Emanuela Morelli

RD-CODOX-M/IVAC with rituximab and intrathecal liposomal cytarabine in adult Burkitt lymphoma and 'unclassifiable' highly aggressive B-cell lymphoma

Specific trials on adult Burkitt lymphoma (BL) and ‘unclassifiable’ lymphomas with features intermediate between BL and diffuse large B‐cell lymphoma (BL/DLBCL) are advocated which include substantial numbers of older patients, to improve treatment feasibility, while countering risks of systemic and central nervous system (CNS) recurrences. We prospectively evaluated a modified CODOX‐M/IVAC (CODOX‐M: cyclophosphamide, vincristine, doxorubicin, high‐dose methotrexate; IVAC: ifosfamide, etoposide and high‐dose cytarabine) regimen by the addition of rituximab (R) and liposome‐encapsulated cytarabine (D) to increase antitumour activity and halve the number of intrathecal treatments. Thirty adults (40% >60 years) with BL (n = 15) and BL/DLBCL (n = 15) were accrued. Primary endpoints were progression‐free survival (PFS), CNS recurrence, and liposomal cytarabine‐associated toxicity. Eighty percent of patients received the whole treatment programme, the remaining cases received at least three full courses. Application of the RD‐CODOX‐M/IVAC regimen resulted in remarkable 4‐year PFS (78%) and complete remission (CR) rates (93%). However, PFS was significantly lower in patients older than 60 years as compared to younger ones (49%vs 93%, P = 0·03; median, 36 months), despite high actual dose‐intensity, CR rate and tolerability. Reduced‐intensity intratechal prophylaxis through liposomal cytarabine was effective because the CNS failure rate was low (3·4%) and without severe neurological toxicities. The RD‐CODOX‐M/IVAC strategy is feasible and highly effective, but improving outcomes in elderly patients remains a priority.

Biweekly rituximab, cyclophosphamide, vincristine, non-pegylated liposome-encapsulated doxorubicin and prednisone (R-COMP-14) in elderly patients with poor-risk diffuse large B-cell lymphoma and moderate to high 'life threat' impact cardiopathy.

This Phase II study assessed feasibility and efficacy of a biweekly R‐COMP‐14 regimen (rituximab, cyclophosphamide, non‐pegylated liposome‐encapsulated doxorubicin, vincristine and prednisone) in untreated elderly patients with poor‐risk diffuse large B‐cell lymphoma (DLBCL) and moderate to high ‘life threat’ impact NIA/NCI cardiac comorbidity. A total of 208 courses were delivered, with close cardiac monitoring, to 41 patients (median age: 73 years, range: 62–82; 37% >75 years) at a median interval of 15·6 (range, 13–29) days; 67% completed all six scheduled courses. Response rate was 73%, with 68% complete responses (CR); 4‐year disease‐free survival (DFS) and time to treatment failure (TTF) were 72% and 49%, respectively. Failures were due to early death (n = 3), therapy discontinuations (no‐response n = 2; toxicity n = 6), relapse (n = 6) and death in CR (n = 3). Incidence of cardiac grade 3–5 adverse events was 7/41 (17%; 95% confidence interval: 8–31%). Time to progression and overall survival at 4‐years were 77% and 67%, respectively. The Age‐adjusted Charlson Comorbidity Index (aaCCI) correlated with failures (P = 0·007) with patients scoring ≤7 having a longer TTF (66% vs. 29%; P = 0·009). R‐COMP‐14 is feasible and ensures a substantial DFS to poor‐risk DLBCL patients who would have been denied anthracycline‐based treatment due to cardiac morbidity. The aaCCI predicted both treatment discontinuation rate and TTF.

The cumulative amount of serum free light chain is a strong prognosticator in chronic lymphocytic leukemia

