Lenalidomide plus R-CHOP21 in newly diagnosed diffuse large B-cell lymphoma (DLBCL): long-term follow-up results from a combined analysis from two phase 2 trials.

Lenalidomide-RCHOP (R2-CHOP21) has been shown to be safe and effective in patients with untreated diffuse large B-cell lymphoma (DLBCL). The aim of this analysis is to report long-term outcome and toxicities in newly diagnosed DLBCL patients who received R2-CHOP21 in two independent phase 2 trials, conducted by Mayo Clinic (MC) and Fondazione Italiana Linfomi (FIL). All patients received R-CHOP21 plus lenalidomide. Long-term progression-free survival (PFS), time to progression (TTP), overall survival (OS) and late toxicities and second tumors were analyzed. Hundred and twelve patients (63 MC, 49 FIL) were included. Median age was 69 years, 88% were stage III-IV. At a median follow-up of 5.1 years, 5y-PFS was 63.5%, 5y-TTP 70.1% and 5y-OS 75.4%; according to cell of origin (COO): 5y-PFS 52.8% vs 64.5%, 5y-TTP 61.6% vs 69.6% and 5y-OS 68.6% vs 74.1% in germinal center (GCB) vs non-GCB respectively. Four patients experienced grade 4-5 late toxicities. Grade ≤ 3 toxicities were infections (N = 4), thrombosis (N = 1) and neuropathy (N = 3). Seven seconds tumors were observed. Long-term follow-up demonstrates that R2-CHOP21 efficacy was maintained with high rates of PFS, TTP, and OS. Lenalidomide appears to mitigate the negative prognosis of non-GCB phenotype. Incidence of therapy-related secondary malignancies and late toxicities were low.

Evaluation of mercury exposure reduction through a fish consumption advisory program for Anishinaabe tribal members in Northern Wisconsin, Michigan, and Minnesota.

The Great Lakes Indian Fish and Wildlife Commission has an extensive program to inform Anishinaabe tribal members from northern Wisconsin, Michigan, and Minnesota who harvest and consume walleye about the health risks of consuming these fish, and to encourage harvest and consumption practices that reduce exposure to MeHg. We report here the results of a probabilistic analysis of exposure to methyl mercury (MeHg) among tribal members who consume walleye. The model predicts that the potential for greatest exposures to MeHg occur among women of child-bearing age and children who consume large walleye from lakes that contain heavily contaminated (MeHg concentration >0.5 mg/kg) fish. The analysis allows GLIFWC to evaluate, focus, and fine-tune its initiatives to protect the health of tribal members in ways that result in exposure and risk reduction for tribal harvesters, women of child-bearing age, and children, while maintaining important tribal lifeways, which include the harvest and consumption of walleye.

Immunological and clinical effects of post-transplant G-CSF versus placebo in T-cell replete allogeneic blood transplant patients: results from a randomized double-blind study.

BACKGROUND: Immunological and clinical effects of post-transplant growth factor administration have not been well studied. This report describes the outcome and immune functions of a total of 50 HLA-matched related donor allogeneic blood stem-cell transplantation patients who received post-transplant G-CSF (10 microg/kg) or placebo. METHODS: Immune status, including number of lymphocyte subsets and their functions, and serum immunoglobulin levels and clinical status--including GvHD, rate of relapse, event-free survival, and overall survival--were determined in the patients enrolled in this study. RESULTS: Twenty-eight patients survived 1 year after transplant, and 15 patients had available results to compare immune function by randomization assignment. At 12 months post-transplant, immune parameters in G-CSF versus placebo groups showed no statistically significant differences in number of circulating lymphocyte subsets CD3, CD4, CD8, CD19 and CD56 in the two groups. There was no significant (NS) difference in immunoglobulin IgG, IgA and IgM levels, NK or LAK cell-mediated cytotoxicity levels, and mitogen-induced proliferation between post-transplant G-CSF and placebo group. In addition, the analyses of immune parameters at earlier time-points on Days 28, 100, 180, and 270 revealed that, except for LAK cytotoxicity at Day 100, there was no differences between the two groups. Fourteen of 26 patients are alive in the G-CSF arm and nine of 24 in the placebo arm. Median follow-up of surviving patients is 43 months. Four year overall and event-free survival in the G-CSF and the placebo group were 53% and 35% (NS), and 44% and 36% (NS) respectively. Bacterial or fungal infections were the cause of six of 12 deaths in the G-CSF arm (all bacterial) and of four of 15 deaths in the placebo arm (two deaths from Aspergillus) (P=0.26). Two patients relapsed in the G-CSF arm and three in the placebo arm. Four year cumulative incidences of relapse were 8% versus 13% in G-CSF versus placebo arms, respectively, (NS). Chronic GvHD developed in 14 of 19 100-day survivors after G-CSF (11 extensive stage), and in 17 of 20 (14 extensive stage) in the placebo arm. The 4-year cumulative incidence of chronic GvHD was 56% [95% confidence interval (CI) 24-88%] after G-CSF and 71% (95% CI 48-94%) after placebo; this difference was not statistically significant (log rank P=0.41). CONCLUSION: In summary, there were no significant immunological or alterations in clinical benefit of post-transplant G-CSF administration in T-replete allotransplant recipients.

