Treatment of splenic marginal zone lymphoma

Splenic marginal zone lymphoma (SMZL) is a distinct lymphoma entity characterized by an indolent clinical course and prolonged survival. Treatment is not standardized, since there are no prospective randomized trials in large series of SMZL patients. Splenectomy and rituximab represent the most effective treatment strategies used so far. The addition of chemotherapy to rituximab has not further improved the outcome, although this issue requires further investigation. Rituximab monotherapy has been associated with high response rates (∼90%), with approximately half of these responses being complete, even at the molecular level. More importantly, many of these responses are long-lasting, with a reported 7-year progression-free survival (PFS) at the rate of 69%. Maintenance rituximab treatment has been associated with further improvement of the quality of response as well as longer response duration in studies derived from one group of investigators. Based on its high efficacy and the good safety profile, rituximab represent one of the best treatment options for SMZL patients. Moreover, rituximab retains its efficacy in the relapse setting in most cases. Splenectomy is a meaningful alternative to rituximab in patients with bulky splenomegaly and cytopenias, without extensive bone marrow infiltration, who are fit for surgery. However splenectomy cannot completely eradicate the disease and it is also associated with greater morbidity or even mortality compared to rituximab. The choice of one of these two treatment approaches (rituximab or splenectomy) should mainly be based on patient's characteristics and on the disease burden. Novel agents are currently testing in low grade lymphomas including a small number of SMZL patients with promising results. © 2016 Elsevier Lt

A new mononuclear cell (MNC) RNase h activity-based parameter (ψ with possible prognostic value in assessing progression in acute myeloid leukaemia

A new biological parameter (ψ has been obtained and proposed here to serve in the assessment of acute myeloid leukemia (AML) progression. It is a function of the activity of RNase H (EC 3.1.4.34), the latter determined in mononuclear cells from the peripheral blood of AML patients. Using a series of patients at the time of diagnosis and after 1-2 cycles of chemotherapy, the enzyme was assayed before the several times during chemotherapy. The derivation of 4 was based on evidence suggesting that the enzyme level correlates with the proliferating leukaemic blasts and their progenitors. Values ψgt;1 signify the presence of clonogenic leukaemic progenitor cells in the peripheral circulation. When these high (> 1) ψ values were found during chemotherapy, in these cases it was possible to predict an increase of the peripheral blast pool, with 82% success, occurring 5-35 days before cytologic relapse. In the patients in whom at some stage during treatment, ψ acquired values above unity or in whom ψ increased progressively, survival time was in linear correlation with the time period from the initiation of treatment to the documentation of this high ψ estimate. These results suggest that a patient's relapse risk can be defined by ψ with some degree of precision. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Current and emerging treatment approaches for splenic marginal zone lymphoma

Introduction: Splenic marginal zone lymphoma (SMZL) represents a distinct entity within the spectrum of marginal zone lymphomas (MZL). Due to its rarity, treatment is not standardized. Areas covered: Currently two therapeutic options have been associated with the best outcome: splenectomy and rituximab. Splenectomy is associated with high response rates (~90%) with a median PFS>5 years. However, responses are not complete and it is associated with increased surgical risk as well as increased risk of septic episodes. Rituximab has shown significant efficacy with minimal toxicity in SMZL. The ORR is > 90%, with half of these responses being complete with a long duration of response. For the small proportion of SMZL with more aggressive clinical behavior, not responding or relapsing shortly after rituximab, novel agents are required. Several new drugs have shown significant activity in other low grade lymphomas. However, there is currently no trial testing the role of these agents specifically in SMZL. Expert opinion: Rituximab monotherapy currently represents the best choice for first line treatment for SMZL. Randomized studies are required in order to improve the outcome, especially for the small proportion of cases with the more aggressive clinical behavior. © 2016 Informa UK Limited, trading as Taylor & Francis Group

Should rituximab replace splenectomy in the management of splenic marginal zone lymphoma?

