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Introduction and epidemiology Solitary plasmacytoma, which accounts for less than 5% of plasma cell dyscrasias is characterized by a localized proliferation of malignant plasma cells in the absence of evident disease elsewhere. Such a proliferation may arise in a bone (solitary bone plasmacytoma or SBP) or an extra-medullary compartment (extramedullary plasmacytoma or EMP). Plasmacytomas may also arise in a multifocal manner without evidence of malignant plasma cells in the intervening tissues. Extra-medullary plasmacytomas may also arise in the context of multiple myeloma. Solitary Bone Plasmacytoma SBP may arise at any age, but the median age of onset at 55 years is 10 years younger than that for myeloma, with a 1.87:1 male to female ratio[1]. Clinical and laboratory features In two-thirds of cases, SBP arises in the axial skeleton, including the spine (thoracic > lumbar > sacral > cervical spine), skull, ribs and sternum and, in one-third, the appendicular skeleton, including the shoulder girdle, pelvic girdle or the extremities [2]. Localized skeletal pain due to the solitary osteolytic lesion is a typical presentation of SBP. If the spine is affected, spinal cord or nerve root compression may be an important clinical consequence. Other presentations include pathological fracture of the affected bone, a soft tissue mass due to extra-medullary extension of the tumor and in a small proportion, symptoms of peripheral neuropathy.

e288 (Mel) a further ASCT seems reasonable. Querying effectivity and efficiency to overcome therapy-induced exhausted bone marrow function in a heavily pre-treated population, we assessed the outcomes of 61 pts. receiving a 3rd Mel-based salvage ASCT (ASCT3) after tandem ASCT as part of 1st line therapy, querying the databases of six German MM centres. 61 pts. with a median age of 63 years at ASCT3 (range, 38-77) were identified. In 5 of 50 available analyses, cytogenetics could be classified high-risk (17p13 del, t(4;14), t(14;16), amp1q21, del1p). At a median nr. of 3 lines of pre-treatment (range, 1-10) 45 pts. had either received bortezomib and/or lenalidomide, and 37 pts. both. 11 pts. had been double refractory and 23 pts. at least had been refractory to one novel agent prior to ASCT3. With a median Mel dose of 100mg/m2 and 3.1x10E6 CD34 cells/kg all pts. achieved stable engraftment despite a median graft age of 52 mos. (range, 1-154). A remarkable improvement of platelet count and haemoglobin (62.3% /49.2% of all pts.) within 3 mos. of ASCT3 could be obtained. Overall response rate ( PR) was 59% with a median PFS of 9 mos. and a median OS of 26 mos. for the entire group, respectively. 3rd salvage ASCT at late relapse is not only effective with an ORR of 59% and associated with a 9 mos.’ PFS interval but also contributes to improved haematopoiesis. Thus, pts. may tolerate further lines of therapy what is suggested by an OS of 26 mos. In addition, ASCT offers a substantial treatment-free interval when compared to either novel drug. Unfavourable cytogenetics were associated with worse PFS of 2 mos. but not median OS (8 mos.), meanwhile being double refractory was linked with an inferior OS compared to non-refractory pts. (8 vs. 23 mos.). However, benefit seems to depend on PFS after initial ASCT ( 18 mos. ->5 mos.’ PFS after ASCT3, 19-36 mos. ->18 mos., >36 mos. ->23 mos.). Figure 1 A) Progression-free survival and B) overall survival of all patients PO-359 Outcome of Pomalidomide Therapy in Relapsed /Refractory Myeloma: A Uk Multi-Centre Experience N. Maciocia, F. Sharpley, E. Belsham, H. Renshaw, S. Schey, S. Cheesman, A. Cerner, A. Rismani, S. D’sa, M. Streetly, B. Reuben, M. Jenner, K. Ramasamy, K. Yong, N. Rabin Haematology, University College London Hospitals NHS Foundation Trust, London; Haematology, Oxford University Hospitals NHS Trust, Oxford; Haematology, University Hospital Southampton NHS Foundation Trust, Southampton; Haematology, King’s College Hospital NHS Foundation Trust, London; Haematology, Guy’s and St Thomas’ NHS Foundation Trust, London Background: Pomalidomide is licensed in Europe for patients with relapsed/refractory myeloma, who have received at least two prior therapies (lenalidomide/bortezomib) plus progressed on their last therapy. In the phase 3 NIMBUS study, pomalidomide/dexamethasone (POMA-DEX) was associated with longer PFS (4.0 v 1.9 months) and OS (12.7 v 8.1 months) compared to dexamethasone alone (San Miguel et al 2013). Aims: To assess the real-world clinical efficacy of POMA-DEX in several large UK centres. Methods: Patients had measurable disease (IMWG criteria) and received at 15th International Myeloma Workshop, September 23-26, 2015 least 1 cycle of POMA-DEX. Response was assessed and high risk disease defined as per IMWG. PFS and OS were estimated using Kaplan-Meier method. Results: 79 patients were identified and 62 (78.5%) included in response analyses. All patients received pomalidomide (2-4mg D1-21) /dexamethasone, 30/79 (38%) received another agent(s) [clarithromycin (23), cyclophosphamide (9), carfilzomib (1), bortezomib (1)]. Median age was 67yrs (range 40-89). Median time from diagnosis was 4.9yrs (range 0.5 to 18); median prior therapy lines was 4 (range 1-8). Prior therapies were lenalidomide (100%), bortezomib (98%), thalidomide (84%), ASCT (61%). 73 patients (92%) were refractory to their last therapy, and 58 (73%) were double refractory (bortezomib/IMiDs). Median FU was 6.4 months (0.92-34.5). Median no of cycles was 4 (range 1-32), and median dose 4 mg. In those with starting GFR /1⁄4 SD was achieved in 58/62 (94%). Median PFS was 4.3 months and OS 13.7 months (Figure 1A+B). Reduced GFR (