Identification of patients at risk of early disease progression is the mainstay of tailored management in chronic lymphocytic leukemia (CLL). Although application of established biomarkers is limited by intrinsic detection/readout complexities, abnormality of κ and λ serum-free light chain ratio [sFLC (κ/λ)] was proposed as a straightforward prognosticator in CLL. By analyzing 449 therapy-naive patients, we show that an abnormal sFLC(κ/λ), along with CD38, ZAP-70, IGHV mutations, cytogenetics and stage, independently predicts treatment-free survival (TFS) but becomes prognostically irrelevant if the cumulative amount of clonal and nonclonal FLCs [sFLC(κ + λ)], a variable associated with cytogenetic risk, exceeds the threshold of 60.6 mg/mL. Patients with sFLC(κ + λ) above cut-off displayed a poorer TFS outcome, irrespective of sFLC(κ/λ). Only ZAP-70, cytogenetics, stage, and TFS remained associated with sFLC(κ + λ) in a multivariate model. By assigning 1 point each for these variables, the 3-year probability of TFS was 94.8%, 84.5%, 61.6%, and 21.1% for patients scoring 0, 1, 2, and 3 + 4, respectively (P < .0001). These data, and the demonstration that monoclonal and polyclonal B cells concur to FLC synthesis in tumor tissues, suggest that sFLC(κ/λ) and sFLC(κ + λ) mirror distinct biologic processes in CLL. sFLC(κ + λ) assessment represents a sensitive and cost-effective tool for identifying CLL patients requiring early treatment.

Erratum to: Multidisciplinary approach and anesthetic management of a surgical cancer patient with methylene tetrahydrofolate reductase deficiency: A case report and review of the literature (Journal of Medical Case Reports (2015) 9:175)

The original version of this article [1] unfortunately contained a mistake. The presentation of the author names is incorrectly marked up and therefore it is presented incorrectly in the HTML version of this article. The corrected author list is given below: Cascella M, Arcamone M, Morelli E, Viscardi D, Russo V, De Franciscis S, Belli A, Accardo R, Caliendo D, De Luca E, Di Caprio B, Di Sauro F, Giannoni G, Iermano C, Maciariello M, Marracino M, Cuomo A. The original article was corrected accordingly.

Multidisciplinary approach and anesthetic management of a surgical cancer patient with methylene tetrahydrofolate reductase deficiency: a case report and review of the literature

IntroductionHyperhomocysteinemia is a known risk factor for myocardial infarction, stroke, peripheral vascular disease, and thrombosis. Elevated plasma homocysteine levels have been demonstrated in patients with recurrent episodes or a single episode of thrombosis. Here we describe the development of cardiovascular disease as a complication of a surgical intervention in a patient with colorectal cancer and hyperhomocysteinemia.Case presentationA 65-year-old Caucasian man complained of pain and constipation, attributed to previously diagnosed adenocarcinoma (stage IIB) of the hepatic flexure. An anamnestic investigation showed that he had undergone two surgical interventions. During both, he suffered thrombotic postoperative complications, a deep vein thrombosis of the upper extremity after the first operation and retinal vein occlusion after the second. He was diagnosed with hyperhomocysteinemia associated with a homozygous C677T mutation of the gene encoding the enzyme methylenetetrahydrofolate reductase. Our patient was initially treated with folic acid and high-dose B vitamins. On day 7 he underwent a right hemicolectomy. Anesthesia was performed with sevoflurane in 40% O2 and without the use of nitrous oxide. Postoperatively, our patient remained on folic acid and B vitamins and was without immediate or subsequent complications.ConclusionsNeoplastic disease and related surgery followed by the administration of chemotherapeutic drugs alter the hemostatic balance in cancer patients. Those suspected of also having a thrombophilic disease require a thorough laboratory diagnostic workup, including a molecular analysis aimed at identifying the genetic mutation responsible for the hyperhomocysteinemia, as indicated. The case described in this report highlights the importance of a multidisciplinary approach that includes expertise in peri-operative anesthesia, surgery, oncology, and hematology.

Efficacy and safety of the third-generation chloroethylnitrosourea fotemustine for the treatment of chemorefractory T-cell lymphomas

Patients with recurring T‐cell non‐Hodgkin lymphoma (T‐NHL) are incurable and candidate for investigational agents. Here, we report on five patients with T‐NHL refractory to multiple chemotherapy lines, including in all cases alkylators and gemcitabine, who received the third‐generation chloroethylnitrosourea fotemustine at a dose of 120 mg/m2 every 21 d, up to eight courses. Median actual dose intensity was 79%; toxicity was manageable and mainly hematological. One complete remission, one partial remission, two protracted disease stabilization, and one transient, minor response were achieved. Time to progression ranged from 48 to 240+ d. This is the first evidence ever reporting the activity of fotemustine in end‐stage T‐NHL. Formal studies with this agent are warranted in T‐cell malignancies.