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Abstract: The prognostic impact of achieving and in particular maintaining measurable residual disease (MRD) negativity in multiple myeloma is now established; therefore, identifying among MRD-negative patients the ones at higher risk of losing MRD negativity is of importance. We analyzed predictors of unsustained MRD negativity in patients enrolled in the FORTE trial (NCT02203643). MRD was performed by multiparameter flow cytometry (sensitivity of 10-5) at premaintenance and every 6 months thereafter. The cumulative incidence (CI) of MRD resurgence and/or progression was analyzed in MRD-negative patients. A total of 306 of 474 (65%) MRD-negative patients were analyzed. After a median follow-up of 50.4 months from MRD negativity, 185 of 306 (60%) patients were still MRD negative and progression free, 118 (39%) lost their MRD-negative status, and 3 patients (1%) died without progression. Amp1q vs normal (4-year CI, 63% vs 34), ≥2 concomitant high-risk cytogenetic abnormalities vs 0 (4-year CI, 59% vs 33%), circulating tumor cells at baseline (high vs low at 4-year CI, 62% vs 32%), and time-to-reach MRD negativity postconsolidation vs preconsolidation (4-year CI, 46% vs 35%) were associated with a higher risk of unsustained MRD negativity in a multivariate Fine-Gray model. During the first 2 years of maintenance, patients receiving carfilzomib-lenalidomide vs lenalidomide alone had a lower risk of unsustained MRD negativity (4-year CI, 20% vs 33%)., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Lenalidomide-dexamethasone (Rd) is standard treatment for elderly patients with multiple myeloma (MM). In this randomized phase 3 study, we investigated efficacy and feasibility of dose/schedule-adjusted Rd followed by maintenance at 10 mg per day without dexamethasone (Rd-R) vs continuous Rd in elderly, intermediate-fit newly diagnosed patients with MM. Primary end point was event-free survival (EFS), defined as progression/death from any cause, lenalidomide discontinuation, or hematologic grade 4 or nonhematologic grade 3 to 4 adverse event (AE). Of 199 evaluable patients, 101 received Rd-R and 98 continuous Rd. Median follow-up was 37 months. EFS was 10.4 vs 6.9 months (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51-0.95; P = .02); median progression-free survival, 20.2 vs 18.3 months (HR, 0.78; 95% CI, 0.55-1.10; P = .16); and 3-year overall survival, 74% vs 63% (HR, 0.62; 95% CI, 0.37-1.03; P = .06) with Rd-R vs Rd, respectively. Rate of ≥1 nonhematologic grade ≥3 AE was 33% vs 43% (P = .14) in Rd-R vs Rd groups, with neutropenia (21% vs 18%), infections (10% vs 12%), and skin disorders (7% vs 3%) the most frequent; constitutional and central nervous system AEs mainly related to dexamethasone were more frequent with Rd. Lenalidomide was discontinued for AEs in 24% vs 30% and reduced in 45% vs 62% of patients receiving Rd-R vs Rd, respectively. In intermediate-fit patients, switching to reduced-dose lenalidomide maintenance without dexamethasone after 9 Rd cycles was feasible, with similar outcomes to standard continuous Rd. This trial was registered at www.clinicaltrials.gov as #NCT02215980., (© 2021 by The American Society of Hematology.)

