Should medical treatment options be exhausted before splenectomy is performed in adult ITP patients? A debate

Patients with primary immune thrombocytopenia (ITP) may require treatment to reduce the risk of serious bleeding if platelets remain consistently below 30 × 10⁹/L. While approximately 70–80% of patients respond to an initial course of corticosteroids, relapse is common. For steroid-refractory patients, there is a choice between surgical splenectomy and further medical treatments, based on many factors including the patient’s bleeding history, fitness for surgery, comorbidities, tolerance of adverse events, lifestyle and preferences. Treatments that have traditionally been used (corticosteroids, azathioprine, danazol) suppress the immune system, potentially predisposing patients to infection. Recent insights into the underlying pathophysiology of the disease have allowed the development of targeted therapies, including the thrombopoietin (TPO) receptor agonists, which enhance platelet production. Phase III trials have found romiplostim and eltrombopag to be well tolerated and effective in elevating platelet counts and reducing bleeding in both splenectomised and nonsplenectomised patients with chronic ITP. The B-cell targeted monoclonal antibody rituximab has also shown some potential in this setting, although data are currently limited and there are toxicity concerns. The decision whether to proceed to splenectomy or try other medical therapies in corticosteroid-refractory patients remains patient-specific. Splenectomy has its risks (including perioperative and long-term risks), and relapse/nonresponse are relatively common, but it offers the possibility of cure in the majority of patients. However, newer treatments may potentially allow splenectomy to be deferred for prolonged periods, as well as providing alternative treatment options for patients who fail splenectomy.     

Idiopathic cyclic thrombocytopenia

Cyclic thrombocytopenia (CTP) is an uncommon disorder characterized by periodic fluctuations in platelet counts, typically resulting in episodes of thrombocytopenia alternating with normal platelet counts. While some CTP cases are associated with a primary hematologic disease, most are idiopathic. Patients with CTP are frequently misdiagnosed as idiopathic thrombocytopenic purpura (ITP) because CTP has clinical features very similar to ITP. When evaluating patients with suspected ITP, CTP should always be included in the differential diagnoses because CTP generally does not respond to standard ITP treatments, including corticosteroids, splenectomy, and intravenous immunoglobulin. Two clinical features relatively unique to CTP besides periodic thrombocytopenia are rebound thrombocytosis unrelated to recent splenectomy and platelet nadirs occurring during menses. When a diagnosis of CTP is made, patients must be offered a period of observation, as many may not require treatment. If treatment is clinically indicated, the literature suggests that hormonal therapy provides the best response.     

Increased number of B-cells in the red pulp of the spleen in ITP

Platelets are targeted by autoantibodies and destroyed in the reticuloendothelial system in the spleen, liver and bone marrow in patients with immune thrombocytopenia (ITP). Other mechanisms such as destruction by cytotoxic T-cells and defective production of platelets in the bone marrow also exist. Splenectomy normalizes the platelet count in 70% of ITP patients, however, precious little is known about the spleen in this disease. Our aim was therefore to investigate the splenic morphology and especially the number and localization of splenic leukocytes in patients with ITP and controls and to evaluate factors predicting outcome of splenectomy. Spleen sections from 29 ITP patients and 11 individuals splenectomized due to trauma were analyzed by immunohistochemistry. All except one of the ITP patients had a normalized platelet count 12 months after splenectomy and the platelet count was inversely correlated with age. ITP patients had an increased number of B-cells in the red pulp. The number of white pulp B-cells and number of T-cells in both compartments was unchanged. In conclusion, B-cells are increased in the red pulp of the spleen and together with cytotoxic T-cells, helper T-cells and macrophages line the sinusoids enabling the immunological attack on platelets in ITP.     

The Sequestration Site of Platelets in Idiopathic Thrombocytopenic Purpura: its Correlation with the Results of Splenectomy

S ummary . The clinical usefulness of external scanning data after infusion of ⁵¹Crlabelled platelets into patients with idiopathic thrombocytopenic purpura (ITP) is a matter of controversy. Observations have been made in 575 patients with ITP. Short-term (6 mth) results of splenectomy were assessed in 206 subjects, and longterm (1-3 yr) in 153. It appears that the site of sequestration is neither a direct function of the severity of the disease nor of the duration of the disease from the clinical onset. Diffuse sequestration, which cannot be taken as an indication for or against splenectomy, is frequently seen in recent and severe cases. Splenic sequestration is more often observed in young patients (72.5% under 30 yr of age) than in older subjects (36% over 30 yr of age).
A good correlation was found between the site of sequestration and the shortand long-term results of splenectomy: success in more than 90% of cases with splenic sequestration but complete failure in 70% with hepatic sequestration. In any patient with ITP splenectomy should be undertaken only after a careful study of the platelet sequestration site.     

