Months Of Treatment Discontinuation Research Articles

Efficacy and Tolerance of the BNT162b2 Vaccine in Children with Acute Leukemia and Their Siblings: Results of the Phase I-II Pacific Trial

Introduction: Severe forms of COVID-19 caused by SARS-CoV-2 have been observed in children with hematological malignancies. Occurrence of the infection during treatment may significantly delay chemotherapy, potentially exposing patients to a higher risk of relapse. Hence, the timely administration of SARS-CoV-2 vaccines represents a compelling preventive strategy. The PACIFIC trial (NCT04969601) aimed to explore the efficacy and tolerance and of SARS-CoV-2 vaccination in these patients population, at a time when the vaccine was not yet approved for children below the age of 12 years. Methods: A phase I-II dose-finding study was conducted from 2021 to 2023 to assess the efficacy and tolerance of two doses of the BNT162b2 vaccine administered 21 days apart in children with acute leukemia (aged 1 to 15 years) and their siblings (aged ≥ 5 to 15 years). Children with acute lymphoblastic leukemia (ALL) received vaccination during maintenance treatment or within 12 months of treatment discontinuation and children with acute myeloblastic leukemia (AML) were vaccinated within 12 months of treatment discontinuation. For patients under the age of 12 years, a dose escalation using a Bayesian dose escalation scheme (10, 20, or 30 µg) was conducted. Tolerance was assessed by dose-limiting toxicity (DLT), which was defined as the presence of a grade 3 or higher adverse event attributable to the vaccine within 7 days of vaccination. The efficacy end-point was an anti-Spike IgG titer ≥ 260 BAU/ml at 2 months after the first injection. If this criterion was not met, a third vaccine dose was administered. Neutralizing anti-Spike IgG antibodies were assessed. Humoral response was studied at 0, 2 and 6 months after the first vaccine injection. The T-cell specific response was also tested by ELISpot at the same time points. Results: Seventy-six children (61 patients and 15 siblings) were included in the study. Characteristics of children at the study entry, 2 and 6 months after the first dose of the SARS-CoV-2 vaccine are summarized in Table 1. No DLT was reported during the dose escalation phase therefore most children received a 30µg vaccine dose ( Figure 1). No vaccine-related serious adverse events were reported. Two months after the first injection, 32 (52%) patients and 15 (100%) siblings showed an anti-Spike IgG titer ≥ 260 BAU/ml. Approximately half (25/52,48%) of the patients and all (11/11) siblings had neutralizing antibodies. Most (44/55,80%) patients and all (15/15) siblings had a significant T-cell response against CoV2-protein S. Humoral response was significantly different in patients in comparison to siblings (p<0,001) whereas T-cell response was equivalent in the two groups (p=0.1). Twenty-four patients (39%) received a third dose. Forty-three percent achieved an anti-Spike IgG titer ≥ 260 BAU/ml one month after. Six months after the first injection, 34/61 (56%) patients and 14/15 (93%) siblings had still an anti-Spike IgG titer ≥ 260 BAU/ml. Most evaluable patients (31/50,62%) and siblings (9/10, 90%) had neutralizing antibodies. Most patients (41/54,76%) and all siblings (13/13) had still a significant T-cell response against CoV2-protein S. Twenty-six documented infections occurred between D0 and M6: 22 infections in patients and 5 in siblings. The number of infections was not statistically different between the two groups. No severe infections were reported. In patients, 15 infections resulted in a delay of chemotherapy from 5 to 14 days. Conclusion: A vaccination regimen with 2 or 3 doses of 30µg of BNT162b2 vaccine was well tolerated and resulted in a significant and prolonged humoral and cellular response in most children with acute leukemia while completed following the most intensive chemotherapy period. These results show that children with acute leukemia are able to respond to RNA vaccines. Utilizing these vaccines for antitumor purposes to prevent relapse should be further explored.

