Lymphocyte recovery is impaired in patients with chronic lymphocytic leukemia and indolent non-Hodgkin lymphomas treated with bendamustine plus rituximab.

The immune system has the potential to either attenuate tumor growth or to promote tumor progression. The goal of cancer immunotherapy is to shift the balance in favor of tumor immunosurveillance, so that the immune system can recognize the tumor, eliminate it, and prevent its recurrence. Bendamustine plus rituximab is generally considered effective and safe in patients with previously untreated chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin lymphomas. To evaluate the effects of bendamustine-rituximab and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on the recuperation of immune system, we analyze the distribution of CD4+ and CD8+ T cells, B cells, and NK cells in peripheral blood of 18 patients who received 4-6 cycles of rituximab-bendamustine (BR) or six R-CHOP before therapy and 6 months after completing treatment. Our results indicate that lymphocyte recovery is impaired in patients with chronic lymphocytic leukemia and indolent lymphomas treated with bendamustine plus rituximab. Low CD4 T cells (<200 cells/µl) induced by bendamustine (BR) suggest prophylaxis should be applied against opportunistic infections. Asymptomatic EBV and CMV reactivations support a negative effect of BR on the immune system. If cellular immune therapy such as lymphokine-activated killer (LAK) or effector lymphocytes infusion is planned, regimes other than BR should be the first choice.

Immunological aspects in chronic lymphocytic leukemia (CLL) development.

Chronic lymphocytic leukemia (CLL) is unique among B cell malignancies in that the malignant clones can be featured either somatically mutated or unmutated IGVH genes. CLL cells that express unmutated immunoglobulin variable domains likely underwent final development prior to their entry into the germinal center, whereas those that express mutated variable domains likely transited through the germinal center and then underwent final development. Regardless, the cellular origin of CLL remains unknown. The aim of this review is to summarize immunological aspects involved in this process and to provide insights about the complex biology and pathogenesis of this disease. We propose a mechanistic hypothesis to explain the origin of B-CLL clones into our current picture of normal B cell development. In particular, we suggest that unmutated CLL arises from normal B cells with self-reactivity for apoptotic bodies that have undergone receptor editing, CD5 expression, and anergic processes in the bone marrow. Similarly, mutated CLL would arise from cells that, while acquiring self-reactivity for autoantigens-including apoptotic bodies-in germinal centers, are also still subject to tolerization mechanisms, including receptor editing and anergy. We believe that CLL is a proliferation of B lymphocytes selected during clonal expansion through multiple encounters with (auto)antigens, despite the fact that they differ in their state of activation and maturation. Autoantigens and microbial pathogens activate BCR signaling and promote tolerogenic mechanisms such as receptor editing/revision, anergy, CD5+ expression, and somatic hypermutation in CLL B cells. The result of these tolerogenic mechanisms is the survival of CLL B cell clones with similar surface markers and homogeneous gene expression signatures. We suggest that both immunophenotypic surface markers and homogenous gene expression might represent the evidence of several attempts to re-educate self-reactive B cells.

Faggot cells in therapy-related acute myeloid leukemia with inv(16).

Faggot cells are an uncommon finding in nonacute promyelocytic leukemia, even rarer when observed in mature granulocytic cells. Inv(16) should be dismissed when pre-eosinophilic granulation and faggot neutrophils are observed.