Splenectomy for immune thrombocytopenic purpura: surgery for the 21st century

Although immune thrombocytopenic purpura (ITP) is the most common autoimmune hematological disorder, there is still controversy regarding the optimal management of this condition. Medical therapy may cure a proportion of patients with ITP but there are still a significant number of these individuals who are at risk for bleeding events. Surgery has become the least popular therapeutic option for ITP as other medical therapies have become available that attempt to avoid splenectomy and its morbidity. However, the clinical response to these therapies has not been overwhelming based on the fairly small number of trials conducted to date. With current minimally invasive surgical techniques, splenectomy should be again regarded as a viable therapeutic option in patients with ITP. The laparoscopic approach avoids much of the morbidity and complications seen with the conventional open surgical approach and studies have demonstrated similar, if not better, outcomes. In addition, the risk of infection following splenectomy is not as high as may be suspected, particularly with current vaccination regiments. It should be a priority for both the hematology and medical community to advocate for clinical trials to rationally study alternatives to splenectomy. In the interim, laparoscopic splenectomy should be considered as an additional front line therapeutic option in ITP patients.     

Approach to the investigation and management of immune thrombocytopenic purpura in children

Childhood immune thrombocytopenic purpura (ITP) is typically a benign, self-limiting disorder occurring in young (<10 years of age) previously healthy children. More than 80% of such children enter a complete sustained remission within a few weeks to a few months of initial presentation, irrespective of any therapy given. The major concern is the small but finite (0.1 to 0.9%) risk of intracranial hemorrhage, which occurs in children with very low platelet counts (<20 x 10(9)/L), and is the justification for treatment to increase the circulating platelet count. Effective treatment strategies are single-dose intravenous immunoglobulin G (IVIgG; approximately 1 g/kg) and medium to high-dose corticosteroids, administered orally or parenterally. The necessity for initial bone marrow aspiration and hospitalization continues to be debated. In children with chronic ITP, defined by persistence of thrombocytopenia for > or =6 months, splenectomy should be considered for the relatively small subgroup with symptomatic, severe thrombocytopenia who have either failed an adequate trial (> or = 12 months) of primary therapy (IVIgG, intravenous anti-D, corticosteroids) or are intolerant of such therapy. Laparoscopic splenectomy is preferred over open splenectomy. Children who fail to respond to splenectomy ( < or = 20% of cases) should be evaluated for the presence of accessory spleens; their management is often difficult and must be individualized. In severe refractory cases, second-line therapies (such as azathioprine or vinca alkaloids) need to be considered. Secondary ITP in children is relatively rare and is sometimes associated with other autoimmune cytopenias (Evan's syndrome, ITP with autoimmune neutropenia). These cases often respond poorly to conventional medical therapies and response rates to splenectomy are considerably lower than in children with primary chronic ITP.     

Laparoscopic splenectomy for primary immune thrombocytopenia:Current status and challenges

Primary immune thrombocytopenia(ITP) is an immunemediated disorder affecting both adults and children, characterised by bleeding complications and low platelet counts. Corticosteroids are the first-line therapy for ITP, but only 20%-40% of cases achieve a stable response. Splenectomy is the main therapy for patients failing to respond to corticosteroids for decades, and about two-thirds of patients achieve a long-lasting response. Although some new drugs are developed to treat ITP as second-line therapies in recent years, splenectomy is still the better choice with less cost and more efficiency. Laparoscopic splenectomy(LS) for ITP proves to be a safe technique associated with lower morbidity and faster recovery and similar hematological response when compared to traditional open splenectomy. Based on the unified hematological outcome criteria by current international consensus, the response rate of splenectomy should be reassessed. So far, there are not widely accepted preoperative clinical indicators predicting favorable response to LS. Since the patients undergoing surgery take the risk of complications and poor hematological outcome, the great challenge facing the doctors is to identify a reliable biomarker for predicting longterm outcome of splenectomy which can help make the decision of operation.     