A phase II protection study of BB-10010 in patients with high grade non-Hodgkin's lymphoma undergoing intensive chemotherapy.

The aim of this study was to determine whether administration of BB-10010, a synthetic stem cell inhibitor, would allow more intensive chemotherapy to be administered to patients with newly diagnosed high grade NHL. Thirteen patients were randomised to receive BB-10010 concurrently with dose-intensified BEMOP/CA chemotherapy (7 patients) or chemotherapy alone (6 patients). Although the mean neutrophil count of BB-10010 treated patients was higher following cycles 1, 2 and 3 of chemotherapy compared with those receiving chemotherapy alone, there was no difference in the mean number of cycles tolerated, blood component usage and hospital admissions due to infections. No specific toxicity of BB-10010 was identified. Whilst BB-10010 can be administered safely, it does not improve the ability of patients to tolerate intensive chemotherapy for high grade NHL.

Reversible posterior leukoencephalopathy syndrome following CHOP chemotherapy for diffuse large B-cell lymphoma.

A 63-year-old female with stage IE diffuse large B-cell lymphoma developed reversible posterior leukoencephalopathy syndrome (RPLS) following CHOP chemotherapy, with typical clinical and radiological findings. RPLS is a rare neurological syndrome characterised by visual disturbances, seizures, headaches and altered conscious level which has been associated with malignant hypertension, pre-eclampsia and some drugs, including ciclosporin. It has not been previously reported following CHOP chemotherapy. Alternative treatment should be considered for patients who develop this rare complication.

Loss of CD20 expression following treatment with rituximab (chimaeric monoclonal anti-CD20): a retrospective cohort analysis.

A retrospective analysis of CD20 expression following rituximab for B-cell non-Hodgkin's lymphoma demonstrated a significant change in immunophenotype in 6/25 (24%) patients with persistent bone marrow (BM) infiltration. In three out of six patients, the B cells were uniformly CD20-/CD79alpha+, consistent with frank loss of CD20 expression. In the remaining three cases, the BM infiltrate was predominantly (> 80%) CD20-/CD79alpha+. Two of the former but none of the latter three cases achieved a clinical response. In three further cases, the post-treatment BM infiltrate was composed entirely of benign or reactive CD3+ T cells. Frank loss of CD20 was not seen in 25 post-treatment lymph node biopsies. Immunophenotyping is therefore an important adjunct in the diagnosis of BM infiltration following rituximab.

Symptomatic improvement after radiofrequency catheter ablation for typical atrial flutter.

OBJECTIVE: To assess the changes in quality of life, arrhythmia symptoms, and hospital resource utilisation following catheter ablation of typical atrial flutter. DESIGN: Patient questionnaire to compare the time interval following ablation with a similar time interval before ablation. SETTING: Tertiary referral centre. PATIENTS: 63 consecutive patients were studied. Four patients subsequently underwent an ablate and pace procedure, two died of co-morbid illnesses, and two were lost to follow up. The remaining 55 patients form the basis of the report. RESULTS: Patients were followed for a mean (SD) of 12 (9.5) months. Atrial flutter ablation resulted in an improvement in quality of life (3.8 v 2.5, p < 0.001) and reductions in symptom frequency score (2.0 v 3.5, p < 0.001) and symptom severity score (2.0 v 3.8, p < 0.001) compared with preablation values. There was a reduction in the number of patients visiting accident and emergency departments (11% v 53%, p < 0.001), requiring cardioversion (7% v 51%, p < 0.001), or being admitted to hospital for a rhythm problem (11% v 56%, p < 0.001). Subgroup analysis confirmed that patients with atrial flutter and concomitant atrial fibrillation before ablation and those with atrial flutter alone both derived significant benefit from atrial flutter ablation. Patients with concomitant atrial fibrillation had an improvement in quality of life (3.5 v 2.5, p < 0.001) and reductions in symptom frequency score (2.3 v 3.5, p < 0.001) and symptom severity score (2.2 v 3.7, p < 0.001) compared with preablation values. CONCLUSIONS: Ablation of atrial flutter is recommended both in patients with atrial flutter alone and in those with concomitant atrial fibrillation.