Background Exercise programmes are beneficial for cancer patients however evidence is limited in patients with multiple myeloma (MM), a cancer that is characterised by osteolytic bone disease, giving rise to high levels of bone morbidity including fractures and bone pain. Methods We conducted a single arm phase 2 study of an exercise programme (EP) as rehabilitation for treated MM patients, to evaluate feasibility, effects on QOL and physiological parameters. Patients were given individualised programmes, comprising stretching, aerobic and resistance exercises, carried out under supervision for 3 months then at home for a further 3 months. Results Study uptake was high, 60 of 75 (80%) patients approached consented to the study. Screen failures (11, due to fracture risk and disease relapse) and patient withdrawals (12) resulted in a final 37 patients enrolling on the programme. These 37 patients demonstrated high attendance rates in the supervised classes (87%), and high levels of adherence in home exercising (73%). Patients reported better QOL following the EP, with improvement in FACT-G and Fatigue scores over time from baseline (p Conclusions An EP in MM patients is feasible and safe, with high attendance and adherence. Benefits in QOL, fatigue and muscle strength await confirmation in randomized studies, prompting urgent evaluation of the benefits of EP in the rehabilitation of MM patients.

About 5 per cent of the overall UK cancer burden can be attributed to occupational exposures. However, occupational physicians in clinical practice are most likely to be called upon to support and advise employed patients with non-occupational cancers. Support services in the UK are being reconfigured to help the growing population of cancer survivors to live full and active lives for extended periods. Returning to the workplace is a part of this goal, and occupational physicians are likely to see increasing numbers of adults seeking still to work after treatment for conditions that in the past would have led to ill health-related retirement. Set against these improvements in clinical outcome, and the increasing emphasis on support for patients who achieve long-term survival, is evidence that many working-age adults treated for the common cancers subsequently encounter financial and occupational difficulties. People with cancer often experience a loss in income as a result of their condition. Thus, although most working adults diagnosed with primary cancer return to work, a significant minority do not. Cancer is increasingly seen as an illness that can be effectively treated, but functional outcomes vary considerably. Cancer survivorship is considered to encompass people who are undergoing primary treatment, in remission following treatment, show no symptoms of the disease following treatment, or are living with active or advanced cancer. Occupational physicians may be requested to assess work capability and provide advice on workplace support for cancer survivors in any of the survivorship states. In the UK, 98 per cent of public sector and 30 per cent of private sector employers have access to occupational health services. Employers will normally seek guidance from these services on how to manage employees who have developed a serious illness such as cancer. This means that occupational physicians can be in a key position to coordinate the vocational rehabilitation of cancer survivors. This chapter offers an overview of the evidence on work capability, rehabilitation, and occupational risk assessment that may apply to adults diagnosed with a range of cancers.

