in 13 cases. Initial treatment intensity or preceding treatment with teniposide did not affect the phenotypic profile at relapse. Complete response (CR) rate to salvage therapy and event-free survival were not influenced by the immunophenotypic shifts, nor by the presence, at relapse, of leukemic cells expressing the myeloid antigens CD13 and/or CD33. Univariate analysis suggested that prognosis after relapse was dependent on the duration of 1st CR, patients' age and immunophenotype at the time of diagnosis, with a worse outcome for patients with T lineage ALL and for patients with the less differentiated subgroup of B lineage ALL (CD19+ and CD10-). Multivariate analysis showed that only two factors, duration of 1st CR and grade of immunologic differentiation at diagnosis, have independent prognostic value in relapsed ALL.

Adolescent↗

PubMed1998

Duration of first remission predicts remission rates and long-term survival in children with relapsed acute myelogenous leukemia.

Although treatment of childhood acute myelogenous leukemia (AML) has substantially improved in the last 15 years, in nearly half of the patients disease recurs. The aim of this study was to establish the prognosis of relapsed childhood AML and to identify prognostic factors for achievement of second remission and survival. From February 1988 to July 1996, 134 children with first relapse of AML were reported to the study center of the AML-BFM group. 102 patients treated intensively to induce second remission were prospectively followed. With various regimens, complete remission was achieved in 52 of 102 patients (51%), 27 children were alive in median 2.5 years (range, 0.4-7 years) after relapse. Disease-free survival was observed in seven of 16 patients transplanted from a matched sibling donor, one of four after matched unrelated bone marrow transplantation, 10 of 22 after autologous transplantation and five of nine patients after chemotherapy alone (two patients were lost to follow-up). Time until relapse reflecting the duration of first remission is the only variable correlating CR and survival rates. Defining early relapse as less than 1.5 years from diagnosis to relapse resulted in a 5-year survival of 10%, s.e. 5% for early relapses and 40%, s.e. 10% for late relapses (P-logrank test, 0.0001). Duration of first remission is a strong predictor for achievement of second CR and survival. It should be considered in reporting results of experimental therapies.

Adolescent↗

PubMed1999

Transplant characteristics: minimal residual disease and impaired megakaryocytic colony growth as sensitive parameters for predicting relapse in acute myeloid leukemia.

Dose escalation during consolidation therapy of de novo AML, including myeloablative chemotherapy supported with autologous peripheral blood stem cell transplantation (aPBSCT), continuously improved outcome. Therefore, quality control of transplants is getting increasing interest. We studied leukapheresis products (LPs), consecutively collected during postremission treatment of 20 patients with de novo AML for minimal residual disease (MRD) by 5-parametric flow cytometry and for myelodysplasia (MDS)-associated alterations by paired lineage-selected colony assays for colony-forming units-megakaryocytes (CFU-mega) and burst-granulocytes-monocytes colony-forming units (CFU) to evaluate the predictive value of these transplant-associated parameters on outcome. We defined the leukemia-associated immunophenotype at diagnosis and studied the impact of MRD detection in LPs collected after double induction with TAD (thioguanine, daunorubicin, cytarabine) and HAM (mitoxantrone, high-dose cytarabine, n=18 patients) and TAD consolidation treatment (n=20 patients) on outcome after aPBSCT. The level of MRD in the transplants correlated with the relapse-free survival (RFS) using a cut-off level of 1 x 10(-3) residual leukemic cells. The median RFS was 6 months for the group with > or = 1 x 10(-3) residual leukemic cells and has not been reached in the group with low MRD levels (< 1 x 10(-3)). By using the same cut-off level a weak correlation could also be demonstrated between MRD in the pregraft bone marrow and RFS (P = 0.04). Quantitatively abnormal megakaryocytic colony growth in the back-up LPs collected after double induction and in the transplant LPs was characterized by the ratio CFU-mega/CFU. In the group of relapsing patients the ratio CFU-mega/CFU was significantly lower than in the group of patients with CCR (P = 0.004), both in the back-ups and in the transplants. All patients with CFU-mega/CFU ratios < 0.12 relapsed, five of seven patients developed MDS before progressing to full leukemic relapse. Using the optimized cut-off level for the ratio CFU-mega/CFU (< vs > or = 0.12), seven of 10 relapsing patients (70%) could be identified to be at risk of relapse, whereas MRD in the transplants identified only 50% of the relapses and MRD in the pregraft bone marrow 25%. In conclusion, the study could identify two pretransplant risk factors predicting relapse in patients with AML receiving aPBSCT in first CR: MRD in transplants as well as MDS-like alterations within the transplants. These results may have multifold implications on the design of risk-adapted chemotherapy as well as on purging techniques and may contribute to a better understanding of leukemogenesis.

Acute Disease↗