Myositis, polyserositis with a large pericardial effusion and constrictive pericarditis as manifestations of chronic graft-versus-host disease after non-myeloablative peripheral stem cell transplantation and subsequent donor lymphocyte infusion.

The clinical features of chronic graft-versus-host disease (cGVHD) following a non-myeloablative peripheral blood stem cell (PBSC) transplant may differ from those that occur after a conventional allograft. We describe a man with Hodgkin's disease refractory to chemotherapy and radiotherapy who was transplanted from an HLA-identical brother, who developed cGVHD characterised, in particular, by polymyositis, polyserositis with a large pericardial effusion and constrictive pericarditis, 1 month after donor lymphocyte infusion for relapsed disease. Constrictive pericarditis has not been previously reported after a conventional allograft, and none of these features have been reported after a non-myeloablative transplant. The course of cGVHD necessitated potent immunosuppression leading to the presumed loss of graft-versus-lymphoma (GVL) effect.

Methods to identify and characterize developmental neurotoxicity for human health risk assessment. I: behavioral effects.

Alterations in nervous system function after exposure to a developmental neurotoxicant may be identified and characterized using neurobehavioral methods. A number of methods can evaluate alterations in sensory, motor, and cognitive functions in laboratory animals exposed to toxicants during nervous system development. Fundamental issues underlying proper use and interpretation of these methods include a) consideration of the scientific goal in experimental design, b) selection of an appropriate animal model, c) expertise of the investigator, d) adequate statistical analysis, and e) proper data interpretation. Strengths and weaknesses of the assessment methods include sensitivity, selectivity, practicality, and variability. Research could improve current behavioral methods by providing a better understanding of the relationship between alterations in motor function and changes in the underlying structure of these systems. Research is also needed to develop simple and sensitive assays for use in screening assessments of sensory and cognitive function. Assessment methods are being developed to examine other nervous system functions, including social behavior, autonomic processes, and biologic rhythms. Social behaviors are modified by many classes of developmental neurotoxicants and hormonally active compounds that may act either through neuroendocrine mechanisms or by directly influencing brain morphology or neurochemistry. Autonomic and thermoregulatory functions have been the province of physiologists and neurobiologists rather than toxicologists, but this may change as developmental neurotoxicology progresses and toxicologists apply techniques developed by other disciplines to examine changes in function after toxicant exposure.

Low-dose continuous chemotherapy (LBCMVD-56) for refractory and relapsing lymphoma.

BACKGROUND: Although lymphoid malignancies are generally chemosensitive, relapse is common. The use of high-dose therapy can make subsequent cytotoxic therapy intolerable. There is a need to develop regimens with low acute toxicity which are suitable for use in patients post-high dose therapy and following the failure of standard protocols. PATIENTS AND METHODS: Twenty-six patients with lymphomas, fifteen of whom had received high-dose therapy, were treated with a novel regimen consisting of low-dose lomustine, chlorambucil, daily subcutaneous bleomycin, vincristine and methotrexate with dexamethasone on an eight-week cycle (LBCMVD-56). A median of three cycles was given. RESULTS: The overall response rate at 12 weeks was 67% (21% complete remission (CR)) with a median overall survival of 13 months. A symptomatic response was seen in 72%. Previous high-dose therapy did not compromise the response rate. Toxicity was acceptable with grade 3-4 haematological toxicity seen in 27% of cycles, gastrointestinal toxicity seen in 11% and pulmonary toxicity seen in 8%. Thirty-one percent of patients required hospitalisation at some point during this treatment most commonly for neutropenic sepsis. CONCLUSIONS: LBCMVD-56 is an inexpensive, outpatient-based regimen with low acute toxicity and a high response rate in this heavily pre-treated group of patients.

A phase II study to evaluate the combination of fludarabine, mitoxantrone and dexamethasone (FMD) in patients with follicular lymphoma.