Immunologic effects of rituximab on the human spleen in immune thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell-related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B-cell depletion in the blood and a significant reduction in splenic B cells, but these patients did not achieve remission. Moreover, whereas the percentage of circulating regulatory T cells (Tregs) was similar to that in controls, splenic Tregs were reduced in ITP patients. Interestingly, the ratio of proinflammatory Th1 cells to suppressive Tregs was increased in the spleens of patients who failed RTX therapy. These results indicate that although B cells are involved in ITP pathogenesis, RTX-induced total B-cell depletion is not correlated with its therapeutic effects, which suggests additional immune-mediated mechanisms of action of this drug.     

Prognostic significance of splenic follicle size in splenectomized idiopathic thrombocytopenic purpura patients

Summary The prognostic significance of splenic follicle (B-lymphocyte compartment) size was studied in 62 patients splenectomized for idiopathic thrombocytopenic purpura (ITP). Patients with hyperplasia of splenic follicles (mean follicle diameter >500 m) were more likely to relapse or to develop additional autoimmune disorders than patients without hyperplastic splenic follicles (mean follicle diameter <500 m) (p<0.01). The enlargement of splenic follicles had a positive predictive value of 27% and a negative predictive value of 100% for a poor outcome of splenectomy. Thus, the histological examination of spleens surgically removed for ITP seems to be an appropriate method to obtain the first indication of the possible long-term effect of splenectomy almost immediately after the operation.     

Current management of adult idiopathic thrombocytopenic purpura in practice: a cohort study of 201 patients from a single center1

To define usefulness and response to therapy and outcome in adults with idiopathic thrombocytopenic purpura (ITP) in clinical practice. We retrospectively reviewed a cohort of 201 consecutive patients with ITP, diagnosed between 1985 and 1994. In particular, we analyzed the therapies used, their response rates, prognostic indicators of response and outcome. In 62 patients, with minor bleeding episodes and a mean (±SD) platelet count of 88 ± 23 × 10⁹/l, no treatment was used and chronic ITP was diagnosed in 59%. A total of 139 patients, with bleeding episodes in 71.2% cases and a mean platelet count of 20 ± 13 × 10⁹/l, received at least one treatment. Three patients died (1.5% of the series). Corticosteroids were used in 118 patients, with an initial response rate of 82.2% and a long‐term complete response (CR) of only 22.9%. Intravenous immunoglobulin was used in 26 patients, with an initial transient response in more than 60%. A splenectomy was performed in 55 patients, with an initial response rate of 92.5% and a long‐term CR in 60%. Young age and prior response to corticosteroids were significant predictors of a durable response to splenectomy. Danazol was given in 37 patients, with a favorable response in 73% of cases. Our results illustrate the guidelines of the American Society of Hematology. Patients with moderate thrombocytopenia do not require treatment. In severe cases, splenectomy is the only treatment giving durable cures in a significant proportion of patients. Despite frequent chronicity, ITP is life‐threatening only in a minor subset of patients.     

Does the site of platelet sequestration predict the response to splenectomy in adult patients with immune thrombocytopenic purpura?

Splenectomy is the only potentially curative treatment for chronic immune thrombocytopenic purpura (ITP) in adults. However, one-third of the patients relapse without predictive factors identified. We evaluate the predictive value of the site of platelet sequestration on the response to splenectomy in patients with ITP. Eighty-two consecutive patients with ITP treated by splenectomy between 1992 and 2013 were retrospectively reviewed. Platelet sequestration site was studied by ¹¹¹Indium-oxinate-labeled platelets in 93% of patients. Response to splenectomy was defined at last follow-up as: complete response (CR) for platelet count (PC) ≥100?×?10⁹/L, response (R) for PC≥30?×?10⁹/L and <100?×?10⁹/L with absence of bleeding, no response (NR) for PC<30?×?10³/L or significant bleeding. Laparoscopic splenectomy was performed in 81 patients (conversion rate of 16%), and open approach in one patient. Median follow-up was 57 months (range, 1–235). Platelet sequestration study was performed in 93% of patients: 50 patients (61%) exhibited splenic sequestration, 9 (11%) hepatic sequestration and 14 patients (17%) mixed sequestration. CR was obtained in 72% of patients, R in 25% and NR in 4% (two with splenic sequestration, one with hepatic sequestration). Preoperative PC, age at diagnosis, hepatic sequestration and male gender were significant for predicting CR in univariate analysis, but only age (HR?=?1.025 by one-year increase, 95% CI [1.004–1.047], p?=?0.020) and pre-operative PC (HR?=?0.112 for?>?100 versus <=100, 95% CI [0.025–0.493], p?=?0.004) were significant predictors of recurrence-free survival in multivariate analysis. Response to splenectomy was independent of the site of platelet sequestration in patients with ITP. Pre-operative platelet sequestration study in these patients cannot be recommended.     