The purposes of this study were to observe the relation between signal intensity (SI) on MR images with a high b value and the apparent diffusion coefficient (ADC) of bone marrow on body diffusion-weighted MR images, to determine cutoff values that enable separation of malignant and normal bone marrow, and to identify the upper ADC values of untreated multiple myeloma lesions and bone metastatic lesions of breast cancer.Retrospective evaluations of 16 patients without bone disease, 21 patients with untreated metastases of breast cancer, and 12 patients with myeloma undergoing body diffusion-weighted MRI were performed (b values, 50 s/mm(2) and 800 or 900 s/mm(2)). Normal yellow and red bone marrow regions were compared with metastatic breast and myeloma bone marrow lesions (one to five regions of interest per patient). SI values were normalized to kidney, muscle, and spinal cord SI. Signal-to-noise ratio and ADC for each lesion were recorded. Nonparametric, receiver operating characteristic, and nonlinear regression analyses were performed.Yellow bone marrow and red bone marrow ADC values were lower than the tumor values (p0.001; area under the curve, 0.94; cutoff, 774 μm(2)/s). Tissue-normalized SI and the signal-to-noise ratio of normal bone marrow were also lower than those in tumor regions (p0.001; area under the curve, 0.86-0.88). Second-order polynomial curve fitting between SI and ADC was observed (muscle normalized SI, R(2) = 0.4). The 95th percentile and maximum values for mean tumor ADC distribution were 1209 μm(2)/s and 1433 μm(2)/s.Both tissue-normalized SI and ADC measurements allow differentiation between normal bone marrow and tumors of myeloma and breast cancer. The presence of a nonlinear relation between bone marrow SI and ADC values enables definition of an upper limit of ADC value for untreated myeloma lesions and metastatic lesions of breast cancer.

A significant minority of patients with diffuse large B-cell lymphoma (DLBCL) who enter a complete remission following standard first-line immunochemotherapy will relapse. A primary aim of follow-up is to detect early relapse, with the hope of improving outcome following salvage chemotherapy. It is often routine to measure lactate dehydrogenase (LDH) as part of follow-up; however, the evidence for the utility of LDH as a predictor for relapse is scant. A retrospective analysis of the LDH results recorded during the follow-up of 102 patients with DLBCL who achieved a CR following treatment was undertaken in order to determine the utility of LDH as a predictor for relapse (median follow-up 24 months). Despite the fact that the sensitivity of LDH was 69% (95% confidence interval [CI] 39-91), the positive predictive value (PPV) of a raised LDH was only 9/63, 14% (95% CI 6.7-25). Furthermore, in eight of the nine patients who had a raised LDH prior to relapse, symptoms suggestive of relapse were documented simultaneously. As the PPV of a raised LDH is so low and because a raised LDH may cause unnecessary worry, leading to unnecessary radiological investigations, routine evaluation of LDH in patients with DLBCL who achieve CR and who are asymptomatic is not recommended.