BACKGROUND: 'Molecular response' is being investigated as a therapeutic goal in follicular lymphoma (FL). High response rates in FL with the fludarabine combination 'FMD' have been associated with 'molecular remission'. A phase II study of FMD in FL was therefore conducted. PATIENTS AND METHODS: Fifty-four patients, ten of whom were newly diagnosed received FMD. Forty-four percent of the previously treated patients had 'chemoresistant' disease. Treatment comprised: fludarabine 25 mg/m2 days 1-3, mitoxantrone 10 mg/m2 day 1, and dexamethasone 20 mg days 1-5. Blood/bone marrow was collected for quantitation of t(14;18) by 'real-time' PCR. RESULTS: The overall response rate was 37 of 54 (69%), complete responses being seen in 11 patients (20%), with no difference between newly diagnosed and the previously treated patients. However, the response rate in 'chemosensitive' relapse was 84% compared to 44% in patients in whom the last prior regimen had failed. Molecular responses were seen in 17 of 25 and PCR negativity in 8 of 25, although molecular and clinical responses did not always correlate. Toxicity was moderate, 19 patients required admission. However, in 6 of 12 patients, subsequent G-CSF mobilised stem cell harvests failed. CONCLUSIONS: FMD was well tolerated but with a lower than expected response rate. Molecular responses were seen in the majority of responding patients however, 'molecular remission' was rare.

A UK multicentre phase II study of rituximab (chimaeric anti-CD20 monoclonal antibody) in patients with follicular lymphoma, with PCR monitoring of molecular response.

Follicular lymphoma (FL) cells express CD20 and are associated in most cases with the t(14;18) chromosomal translocation. A multicentre study was undertaken between January 1997 and January 1998 to assess the complete response rate (CR) and overall response rate (RR) to rituximab, a chimaeric anti-CD20 monoclonal antibody. Seventy patients with previously treated FL received rituximab (375 mg/m2/week x4, by intravenous infusion). Restaging studies were performed 1 and 2 months after therapy. Molecular monitoring for the presence of cells harbouring the Bcl-2/JH gene rearrangement in the peripheral blood (PB) and bone marrow (BM) was performed before and after treatment using a two-step semi-nested polymerase chain reaction (PCR) assay. The overall RR was 32/70 (46%), being highest in patients who had received only one previous treatment (12/15, 80%). However, only two patients achieved a CR. The median duration of response was 11 months. Thirteen of 21 evaluable 'PCR-positive' patients (62%) became 'PCR-negative' in PB and/or BM samples 1 month after rituximab, although this did not correlate with clinical response. Treatment was generally well tolerated, although one patient developed Stevens-Johnson syndrome. Rituximab was shown to be active in FL, and in some cases PB and/or BM became PCR negative. Studies in combination with cytotoxic chemotherapy to increase the CR rate are warranted.

Therapy-related myelodysplasia and secondary acute myelogenous leukemia after high-dose therapy with autologous hematopoietic progenitor-cell support for lymphoid malignancies.

PURPOSE: To evaluate the incidence of and risk factors for therapy-related myelodysplasia (tMDS) and secondary acute myelogenous leukemia (sAML), after high-dose therapy (HDT) with autologous bone marrow or peripheral-blood progenitor-cell support, in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between January 1985 and November 1996, 230 patients underwent HDT comprising cyclophosphamide therapy and total-body irradiation, with autologous hematopoietic progenitor-cell support, as consolidation of remission. With a median follow-up of 6 years, 27 (12%) developed tMDS or sAML. RESULTS: Median time to development of tMDS or sAML was 4.4 years (range, 11 months to 8.8 years) after HDT. Karyotyping (performed in 24 cases) at diagnosis of tMDS or sAML revealed complex karyotypes in 18 patients. Seventeen patients had monosomy 5/5q-, 15 had -7/7q-, seven had -18/18q-, seven had -13/13q-, and four had -20/20q-. Twenty-one patients died from complications of tMDS or sAML or treatment for tMDS or sAML, at a median of 10 months (range, 0 to 26 months). Sixteen died without evidence of recurrent lymphoma. Six patients were alive at a median follow-up of 6 months (range, 2 to 22 months) after diagnosis of tMDS or sAML. On multivariate analysis, prior fludarabine therapy (P =.009) and older age (P =.02) were associated with the development of tMDS or sAML. Increased interval from diagnosis to HDT and bone marrow involvement at diagnosis were of borderline significance (P =.05 and.07, respectively). CONCLUSION: tMDS and sAML are serious complications of HDT for NHL and are associated with very poor prognosis. Alternative strategies for reducing their incidence and for treatment are needed.