Background: Thalidomide plus dexamethasone (TD) is a standard induction therapy for myeloma. We aimed to assess the efficacy and safety of addition of bortezomib to TD (VTD) versus TD alone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma., Methods: Patients (aged 18-65 years) with previously untreated symptomatic myeloma were enrolled from 73 sites in Italy between May, 2006, and April, 2008, and data collection continued until June 30, 2010. Patients were randomly allocated (1:1 ratio) by a web-based system to receive three 21-day cycles of thalidomide (100 mg daily for the first 14 days and 200 mg daily thereafter) plus dexamethasone (40 mg daily on 8 of the first 12 days, but not consecutively; total of 320 mg per cycle), either alone or with bortezomib (1·3 mg/m(2) on days 1, 4, 8, and 11). The randomisation sequence was computer generated by the study coordinating team and was stratified by disease stage. After double autologous stem-cell transplantation, patients received two 35-day cycles of their assigned drug regimen, VTD or TD, as consolidation therapy. The primary endpoint was the rate of complete or near complete response to induction therapy. Analysis was by intention to treat. Patients and treating physicians were not masked to treatment allocation. This study is still underway but is not recruiting participants, and is registered with ClinicalTrials.gov, number NCT01134484, and with EudraCT, number 2005-003723-39., Findings: 480 patients were enrolled and randomly assigned to receive VTD (n=241 patients) or TD (n=239). Six patients withdrew consent before start of treatment, and 236 on VTD and 238 on TD were included in the intention-to-treat analysis. After induction therapy, complete or near complete response was achieved in 73 patients (31%, 95% CI 25·0-36·8) receiving VTD, and 27 (11%, 7·3-15·4) on TD (p<0·0001). Grade 3 or 4 adverse events were recorded in a significantly higher number of patients on VTD (n=132, 56%) than in those on TD (n=79, 33%; p<0·0001), with a higher occurrence of peripheral neuropathy in patients on VTD (n=23, 10%) than in those on TD (n=5, 2%; p=0·0004). Resolution or improvement of severe peripheral neuropathy was recorded in 18 of 23 patients on VTD, and in three of five patients on TD., Interpretation: VTD induction therapy before double autologous stem-cell transplantation significantly improves rate of complete or near complete response, and represents a new standard of care for patients with multiple myeloma who are eligible for transplant., Funding: Seràgnoli Institute of Haematology at the University of Bologna, Bologna, Italy., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Postoperative ischemia may complicate cardiac surgery, despite myocardial protection and recent technical developments. Its medical management in the intensive cardiac care unit is usually efficient, although sometimes it requires the revision of the surgical site. In other cases, urgent coronary angiography and subsequent coronary stenting may resolve the situation. Ostial stenosis of coronary anastomoses is a well-known uncommon but dramatic complication after aortic surgery causing myocardial ischemia. Cases of effort angina have been described several months after surgery, but in some cases, acute myocardial infarction may occur days or weeks after intervention. We here describe an anteroseptal ST-elevation myocardial infarction soon after a Bentall aortic root replacement due to compression of the left main ostium by surgical glue, which has been effectively treated by emergency coronary stenting. This case highlights the importance of a joint management of acute myocardial ischemia after cardiac surgery by the cardiac surgeon and the interventional cardiologist., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: This study was designed to evaluate if patients in whom in-stent restenosis developed had an higher risk of early venous graft failure compared with normal patients., Methods: The study cohort comprised 120 patients (60 with previous in-stent restenosis and 60 controls) who received a total of 165 complementary venous grafts on the circumflex or right coronary artery system (84 in the restenosis group and 81 in the control group). All patients were prospectively followed-up and underwent reangiography at 5-years follow-up., Results: In the restenosis group, 28 venous grafts (33.%) were perfectly patent, 10 showed major irregularities, and 46 were occluded. In the control patients, 50 grafts (61.7%) were perfectly patent (p < 0.001 compared with the restenosis series), 12 showed major irregularities (p = .74), and 19 were occluded (p < 0.0001). In contrast, the 5-year outcome of internal thoracic artery grafts was not affected by history of in-stent restenosis., Conclusions: Patients who developed in-stent restenosis have an higher risk of early venous graft failure compared with the control patients. Arterial grafts should probably be preferred in these patients.

