Age and dPCR can predict relapse in CML patients who discontinued imatinib: the ISAV study.

Imatinib is effective for the treatment of chronic myeloid leukemia (CML). However even undetectable BCR-ABL1 by Q-RT-PCR does not equate to eradication of the disease. Digital-PCR (dPCR), able to detect 1 BCR-ABL1 positive cell out of 10(7) , has been recently developed. The ISAV study is a multicentre trial aimed at validating dPCR to predict relapses after imatinib discontinuation in CML patients with undetectable Q-RT-PCR. CML patients under imatinib therapy since more than 2 years and with undetectable PCR for at least 18 months were eligible. Patients were monitored by standard Q-RT-PCR for 36 months. Patients losing molecular remission (two consecutive positive Q-RT-PCR with at least 1 BCR-ABL1/ABL1 value above 0.1%) resumed imatinib. The study enrolled 112 patients, with a median follow-up of 21.6 months. Fifty-two of the 108 evaluable patients (48.1%), relapsed; 73.1% relapsed in the first 9 months but 14 late relapses were observed between 10 and 22 months. Among the 56 not-relapsed patients, 40 (37.0% of total) regained Q-RT-PCR positivity but never lost MMR. dPCR results showed a significant negative predictive value ratio of 1.115 [95% CI: 1.013-1.227]. An inverse relationship between patients age and risk of relapse was evident: 95% of patients <45 years relapsed versus 42% in the class ≥45 to <65 years and 33% of patients ≥65 years [P(χ(2) ) < 0.0001]. Relapse rates ranged between 100% (<45 years, dPCR+) and 36% (>45 years, dPCR-). Imatinib can be safely discontinued in the setting of continued PCR negativity; age and dPCR results can predict relapse.

Comparison of clinical competency self-assessments among Advanced Education in General Dentistry (AEGD) residents before and during COVID-19 pandemic.

PURPOSE/OBJECTIVES: Self-assessment of clinical competence is an important tool for effective learning and training for some educational programs. The New York University (NYU) Langone Hospital's Advanced Education in General Dentistry (AEGD) Program has had its residents complete self-assessment of clinical competency evaluations for many years. The evaluation is used to understand the residents' perception of their own clinical skill upon beginning the program and to determine the necessary resources to provide to the residents for them to meet program standards. The same evaluation is completed by the residents 6 months later to determine if they perceived advancement in their clinical performance while in the program. Dental education, along with other fields of education was disrupted by the coronavirus disease 2019 (COVID-19) pandemic. The purpose of this study was to examine the impact of COVID-19 on clinical competency self-assessments among the NYU Langone AEGD residents before and during the pandemic. METHODS: In this cross-sectional study, data was collected from two AEGD cohorts representing 2019-2020 and 2020-2021 academic years; from July 2019 (n = 196) to January 2020 (n = 189) and July 2020 (n = 202) to January 2021 (n = 184). The self-assessment evaluations were administered via an online residency management platform on the first days of July and January of the academic year. The survey consisted of 48 questions on "clinical skills and performance" as established by CODA standards for postdoctoral general dentistry programs. RESULTS: Survey response rate was 100% for both cohorts. When comparing results, the findings indicate the COVID-19 pandemic had interrupted clinical learning during dental school. However, training through the AEGD program led to improvements in perceived clinical competence by the residents in mid-program evaluation. CONCLUSION: The self-assessment evaluation can be used as a tool to enhance training as part of the AEGD program's performance improvement plan.

Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib.

BACKGROUND: Imatinib slows development of chronic myeloid leukemia (CML). However, available information on morbidity and mortality is largely based on sponsored trials, whereas independent long-term field studies are lacking. PATIENTS AND METHODS: Consecutive CML patients who started imatinib treatment before 2005 and who were in complete cytogenetic remission (CCyR) after 2 years (± 3 months) were eligible for enrollment in the independent multicenter Imatinib Long-Term (Side) Effects (ILTE) study. Incidence of the first serious and nonserious adverse events and loss of CCyR were estimated according to the Kaplan-Meier method and compared with the standard log-rank test. Attainment of negative Philadelphia chromosome hematopoiesis was assessed with cytogenetics and quantitative polymerase chain reaction. Cumulative incidence of death related or unrelated to CML progression was estimated, accounting for competing risks, according to the Kalbleisch-Prentice method. Standardized incidence ratios were calculated based on population rates specific for sex and age classes. Confidence intervals were calculated by the exact method based on the χ(2) distribution. All statistical tests were two-sided. RESULTS: A total of 832 patients who were treated for a median of 5.8 years were enrolled. There were 139 recorded serious adverse events, of which 19.4% were imatinib-related. A total of 830 nonserious adverse events were observed in 53% of patients; 560 (68%) were imatinib-related. The most frequent were muscle cramps, asthenia, edema, skin fragility, diarrhea, tendon, or ligament lesions. Nineteen patients (2.3%) discontinued imatinib because of drug-related toxic effects. Forty-five patients lost CCyR, at a rate of 1.4 per 100 person-years. Durable (>1 year) negative Philadelphia chromosome hematopoiesis was attained by 179 patients. Twenty deaths were observed, with a 4.8% mortality incidence rate (standardized incidence ratio = 0.7; 95% confidence interval = 0.40 to 1.10, P = .08), with only six (30%) associated with CML progression. CONCLUSIONS: In this study, CML-related deaths were uncommon in CML patients who were in CCyR 2 years after starting imatinib, and survival was not statistically significantly different from that of the general population.

