The prognosis of diffuse large B‐cell lymphoma (DLBCL) patients depends on lymphoma‐ and patient‐related risk factors and is best estimated by the international prognostic index (IPI). The aim of the study was to determine whether the average relative dose intensity (ARDI) of an anthracycline‐containing regimen could predict DLBCL outcome independently from the IPI. We analyzed 223 white Caucasian DLBCL patients who completed at least four cycles of first‐line immunochemotherapy with rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R‐CHOP). The ARDI was calculated by specially developed software in each individual patient, simultaneously with the chemotherapy prescription, which instantly revealed all causes of its decrease. The relevance of the ARDI for progression‐free/overall survival (PFS/OS) was evaluated. Prolonged intervals between cycles of immunochemotherapy—the most common cause of decreased ARDI (49.3%, 110/223)—were due to neutropenia (absolute neutrophil count <1.0 × 109/L) and infections. Reductions in cytostatic doses were observed in 19.7% (44/223) of patients, mainly as the consequence of cardiotoxicity (23/223, 10.3%). The OS varied significantly when the ARDI was >90% (P < 0.00001). Multivariate analysis confirmed that an ARDI>90% was an IPI‐independent predictor of prolonged PFS (HR = 0.31; 95%CI: 0.20‐0.47; P < 0.00001) and OS (HR = 0.32; 95%CI: 0.21‐0.48; P < 0.00001). With an analytic tool allowing real‐time ARDI assessment, it was possible to maintain an ARDI above 90% in 161 of 223 patients (72%). DLBCL patients with an ARDI >90% have significantly better outcome regardless of the IPI; therefore, our official recommendation is an adequate dose density through efficient neutropenia prophylaxis and cardiac protection.
Background: Advances in anti-lymphoma therapy prolong overall survival, making late adverse effects, like doxorubicin-related cardiotoxicity, an even more important clinical issue. The effectiveness of cardioprotective strategies with close monitoring, angiotensin-converting enzyme inhibitors and/or β-blockers as well as liposomal doxorubicin are still unconfirmed in clinical practice. Methods: This study evaluated the role of a primary cardioprotection strategy in preventing cardiovascular mortality and heart failure occurrence in non-Hodgkin lymphoma (NHL) patients with a high risk of anthracycline cardiotoxicity. Thirty-five NHL patients were subjected prospectively to ramipril and/or bisoprolol at NHL diagnosis, before implementing doxorubicin-containing regimens. Additionally, patients with a diagnosis of asymptomatic/mild heart failure received the liposomal form of doxorubicin. The clinical outcome and frequency of all serious cardiac events were compared with the results in a historical cohort of 62 high-risk cases treated without primary cardioprotection. Results: NHL patients with a primary cardioprotection strategy did not experience cardiovascular deaths in contrast to the retrospective control group where cardiovascular mortality was 14.5% at 3 years (p < 0.05). Primary cardioprotection also decreased the frequency of new cardiotoxicity-related clinical symptoms (2.8 vs. 24.1%; p < 0.05) and prevented the occurrence of cardiac systolic dysfunction (0 vs. 8.5%, respectively; p < 0.05). Although the study was not planned to detect any survival benefit, it demonstrated a trend towards increased response rates (complete response 82 vs. 67%; p not significant) and prolonged survival (projected 5-year overall survival 74 vs. 60%; p < 0.05) for patients treated with primary cardioprotection. Conclusions: A primary personalized cardioprotection strategy decreases the number of cardiac deaths and may potentially prolong overall survival in NHL patients with increased risk of anthracycline cardiotoxicity.
Lymphomas with primary or secondary involvement of central nervous system (CNS) have poor prognosis despite specific treatment protocols which include whole brain radiotherapy and high-dose systemic and/or intrathecal chemotherapy. Toxicity of intrathecal liposomal cytarabine-based regimens collected between November 2006 and January 2012 was assessed retrospectively. Data from 120 adult lymphoma patients with, or at high risk of CNS involvement who received intrathecal liposomal cytarabine-based regimens at six Polish Lymphoma Research Group centres between November 2006 and January 2012 were assessed retrospectively. Patients were divided into three cohorts: A (high risk of CNS disease, n = 88), B (cerebrospinal fluid pleocytosis without neurological symptoms or pathological imaging findings, n = 7), and C (CNS disease/neurological involvement; n = 25). In all examined groups, toxicity of treatment was found to be acceptable (including the prophylactic setting). None of the patients in cohorts A or B who took intrathecal liposomal cytarabine 50 mg, repeated every 2–4 weeks (mean 3.8 doses) had experienced a CNS relapse at a median follow-up time of 3 years. Patients in cohort C had a 76 % overall neurological response rate (including a 40 % complete response rate) and median overall survival of 4.8 years. Regimens incorporating liposomal cytarabine seem to be safe and effective treatments for lymphomas with CNS involvement.
Autologous hematopoietic stem cell transplantation (autoHSCT) requires collection of sufficient number of hematopoietic stem cells. The goal of this study was to evaluate efficacy of plerixafor used in patients with lymphoid malignancies failing conventional stem cell mobilization.This was a prospective, non-interventional study. All consecutive patients (n = 109) treated with plerixafor in 11 centers were reported. The drug was used either in case of previous mobilization failure (n = 67) or interventionally, in case of insufficient CD34+ cell output during current mobilization (n = 42). Successful mobilization was defined as resulting in collection of ≥ 2 × 106 CD34+ cells/kg for single autoHSCT or ≥ 4 × 106 CD34+ cells/kg for double procedure.The overall rate of successful mobilization was 55% (55% for single and 56% for double autoHSCT). The median total number of collected CD34+ cells/kg was 2.4 (range, 0-11.5) for patients intended for a single transplantation while 4.0 (0.6-16.9) for double procedure. The number of circulating CD34+ cells increased after the use of plerixafor regardless of baseline values. The median fold increase was 3.3 (0.3-155). Data from this observational study confirm high efficacy of plerixafor used in routine clinical practice as salvage for patients with lymphoid malignancies failing conventional stem cell mobilization.
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