Background. Recent advances in MM therapy create a need for multi-modality response assessments, in order to optimise patient outcomes. Radiological tools can assess the entire skeleton, with the potential to depict heterogeneity of response and help target biopsy of resistant lesions. MRI-based assessment of focal lesions (FL) has been incorporated into the definition of symptomatic MM, providing the rationale for exploring MRI-based response assessment biomarkers. Diffusion weighted imaging derived apparent diffusion coefficient (ADC) has been studied, but standardisation of ADC values across MRI scanners is challenging, limiting generalisability. Fat fraction (FF), also evaluable by MRI, may be a more reliable parameter that could be expected to increase following response to therapy. Methods. This study aimed to evaluate changes in FF in FLs of newly diagnosed MM patients by whole body MRI (WB-MRI) prior to treatment (Pre) and after 8 weeks (8W). WB-MRI was performed on a 3.0 T scanner. Whole-body T2 weighted imaging and axial DWI MRI were supplemented by pre- and post-contrast coronal 2-point mDixon imaging for evaluation of FF. mDixon images were reconstructed as fat only and water only studies. For each patient, up to 20 FLs were localised for analysis by 2 radiologists in consensus, who prospectively scored (score 1-5, 1=highly unlikely, 5=highly likely) involvement of each of 10 anatomical regions. FLs > 5mm with score 4 or 5 were selected for quantitative analysis. A matched region of interest (ROI) was contoured for each FL on water only and fat only mDixon images as well as DWI images. FF was derived from ROI signal intensity (SI) by: SIfat/SIwater+SIfat. Estimated tumour volume (eTV) and DWI's ADC of each FL was also calculated. Difference in FF, eTV and ADC between Pre and 8W studies was assessed by Wilcoxon matched pairs test. Disease response was assessed by IMWG criteria. FF, eTV and ADC receiver operating characteristic (ROC) area under the curve (AUC) analysis was conducted for prediction of non-responders at the end of induction. Results. 21 patients (13 male), median age 52 (range 36-69) were enrolled. Patients had IgG (13), IgA (4) or LC MM (4), and 7 had adverse FISH results [t(4;14), t(14;16), 1q+ or del(17p)] with median ISS II (ISS I (8), II (10), III (3)). Each received a bortezomib induction regimen (16 PAD, 3 CVD, 2 VTD) for 4-6 cycles. A total of 325 FLs were analysed in the entire cohort, with a median of 20 (IQR 10-20, mean 15.5) FLs per patient. At baseline (Pre), median or mean eTV, FF or ADC was found to be independent of ISS stage or genetic risk. Fifteen patients (71%) had an overall response (³PR) to induction therapy. Response was not found to correlate with median FL count, baseline (Pre) FF, eTV or ADC. However, at 8W a significant increase in FF was observed in responders (from median 0.25 to 0.47 a.u. at 8W, p One responding patient had only 1 FL and was excluded from per patient analysis. Of the remaining 14 responders, 13 had a significant increase in FF (p All patients who failed to achieve at least PR (6) had no changes in FF (p values 0.10-0.80); 4/6 had no change in ADC (p=0.10-0.84) whilst 2/6 showed a significant increase (p=0.02, 0.03). All non-responders (6/6) had a significant decrease in eTV (p Conclusions. WB-MRI derived FF change of FLs at 8 weeks following induction therapy differentiates responders from non-responders in newly diagnosed MM patients. This may have utility to act as both an early response and predictive imaging biomarker. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Yong: Takeda: Honoraria; Amgen: Honoraria; BMS: Honoraria; Novartis: Consultancy; Janssen: Honoraria; Autolous: Consultancy. Popat:Janssen: Honoraria.

Supportive care plays an increasingly important role in the modern management of multiple myeloma. While modern treatments have significantly prolonged overall and progression free survival through improved disease control, the vast majority of patients remain incurable, and live with the burden of the disease itself and the cumulative side effects of treatments. Maintenance of quality of life presents challenges at all stages of the disease from diagnosis through the multiple phases of active treatment to the end of life. Written on behalf of the British Committee for Standards in Haematology (BCSH) and the UK Myeloma Forum (UKMF), these evidence based guidelines summarize the current national consensus for supportive and symptomatic care in multiple myeloma in the following areas; pain management, peripheral neuropathy, skeletal complications, infection, anaemia, haemostasis and thrombosis, sedation, fatigue, nausea, vomiting, anorexia, constipation, diarrhoea, mucositis, bisphosphonate-induced osteonecrosis of the jaw, complementary therapies, holistic needs assessment and end of life care. Although most aspects of supportive care can be supervised by haematology teams primarily responsible for patients with multiple myeloma, multidisciplinary collaboration involving specialists in palliative medicine, pain management, radiotherapy and surgical specialities is essential, and guidance is provided for appropriate interdisciplinary referral. These guidelines should be read in conjunction with the BCSH/UKMF Guidelines for the Diagnosis and Management of Multiple Myeloma 2011.

Keywords: bone marrow pathology; Waldenstrom macroglobulinaemia; monoclonal gammopathy of undetermined significance

In 2001, reference to the use of imaging in the British Committee for Standards in Haematology guidelines for the diagnosis and management of myeloma was confined to the standard use of plain X-rays in the diagnostic skeletal survey and emergency use of computed tomography (CT) and magnetic resonance (MR) imaging in the setting of cord compression. Since then, there has been a steady rise in interest in the use of various imaging techniques in the management of myeloma. The purpose of imaging in the management of myeloma includes the assessment of the extent and severity of the disease at presentation, the identification and characterisation of complications, and the assessment of response to therapy. Plain radiography, CT, and MR imaging are generally established examination techniques in myeloma whilst positron emission tomography (PET) and (99)Technetium sestamibi (MIBI) imaging are promising newer scanning techniques under current evaluation. These stand-alone imaging guidelines discuss recommendations for the use of each modality of imaging at diagnosis and in the follow up of patients with myeloma.