The choice of second‐line therapy in steroid‐resistant immune thrombocytopenia: Role of platelet kinetics in a single‐centre long‐term study

Splenectomy is a time‐honoured well established approach for patients with steroid‐resistant immune thrombocytopenia (ITP). However, due to the more recent availability of therapeutic options alternative to splenectomy, such as rituximab and agonists of the thrombopoietin‐receptor, the choice of second‐line therapy is challenging. Platelet kinetics has been widely used to predict response to splenectomy. We describe the outcome of 70 chronic ITP patients who performed a platelet kinetic study after failure of front‐line corticosteroids and subsequently underwent open splenectomy. After a median follow‐up from surgery of 20 years, 62 (88.5%) patients responded to splenectomy and 9 patients (13%) relapsed. Achieving a complete response (CR) significantly predicted a higher probability long‐term stable response. The pattern of platelet sequestration was predominantly splenic in 52 patients (74%), predominantly hepatic in 12 patients (17%), and diffuse in 6 (9%). Patients with nonsplenic (diffuse and hepatic) sequestration showed significantly lower overall responses compared to patients with splenic captation (P = 0.002). A nonsplenic sequestration significantly correlated with lower CR rate and, among CR patients, predicted an increased risk of relapse. Also, the probability of stable responses in nonsplenic uptake patients was substantially lower than in patients with splenic uptake (85% vs. 50%, P = 0.0083). Platelet life span and platelet turnover did not correlate with response and relapse rate. Overall, splenic sequestration was able to predict not only a better quality, but also a higher durability of the responses. However, it should be enphasized that the response rate and duration of response even in patients with nonsplenic uptake were similar or even superior to those reported in patients treated with rituximab as first option. Am. J. Hematol. 89:1047–1050, 2014. © 2014 Wiley Periodicals, Inc.     

Serum IL-2 and platelet-associated immunoglobulins are good prognostic markers in immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is an acquired disease in which autoantibodies to platelets cause their sequestration and destruction by mononuclear macrophages, principally in the spleen. While most children with the disease experience a relatively short and benign clinical course, ITP in adults often lasts more than 6 months (chronic ITP) and is resistant to conventional treatment (corticosteroids, intravenous immunoglobulin, or splenectomy). This work was done to study the immunological difference between acute and chronic ITP, the effect of treatment on the studied immunological parameters, and to evaluate the role of prednisone therapy in chronic ITP. The study included 49 patients, twenty-three children with acute ITP, and twenty-six with chronic ITP. After taking the history, clinical examination was performed for all patients and control subjects. Laboratory investigations included complete blood count, bone marrow aspirate examination (patients), direct and indirect Coombs' test, antinuclear antibodies, lymphocyte phenotyping, cytokine (IL-2, IFN-gamma, and IL-6) measurement, and platelet antibodies by immunofluorescence. Results showed that acute ITP is more prevalent in preschool children and its relapse is lower when steroids are used for treatment. Platelet counts were significantly elevated in both acute and chronic ITP, especially with good response to steroids. Also, CD4 and CD4/CD8 were significantly reduced in chronic ITP with good response to therapy. Both IL-2 and IFN-gamma were significantly increased in chronic ITP when compared to acute ITP or control. Platelet associated IgM was detected more in acute than in chronic ITP, while IgG was equally detectable in both cases. This work shows that IL-2 is a good prognostic factor in chronic ITP and steroids are important for its treatment. It also shows that platelet associated IgG is a good monitoring parameter for response to treatment.     