The aim of the present study was to compare thalidomide-dexamethasone (Thal-Dex) and vincristine-doxorubicin-dexamethasone (VAD) as primary therapy in preparation for autologous peripheral blood stem-cell (PBSC) transplantation for multiple myeloma (MM). For this purpose, we performed a retrospective matched case-control analysis of 200 patients who entered 2 consecutive studies from 1996 to 2004 and received Thal-Dex (n = 100) or VAD (n = 100) administered for 4 months before collection of PBSCs and autologous transplantation. Matching criteria included age, clinical stage, and serum beta2-microglobulin levels. In comparison with VAD, Thal-Dex resulted in a significantly higher response rate (52% versus 76%, respectively; P < .001) and effected more profound reduction in myeloma cell mass of both immunoglobulin G (IgG; P = .02) and IgA (P = .03) type. More frequent toxicities included nonfatal deep vein thrombosis with Thal-Dex (15%) and granulocytopenia with VAD (12%). In each of the 2 treatment groups, 91% of patients proceeded to PBSC mobilization. The median number of collected CD34+ cells was 7.85 x 10(6)/kg in the Thal-Dex group and 10.5 x 10(6)/kg in the control group. Thal-Dex may be considered an effective and relatively well-tolerated oral alternative to the more complex VAD regimen as front-line therapy for MM patients who are candidates for subsequent autologous transplantation.

We used a sensitive real-time reverse transcription-polymerase chain reaction assay to quantify cyclin D1 mRNA levels in bone marrow samples collected at diagnosis from 74 newly diagnosed multiple myeloma (MM) patients who were randomized to undergo either single or double autologous peripheral blood stem cell transplantation as part of first-line therapy for their malignancy. In 46 cases, fluorescence in situ hybridization (FISH) analysis and/or conventional cytogenetics were performed to detect chromosome 11 abnormalities. Patients with the t(11;14) or trisomy 11 significantly overexpressed cyclin D1 (P <.0001) in comparison with patients without 11q abnormalities, who had cyclin D1 mRNA levels similar to healthy donors. Overall, 32 (43%) of 74 patients showed cyclin D1 overexpression. No difference was found between cyclin D1-positive (group A) and cyclin D1-negative (group B) patients with respect to presenting clinical and laboratory characteristics, including chromosome 13 abnormalities, as well as to response to therapy and overall survival, both of which were calculated on an intent-to-treat basis. Patients who overexpressed cyclin D1 had significantly longer duration of remission in comparison with patients who did not (41 vs 26 months, respectively; P =.02). As a result, median event-free survival (EFS) was longer in group A than in group B (33 vs 24 months, respectively; P =.055). We concluded that cyclin D1 overexpression is closely associated with 11q abnormalities and identifies a subset of MM patients who are more likely to have prolonged duration of remission and EFS following autologous transplantation.

We assessed the hematopoietic recovery and transplantation-related mortality (TRM) of patients who had failed peripheral blood stem cell mobilization and subsequently received high-dose chemotherapy supported by granulocyte colony-stimulating factor (G-CSF)-primed bone marrow (BM). Studied were 86 heavily pretreated consecutive patients with acute leukemia (n = 21), refractory/relapsed non-Hodgkin lymphoma (n = 41) and Hodgkin disease (n = 17), and multiple myeloma (n = 7). There were 78 patients who showed insufficient mobilization of CD34+ cells (< 10 cells/microL), whereas 8 patients collected less than 1 x 106 CD34+ cells/kg. BM was primed in vivo for 3 days with 15 to 16 microg/kg of subcutaneous G-CSF. Median numbers of nucleated cells, colony-forming unit cells (CFU-Cs), and CD34+ cells per kilogram harvested were 3.5 x 10(8), 3.72 x 10(4), and 0.82 x 10(6), respectively. Following myeloablative chemotherapy, median times to achieve a granulocyte count higher than 0.5 x 10(9)/L and an unsupported platelet count higher than 20 and 50 x 10(9)/L were 13 (range, 8-24), 15 (range, 12-75), and 22 (range, 12-180) days, respectively, for lymphoma/myeloma patients and 23 (range, 13-53), 52 (range, 40-120), and 90 (range, 46-207) days, respectively, for leukemia patients. Median times to hospital discharge after transplantation were 17 (range, 12-40) and 27 (range, 14-39) days for lymphoma/myeloma and acute leukemia patients, respectively. TRM was 4.6%, whereas 15 patients died of disease. G-CSF-primed BM induces effective multilineage hematopoietic recovery after high-dose chemotherapy and can be safely used in patients with poor stem cell mobilization.