BackgroundUK WM Guidelines recognise 2 mechanisms of nervous system involvement either direct tumour invasion of the CNS or antibody mediated damage to peripheral nerves. We present 5 cases illustrating an extended diversity of PNS involvement in WM with implications for treatment and outcome.CasesA 73 year-old man (IgMκ WM) developed progressively disabling tremor with stable WM. Neurophysiology was demyelinating with disproportionate DMLs; anti-MAG antibodies were strongly positive. He was treated with DRC with symptom stabilisation.A 64 year-old woman (IgMκ) with typical anti-MAG neuropathy developed severe episodic foot pain and ulceration. Skin biopsy confirmed leucocytoclastic vasculitis. She was treated with DRC but died from sepsis.A 43 year-old man (IgMκ WM) with rapidly progressive sensorimotor neuropathy had lymphplasmacytoid cellular infiltrate in sural nerve. He was successfully treated with IDARAM.A 59 year-old man (IgMλ WM) developed small then large fibre axonal neuropathy with autonomic symptoms within 2 years. A SAP scan showed moderate kidney uptake. MRI neurography directed biopsy and confirmed amyloid. Palliative treatment was offered.A 70 year-old woman (IgMλ WM) developed severe burning pains in her feet and became ataxic 2 months later. Sural nerve biopsy confirmed endoneurial amyloid. DRC was given.DiscussionThese cases highlight the importance of accurate diagnosis in WM-associated neuropathy. We propose a novel diagnostic algorithm.

BackgroundBing-Neel syndrome (BNS) is a rare manifestation of Waldenstrom's Macroglobulinaemia (WM) due to direct infiltration of the central nervous system. Isolated peripheral nerve infiltration has not been described but as the blood-nerve-barrier has similar characteristics to the blood-brain-barrier, CNS-penetrating chemotherapy would be required.CaseA 43 year-old man was diagnosed with WM after presenting with constitutional symptoms; IgMk paraprotein (34.6 g/L) and lymphoplasmacytoid cells in the bone marrow. He received R-CVP (Rituximab, Cyclophosphamide, Vincristine, and Prednisolone) with good partial haematological response and minimal distal sensory vincristine-related neuropathy. Ten months later he developed a rapidly progressive, symmetric sensorimotor deficit in all four limbs with impairment of walking and hand clumsiness, MRC sum score=61/70. Electrophysiology showed a non-length dependant axonal neuropathy with patchy slowing. Sural nerve biopsy revealed a patchy infiltrate WM cells. He tolerated 4 cycles of blood-nerve-barrier penetrating multi-agent chemotherapy, IDARAM (idarubicin, dexamethasone, cytosine arabinoside, methotrexate, cytosine arabinoside plus intrathecal methotrexate). A marked improvement was seen during treatment and by 3 months later MRC score was 70/70. No electrophysiological difference was detectable at this stage.DiscussionPeripheral BNS is not a recognised neurological manifestation of WM but with appropriate treatment a good outcome may be achieved.