Factors associated with early relapse of infantile haemangioma in children treated for at least six months with oral propranolol: A case-control study using the 2014–2021 French Ouest DataHub

BackgroundThe factors associated with early relapse of infantile haemangioma (IH) after a first course of treatment with oral propranolol for at least six months (initiated after the marketing authorization had been granted) have not previously been investigated. ObjectivesTo identify factors associated with the risk of early relapse in children with IH treated with oral propranolol according to the current prescribing guidelines. MethodsWe performed a multicentre, retrospective, case-control study, using the Ouest Data Hub database. All children treated for at least 6 months with oral propranolol for IH between 31 June 2014 and 31 December 2021, and with a follow-up visit at least three months after treatment discontinuation were included. A case was defined as relapse of IH within three months of treatment discontinuation; each case was matched for age at treatment initiation and for centre, with four (relapse-free) controls. The association between relapse and treatment or IH characteristics was expressed as an odds ratio (OR) from univariate and multivariate conditional logistic regressions. ResultsA total of 225 children were included. Of these, 36 (16%) relapsed early. In a multivariate analysis, a deep IH component was a risk factor for early relapse [OR = 8.93; 95%CI: 1.0–78.9, p = 0.05]. A propranolol dosage level of less than 3 mg/kg/day protected against early relapse [OR = 0.11; 95%CI: 0.02–0.7, p = 0.02]. Tapering before propranolol discontinuation was not associated with a lower risk of early relapse. ConclusionThe risk factors for late and early relapse are probably different. Investigation of the risk factors for early vs. late IH relapse is now warranted.

Change of CGRP Plasma Concentrations in Migraine after Discontinuation of CGRP-(Receptor) Monoclonal Antibodies.

Discontinuation of treatment with monoclonal antibodies (mAb) targeting the Calcitonin Gene-Related Peptide (CGRP) pathway leads to an increase in migraine frequency. We aimed to assess changes in free and total CGRP plasma concentrations after the discontinuation of CGRP(-receptor) mAbs. This prospective analysis included 59 patients with migraine (n = 25 erenumab, n = 25 galcanezumab, n = 9 fremanezumab) who discontinued mAbs after ≥8 months of treatment. Patients were visited at the time of the last mAb injection (V1) and 16 weeks later (V2). For control, 30 migraine patients without preventive drug therapy were included. We measured free CGRP plasma concentrations in the erenumab and fremanezumab group and total CGRP concentrations in the galcanezumab group. Free CGRP plasma concentrations did not change after treatment discontinuation [erenumab: V1 31.2 pg/mL (IQR 25.8−45.6), V2 30.3 pg/mL (IQR 22.9−47.6), p = 0.65; fremanezumab V1 29.4 pg/mL (IQR 16.4−61.9), V2 34.4 (19.2−62.0), p = 0.86]. Controls had similar CGRP values of 32.6 pg/mL (IQR 21.3−44.6). Total CGRP concentrations in the galcanezumab group were 5439.3 pg/mL (2412.7−6338.1) at V1, and decreased to 1853.2 pg/mL (1136.5−3297.0) at V2 (p < 0.001). Cessation of treatment with CGRP(-R) mAbs did not have an impact on the free-circulating CGRP concentrations. Total CGRP decreased significantly after three months of treatment discontinuation.

Predictive value of FDG-PET imaging for relapse in metastatic melanoma patients treated with immunotherapy.

Anti-PD1 immunotherapy has shown a sustainable clinical activity in patients with metastatic melanoma. However, strong predictive factors of the long-term response or risk of relapse remain to be identified. To determine whether FDG-PET imaging could be superior to CT scan in distinguishing residual tumours versus the absence of tumour in patients with a partial response (PR) or stable disease (SD) and whether a complete metabolic response (CMR) was associated with better outcomes. Retrospective study conducted in all patients with metastatic melanoma treated with anti-PD1 immunotherapy between October 2014 and October 2017 considered to be in complete remission. The primary outcome was the occurrence of a relapse during the follow-up. CT scan and FDG-PET scan had to be performed within a maximum of 2months of treatment discontinuation. For CT imaging, the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 were used and included progressive disease (PD), SD, PR and complete response (CR). For FDG-PET imaging, the metabolic responses were classified as progressive metabolic disease, stable metabolic disease, residual FDG avidity (RFA) and CMR. Twenty-six patients were in complete remission after collegial decision. Two patients had a SD on CT scan and a CMR on FDG-PET scan, and none of them relapsed. Ten patients had a PR on CT scan and a CMR on FDG-PET scan, and none of them relapsed. The mean treatment duration to achieve a complete remission was 7months (3-23). A univariate analysis showed that a RFA assessed on the FDG-PET scan was significantly associated with a relapse (P=0.00231). Most patients with a PR on the CT scan and a CMR on the FDG-PET scan should be considered with a CR. Our study showed that FDG-PET imaging could play a crucial role in predicting the long-term outcome and help to decide whether treatment should be discontinued.

Phase II study of avelumab plus intermittent axitinib in previously untreated patients with metastatic renal cell carcinoma (Tide-A study).

