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W1990464386 abstract "The guideline group was selected to be representative of UK-based medical experts and patients representatives. Ovid MEDLINE, EMBASE and NCBI Pubmed were searched systematically for publications in English from 1980 to 2011 using the MeSH subheading ‘lymphoma, mantle cell’ and ‘lymphoma, mantle cell’ as a keyword, as well as all subheadings. In addition, all references to mantle cell lymphoma in the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissue (Swerdlow et al, 2008) and the British Committee for Standards in Haematology (BCSH) Guideline: Best Practice in Lymphoma Diagnosis and Reporting (Parker et al, 2010) have been included. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemato-oncology Task Force of the BCSH. The guideline was then reviewed by a sounding board of approximately 50 UK haematologists, the BCSH and the British Society for Haematology Committee and comments incorporated where appropriate. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found in Appendix I. The objective of this guideline is to provide healthcare professionals with clear guidance on the investigation and management of patients with mantle cell lymphoma. The guidance may not be appropriate to patients with other lymphoma sub-types and in all cases individual patient circumstances may dictate an alternative approach. This guideline is the first BCSH guideline on the topic of mantle cell lymphoma, and therefore, does not supersede any previous guidance. The section on diagnosis of mantle cell lymphoma, should be considered supplementary to the BCSH Guideline: Best Practice in Lymphoma Diagnosis and Reporting (Parker et al, 2010). The guideline is in date at time of publication. Any updates will be posted on the BCSH website (http://www.bcshguidelines.com/). Mantle cell lymphoma (MCL) is a B-cell malignancy with unique biological, pathological and clinical features, which comprises approximately 3–10% of all non-Hodgkin lymphomas (NHLs) (Swerdlow et al, 2008). It is characterized by the chromosomal translocation t(11;14)(q13;q32), which results in overexpression of the cell cycle protein cyclin D1 (Akiyama et al, 1994; Campo et al, 1999). MCL arises in older adults (median age of presentation 60–65 years) and has a male predominance (Argatoff et al, 1997; Bosch et al, 1998). The challenge of MCL is that it has the worst features of both high and low grade NHL; an aggressive clinical course, but with a pattern of resistant and relapsing disease rendering it incurable to standard therapy. Median survival is 4–5 years (Herrmann et al, 2009). There is evidence to suggest that this has increased over recent years from the previous median survival of 2–3 years, as a result of improved combination chemotherapies (discussed below) and supportive care. However, no standard of care is recognized, and this disease remains very difficult to manage. A number of studies have described the clinical presentation of MCL (Zucca et al, 1995; Argatoff et al, 1997; Bosch et al, 1998; Tiemann et al, 2005). The majority (> 90%) of patients present with advanced stage (Ann Arbor III-IV) disease. Lymphadenopathy is generally widespread at diagnosis, and splenomegaly, bone marrow infiltration and leukaemic involvement are common. Bulk disease at diagnosis and B-symptoms are less common. Extranodal involvement is frequent, particularly affecting the gastro-intestinal (GI) tract (Romaguera et al, 2003) and liver, but involvement of breast, lung, skin, soft tissue, salivary gland and orbit are also seen. Involvement of more than two extranodal sites is seen in 30–50% of patients (Jares & Campo, 2008). Spread to the central nervous system (CNS) can occur, but is rare at diagnosis, tending to occur as a late event in the course of the disease, where it is associated with widespread relapse and short survival (Ferrer et al, 2008). The clinical course is heterogeneous. Clinical presentation can correlate with pathological sub-type (discussed below); patients with the blastoid variant tend to have a very aggressive clinical course, may be refractory to treatment and have short survival. In contrast, it is recognized that a proportion of cases (10–30%) may present with more indolent disease (Eve et al, 2009a; Martin et al, 2009). These patients usually present with splenomegaly and a peripheral blood lymphocytosis, and lack significant nodal disease (Nodit et al, 2003; Orchard et al, 2003). Survival is in the order of 5–12 years. Even outside these extremes, the heterogeneity of the disease, and the elderly population in which it presents, frequently necessitate an individualized approach, although clinical trial data are beginning to provide a stronger evidence-base for treatment of patients with MCL. The diagnosis of MCL should be made by an excision biopsy or adequate core biopsy of an involved lymph node or extranodal site or by bone marrow trephine biopsy in the majority of cases. Computerized tomography (CT)- or ultrasound-guided biopsy may be needed to obtain diagnostic material if open biopsy is difficult. A primary diagnosis may also be made on a peripheral blood specimen in cases with a leukaemic presentation. In the classical variant, which accounts for 87% of cases, the architecture of the involved lymph node is usually completely effaced and is replaced by a diffuse or, less commonly, a nodular infiltrate composed of a monomorphic population of small to intermediate sized cells with irregular, often cleaved nuclei resembling centrocytes (Swerdlow et al, 1983; Argatoff et al, 1997; Tiemann et al, 2005). A mantle zone pattern is seen in a minority of cases (Tiemann et al, 2005). Vascular hyalinization is often conspicuous and there may also be prominent single epithelioid histiocytes, especially in cases with a higher proliferation fraction. A small cell variant resembling small lymphocytic lymphoma, though lacking proliferation centres, is recognized. Other subtypes include the blastoid variant, resembling lymphoblastic lymphoma and the pleomorphic variant, which may be confused on morphological grounds with diffuse large B-cell lymphoma (DLBCL) (Swerdlow et al, 1983; Norton et al, 1995; Argatoff et al, 1997; Ott et al, 1997; Tiemann et al, 2005). The same cytomorphological features are identified in biopsies of extranodal sites, such as colon, stomach and salivary gland. In trephine biopsy specimens, the infiltrate is most commonly nodular and interstitial and less often is paratrabecular or diffuse (Argatoff et al, 1997; Cohen et al, 1998). Trephine biopsy examination should include haematoxylin & eosin (H&E) and reticulin staining, in addition to immunophenotyping. Immunophenotyping may be carried out on paraffin-embedded material by immunohistochemistry or on liquid-based specimens by flow cytometry. In order to accurately diagnose MCL, a full immunohistochemical panel including anti-cyclin D1 should be employed in all biopsies suspicious of B-cell lymphoma (see Table 1). The majority of MCL cases co-express CD20, CD5, BCL2 and cyclin D1. The infiltrate is usually negative for CD10, BCL6 and CD23 (Alkan et al, 1995; Swerdlow et al, 1995; Argatoff et al, 1997; Sander, 2011). CD23 highlights a diffuse disorganized network of follicular dendritic cells though this may be variable in extent. Interpretation of CD5 expression in paraffin-embedded material may be difficult in view of the presence of large numbers of reactive CD5-expressing T-cells. A close comparison with the immunostaining pattern for CD3 is essential in such cases. MCL with an aberrant immunophenotype is well described. CD5 negativity is seen in approximately 5–10% of cases (Wlodarska et al, 1999; Zanetto et al, 2008; Espinet et al, 2010; Gualco et al, 2010). Expression of CD10, BCL6 and CD23 is recognized in a minority of cases and may lead to an erroneous diagnosis (Schlette et al, 2003; Camacho et al, 2004; Zanetto et al, 2008; Gualco et al, 2010). Nuclear expression of cyclin D1 is seen in the vast majority of cases and lack of expression should call into question the diagnosis of MCL (Alkan et al, 1995; Swerdlow et al, 1995). Modern antibodies to cyclin D1 (SP4 clone) are highly sensitive and lack of staining is usually related to poor fixation or lack of adequate antigen retrieval (Fu et al, 2005; Krenacs, 2005). In cases with equivocal staining, fluorescence in situ hybridization (FISH) may be performed for the t(11;14) translocation on both paraffin-embedded material and peripheral blood samples to confirm the diagnosis (Remstein et al, 2000; Sander et al, 2007). SOX11 is highly expressed in classical MCL (Ek et al, 2008; Dictor et al, 2009). It is possible that SOX11 immunostaining may have a role in the characterization of MCL in the future when sensitive and specific antibodies become generally available. Flow cytometry on peripheral blood or bone marrow can be equally informative in terms of making a diagnosis of MCL. Typically, MCL expresses CD19, CD20, CD79b, CD22, CD5 with FMC7 and moderately intense expression of surface light chains (see Table 1). CD10 expression is seen in a small proportion of cases, particularly in those with blastoid morphology (Zanetto et al, 2008). Flow cytometry is not suitable for assessment of cyclin D1, although in patients with a leukaemic presentation, cyclin D1 immunostaining may be carried out on paraffin-embedded preparations of density-gradient isolated peripheral blood lymphocytes. Although MCL, like chronic lymphocytic leukaemia (CLL), often shows CD5 positivity, these two entities should not be confused: CLL is normally FMC7 negative, CD79b negative/weak, CD23 positive, CD20 weak positive with weak surface light chain expression. The characteristic cytogenetic abnormality of MCL is the t(11;14)(q13;q32) translocation, resulting in overexpression of cyclin D1 (encoded by the CCND1 gene at 11q13) contributing to deregulated cell cycle progression at the G1-S phase boundary (Vandenberghe et al, 1991; Williams et al, 1993). The