Introduction: The role of autologous stem cell transplantation (ASCT) as first line treatment for newly diagnosed patients with myeloma is currently under evaluation given the high response rates to novel induction treatment. The outcomes for patients that do not proceed to ASCT following induction remain unclear and are likely to be determined by genetic risk and response to therapy. In order to evaluate this further, this single arm phase 2 clinical trial conducted at 13 sites in the UK was designed to determine the 2 year progression free survival for patients that achieved ≥ very good partial response (VGPR) following induction therapy without ASCT. Those achieving partial response (PR) were consolidated with ASCT according to routine practice. In this first analysis we report secondary endpoints: disease response and regimen-related toxicity in patients completing induction, including minimal residual disease (MRD) negativity by multiparameter flow cytometry. Methods: Patients with newly diagnosed myeloma eligible for ASCT received PAD (bortezomib 1.3mg/m2 days 1, 4, 8, 11; doxorubicin 9mg/m2 days 1-4 and dexamethasone 40mg days 1-4 (and days 8-11 and 15-18 for the first cycle only)) for up to 6 cycles (minimum of 4). Bortezomib was initially given intravenously (IV), but once approved this was switched to sub-cutaneous (SC). Those failing to achieve PR were offered salvage therapy off protocol. All others had peripheral blood stem cell (PBSC) mobilisation using cyclophosphamide + GCSF, followed by MRD assessment on bone marrow aspirates using multi-parameter flow cytometry. Depending on disease response, patients were then stratified to ASCT (PR) or no further treatment (≥VGPR). Responses were assessed using International uniform response criteria (Durie 2006) by intent-to-treat and toxicity scored according to CTCAE version 4.0. High risk disease was defined by the presence of one or more adverse FISH lesions (t(4;14), t(14;16), t(14;20), del(17p13), +1q21) as described in the MRC Myeloma IX trial. Results: Between March 2011 and January 2014, 153 patients were enrolled (median age of 55, range 28-71 years). 139 (91%) received between 4-6 cycles of PAD. The majority (135, 88%) received SC only bortezomib and 18 (12%) received at least 1 cycle IV. The overall response rate to PAD was 81% with 46% achieving ≥VGPR (sCR: 6 (4%), CR: 13 (8%), VGPR: 51 (33%), PR: 54 (35%)). FISH data was available for 122 patients, 91 (75%) patients were standard risk and 31 (25%) were adverse. Responses were similar irrespective of ISS or genetic risk (standard, ≥VGPR 44%, PR 34%; adverse, ≥VGPR 55%, PR 29%). MRD results are currently available in 70 of the 124 patients achieving PR post PBSC harvest. Of this group 41 achieved ≥VGPR post-harvest (22 MRD+ and 19 MRD-) and hence did not proceed to ASCT, 13 patients achieved CR of which 8 were MRD negative. Toxicity was as expected for PAD and predominantly haematological. Notably the incidence of neuropathy was lower than that previously reported with IV bortezomib. Grade 3-4 events were: neutropenia: 18%; thrombocytopenia 7%. Grade 2-4 peripheral neuropathy was reported in 27% compared to 40% in the HOVON-65/ GMMG-HD4 Trial using IV bortezomib. Grade 1-2 neuropathy was similar for patients who received IV (55.6%) or SC (60%) bortezomib; however only 7% of patients receiving SC bortezomib developed grade 3 neuropathy compared to 28% with the IV route. Conclusions: SC PAD is a highly effective induction regimen for patients with newly diagnosed myeloma achieving a ≥VGPR of 46%. Of the 41 patients achieving ≥VGPR post-harvest with MRD result available, 46% were MRD negative. Response rates were similar across ISS and with adverse FISH. The use of SC bortezomib improved tolerability and substantially reduced neurotoxicity. ISRCTN no: 03381785. Disclosures Popat: Janssen: Honoraria. Cavenagh:Janssen: Honoraria. Schey:Janssen: Consultancy, Honoraria. Cook:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Cook:Janssen: Honoraria, Research Funding. Yong:Janssen: Honoraria.

This study aimed to determine the outcome of patients with relapsed or refractory lymphoma who have an inadequate response to first-line salvage therapy (1 degrees ST) and who subsequently receive a second-line salvage regimen (2 degrees ST) with the intention of ultimately proceeding to high-dose therapy. The outcome of 57 patients [Hodgkin's Lymphoma 17, histologically-aggressive non-Hodgkin's Lymphoma (NHL) 26, histologically-indolent NHL 14] who received more than one modality of conventional-dose salvage therapy was analysed. Sixteen patients had a partial response (PR) to 1 degrees ST, but subsequently received 2 degrees ST because the PR was judged to be inadequate (iPR) because of persisting disease bulk or marrow infiltration. Of these 16 patients, 10 (63%) continued to respond to 2 degrees ST. Of the 15 patients who had stable disease following 1 degrees ST, 5 (33%) responded to 2 degrees ST. Only one of the 24 (4%) with progressive disease (PD) following 1 degrees ST, responded to 2 degrees ST. 25 of the 57 patients ultimately underwent stem cell transplantation. The 2-year progression-free survival (PFS) and the 3-year overall survival (OS) for all patients was 24% and 31%, respectively. Long-term survival was highly dependent on response to 1 degrees ST (P = 0.0001); in patients with PD following 1 degrees ST, the PFS and OS at 3 years was only 4%. This analysis indicates that patients with malignant lymphomas, who have PD on 1 degrees ST, are not rescued by subsequent salvage regimens. They should either be treated palliatively or novel approaches should be explored.