Prolonged overall survival with second on-demand autologous transplant in multiple myeloma.

Between August 1993 and March 2003, 130 consecutive multiple myeloma (MM) patients eligible for high-dose treatment were offered a program including up-front autologous stem cell transplantation (ASCT) after conditioning with 200 mg/m(2) melphalan followed by a second ASCT in case of relapse or progression. A total of 107 (82%) patients completed the first ASCT. The best response obtained after ASCT was complete response (CR) 23%, very good partial response (VGPR) 28%, partial response (PR) 42%, and minimal response (MR) 7%. Median overall survival (OS) and event-free survival (EFS) were 65.4 and 27.7 months, respectively. Relapse or progression occurred in 70 patients; 26 received a second ASCT (with a median time of 20.4 months from first ASCT). A major response (> or =PR) was obtained in 69% of these patients. Median OS and EFS after the second ASCT were 38.1 and 14.8 months. Treatment-related mortality was 1.9% after the first ASCT but no deaths occurred after the second. Our experience suggests that elective up-front single ASCT followed by second ASCT after relapse or progression is a safe and effective global strategy to treat MM patients.

Association between Enterococcus bacteraemia and death in neutropenic patients with haematological malignancies.

Fatality rates and prognostic factors for mortality due to Enterococcus spp. bacteraemia have not yet been fully defined in the setting of neutropenic patients affected with haematological malignancies. We have performed a retrospective, multi-centre cohort study on 98 episodes of Enterococcus bacteraemia occurring in patients hospitalised from January 1984 to December 2001 at the oncohaematology units in two tertiary-care hospitals (Verona Hospital and Vicenza Hospital, in north-east Italy). E. faecalis was isolated in 52 cases (53%), E. faecium in 39 (39.8%), E. avium in four, E. durans in one, and untyped Enterococcus spp. in two other cases; vancomycin resistance was detected in 15 (15.3%) isolates. A global mortality rate of 41.8% (41/98 cases) was revealed; Enterococcus spp. bacteraemia was associated with a fatal outcome in 29/98 cases (29.5%). The following variables were independently associated with an increased risk of death by multivariate analysis of survival: age > or =50 years (OR 3.74; 95% CI 1.35-10.32), pneumonia (OR 4.70; 95% CI 1.67-13.20), and shock (OR 13.7; 95% CI 1.23-152.43), while the initial phase of haematological disease (responsive to chemotherapy) appeared to be protective (OR 0.23; 95% CI 0.008-0.64, P level 0.005); however, pneumonia alone (OR 7.2, 95% CI 2.52-20.88) was independently associated with fatal outcome by multivariate analysis for death related to enterococcal bacteraemia. In our experience, the poor outcome proper to enterococcal bacteraemia appears to be directly related to underlying disease, patient's age, presence of pneumonia and shock; in contrast, severe neutropaenia, antibiotic resistance, and species of Enterococcus do not appear to affect the fatality rate significantly.

Transplant-finalized salvage of adult acute lymphoblastic leukemia: results of a mitoxantrone- and methotrexate-based regimen in 36 patients.

Idarubicin-based induction programs in acute lymphoblastic leukemia (ALL) account for 75?-?85% of complete remission rate. A small amount of patients exhibit primary refractoriness, and approximately 60% of those achieving a remission eventually relapse. The present study aimed to review the outcome of patients relapsing after or resistant to an idarubicin-based, induction-consolidation regimen (with/without additional high dose cytarabine). The 'ABC' phase II trial consisted of mitoxantrone (50 mg/m(2) over 5 days) associated with high-dose methotrexate (1.5 g/m(2) over 24 h, followed by folinic acid rescue), high-dose methyl-prednisolone (125 mg b.i.d.) and vincristine, plus granulocyte colony-stimulating factor. Eligible patients were treated with two courses ('A' and 'B', the latter with reduced drug dosages), followed by allogeneic or autologous haematopoietic stem cell transplantation (HSCT, 'C'). Thirty-six patients (3 primary resistant, 33 at first marrow relapse) were evaluated. With 'A', 21 achieved a complete remission (CR), 10 were refractory and 5 died early. Eighteen patients received 'B' (with one more CR, for an overall CR rate of 61%) and, eventually, 12 patients had 'C' procedures (7 autologous, 5 allogeneic HSCT). WHO grade >or=3 treatment-related toxicity developed in 50% and 34% of 'A' and 'B' courses, respectively. The median duration of CR was 5.2 (range 0.5-19.7) months and median overall survival was 7.6 (range 0.5-20) months. In spite of 12 HSCTs, there was no long-term survivor. 'ABC' salvage proved feasible and comparable to reported rescue chemotherapic regimens, but the achievement of cure in refractory/relapsing ALL remains an outstanding clinical task.