translocation may be detected by classical cytogenetics or FISH (Belaud-Rotureau et al, 2002; Dubus et al, 2002; Reichard et al, 2006). The latter has the advantage that it can be performed on paraffin-embedded material and therefore can be applied to core and endoscopic biopsies. In practice, the presence of the t(11;14) translocation should be demonstrated in cases with atypical morphology, an aberrant immunophenotype, equivocal cyclin D1 positivity or unusual clinical presentation. Demonstration of clonality may be achieved by detection of light chain restriction by flow cytometry or by polymerase chain reaction (PCR) for immunoglobulin heavy variable gene (IGHV) rearrangement. Secondary cytogenetic abnormalities are common in MCL and the degree of karyotypic complexity is negatively associated with patient survival (Cuneo et al, 1999; Wlodarska et al, 1999; Parry-Jones et al, 2007; Katzenberger et al, 2008). MCL is associated with a relatively poor prognosis, though there is some variation in outcomes within the group. Many biological features have been examined such as growth pattern, blastoid morphology, TP53 (p53) expression and secondary cytogenetic abnormalities with varying reports of their significance (Norton et al, 1995; Argatoff et al, 1997; Ott et al, 1997; Katzenberger et al, 2006). Identification of blastoid morphology may be difficult in view of variation in fixation and the subjective nature of assessing cell size. Proliferative activity is the most important prognostic factor in routine diagnostic practice (Table 2) (Tiemann et al, 2005; Katzenberger et al, 2006; Determann et al, 2008). Inter-observer variability in assessment of the proliferation index is well recognized; guidance has been produced by the European MCL Network, which suggested that counting the positive cells among 100 lymphoma cells in each of two representative high-power fields generated improved consistency in this respect (Klapper et al, 2009). As mentioned in the introduction, a proportion of patients present with indolent disease. Identification of this variant at presentation is difficult. Some suggest that lack of nuclear expression of SOX11 is associated with indolent disease (Fernandez et al, 2010). The leukaemic cells in indolent MCL have been found to be kappa light chain-restricted in contrast to the lambda restriction usually seen in classical MCL. Some CD23 expression is also detected in this group by flow cytometry (Ondrejka et al, 2011). None of these factors is currently robust enough to serve as a basis for modification of treatment. Failure to diagnose MCL can occur as a result of omission of immunostaining for cyclin D1 in the standard lymphoma panel, especially when CD5 is negative or weakly expressed. Poor quality immunohistochemistry and inadequate antigen retrieval may lead to false negative reactions and failure to achieve diagnosis. An aberrant immunophenotype, such as CD23 or CD10 positivity, may mislead the reporting pathologist. Cyclin D1 is weakly expressed by hairy cell leukaemia and may be detected in up to 25% of multiple myeloma cases, which may give rise to confusion in bone marrow trephine biopsy assessment. Performing a full immunohistochemical panel, reviewing the bone marrow aspirate and clinicopathological correlation should enable accurate diagnosis. A small proportion of CD5-negative DLBCL cases express cyclin D1 weakly (Ehinger et al, 2008). Epithelial malignancies often display nuclear positivity for cyclin D1, which may cause confusion in biopsies of undifferentiated nasopharyngeal carcinoma where the epithelial nature of the malignancy is often obscured by an intense lymphocytic reaction. Genuine cyclin D1-negative cases of MCL lacking the t(11;14) translocation have recently been recognized through gene expression profiling (Fu et al, 2005; Herens et al, 2008; Quintanilla-Martinez et al, 2009). The cytomorphology, immunophenotype (other than cyclin D1 negativity) and clinical course are identical to cases of classical MCL. The lymphoma is characterized by overexpression of cyclin D2 or cyclin D3, and has a variant translocation. These lymphomas have an identical gene expression profile to typical MCL and are therefore regarded as a variant of this condition and should be treated as such. The detection of nuclear SOX11 expression has been suggested as a simple means of recognizing this entity (Mozos et al, 2009). Variable results have been obtained with this antibody, and as yet, a reliable simple diagnostic test is not widely available. It is important for the haematopathologist to be aware of this entity and to consider the diagnosis when confronted with a CD5-positive/cyclin D1-negative B-cell lymphoma with morphological features of MCL. Referral to a specialist centre for further investigation should be considered. Initial investigations performed in a patient with confirmed MCL serve to provide information to guide management. Such investigations are useful to describe the stage or extent of