Background: SMZL is a relatively rare low grade B-cell lymphoma, characterized usually by an indolent clinical behavior. Since there is no prospective randomized trials to establish the best treatment approach, decision on therapeutic management should be based on the available retrospective series. Based on these data, rituximab and splenectomy appear to be the most effective. Splenectomy represented the standard treatment modality until early 2000s. More than 90% of the patients present quick amelioration of splenomegaly related symptoms along with improvement of cytopenias related to hypersplenism. The median progression free survival was 8.25 years in the largest series of patients published so far, while the median 5- and 10- year OS were 84% and 67%, respectively. Responses to splenectomy are not complete since extrasplenic disease persists. Patients with heavy bone marrow infiltration, lymphadenopathy or other disease localization besides the spleen are not good candidates for splenectomy. Furthermore splenectomy is a major surgical procedure accompanied by acute perioperative complications as well as late toxicities mainly due to infections. For that reasons splenectomy is not appropriate for elderly patients or patients with comorbidities with a high surgical risk. On the other hand rituximab monotherapy displays high efficacy with minimal toxicity. Several published series have shown an ORR more than 90%, with high CR rates (∼50%). The 10-year PFS and OS were 63% and 85%, respectively in a series of 104 SMZL patients. The role of rituximab maintenance has been investigated by only one group. Based on these data, maintenance with rituximab further improved the quality of responses by increasing significantly the CR rates (from 42% at the end of induction to 71% at the end of maintenance treatment), as well as the duration of responses: 7-year PFS was 75% for those patients who received maintenance vs 39% for those who did not (p < 0.0004). However no difference in OS has been noticed between the two groups, so far. Summarizing the above data, it is obvious that Rituximab monotherapy is associated with high response rates, long response duration and favorable safety profile, rendering it as the treatment of choice in SMZL. © 2017 Elsevier Lt

Activity and function of hybrid ribonuclease in cells of acute and chronic myelogenous leukemia

The activity of hybrid ribonuclease (ribonuclease H) has been determined in mononuclear blood cells (lymphocytes plus monocytes) from 23 normal individuals and cells (pool of immature granulocytes, metamyelocytes and lymphocytes) from 35 untreated acute and chronic myelogenous leukemia cases. It was found that in 86% of the leukemic samples the activity of ribonuclease H was above two standard deviations from the mean activity level drawn for the group of normal samples along the 0-100% substrate hydrolysis scale. The activity of the enzyme in leukemic cells correlated linearly with the DNA-synthesizing activity of the cells in vitro and in the examined CML cases it paralleled the inverse relationship of the incorporation of tritiated thymidine into DNA to the size of the pool of immature granulocytes. In one CML patient who received chemotherapy with Myleran, the activity of ribonuclease H, high at the initiation of drug therapy, was reduced to a normal level at remission, but increased again at the stage of subsequent relapse. These findings indicate that the levels of ribonuclease H in leukemic cells reflect the proliferative activity of the population in the cases of untreated myelogenous leukemias. © 1987 S. Karger AG, Basel

Nodal marginal zone lymphoma

Nodal marginal zone lymphoma (NMZL) is one of the three well-recognized entities within the broad category of marginal zone lymphoma, representing approximately 10% of the cases in this group. Patients typically present with nodal disease, usually at advanced stages, and a thorough work-up and staging are necessary in order to exclude occult extranodal involvement. NMZL shares many similarities with splenic marginal zone (SMZL) and mucosa-associated lymphoid tissue (MALT) lymphomas, such as cytology, immunophenotype, genetic abnormalities and maybe even a common cell of origin: a post-germinal memory B-cell. NMZL is characterized by an indolent course, but its prognosis is generally considered less favorable than that of SMZL and MALT lymphoma, with reported 5-year overall survival rates ranging between 55% and 89%. Therapeutic recommendations for NMZL are derived from small retrospective series or studies on larger cohorts of indolent lymphomas, which include a limited number of patients with NMZL. For localized disease, radiotherapy appears to be the treatment of choice, while rituximab-containing therapy is recommended for advanced stage disease. Due to the rarity of NMZL it is very difficult to perform prospective trials, and an international collaborative effort is necessary in order to better understand the biological features and provide evidence-based treatment recommendations. © 2014 Informa UK, Ltd