Treatment of mantle-cell lymphoma with Rituximab (chimeric monoclonal anti-CD20 antibody): analysis of factors associated with response.

BACKGROUND: A retrospective analysis was performed to delineate the factors associated with response, and to determine the duration of response, in 87 patients with CD20-positive mantle-cell lymphoma (MCL) treated with Rituximab (chimeric monoclonal anti-CD20 antibody) in two prior studies. PATIENTS AND METHODS: Patients with newly-diagnosed MCL (MCL1, n = 37), and previously-treated MCL (MCL2, n = 50), received single-agent Rituximab, in the context of two multicentre clinical studies using different schedules and doses, conducted in 1996 and 1997. A follow-up analysis was performed at the end of 1998, including all 81 patients who completed therapy. Statistical modeling of factors associated with response was performed using ordered logistic regression. The duration of complete (CR) and partial response (PR), and the time to disease progression (TTP), were also derived. RESULTS: The overall response rate (RR) was 34% (30 of 87) (81 evaluable patients, RR 37%; CR 14%), and was equivalent for MCL1 and MCL2. On univariate analysis, elevated LDH (P = 0.004); prior therapy with alkylating agents (P = 0.01) or fludarabine phosphate (P = 0.04); WHO performance status = 2 (P = 0.02); MCL2 refractory to last prior therapy (P = 0.04); and splenomegaly (P = 0.04), each at the time of treatment with Rituximab, were significantly associated with a lower RR. On multivariate analysis, only LDH (P = 0.007) and prior alkylating agents (P = 0.03) retained statistical significance. At a median follow-up of 1.4 years, the median TTP was 7 months. The median duration of response was one year, and was significantly longer for patients achieving CR vs. PR (P = 0.04). CONCLUSIONS: Rituximab is active in MCL, and can induce complete responses in a minority of patients. Elevated LDH at the time of therapy, and prior therapy with alkylating agents, are associated with a significantly lower RR. The duration of response of one year is similar to that previously reported in follicular lymphoma.

European phase II study of rituximab (chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle-cell lymphoma and previously treated mantle-cell lymphoma, immunocytoma, and small B-cell lymphocytic lymphoma.

PURPOSE: Mantle-cell lymphoma (MCL), immunocytoma (IMC), and small B-cell lymphocytic lymphoma (SLL) are B-cell malignancies that express CD20 and are incurable with standard therapy. A multicenter phase II study was conducted to assess the toxicity and the overall response rates (RR) and complete response (CR) rates to rituximab (chimeric anti-CD20 monoclonal antibody). PATIENTS AND METHODS: Between January 1997 and January 1998, 131 patients with newly diagnosed MCL (MCL1; n = 34) and previously treated MCL (MCL2; n = 40), IMC (n = 28), and SLL (n = 29) received rituximab 375 mg/m(2)/wk for 4 weeks via intravenous infusion. Restaging studies were performed 1 and 2 months after treatment. An analysis of the duration of response was conducted in December 1998. RESULTS: Eleven patients were unassessable, including one who died of splenic rupture after the first infusion. The RR among the 120 assessable patients was 30% (36 of 120 patients). The RR by histology was as follows: MCL1, 38%; MCL2, 37%; IMC, 28%; and SLL, 14%. Ten patients, all with MCL, achieved CR. The median duration of response in MCL was 1.2 years. Immediate side effects were common and usually responded to adjustments in the infusion rate. There were 31 episodes of infection after treatment; most cases were mild. Cardiac arrhythmia and ophthalmologic side effects occurred in 10 and nine patients, respectively, including one case of severe loss of visual acuity. CONCLUSION: Single-agent rituximab has moderate activity in MCL and IMC but only limited activity in SLL. The duration of response in MCL was similar to that previously reported in follicular lymphoma. Its use in combination with cytotoxic chemotherapy to increase the CR rate is warranted in MCL and IMC.

Factors which predict unsuccessful mobilisation of peripheral blood progenitor cells following G-CSF alone in patients with non-Hodgkin's lymphoma.