TPS762 Background: The combination of avelumab plus axitinib has been recently reported to be superior than sunitinib alone for treatment of previously untreated mRCC patients (Motzer, NEJM 2019). The study reported a median PFS of 13.8 for the combination of avelumab plus axitinib compared to 8.4 months for sunitinib (p&lt;0.001) with an ORR of 48% vs 24%, respectively. To improve treatment efficacy and safety, TKI discontinuation has been considered in patients treated with sunitinib leading to a longer definitive progression free survival (22.4 months) and overall survival (34.8 months) with a better safety profile (Ornstein, JCO 2017). Despite a new tumor response at TKI reintroduction, many patients progressed after the first months of treatment discontinuation suggesting the necessity to maintain the previous response. This study aims to test if patients achieving a tumor response with the combination of avelumab plus axitinib, can discontinue the TKI in order to delay the resistance and decrease the toxicity related to the combination of therapies. Methods: The single arm, phase II TIDE-A trial, aims to evaluate the activity of avelumab as maintenance therapy in patients with mRCC who achieved a tumor response after the induction phase of therapy with the combination of avelumab and axitinib. Eligible patients have clear cell carcinoma, ECOG performance status 0 or 1, measurable, no bulky disease without tumor-related symptoms or hepatic metastases. Eligible patient will receive the combination of avelumab plus axitinib for 36 weeks. Patients achieving RECIST 1.1 partial response discontinue the axitinib and continue avelumab. At tumor progression, the axitinib will be restarted for at least six months. If a new tumor response is achieved, axitinib will be discontinued again until tumor progression. Patients with RECIST 1.1 stable disease continue the combination of avelumab and axitinib until progression of disease. The primary endpoint is to evaluate the rate of patients free of progression after 8 weeks from axitinib discontinuation. The study is currently ongoing in twenty centres in Italy.

Computational Mechanisms of Effort and Reward Decisions in Patients With Depression and Their Association With Relapse After Antidepressant Discontinuation

Nearly 1 in 3 patients with major depressive disorder who respond to antidepressants relapse within 6 months of treatment discontinuation. No predictors of relapse exist to guide clinical decision-making in this scenario. To establish whether the decision to invest effort for rewards represents a persistent depression process after remission, predicts relapse after remission, and is affected by antidepressant discontinuation. This longitudinal randomized observational prognostic study in a Swiss and German university setting collected data from July 1, 2015, to January 31, 2019, from 66 healthy controls and 123 patients in remission from major depressive disorder in response to antidepressants prior to and after discontinuation. Study recruitment took place until January 2018. Discontinuation of antidepressants. Relapse during the 6 months after discontinuation. Choice and decision times on a task requiring participants to choose how much effort to exert for various amounts of reward and the mechanisms identified through parameters of a computational model. A total of 123 patients (mean [SD] age, 34.5 [11.2] years; 94 women [76%]) and 66 healthy controls (mean [SD] age, 34.6 [11.0] years; 49 women [74%]) were recruited. In the main subsample, mean (SD) decision times were slower for patients (n = 74) compared with controls (n = 34) (1.77 [0.38] seconds vs 1.61 [0.37] seconds; Cohen d = 0.52; P = .02), particularly for those who later relapsed after discontinuation of antidepressants (n = 21) compared with those who did not relapse (n = 39) (1.95 [0.40] seconds vs 1.67 [0.34] seconds; Cohen d = 0.77; P < .001). This slower decision time predicted relapse (accuracy = 0.66; P = .007). Patients invested less effort than healthy controls for rewards (F1,98 = 33.970; P < .001). Computational modeling identified a mean (SD) deviation from standard drift-diffusion models that was more prominent for patients than controls (patients, 0.67 [1.56]; controls, -0.71 [1.93]; Cohen d = 0.82; P < .001). Patients also showed higher mean (SD) effort sensitivity than controls (patients, 0.31 [0.92]; controls, -0.08 [1.03]; Cohen d = 0.51; P = .05). Relapsers differed from nonrelapsers in terms of the evidence required to make a decision for the low-effort choice (mean [SD]: relapsers, 1.36 [0.35]; nonrelapsers, 1.17 [0.26]; Cohen d = 0.65; P = .02). Group differences generally did not reach significance in the smaller replication sample (27 patients and 21 controls), but decision time prediction models from the main sample generalized to the replication sample (validation accuracy = 0.71; P = .03). This study found that the decision to invest effort was associated with prospective relapse risk after antidepressant discontinuation and may represent a persistent disease process in asymptomatic remitted major depressive disorder. Markers based on effort-related decision-making could potentially inform clinical decisions associated with antidepressant discontinuation.

