Poster Session II: Bone marrow failure syndromes incl PNH - Clinical
Late onset neutropenia (LON) has been recognized as a side effect of therapy with rituximab, defined as grade III-IV neutropenia (CTCAE) 3-4 weeks after the last dose with rituximab without any other aetiology. The post-commercialization rate has been reported 0.02% in over 30,000 patients, but according to different studies, the rate of LON is considerably higher. It's necessary to distinguish between this adverse effect and another dreaded complication as therapy related Myelodysplastic syndromes.
is to describe the prevalence of late onset neutropenia in a population of NHL patients treated with rituximab
Two cohorts including patients with Diffuse Large B-Cell Lymphoma (DLBCL) and Follicular Lymphoma (FL) diagnosed between January 2011 and December 2015 were reviewed. Patients were were eligible if they were treated with chemotherapy + rituximab, achieved complete hematologic recovery(at the end of chemotherapy), lasting for at least 4 months, and thereafter developed cytopenias In all patients: infectious causes were requested (HIV, HBV; HCV), abdomen US, and if none peripheral comorbidity was documented, a bone marrow aspiration with cytogenetic analysis was done, to search t-MDS. The following factors were analyzed as risk factors to develop cytopenias: history of febrile neutropenia during chemotherapy, number of cycles with rituximab, bone marrow infiltration, IPI, clinical stage, ECOG, B symptoms, number of nodal sites, and the presence of cytopenias at diagnosis. Descriptive and Cox-regression analysis was done.
840 patients (DLBCL = 696 and FL = 145) were treated with schemas including rituximab, and achieved complete hematologic recovery. From them: 33 developed late onset cytopenias (66.7% with DLBCL and 33.35 with FL), 22 females and 11 males, with a median age of 60 years. At the end of treatment 12.1% developed LON (lowest absolute neutrophil count 400mm3) and 9.1% thrombocytopenia (lowest platelet count = 8,000/K). Interestingly, 91% of the patients with cytopenia had complete response compared with 58.9% of complete responses in patients without cytopenia which could be associated with the effectiveness of rituximab as reported in previous studies. The presences of Hb <12 g/dl and >6 nodal sites were related to the development of LON in patients with FL. Thrombocytopenia has also been described in patients receiving rituximab, and 9.1% of our patients developed only thrombocytopenia (15% of the patients developed combinations of thrombocytopenia with anemia or lymphopenia), with 9.1% requiring platelet transfusions; there are still no prospective studies which can help to define it as an entity as LON.
Due to the spectacular benefits of the treatment with rituximab it is now considered as a standard of care for multiple lymphomas, we are able to recognize multiple complications associated as cytopenias in increasing frequency, and morbidity associated to infections that require hospitalization must be considered. Interestingly, the development of LON was associated with an increase in complete response and reduced rate of relapse, for reasons still to be discovered.