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The use of non-pegylated liposomal doxorubicin (Myocet ® ) in diffuse large B-cell lymphoma (DLBCL) has been investigated in retrospective and single-arm prospective studies. This was a prospective phase 2 trial of DLBCL patients ≥60 years old with left ventricular ejection fraction (LVEF) ≥55% randomized to standard R-CHOP or investigational R-COMP (with Myocet ® instead of conventional doxorubicin). The primary end point was to evaluate the differences in subclinical cardiotoxicity, defined as decrease in LVEF to <55% at the end of treatment. Secondary objectives were efficacy, safety, and variations of troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and LVEF along follow-up. Ninety patients were included, 45 in each group. No differences were observed in the percentage of patients with LVEF <55% at end of treatment (11% in R-CHOP arm vs. 7% in R-COMP arm, p = 0.697) or at 4 months (10% vs. 6%, respectively, p = 0.667) and 12 months (8% vs. 7%, respectively, p = 1). However, a higher percentage of R-CHOP compared with R-COMP patients showed increased troponin levels in cycle 6 (100% vs. 63%, p = 0.001) and at 1 month after treatment (88% vs. 56%, respectively, p = 0.015). Cardiovascular adverse events were seen in five R-CHOP patients (nine episodes, four grade ≥3) and in four R-COMP patients (five episodes, all grade 1-2). No significant differences in efficacy were observed. In conclusion, R-COMP is a feasible immunochemotherapy schedule for DLBCL patients ≥60 years, with similar efficacy to R-CHOP. However, the use of non-pegylated doxorubicin instead of conventional doxorubicin was not associated with less early cardiotoxicity, although some reduced cardiac safety signals were observed. Trial registration: ClinicalTrials.gov Identifier: NCT02012088., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The International Prognostic Index (IPI) is the most widely used score for non-Hodgkin lymphoma but lacks the ability to identify a high-risk population in diffuse large B-cell lymphoma (DLBCL). Low absolute lymphocyte count and high monocytes have proved to be unfavourable factors. Red-cell distribution width (RDW) has been associated with inflammation and beta-2 microglobulin (B2M) with tumour load. The retrospective study included 992 patients with DLBCL treated with R-CHOP. In the multivariate analysis, age, Eastern Cooperative Oncology Group performance status (ECOG-PS), stage, bulky mass, B2M, RDW, and lymphocyte/monocyte ratio (LMR) were independently related to progression-free survival (PFS). A new prognosis score was generated with these variables including age categorized into three groups (0, 1, 2 points); ECOG ≥ 3-4 with two; stage III/IV, bulky mass, high B2M, LMR < 2·25 and RDW > 0·96 with one each; for a maximum of 9. This score could improve the discrimination of a very high-risk subgroup with five-year PFS and overall survival (OS) of 19% and 24% versus 45% and 59% of R (revised)-IPI respectively. This score also showed greater predictive ability than IPI. A new score is presented including complete blood cell count variables and B2M, which are readily available in real-life practice without additional tests. Compared to R-IPI, it shows a more precise high-risk assessment and risk discrimination for both PFS and OS., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Background and Objective: The standardization of treatment of older adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) is challenging, especially in the age range of 55-65 years. This study aimed to compare intensive, pediatric-inspired therapy with non-intensive therapy in this population of patients., Patients and Methods: The outcomes of 67 patients prospectively included in two consecutive pediatric-inspired intensive protocols (ALL-HR03 and ALL-HR11) from the Spanish PETHEMA Group were compared with those from 44 patients