Multiparameter Single Cell Analysis to Identify Immune Cell States That May Contribute to Successful Treatment Discontinuation in Patients with Chronic Myeloid Leukemia

Background: Recently, numerous clinical trials have demonstrated that approximately half of CML patients who have achieved deep and durable remissions on TKI therapy can enjoy prolonged treatment-free remissions. A major question in the field concerns why treatment interruption is not universally successful. Two non-mutually exclusive theories have been proposed to explain successful discontinuation: CML stem cell exhaustion, and immune surveillance. Identification of mediators of CML stem cell exhaustion or successful immune surveillance could lead to adjunctive therapeutic approaches. We set out to determine potential immune mediators of disease control through interrogation of clinical samples using emerging technologies.Results: Consenting patients who discontinued TKI at our institution were grouped into three categories based upon BCR-ABL1 transcript kinetics following treatment discontinuation. Group 1 is characterized by stable undetectable or minimally detectable BCR-ABL1 transcripts. Group 2 exhibited molecular relapse, defined as loss of major molecular response (MMR) requiring treatment re-initiation, typically within the first 3-9 months of treatment discontinuation. Group 3 displays kinetics that are particularly intriguing, whereby the transcript level rises substantially upon treatment cessation, but remains below the MMR threshold despite remaining off TKI therapy. We hypothesize that disease control in group 3, and a subset of patients in Group 1, is mediated by the immune system.To investigate the immune system difference between these groups, we performed single cell immune profiling in the pre- (~ 1 week) and post- (~ 3 months) discontinuation PBMC samples obtained from 15 patients through CyTOF and 10x single cell RNA sequencing. Group 1 consist of 5 patients, group 2 consist of 8 patients, and group 3 consist of 2 patients, respectively. There were no meaningful differences in the immune cell composition prior to TKI discontinuation. Assessment of the immune phenotype 3 months after discontinuation in each group by CyTOF revealed an increase in the CD4+ T cell population in group 3 following TKI discontinuation. Specifically, memory CD4+ T cells and CD38+/HLA-DR+ activated CD4+ T cells were increased in group 3. While patients in groups 1 and 2 showed only decrease or moderate change in memory CD4+ T cells and activated CD4+ T cells, group 3 showed 53% increase of memory CD4+ T cells (21% to 32%) and 640% increase of activated CD4+ T cells (0.4% to 3.3%) following TKI discontinuation. While CD45RA-/CD4+ T cells were increased in abundance, the CD45RA- population was unchanged in CD8+ T cells. 10x single cell RNA sequencing of these samples is ongoing and will be presented.Conclusions: We have conducted multiparameter single cell immune profiling in CML patients with sustained deep molecular remission, loss of MMR, or maintenance of MMR despite a sustained rise in BCR-ABL1 transcript level. Our results suggest that an increase in memory and activated CD4+ T cells following TKI discontinuation may correlate with successful immune surveillance of CML. Assessment of a larger cohort of samples is required to confirm our findings. DisclosuresShah:ARIAD: Research Funding; Bristol-Myers Squibb: Research Funding.

Antiviral response is not sustained after cessation of lamivudine treatment in chronic hepatitis B patients: A 10-year follow-up study

Although the ideal end point for antiviral treatment in patients with chronic hepatitis B (CHB) is loss of HBsAg, the typical clinical end points are HBeAg seroconversion in HBeAg-positive patients and long-term DNA suppression in HBeAg-negative patients. We evaluated the long-term antiviral response after cessation of lamivudine treatment in CHB patients. A total of 157 patients who had discontinued lamivudine between 1997 and 2014 were enrolled (97 HBeAg-positive and 60 HBeAg-negative CHB patients). The long-term durability of the antiviral response (viralogical relapse; HBV DNA ≥104 copies/ml) and the clinical course of these patients were analyzed retrospectively. In HBeAg-positive patients, the mean follow-up period after discontinuation was 72.3 months. The cumulative probabilities of virological relapse at 1, 12, 24, 48, 60, 96, and 120 months were 10.3%, 40.2%, 55.6%, 62.8%, 65.9%, 67.0%, and 67.0%, respectively. In HBeAg-negative patients, the cumulative probabilities of a virological relapse at 1, 12, 24, 48, 60, 96, and 120 months were 25.0%, 35.0%, 41.7%, 43.3%, 43.3%, 46.7%, and 48.3%, respectively. Younger age (HR 1.732, 95%CI: 1.058-2.835, P = 0.02) was predictive of non-virological relapse in HBeAg-positive patients. And achievement of undetectable HBV DNA level within 3 months of treatment discontinuation was associated with decreased rate of virological relapse (HR 0.159, 95%CI: 0.069-0.367 P < 0.01) in HBeAg-negative patients. Despite meeting the requirements for treatment discontinuation, approximately half of the CHB patients treated with lamivudine relapsed. Thus, the antiviral response is not reliably sustained after lamivudine treatment cessation. J. Med. Virol. 89:849-856, 2017. © 2016 Wiley Periodicals, Inc.