Rituximab in immune thrombocytopenia: transient responses,low rate of sustained remissions and poor response to further therapy in refractory patients

Management of patients with immune thrombocytopenia (ITP) refractory to standard treatment is difficult. Recent studies show that rituximab, a chimeric anti-CD20 monoclonal antibody, is useful in the treatment of ITP. We retrospectively studied 24 patients who received 29 rituximab treatments for relapsed or refractory ITP. Patients had received a median of 3 treatment regimens before (range 1–8) and 11 patients had prior splenectomy. Responses were achieved in 19 of 29 (66%) treatments. The median time to response was 3 weeks (range 1–20) from the start of therapy and median duration of response was 13 weeks (range 1 week–55 months). Responses were mostly short lived and after a median follow-up of 22 months (range 2–70), 10 (34%) responses were sustained after 6 months, 7 (24%) responses sustained after 1 year and only 5 patients continued to have a response at last visit after 8, 10, 24, 30 and 54 months of follow-up. Previous splenectomy was associated with a poor response (p = 0.034). Patients who failed rituximab and had prior multiple treatments including splenectomy, had a poor outcome of further therapies. We conclude that rituximab is well tolerated and is useful in some patients with relapsed or refractory ITP; however, only about one-fifth of patients achieved sustained remissions. Patients refractory to rituximab had a poor response to further treatment.     

Danazol therapy in patients with chronic idiopathic thrombocytopenic purpura: long-term results

BACKGROUND: Adults with chronic idiopathic thrombocytopenic purpura (ITP) in whom standard-dose corticosteroids and splenectomy have failed or who have contraindications to these therapies often require further treatment for life-threatening thrombocytopenia or bleeding. We studied whether danazol, an attenuated androgen, is useful in this setting. METHODS: To assess both clinical outcome and tolerance issues, 57 patients who had refractory chronic ITP (n = 27) or who had contraindications to splenectomy or corticosteroids or who refused these therapeutic options (n = 30) were studied. RESULTS: Thirty-eight patients experienced a partial or complete response to therapy (67%), among whom 27 (46%) remained in remission at a median (+/- SD) of 119 +/- 45 months. Treatment tolerance was acceptable, although severe adverse events were reported in 9 patients (16%). CONCLUSION: Our findings suggest that danazol therapy may be beneficial in the management of refractory chronic ITP or when there are contraindications to splenectomy or corticosteroids (or both).     

The site of platelet destruction in thrombocytopenic purpura as a predictive index of the efficacy of splenectomy

The significance of the site of platelet sequestration in determining the indication for splenectomy in idiopathic thrombocytopenic purpura (ITP) is a controversial subject. However, most of the negative conclusions are based on 51chromium labelling of homologous platelets. We report here the results of an analysis of 222 cases in which the kinetic study of 111indium-oxinate-labelled autologous platelets was performed under homogeneous technical conditions. 103 of these patients subsequently underwent splenectomy. This study demonstrates that the site of platelet sequestration in active ITP constitutes a variable independent of the patient's age, history of the disease and its severity (platelet count, lifespan). The sequestration site is a good predictive element of the short-term efficacy of splenectomy (71/76 cases with splenic sequestration obtained a platelet count exceeding 100 x 10(9)/l versus 7/13 cases with mixed sequestration and 1/14 cases with hepatic sequestration), and the long-term results (6 months to 5 years after splenectomy) do confirm the clinical value of this study.     

Idiopathic thrombocytopenic purpura in elderly patients: a study of 47 cases from a single reference center

BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is often diagnosed in the elderly, but no specific guidelines exist for such patients. We describe our experience with ITP management in elderly patients and analyze the therapeutic response. METHODS: We retrospectively reviewed a cohort of 47 consecutive elderly ITP patients (> or =60 years old) followed in a single reference center. We specifically analyzed the clinical characteristics, therapies used, patient response rates, and side effects. RESULTS: The mean age of the 47 patients was 66 (range 60-82) years; 31 patients were female. Their initial presentation included bleeding limited to the skin (n=10, 21%) and bleeding at one or more other sites (n=26, 56%); 11 patients (23%) were asymptomatic. The mean platelet count was 52 x 10(9)/L (range 1-120 x 10(9)/L). After 1 and 6 months, the overall response rate was: 61% and 33% with corticosteroids (n=43), 80% and 50% with splenectomy (n=10), and 14% and 60% with danazol (n=15), respectively. Side effects of these therapies were reported in 100% of these elderly ITP patients, 60% and 50% with these drugs, respectively. No response was reported using IVIg. One case of fatal sepsis was noted after splenectomy. CONCLUSIONS: The results confirm (1) that age influences the hemorrhagic pattern of ITP expression, response, and adverse effects of conventional ITP therapies, and (2) that danazol has the potential to be an effective therapeutic alternative to splenectomy in elderly ITP patients.     