included in a contemporary semi-intensive protocol (ALL-OLD07)., Results: Baseline patient and ALL characteristics were similar in both groups, except for a younger median age in the intensive group (medians: 58 vs. 62 years). Patients treated intensively had a higher complete remission rate (85% vs. 64%, p = 0.005), a lower cumulative incidence of relapse (39% [95%CI, 25% to 52%] vs. 60% [95%CI, 38% to 77%], p = .003), a similar cumulative incidence of treatment-related mortality (28% [95% CI, 18%, 40%] vs. 21% [95% CI, 10%, 34%]) and superior event-free survival at 2 years (37% [95%CI, 25%-49%) vs. 21% [8%-34%], p = 0.002). On multivariable analysis the type of protocol was the only variable with independent significance for event-free survival (HR [95% CI]: 2 [1.3, 3], p = .002)., Conclusions: Compared with less intensive chemotherapy, pediatric-inspired intensive chemotherapy significantly improves the outcome of older adults with Ph-negative ALL in the age range of 55-65 years., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Follicular lymphoma is characterized by a good response to immunochemotherapy (ICT). However, a small percentage of patients responds poorly to treatment and seems to have a worse outcome. This study attempted to identify the predictive factors and outcome of refractoriness to first-line ICT. All patients diagnosed with stage II to IV follicular lymphoma between 2002 and 2014 and treated with first-line ICT in 4 Spanish institutions were analyzed. Those with no response or progression or relapse within 6 months of first-line response assessment were considered ICT refractory. Three hundred forty-three patients were included (median age 58 years, 48% male), of whom 53 (15%) were ICT refractory. On multivariate analysis, high-risk follicular lymphoma international prognostic index (FLIPI) score, B symptoms, and elevated β2-microglobulin were correlated with refractoriness, and refractoriness, high-risk FLIPI score, and β2-microglobulin were correlated with overall survival (OS). Compared with ICT-sensitive, ICT-refractory patients had a higher incidence of histological transformation (5-year cumulative incidence 25% [14%-39%] vs. 6% [3%-10%], P < .001), a higher rate of refractoriness to second-line therapy (16/33 [48%] vs. 13/57 [23%], P = .01), and a lower OS (5-year OS probability 38% [95% CI 23%-53%] vs. 87% [82%-92%%], P < .001). In conclusion, refractoriness to ICT was seen in 15% of patients and was predicted by high-FLIPI scores, B symptoms, and elevated serum β2-micrglobulin. Immunochemotherapy-refractory patients had a worse prognosis than ICT-sensitive patients, and current treatment options for this subgroup are not satisfactory., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background and Purpose: Mantle cell lymphoma (MCL) is a rare lymphoproliferative disorder, with frequent relapses and a poor prognosis. This study analyzes response to treatment and prognosis in a series of MCL patients., Patients and Method: Retrospective study of MCL patients diagnosed in a single institution between 1996 and 2013. The cohort was divided according to the treatment received., Results: Forty-five patients were included (32 male) with a median age of 66 years old. Twenty-one received intensive chemotherapy or chemoimmunotherapy (based on high-dose cytarabine), 13 semi-intensive (without high-dose cytarabine), 8 not intensive and 3 did not require treatment. Overall response rate was 85% in the intensive and 77% in the semi-intensive treatment groups. In multivariate analysis, intensive treatment was correlated with a longer progression-free survival (hazard ratio 9.8 [95% CI 2.7-35.5], P=.001) and overall survival (4.5 [1.2-17.8], P=.03)., Conclusions: In this retrospective series of MCL patients, intensive treatment was correlated with better outcomes than the other treatment modalities., (Copyright © 2016 Elsevier España, S.L.U. All rights reserved.)