Second Attempt to Discontinue TKI in CML Patients Who Have Sustained CMR for over 2 Years Is Rarely Successful Even with the Use of Second Generation TKIs

Second Attempt to Discontinue TKI in CML Patients Who Have Sustained CMR for over 2 Years Is Rarely Successful Even with the Use of Second Generation TKIs

Clinical features and characteristics of Clostridium difficile PCR-ribotype 176 infection: results from a 1-year university hospital internal ward study.

BackgroundClostridium difficile infection (CDI) is a major cause of antibiotic-associated diarrhoea. Given an increasing CDI incidence and global spread of epidemic ribotypes, a 1-year study was performed to analyse the molecular characteristics of C. difficile isolates and associated clinical outcomes from patients diagnosed with CDI in the Internal Medicine department at University Hospital Motol, Prague from February 2013 to February 2014.ResultsA total of 85 unformed stool samples were analysed and CDI was laboratory confirmed in 30 patients (6.8 CDI cases per 10,000 patient bed days and 50.6 CDI cases per 10,000 admissions). The CDI recurrence rate within 3 months of treatment discontinuation was 13.3% (4/30). Mortality within 3 months after first CDI episode was 26.7% (8/30), with CDI the cause of death in two cases. 51.9% of C. difficile isolates belonged to PCR-ribotype 176. MLVA of ribotype 176 isolates revealed two clonal complexes formed by 10/14 isolates. ATLAS scores and Horn’s index were higher in patients with ribotype 176 infections than with non-ribotype 176 infections.ConclusionThis study highlights the clinical relevance of C. difficile PCR-ribotype 176 and its capacity to spread within a healthcare facility.

Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia patients - worldwide battlefield.

Advances in understanding the pathogenesis of chronic myeloid leukemia (CML) and implementation of the therapy with tyrosine kinase inhibitors (TKI) could be considered as aprototype of successful fight against cancer. However, for an optimally responding patient it is recommended to follow the TKI therapy indefinitely. The question about the possibility of safe TKI treatment discontinuation in certain clinical situations was raised and is currently under close investigation worldwide. Currently, imatinib discontinuation trails have shown that about 60% of eligible patients experienced molecular recurrence within 6 months of treatment discontinuation, while the remaining 40% remained in defined deep molecular response throughout the duration of mostly two years follow-up. Interestingly, retreatment with the same TKI or another TKI was successful in the vast majority of patients demonstrating molecular recurrence of the disease. These findings support the concept of safe TKI treatment discontinuation and its usefulness for aspecific subset of CML patients. However, recent data are not sufficient for TKI discontinuation attempts outside clinical trials yet. Because of the high risk of potentially problematic molecular recurrences of the pathological clones, the key question is to find the right predictive marker of TKI discontinuation success, however it stays unsolved yet. This minireview brings aconcise summary of this hot topic with arealistic view from clinical routine. tyrosine kinase inhibitors, imatinib, discontinuation, chronic myeloid leukemia.

Relapse of chronic hepatitis B after discontinuation of nucleos(t)ide analogs: Is the glass half full or half empty?

Relapse of chronic hepatitis B after discontinuation of nucleos(t)ide analogs: Is the glass half full or half empty?

Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: A randomized blinded phase 2 clinical trial

Introduction Denosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclear factor-kappa B ligand (RANKL), an essential mediator of osteoclast formation, function, and survival that has been shown to decrease bone turnover and increase bone mineral density (BMD) in treated patients. We assessed the long-term efficacy and safety of denosumab, and the effects of discontinuing and restarting denosumab treatment in postmenopausal women with low bone mass. Methods Postmenopausal women with a lumbar spine T-score of − 1.8 to − 4.0 or proximal femur T-score of − 1.8 to − 3.5 were randomized to denosumab every 3 months (Q3M; 6, 14, or 30 mg) or every 6 months (Q6M; 14, 60, 100, or 210 mg); placebo; or open-label oral alendronate weekly. After 24 months, patients receiving denosumab either continued treatment at 60 mg Q6M for an additional 24 months, discontinued therapy, or discontinued treatment for 12 months then re-initiated denosumab (60 mg Q6M) for 12 months. The placebo cohort was maintained. Alendronate-treated patients discontinued alendronate and were followed. Changes in BMD and bone turnover markers (BTM) as well as safety outcomes were evaluated. Results Overall, 262/412 (64%) patients completed 48 months of study. Continuous, long-term denosumab treatment increased BMD at the lumbar spine (9.4% to 11.8%) and total hip (4.0% to 6.1%). BTM were consistently suppressed over 48 months. Discontinuation of denosumab was associated with a BMD decrease of 6.6% at the lumbar spine and 5.3% at the total hip within the first 12 months of treatment discontinuation. Retreatment with denosumab increased lumbar spine BMD by 9.0% from original baseline values. Levels of BTM increased upon discontinuation and decreased with retreatment. Adverse event rates were similar among treatment groups. Conclusions In postmenopausal women with low BMD, long-term denosumab treatment led to gains in BMD and reduction of BTM throughout the course of the study. The effects on bone turnover were fully reversible with discontinuation and restored with subsequent retreatment.

Effects of long-term methylphenidate treatment: A pilot follow-up clinical and SPECT study

Background Although abnormalities in the regional cerebral blood flow (rCBF) responses to methylphenidate (MPH) treatment have been reported in children with attention deficit hyperactivity disorder (ADHD), there are few prospective longitudinal studies assessing the long-term effects of MPH and discontinuation effects after chronic treatment. Methods The authors studied ten drug-naive children (2 girls, 8 boys, mean age ± S.D. = 9.60 ± 1.96) diagnosed with ADHD by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnostic criteria, using 99mTc-HMPAO-single photon emission computed tomography (SPECT). Patients were studied at baseline (visit 1), after 2 months of MPH treatment (visit 2) and after a drug-free period of 2 months following 12 months of MPH treatment (visit 3) at doses of 1 mg/kg/day. We evaluated SPECT data visually and semi-quantitatively. Results Two months of chronic MPH treatment resulted in visually detectable improvement in hypoperfusion in the right frontal cortex and all areas of temporal cortex with the exception of left lateral temporal cortex. This improvement was still detectable on visual evaluations of SPECT data after 2 months of treatment discontinuation. The treatment effects that were detected visually were not statistically significant in semi-quantitative analyses. Conclusions Treatment effects of chronic MPH treatment may persist long after the discontinuation of the treatment.

Follow-up of complete cytogenetic remission in patients with chronic myeloid leukemia after cessation of interferon alfa.

A small proportion of patients with chronic myeloid leukemia (CML) achieve a complete cytogenetic response (CCR), defined as the disappearance of Philadelphia (Ph) chromosome-positive metaphases, after treatment with interferon alfa (IFN). In this population of patients, the question of whether treatment should then be withdrawn is not yet resolved. In the present study, we followed 15 patients who stopped IFN after achieving CCR. In nine patients IFN was stopped in view of adverse reactions (n = 8) or patient's choice (n = 1). For the remaining six patients, the treatment was stopped because no BCR/ABL rearrangement could be detected by reverse transcriptase polymerase chain reaction (RT-PCR) in four successive analyses using peripheral-blood samples. Loss of CCR and survival were not statistically different (P =.48; P =.7) for the 15 patients who stopped IFN compared with 41 other CCR patients who continued IFN therapy in our institution. The median follow-up after discontinuation of IFN treatment was 36 months (range, 6 to 108 months). Seven patients (47%) (females, or CCR > 24 months and RT-PCR negative before IFN cessation; P <.0001) did not relapse. Eight other patients (53%) relapsed (lost CCR) within 3 to 33 months of treatment discontinuation. One of them relapsed in major cytogenetic remission (MCR) and was still in MCR 87 months after stopping therapy without any treatment. It is possible to stop IFN treatment at least in some patients with CML who achieve a prolonged period of CCR. This study also illustrates the hypothesis that persistence of low numbers of Ph-positive cells does not necessarily imply hematologic relapse.