disease, prognosticate and evaluate fitness for therapy. Assessment of performance status at baseline using a standard tool such as the World Health Organization/Eastern Cooperative Oncology Group (ECOG) performance status (Oken et al, 1982) is recommended. CT of the neck, thorax, abdomen and pelvis should be included with oral contrast and intravenous contrast where appropriate. Magnetic resonance imaging (MRI) may be useful for assessment of CNS disease, with gadolinium enhancement where clinical suspicion is high (Ferrer et al, 2008; Gill & Seymour, 2008; Gill et al, 2009). (18F)Fluorodeoxyglucose positron emission tomography (FDG-PET) is now used in the assessment of many types of lymphoma, although its exact role remains to be established in many cases. It has been shown that MCL is FDG-avid, particularly the blastoid variant and nodal disease (Brepoels et al, 2008). However, in contrast to other high grade NHLs, FDG-PET has been shown to have lower sensitivity in staging MCL, particularly extranodal disease (Rusconi et al, 2010) and routine use of FDG-PET in the staging of MCL, outside the context of a clinical trial, cannot be recommended. Baseline peripheral blood tests should include a full blood count and peripheral blood film morphology. A frank peripheral blood lymphocytosis is seen in 20–40% of patients with MCL, and when present, immunophenotyping by flow cytometry is recommended. Baseline biochemistry should include urea, creatinine and electrolytes, liver function tests, adjusted calcium, albumin, urate and lactate dehydrogenase. Bone marrow examination should include an aspirate for immunophenotyping by flow cytometry, and a trephine biopsy for histological examination (as discussed above). Lumbar puncture and cytological examination of cerebrospinal fluid by cytospin, together with flow cytometry should be performed if there is any clinical suspicion of CNS disease, and can be considered in blastoid variant disease. Enteroscopy – some authorities recommend routine colonoscopy and upper GI endoscopy as part of staging investigations in MCL (Zelenetz et al, 2011), on the basis that prospective studies have identified microscopic involvement by MCL of the GI tract in 92% of cases (Salar et al, 2006). However, it has been demonstrated that this finding only rarely (in <4% of cases) changes clinical management. (Romaguera et al, 2003) Therefore, routine endoscopy and colonoscopy cannot be recommended for all patients at baseline. Instead, enteroscopy should be performed on the basis of clinical indication, where there are any significant enteric symptoms, or if clinical stage 1A disease is present and radiotherapy with curative intent is planned. Where enteroscopy is performed, biopsies of any suspicious lesions, and also macroscopically normal areas, should be taken for cyclin D1 immunohistochemistry. Virology – where rituximab therapy is considered, it is recommended that patients undergo testing for hepatitis B and C; hepatitis B surface antigen and core antibody in patients with no other risk factors hepatitis e antigen should be added where risk factors exist. Where testing confirms hepatitis B or C infection, viral load should be assessed using local protocols, and the patient discussed with the local infectious disease or gastroenterology service. Similarly, serological testing for human immunodeficiency virus (HIV) is recommended prior to commencement of therapy, but is not essential. Pregnancy testing – although MCL is uncommon in women of childbearing age, it is recommended that a pregnancy test be performed before chemotherapy is administered in this group. Although previously regarded as a disease with generally poor outcome, it has become clear that MCL behaves more heterogeneously than previously thought, and for this reason, attempts have been made to identify features that may influence prognosis. As has been discussed above, histological features may be important indicators of outcome. The staging system used to assess MCL is the same as the modified Ann Arbor staging used in Hodgkin lymphoma and most other types of NHL (see Table 3). As most patients with MCL have blood and bone marrow involvement at presentation, clinical stage used in isolation is not prognostically useful. The international prognostic index (IPI) does not perform well when used in populations of patients with MCL, and is therefore not applicable in this setting (Moller et al, 2006; Hoster et al, 2008a). A prognostic scoring system specific for MCL, the MCL international prognostic index (MIPI) has been devised, based on modeling using features of the IPI in 455 patients with advanced stage MCL (Hoster et al, 2008a). This model separates patients into three groups; low risk (LR), intermediate risk (IR), and high risk (HR) with good separation of the survival curves. For ease of access to this score, the European MCL Network provides an online calculator at http://www.european-mcl.net/en/clinical_mipi.php. However, acknowledging that simplifying the scoring