Background and Objective: The prognosis of acute lymphoblastic leukemia (ALL) is poor in older adults and elderly patients, and subtype-oriented prospective trials are scarce in these patients. We present the results of three prospective parallel subtype-oriented protocols in fit patients older than 55 years., Patients and Methods: In 2008, three prospective phase II trials in patients older than 55 years were activated: ALLOLD07 for Philadephia (Ph) chromosome-negative ALL, ALLOPH07 for Ph-positive ALL, and BURKIMAB08 for mature B-ALL. Early death (ED), complete remission (CR), disease-free survival (DFS), overall survival (OS) and toxicity were analyzed., Results: 56, 53 and 21 patients from the ALLOLD07, ALLOPH07 and BURKIMAB08 trials, respectively, were evaluable. CR was 74%, 87% and 70%, with an ED rate of 13%, 11% and 15%, respectively. The medians of DFS were 8 and 38 months for ALLOLD07 and ALLOPH07 protocols, not being achieved in the BURKIMAB08 trial (p=0.001), and the median OS was 12, 37 and 25 months, respectively (p=0.030). Neutropenia, thrombocytopenia and infections were less frequent in the ALLOPH07 trial vs. ALLOLD07 and BURKIMAB trials, and renal toxicity and mucositis were more frequent in the BURKIMAB08 trial vs. the ALLOLD07 and ALLOPH07 trials. ECOG score and WBC count had prognostic significance for OS in ALLOPH07 and BURKIMAB08 trials, whereas no prognostic factors were identified in ALLOLD07 protocol., Conclusion: Subtype-oriented treatment had an impact in the outcome of older adults with ALL. The poorest outcome was observed in Ph-negative non-Mature B-cell ALL patients, for whom improvements in therapy are clearly needed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Local (involved-field or recently involved-site) radiotherapy is the standard therapy in limited-stage follicular lymphoma (FL). We retrospectively analyzed the value of chemotherapy in 130 patients with limited-stage FL (46 treated with radiotherapy alone [RT group], 30 with radiotherapy plus chemotherapy [COMBINED group] and 43 with chemotherapy alone [CHEMO group], 11 were managed with observation). Ninety-six percent of patients responded (RT 98%, COMBINED 100%, CHEMO 91%, p=0.179), and 37% (40/107) of patients in complete response relapsed (RT 42%, COMBINED 27%, CHEMO 41%, p=0.371). Progression-free survival (PFS) and overall survival (OS) probabilities at 10 years were similar in RT, COMBINED and CHEMO patients (PFS 41%, 61% and 39% [p=0.167], and OS 77%, 81% and 72% [p=0.821], respectively), while the COMBINED group showed a trend to better time-to-progression (TTP 43%, 72% and 47% [p=0.055]). On multivariate analysis, only a FLIPI score ≥2 showed a trend to influence PFS (HR 2.1 [95% confidence interval 0.9-4.6], p=0.067), and OS (HR 2.4 [0.9-6.5], p=0.084), while patients treated with radiotherapy plus chemotherapy (COMBINED group) showed a significantly better TTP compared with those receiving only RT (HR 0.3 [0.1-0.8], p=0.024). In our study no benefit was observed in survival with the use of systemic therapy compared with local radiotherapy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The results of intensive immunochemotherapy were analyzed in human immunodeficiency virus (HIV)-related Burkitt lymphoma/leukemia (BLL) in two cohorts (Spain and Germany). Alternating cycles of chemotherapy were administered, with dose reductions for patients over 55 years. Eighty percent of patients achieved remission, 11% died during induction, 9% failed and 7% died in remission. Four-year overall survival (OS) and progression-free survival (PFS) probabilities were 72% (95% confidence interval [CI]: 62-82%) and 71% (95% CI: 61-81%). CD4 T-cell count < 200/μL and bone marrow involvement were associated with poor OS (hazard ratio [HR] 3.2 [1.2-8.3] and HR 2.7 [1.1-6.6]) and PFS (HR 3.5 [1.3-9.1] and HR 2.4 [1-5.7]), bone marrow involvement with poor disease-free survival (DFS) (HR 14.4 [1.7-119.7] and Eastern Cooperative Oncology Group (ECOG) score > 2 (odds ratio [OR] 11.9 [1.4-99.9]) with induction death. In HIV-related BLL, intensive immunochemotherapy was feasible and effective, but toxic. Prognostic factors were performance status, CD4 T-cell count and bone marrow involvement.