INTRODUCTION: High-dose therapy with haematopoietic progenitor cell support has increasingly been utilised for patients with haematological malignancies. Peripheral blood is the stem cell source of choice, however, various mobilisation strategies are used by different centres. PATIENTS AND METHODS: Over a 2-year period, 52 patients with non-Hodgkin's lymphoma (median age 47 years, range 16-64 years) underwent peripheral blood progenitor cell mobilisation using G-CSF alone (16 microg/kg/day). The harvest was considered successful if > or =1 x 10(6) CD34(+) cells/kg were collected by leukapheresis. The histological subtypes of non-Hodgkin's lymphoma comprised: follicular (24 patients), diffuse large B-cell (14 patients), lymphoplasmacytoid (four patients), mantle cell (three patients), lymphoblastic lymphoma (one patient) and small lymphocytic lymphoma/chronic lymphocytic leukaemia (six patients). The median interval from diagnosis of non-Hodgkin's lymphoma to mobilisation was 27 months (range 2 months to 17 years). The median number of prior treatment episodes was 2 (range 1-5); 26 patients had received fludarabine alone or in combination. At the time of peripheral blood progenitor cell mobilisation, 20 patients were in 1st remission and 32 were in > or =2nd remission; 30 patients were in partial remission and 22 were in complete remission; the bone marrow was involved in nine patients. RESULTS: Peripheral blood progenitor cell mobilisation/harvest was unsuccessful in 19 out of 52 (37%) patients (mobilisation: 18, harvest: 1). The factors associated with unsuccessful mobilisation or harvest were: prior fludarabine therapy (P=0.002), bone marrow involvement at diagnosis (P=0.002), bone marrow involvement anytime prior to mobilisation (P=0.02), histological diagnosis of follicular, mantle cell, or lymphoplasmacytoid lymphoma, or small lymphocytic lymphoma/chronic lymphocytic leukaemia (P=0.03) and female gender (P=0.04). CONCLUSION: Although peripheral blood progenitor cells can be successfully mobilised and harvested from the majority of patients with non-Hodgkin's lymphoma after treatment with G-CSF alone, the latter is unsuccessful in approximately one-third of patients. These factors should be taken into account when patients are being considered for high-dose treatment.

Immunocytoma: a retrospective analysis from St Bartholomew's Hospital-1972 to 1996.

PURPOSE: To analyze the presentation features and outcome for patients with immunocytoma (IMC) managed at St Bartholomew's Hospital (SBH), London, United Kingdom, between 1972 and 1996. Outcome was compared with that of patients with small lymphocytic lymphoma (SLL)/B-cell chronic lymphocytic leukemia (B-CLL) treated at SBH during the same period. PATIENTS AND METHODS: One hundred twenty-six patients with newly diagnosed IMC were identified. Patients were subclassified (using the Kiel classification) as having lymphoplasmacytoid (n =92), lymphoplasmacytic (n = 24), polymorphous (n = 9), or undetermined (n = 1) IMC. Six patients (5%) had stage I to IIE disease; the rest had advanced disease. Treatment was given according to disease stage. Seven patients were managed expectantly. RESULTS: Eighty-two (69%) of 119 patients responded to treatment, but complete remission was seen in only 15 (13%) of 119. Treatment failed in 29 (24%) of 119 patients. There were three treatment-related deaths; five patients were not assessable for response. When survival of patients with IMC was compared with that of patients with B-CLL/SLL, a significant difference was found (P <. 01); this difference was maintained when only patients in whom the diagnosis was based on lymph node biopsy were considered (P =.01). A comparison of the three IMC subgroups showed that there was a trend (P =.06) toward a difference between B-CLL/SLL and the lymphoplasmacytoid subtype. CONCLUSION: Patients diagnosed with IMC are generally older and present with advanced disease. Conventional therapies usually result in incomplete responses of short duration. Overall, these results support the proposed World Health Organization reclassification of IMC to include lymphoplasmacytoid lymphoma (Kiel classification) as a variant of B-CLL/SLL.

Monoclonal Epstein-Barr virus-related lymphoproliferative disorder following adult acute lymphoblastic leukaemia.

A 31-year-old patient in remission of acute lymphoblastic leukaemia (ALL), receiving oral maintenance chemotherapy (6-mercaptopurine, methotrexate (MTX), cyclophosphamide), developed a monoclonal, Epstein-Barr virus (EBV)-related lymphoproliferative disorder (LPD). Treatment consisted of excisional biopsy and the discontinuation of maintenance chemotherapy. To our knowledge, this is the first such report in an adult. The histological similarity to previous reports of 'lymphomatoid granulomatosis' following paediatric ALL suggests that they are the same disease. MTX may play a central role in the development of LPD in this setting. Although it is a rare complication of ALL, EBV-related LPD should be considered in patients who develop lymphadenopathy.