Myeloma remains incurable with a median survival of 4 years, but outcome can be improved by the use of high-dose therapy. We used the etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) regimen as second-line therapy in 42 newly diagnosed myeloma patients who had failed vincristine, adriamycin and dexamethasone (VAD)- type therapy (n = 36), responded to first-line treatment but persisted in having significant residual marrow plasmacytosis (n = 5) or failed prior stem cell harvesting (n = 1), with the dual aim of improving disease response and mobilizing peripheral blood stem cells. Fourteen of 21 (67%) patients with no change or progressive disease after VAD responded to ESHAP; seven of 12 (58%) patients with minor response converted to partial response. Marrow plasmacytosis fell from a median of 52% at diagnosis to 23.5% after primary therapy and to15% after ESHAP. ESHAP chemotherapy was well-tolerated. There were 11 admissions due to febrile neutropenia (n = 7), nausea and vomiting (n = 2), pneumonia (n = 1) and perforated bowel (n = 1). Renal function deteriorated in 13 of 42 patients after ESHAP, but none required renal support. ESHAP mobilization was performed in 32 patients of whom 87% achieved a CD34(+) yield2 x 10(6)/kg. In all, 38 patients proceeded to high-dose therapy. The overall survival for all patients was 62% at 4 years following ESHAP. We conclude that ESHAP has acceptable toxicity and efficient stem cell mobilizing capability, effectively cytoreduced this chemoresistant group of patients, and did not appear to adversely affect transplant outcome.

Summary. Immune reconstitution after conventional allogeneic transplantation is a major determinant of survival. We conducted a detailed investigation of T- and B-cell immune reconstitution and clinical outcome in 19 patients with multiple myeloma undergoing reduced-intensity stem cell transplantation using in vivo T-cell depletion with alemtuzumab. These patients experienced delayed T-cell recovery, particularly in the naive (CD45 RA+) CD4 compartment. T-cell receptor spectratype analysis showed a reduced repertoire diversity, which improved rapidly after the administration of donor leucocyte infusions and subsequent conversion to full donor T-cell chimaerism. Post-transplant recovery of CD19+ B cells was also delayed for up to 18 months. Spectratype analysis of IgH CDR3 repertoire revealed a gradual normalization in IgM spectratype complexity by 6–12 months after transplant. There was a high incidence of viral infection, particularly cytomegalovirus reactivation, but the regimen-related mortality was low, perhaps because of the very low incidence of acute graft-versus-host disease (GVHD; grade I-II skin GVHD was seen in 5/19 patients). Over 80% of all patients have relapsed at a median of 283 (range 153–895) d after transplant, suggesting that the initially low rate of GVHD comes at a high price with regard to the desired graft-versus-myeloma effect.

Reduced-intensity conditioning regimens allow application of allogeneic stem cell transplantation to greater numbers of patients with myeloma by reducing transplantation-related mortality. We prospectively evaluated the role of an approach incorporating in vivo T-cell depletion and subsequent adjuvant donor lymphocyte infusions (DLIs) as part of front-line therapy for chemotherapy-sensitive multiple myeloma. Twenty patients with HLA-matched related (n = 12) or unrelated (n = 8) donors entered the study. None had previously undergone autologous transplantation. Acute graft-versus-host disease (GVHD) following transplantation was minimal (3 grade II and no grade III or IV). Nonrelapse mortality rate was relatively low (15%) compared with conventional myeloablative allogeneic transplantation series, although it remained significantly higher than in the autologous setting. Disease responses by 6 months posttransplantation were modest (2 in complete remission, 4 in partial remission, 2 were minimally responsive, 6 had no change, 3 had progressive disease, and 3 were not evaluable). Fourteen patients received escalating-dose DLI for residual/progressive disease. Three developed acute GVHD and 2 developed limited chronic GVHD. Seven demonstrated further disease responses, which appeared to be more common in those developing GVHD (5 of 5 versus 2 of 9; P = .02). All responses were associated with conversion from mixed to full donor T-cell chimerism. Response durations were disappointing (5