Background: The use of rituximab together with intensive chemotherapy in Burkitt's lymphoma or leukemia (BL) has been scarcely explored. This study prospectively evaluated and compared the outcome and toxicity of human immunodeficiency virus (HIV)-positive and HIV-negative patients with BL who were treated in an intensive immunochemotherapy-based and age-adapted trial., Methods: A total of 118 adult patients (80 HIV-negative and 38 HIV-positive) aged 15 to 83 years were treated with 4 (nonbulky stages I-II) or 6 (stages II bulky, III-IV) cycles of intensive chemotherapy combined with rituximab. Reduction in chemotherapy doses and modification of the cycle schedules was performed in patients older than 55 years., Results: The clinical characteristics of HIV-positive patients were comparable with those who were HIV-negative. Complete remission rates were 82% and 87%, respectively, and 9 patients died in induction, 9 died in remission, and 7 relapsed. After a median follow-up of 2.5 years, nonsignificant differences were observed in the 4-year disease-free survival and overall survival (OS) probabilities (77% and 63% for HIV-positive and 80% and 78% for HIV-negative patients, respectively). Young HIV-infected patients presented higher incidences of grade 3 or 4 mucositis and severe infectious episodes. Poor general status and bone marrow involvement, but not advanced age, were associated with a shorter OS, allowing the definition of 3 prognostic groups, with the OS ranging from 50% to 92%., Conclusions: Age-adapted intensive immunochemotherapy is highly effective in both HIV-negative and HIV-positive patients, with a higher toxicity in the latter group. Poor general status and bone marrow involvement had a negative impact on survival., (Copyright © 2013 American Cancer Society.)

The main outcomes of the Programa Español para Tratamiento de Hemopatías (PETHEMA)-acute lymphoblastic leukaemia (ALL)-Ph-08 trial were described and compared with those of the historical PETHEMA-CSTIBES02 trial. The trials differed in imatinib dose (600 vs. 400 mg/d) and amount of chemotherapy (one vs. two consolidation cycles) before stem cell transplantation (SCT). All patients (n = 29) enrolled in the ALL-Ph-08 trial achieved complete remission (CR) (vs. 90% in CSTIBES02), and SCT was performed in CR in 90% (vs. 78%). The reduction in early death, relapse before SCT and transplant-related mortality observed in the ALL-Ph-08 trial resulted in an improved 2-year event-free survival (63% vs. 37%, P = 0·009)., (© 2012 Blackwell Publishing Ltd.)

Background and Objectives: Non-pegylated liposomal doxorubicin is associated with lower cardiac toxicity than conventional doxorubicin, and for that reason it has been used in the treatment of non-Hodgkin's lymphoma (NHL) in old patients or patients with cardiac disease. The objective of this study was to evaluate the efficacy and safety of chemotherapy schedules including non-pegylated liposomal doxorubicin in patients with NHL., Patients and Methods: Retrospective study of NHL patients treated with non-pegylated liposomal doxorubicin in two hospitals. In each patient demographic data, clinical and biological variables, as well as therapy, response and toxicity were recorded., Results: Twenty-six patients were included, 14 (58%) of them were women. Median age was 76 years (range 42-86). The most frequent histological diagnosis was diffuse large B cell lymphoma (DLBCL, 20 patients). The stage disease at diagnosis was III/IV in 19 (73%) patients whereas 12 (57%) of the 21 patients with DLBCL and grade 3 follicular lymphoma had a high-risk International Prognostic Index. Three patients had a left ventricular ejection fraction lower than 50% at the time of starting treatment. The most frequent cardiovascular risk factor was hypertension (50% of the patients) and 6 (23%) had previous heart disease. In all cases non-pegylated liposomal doxorubicin was administered as part of the R-COMP schedule (rituximab, cyclophosphamide, vincristin, non-pegylated liposomal doxorubicin and prednisone), in 20 cases (73%) as first-line treatment and in the remaining 6 as salvage therapy. Two patients died after the first cycle of chemotherapy (one because of sudden death and the other due to disease progression). Eleven (61%) out of the 18 patients receiving R-COMP as first-line therapy achieved a complete response (CR), 5 (28%) achieved partial response (PR) and 2 showed progression. Only one out of the 6 patients receiving R-COMP as salvage therapy achieved CR, whereas 3 had PR and 2 did not respond. Grade 3 or 4 neutropenia was observed in 11 (46%) patients and febrile neutropenia in 10 (42%), while only one patient developed grade 4 thrombocytopenia. The median overall survival was 50,7 months (95% confidence interval [95% CI] 8-93.3) and the median disease free survival was 18,4 months (95% CI 18.1-18.7)., Conclusions: In this cohort of patients, most of them old and with cardiovascular risk factors, the administration of non-pegylated liposomal doxorubicin as part of R-COMP regimen was effective and safe., (Copyright (c) 2009 Elsevier España, S.L. All rights reserved.)