Cost-effectiveness of second-line therapies in adults with chronic immune thrombocytopenia

Major options for second-line therapy in adults with chronic immune thrombocytopenia (ITP) include splenectomy, rituximab, and thrombopoietin receptor agonists (TRAs). The American Society of Hematology guidelines recommend rituximab over splenectomy, TRAs over rituximab, and splenectomy or TRAs while noting a lack of evidence on the cost-effectiveness of these therapies. Using prospective, observational, and meta-analytic data, we performed the first cost-effectiveness analysis of second-line therapies in chronic ITP, from the perspective of the U.S. health system. Over a 20-year time-horizon, our six-strategy Markov model shows that a strategy incorporating early splenectomy, an approach at odds with current guidelines and clinical practice, is the cost-effective strategy. All four strategies utilizing TRAs in the first or second position cost over $1 million per quality-adjusted life-year, as compared to strategies involving early use of splenectomy and rituximab. In a probabilistic sensitivity analysis, early use of splenectomy and rituximab in either order was favored in 100% of 10 000 iterations. The annual cost of TRAs would have to decrease over 80% to begin to become cost-effective in any early TRA strategy. Our data indicate that effectiveness of early TRA and late TRA strategies is similar with the cost significantly greater with early TRA strategies. Contrary to current practice trends and guidelines, early use of splenectomy and rituximab, rather than TRAs, constitutes cost-effective treatment in adults with chronic ITP.     

Second-line treatments in children with immune thrombocytopenia: Effect on platelet count and patient-centered outcomes

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and hemorrhagic risk. While many children with ITP can be safely observed, treatments are often needed for various reasons, including to decrease bleeding, or to improve health related quality of life (HRQoL). There are a number of available second-line treatments, including rituximab, thrombopoietin-receptor agonists, oral immunosuppressive agents, and splenectomy, but data comparing treatment outcomes are lacking. ICON1 is a prospective, multi-center, observational study of 120 children starting second-line treatments for ITP designed to compare treatment outcomes including platelet count, bleeding, and HRQoL utilizing the Kids ITP Tool (KIT). While all treatments resulted in increased platelet counts, romiplostim had the most pronounced effect at 6 months (P = .04). Only patients on romiplostim and rituximab had a significant reduction in both skin-related (84% to 48%, P = .01 and 81% to 43%, P = .004) and non-skin-related bleeding symptoms (58% to 14%, P = .0001 and 54% to 17%, P = .0006) after 1 month of treatment. HRQoL significantly improved on all treatments. However, only patients treated with eltrombopag had a median improvement in KIT scores at 1 month that met the minimal important difference (MID). Bleeding, platelet count, and HRQoL improved in each treatment group, but the extent and timing of the effect varied among treatments. These results are hypothesis generating and help to improve our understanding of the effect of each treatment on specific patient outcomes. Combined with future randomized trials, these findings will help clinicians select the optimal second-line treatment for an individual child with ITP.     

Front‐line management of indolent non‐Hodgkin lymphoma in Australia. Part 2: mantle cell lymphoma and marginal zone lymphoma

Mantle cell lymphoma (MCL) and the marginal zone lymphoma (MZL) subtypes (nodal MZL, extra‐nodal MZL of mucosa‐associated lymphoid tissue (MALT lymphoma) and splenic MZL) are uncommon lymphoma subtypes, accounting for less than 5–10% of all non‐Hodgkin lymphoma. The evidence base for therapy is therefore limited and enrolment into clinical trials is preferred. Outcomes for patients with MCL have been steadily improving mainly due to the adoption of more intense strategies in younger patients, the use of rituximab maintenance and the recent introduction of bendamustine in older patients. MZL is a more heterogeneous group of cancer with both nodal, extra‐nodal and splenic subtypes. Extranodal MZL may be associated with autoimmune or infectious aetiologies, and can respond to eradication of the causative pathogen. Proton pump inhibitor plus dual antibiotics in Helicobacter pylori positive gastric MALT lymphoma is curative in many patients. Watchful waiting is appropriate in most patients with asymptomatic advanced stage disease, which tends to behave in a particularly indolent manner. Other options for symptomatic disease include splenectomy, chemoimmunotherapy with rituximab and, more recently, targeted therapies.