Alberto De Crescenzo

The lymphocyte to monocyte ratio improves the IPI‐risk definition of diffuse large B‐cell lymphoma when rituximab is added to chemotherapy

The peripheral blood lymphocyte to monocyte ratio (LMR) at diagnosis can be clinically relevant in patients with diffuse large B‐cell lymphoma (DLBCL). We reviewed the outcome of 1,057 DLBCL patients followed from 1984 to 2012 at four centers. LMR was analyzed as a clinical biomarker by receiver‐operating characteristic (ROC) analysis and Harrells C‐statistics. Patients were characterized by a median age of 61 years, International Prognostic Index (IPI) score of >2 in 39%, and were treated with a rituximab‐containing chemotherapy in 66%. LMR proved strongly predictive for survival in patients treated with rituximab‐based programs, but not in those receiving chemotherapy alone. Additionally, an LMR value of ≤2.6 (as determined by ROC analysis) was associated with a worst performance status, a higher lactate dehydrogenase (LDH) level, an advanced clinical stage, and a higher IPI score (P = 0.000). In patients treated with rituximab‐supplemented chemotherapy programs, an LMR value of <2.6 was found in most of the primary refractory patients (75%) which proved as the best cutoff to predict both response and survival (P = 0.018). Finally, multivariate analysis and Harrells C‐statistics confirmed the IPI‐independent role of LMR on survival (P = 0.0000). In conclusion, LMR is a potent predictor of clinical response and survival in DLBCL treated with rituximab‐containing chemotherapy. Am. J. Hematol. 88:1062–1067, 2013.

Efficacy of rituximab-bendamustine in cold agglutinin haemolytic anaemia refractory to previous chemo-immunotherapy: a case report

Primary cold agglutinin disease (CAD) is a haemolytic anaemia caused by high titres of cold antibodies, usually IgM, directed against red blood cells1,2. Cold agglutinins are present at low titres in all normal individuals, but at high concentrations, the agglutinins can have pathological consequences. In the cool peripheral circulation, cold agglutinin-coated red blood cells activate the complement cascade to the C3b/C3d stage and in the hepatic circulation C3b+ erythrocytes trigger phagocytosis by macrophages. An autoimmune disorder is responsible for the high titres of circulating cold antibodies and CAD accounts for approximately 13–15% of cases of autoimmune haemolytic anaemia3. Moreover, CAD has been found to be associated with a clonal lymphoproliferative disorder in many cases. Indeed, the cold agglutinins are monoclonal IgM in more than 90% of CAD patients and the presence of a lymphoid neoplasm, in particular B-cell non-Hodgkin’s lymphoma (NHL), has been observed in approximately 75% of patients with primary CAD4,5. Treatments, including corticosteroids or alkylating agents, which are effective in other forms of autoimmune haemolytic anaemia are usually ineffective in CAD. On the other hand, half of the patients with CAD respond to rituximab alone, a drug that has markedly improved the prognosis of patients with B-cell lymphomas. Moreover, combining rituximab with fludarabine has further improved the outcome of CAD patients, with a 75% overall response rate being achieved in a recent, prospective trial6. Most CAD patients are elderly and their advanced age makes the use of potentially harmful therapies questionable. It is, therefore, reasonable to search for less toxic regimens for CAD patients. Recently, bendamustine, a molecule analogous to fludarabine, has been successfully employed in the treatment of low-grade B-cell NHL7,8. Compared to fludarabine, bendamustine has fewer side effects and an excellent tolerability. Thus, bendamustine with rituximab might be an effective chemo-immunotherapy option for elderly patients with CAD. The case report here presented, gives support to the use of bendamustine in CAD.

The issue of refractory disease in follicular and other lymphoma subtypes

A evolucao dos linfomas tem sido definitivamente melhorada ao longo das ultimas decadas. Isto se deve principalmente devido a introducao e desenvolvimento de novas e efetivas abordagens terapeuticas. Apesar disto, uma pequena parcela deste notavel grupo de pacientes pode apresentar uma pobre resposta aos tratamentos, com uma verdadeira refratariedade, ou com resposta transitoria e precocemente uma recidiva. A presente revisao aborda este assunto da doenca refrataria nos pacientes com linfoma, enfocando sua incidencia global e os principais aspectos clinicos associados a refratariedade.