system would make its use more practical and accessible, the authors also modelled a simplified scoring system, allocating weighted point scores at cut-offs of age, ECOG performance score, lactate dehydrogenase and white blood cell count (see Table 4). This simplified MIPI (sMIPI) also clearly separated patients into the three groups of LR, IR and HR, and was just as powerful as the MIPI whilst being simpler to use. Both the MIPI and the sMIPI have been validated in large independent cohorts (Budde et al, 2011; van de Schans et al, 2010). It is acknowledged by the authors of the score that prospective, external validation of its prognostic value will be required before it can be used for the selection of therapies in individual patients (van de Schans et al, 2010; Hoster et al, 2008b; Ghielmini & Zucca, 2009). In spite of this, as a practical tool, it can still provide valuable information to the clinician at baseline. As Ki67, as described above, is prognostic independent of the MIPI, an alternative is to combine these, to provide a more powerful prognostic system, [the MIPI biological (MIPIb); Hoster et al, 2008a]. The MIPIb and sMIPIb retained prognostic significance in independent validation cohorts (Geisler et al, 2010). Provided that more reproducible methods of Ki67 quantification are used, the MIPIb may be a useful prognostic marker at baseline. There is a lack of definitive data to guide treatment of MCL, partly because it is a relatively uncommon condition and partly because it was only recognized as a specific entity in the revised European-American classification of lymphoid neoplasms (REAL classification) published in 1994 (Harris et al, 1994). In addition, MCL patients have frequently been included with other NHL types in clinical studies. Therefore, it is recommended that, where possible, patients with MCL should be managed within the context of a clinical trial. Details of how to obtain information regarding UK clinical trials for patients with MCL can be found in Appendix II. The guidance below suggests options and recommendations for patients not treated in a clinical trial. Where possible, discussion is restricted to published studies including more than 15 MCL patients. Four very large studies currently published in abstract form are considered of major significance in the field (Le Gouill et al, 2010; Kluin-Nelemans et al, 2011; Hermine et al, 2010; Rule et al, 2011) and, as other published data are not available to answer the research questions they address, are included in the discussion. A very small proportion of patients will present with localized MCL. As such, evidence for management of this group is scarce. However, in this situation, involved field radiotherapy may be appropriate and can result in long-term remissions. MCL is radiosensitive, and radiotherapy has been used as single agent therapy for localized disease with good responses (Rosenbluth & Yahalom, 2006). Another retrospective study reported outcomes in 26 patients with low-bulk stage IA and IIA MCL (Leitch et al, 2003). Radiotherapy was administered to 17 of the patients, in combination with chemotherapy in six of those patients. In spite of small numbers, the study did demonstrate an advantage of radiotherapy in this group; 5-year progression-free survival (PFS) of 68%, compared with 11% for those not receiving RT. In addition, a retrospective analysis from the British National Lymphoma Investigation Group (BNLI) (Vandenberghe et al, 1997) examined 65 cases treated with non-intensive therapy. Fifteen patients had stage I or II disease, and were treated with local radiotherapy. Twelve (80%) of these patients attained a complete response (CR). Responses were sustained; eight of the 12 responding patients relapsed at 8–90 months and three patients remained in sustained CRs at 156, 190 and 192 months, suggesting that localized MCL may be curable with radiotherapy in a small proportion of cases. If early-stage disease is suspected, staging should be confirmed with bone marrow examination and GI investigations as described above. Outside the context of a clinical trial, radiotherapy, with or without chemotherapy, would be a reasonable approach. MCL is now recognized as having the worst outlook of all subtypes of lymphoma. Although many patients respond well to initial chemotherapy, remission duration is short and overall survival (OS) is poor. As has been discussed in the introduction, a small subgroup of patients has disease that behaves in a more indolent fashion. If they are asymptomatic, it is reasonable to adopt a watch and wait policy. A retrospective study of 97 patients demonstrated that for 30% of patients who were managed initially by observation only (‘watch and wait’), treatment was deferred for a median of 12 months (range 4–128 months) with acceptable outcomes (Martin et al, 2009). It is of note, however, that patients in this study were monitored closely, and generally started treatment after months rather than years. The majority of patients