Purpose: In the last years, fludarabine (FLU) alone or in combination with other drugs has been reported to be effective in the treatment of previously treated low-grade non-Hodgkin's lymphomas (LG-NHL). The aim of this study was to define the therapeutic efficacy and toxicity of a combination of FLU and mitoxantrone (FN regimen) in untreated LG-NHL., Patients and Methods: We used a two-drug combination of FLU (25 mg/m2 i.v. on days 1 to 3) and mitoxantrone (10 mg/m2 i.v. on day 1) to treat 27 previously untreated patients with LG-NHL, Chemotherapy was repeated every four weeks for a total of six cycles. Among 27 patients, 17 (63%) were diagnosed with follicular, 6 (22%) with small lymphocytic, and 4 (15%) with immunocytoma subtypes., Results: Of the 27 patients, 18 (67%) achieved complete response (CR) and 6 (22%) partial response, while the remaining 3 (11%) showed no benefit from the treatment. Regarding histology, in the follicular subtype we observed an overall response rate of 94%, with a 76.5% CR rate. The estimated two-year relapse-free survival was 83%, and overall survival was 92%. Hematologic grade 3-4 toxicity was seen in only five (3.3%) patients; no opportunistic infections or deaths were associated with the administration of the FN regimen., Conclusions: These preliminary data show that the FN regimen is a very active, well-tolerated combination chemotherapy for untreated patients with advanced LG-NHL.

Background: Treatment of both Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL) with abdominal presentation at the time of diagnosis is often followed by detection of residual masses by computed tomography (CT). However, CT is usually unable to discriminate between residual tumor and fibrosis/necrosis. We investigated the ability of fluorine-18 fluorodeoxyglucose positron emission tomography (PET) to differentiate between residual active tumor tissue and fibrosis., Patients and Methods: Forty-four patients with HD or aggressive NHL presenting abdominal involvement (41% with bulky mass) were studied with CT and PET at the end of chemotherapy +/- radiation therapy., Results: After treatment, seven patients had negative PET and CT, and none of them relapsed. The remaining 37 patients all had positive CT (abnormalities < or = 10%). All of the 13 who also had positive PET relapsed (100%). By contrast, there was only 1 (4%) relapse among the 24 patients who were positive at CT but negative at PET. The two-year actuarial relapse-free survival rate was 95% for those with negative PET compared with 0% for positive PET patients (P < 0.000000)., Conclusions: In lymphoma patients with abdominal masses who present CT positivity at restaging, PET should be considered the noninvasive imaging modality of choice for differentiating early recurrences or residual disease from fibrosis.

Background: This study was designed to evaluate the efficacy of a protocol of systematic screening of the ascending aorta and internal carotid arteries and individualization of the surgical strategy to the ascending aorta and internal carotid arteries status in reducing the stroke incidence among patients undergoing coronary artery bypass grafting., Methods: On the basis of a pre- and intraoperative screening of the ascending aorta and internal carotid arteries, 2,326 consecutive patients undergoing coronary artery bypass grafting were divided in low, moderate, and high neurologic risk groups. In the high-risk group dedicated surgical techniques were always adopted and the reduction of the neurologic risk was considered more important than the achievement of total revascularization., Results: The incidence of perioperative stroke in the high-risk group was similar to those of the other two groups (1.1 versus 1.3 and 1.1%, respectively; p = not significant); however, angina recurrence was significantly more frequent in the high-risk group., Conclusions: The described strategy allows a low rate of perioperative stroke in high-risk patients undergoing coronary artery bypass grafting. Whether the reduction of the neurologic risk outweighs the benefits of complete revascularization remains to be determined.