will, however, require chemotherapy. Once the decision is made to treat the patient, the choice of regimen will depend on the overall aim of therapy. Clinical trials of first-line treatment in MCL are summarized in Table 5. An early distinction should be made between younger patients fit to undergo autologous peripheral blood stem cell transplantation (ASCT), and those less fit patients for whom this is not an option. For younger, fitter patients where the aim is to proceed to high dose (HD) therapy and autograft in first remission, chemotherapy should be given with the aim of obtaining as good a remission as possible. However, the majority of patients are elderly, where a high-dose therapy approach is not feasible. For these patients, a range of chemotherapy options is available, in combination with rituximab, and these are discussed below. It is acknowledged however, that for this group, there is no gold-standard therapy, and it is difficult to recommend any specific regimen. Historically, MCL was grouped with low-grade lymphomas in clinical studies and treated with regimens including CVP (cyclophosphamide, vincristine, prednisone) (Meusers et al, 1989; Teodorovic et al, 1995; Unterhalt et al, 1996), fludarabine-based regimens (Cohen et al, 2001), and CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) (Meusers et al, 1989; Lenz et al, 2005; Nickenig et al, 2006). Most of the studies had small numbers but the general pattern was of reasonable overall response rates (ORR, 60–88%), but short PFS (7–21 months) and poor OS of 40–85% at 2 years. No particular combination appears superior in terms of OS. In particular, addition of an anthracycline in the only randomized controlled trial (RCT) performed (Meusers et al, 1989) did not confer a survival benefit. This has been confirmed in large retrospective analyses. The Nebraska Lymphoma Study Group demonstrated that, although 79% of patients were treated with anthracycline-containing regimens, no survival benefit of anthracycline could be demonstrated (Weisenburger et al, 2000). Similarly, the Barcelona experience showed an ORR of 61% in patients receiving anthracycline-containing regimens, and 66% in those treated without anthracyclines (Bosch et al, 1998). In those not fit for the more intensive induction regimens discussed below, there is no evidence that adding anthracycline confers any advantage. However, despite the lack of robust evidence, R-CHOP (CHOP + rituximab) remains a widely used combination chemotherapy regimen in this disease and forms the control arm in many randomized studies. For this reason, we have included it as a treatment option. The effectiveness of purine analogues in MCL has been studied in the front-line setting, with mixed results. When used as a single agent, ORRs of around 30% are seen (Ghielmini et al, 2005; Grillo-Lopez, 2005). However, when used in combination with cytotoxic agents, such as idarubicin or cyclophosphamide, ORRs increase to approximately 60% (Zinzani et al, 1999, 2000; Cohen et al, 2001). The haematological toxicity of the purine analogues must not be forgotten however, and, in addition to the recognized infectious morbidity, they may cause difficulty with stem-cell mobilization when this is undertaken (Dreyling & Hiddemann, 2008; Eve et al, 2009b). A large study of the European MCL Network randomized 560 elderly patients between R-CHOP ×8 and R-FC (rituximab, fludarabine, cyclophosphamide) ×6 (Kluin-Nelemans et al, 2011). Response rates were poorer in the R-FC arm and, of note, OS was lower in the R-FC arm (40 vs. 60 months, P = 0·0072), with particularly high infection rates, reinforcing the notion that the haematological toxicities of purine analogues mean that caution should be exercised when administering these agents to elderly MCL patients. Age, platelet count and renal function should be taken into any decision to include a purine analogue in treatment, and purine analogues are not recommended as part of first-line treatment where ASCT is considered. Chlorambucil has activity in MCL, however the evidence suggests that it be used in combination with rituximab for meaningful responses to be seen (Bauwens et al, 2005; Sachanas et al, 2011). Bendamustine has efficacy in MCL (Rummel et al, 2005; Herold et al, 2006) and, having a favourable toxicity profile compared to CHOP, may have an increasing role to play in treatment, particularly where less aggressive therapy is preferred. The combination of bendamustine and rituximab demonstrated an ORR of 75% (CR 50%) (Rummel et al, 2005). A CR rate of 22% was reported with the BOP regimen (bendamustine, vincristine and prednisone), however this study (Herold et al, 2006) included patients with different ty" @default.
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W1990464386 date "2012-09-21" @default.
W1990464386 modified "2023-09-25" @default.
W1990464386 title "Guidelines for the investigation and management of mantle cell lymphoma" @default.
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