VEGF is diagnostically markedly elevated in patients with POEMS syndrome and is also a disease biomarker. However, VEGF can be elevated in other illnesses, which might be misleading. We asssayed serum VEGF levels from clinical requests in samples from 206 consecutive patients with a neuropathy at Queen Square. Sensitivity and specificity of VEGF in the diagnosis of POEMS were calculated and other potential causes of VEGF elevation explored. Elevated sVEGF had a sensitivity of 100% and a specificity of 90% for the diagnosis of POEMS syndrome, with positive and negative predictive values of 60% and 100%. sVEGF was much higher in POEMS syndrome and higher in CIDP and anti-MAG neuropathy. Multiple logistic regression showed anaemia with low iron and COPD/OSAHS were significant predictors for elevated sVEGF. There was a tendency for cancers, anti-MAG neuropathy and Waldenstrom9s disease to be predictors of elevated sVEGF, which are supported by previous studies. Other potential factors for VEGF elevation have been described, but not identified in this cohort. We confirmed the high sensitivity and specificity of elevated VEGF for POEMS syndrome diagnosis. However, when VEGF is significantly elevated, anaemia with low iron, cancers, haematological malignancies, OSAHS, COPD and chronic inflammatory diseases should be excluded.

Clopidogrel is a novel antiplatelet agent that has a different mechanism of action to aspirin. Clopidogrel is chemically related to ticlopidine, both of which are more effective than aspirin in preventing some thrombotic events, but it has a safer sideeffect profile than ticlopidine. It is likely to add to the antithrombotic armoury and reduce vascular mortality and morbidity more than current therapies.

Introduction High dose therapy with autologous stem cell transplant (ASCT) represents the standard of care for untreated patients with multiple myeloma (MM) who are young and fit. Novel agents are changing the landscape of pre- and post-ASCT therapies, but benefits may not apply to all patients. We report 338 MM patients treated with up-front ASCT at University College Hospital London from September 1993 - December 2010. Results Patient characteristics are described in Table 1. 90 (27%) received novel agents (thalidomide, bortezomib or lenalidomide) prior to transplant, and the remainder had VAD (vincristine, doxorubicin, dexamethasone)-based regimens. Most patients (64%) had 1 line of therapy prior to ASCT, 26% had 2 lines and 11% >/=3 lines. Responses to first line therapy were 24% >/= VGPR, 45% PR, ORR 69%. Best response prior to ASCT was: 27% >/= VGPR, 59% PR, ORR of 86%. 42 patients (12%) had stable disease or worse pre-ASCT. Transplant-related mortality at 100 days was 3.3%, 166 patients (49%) attained >/= VGPR at 3 months and 126 (37%) PR. Maintenance/consolidation regimens were interferon or thalidomide-based. Median follow-up was 6.1 yrs, progression-free survival (PFS) 2.0 yrs and overall survival was (OS) 5.8 yrs from ASCT and 6.8 yrs from diagnosis. 266 patients have relapsed, and 169 have died. On multivariate analysis, international staging system (ISS) stage 1, female gender, use of novel agents first-line and disease response (>/=VGPR pre- and 3 months post-ASCT) predicted longer PFS (p's < 0.05). Timing of relapse was the most important predictor of survival (median OS 1.6yrs if relapse within 12 months vs 7.2yrs if not, HR = 6.7, p/= 2005) cohorts (OS 1.6 v 1.7 yrs, p = NS, Fig 2). Median post-relapse survival (PRS) was 2.6 yrs. Factors predicting longer PRS included IgG isotype, CD56-positivity, later year of ASCT and of relapse, younger age at ASCT, longer PFS from ASCT and the use of novel agents at relapse. Patients relapsing in 2005 and later had longer PRS (3.6 v 1.3 yrs, HR = 0.4, p = 0.0001). Prior treatment with maintenance/consolidation did not impact PRS (PRS 3.1 v 2.4 yrs, p = NS). Conclusions These data indicate that post-ASCT strategies and choice of agent at relapse may be as important determinants of outcome as disease response pre-ASCT. Early relapse was the most important predictor of death following ASCT and may outweigh the impact of adverse CGN. The adverse outcome of patients relapsing early is not salvaged using contemporary treatment strategies at relapse. The benefit of CD56 expression on OS, but not on PFS suggests this denotes disease that remains chemo-responsive disease through relapses. Maintenance or consolidation therapy following ASCT appears to prolong PFS and OS without impacting post-relapse survival. Disclosures: No relevant conflicts of interest to declare.

A 29-year-old man presented with a large right supraclavicular mass, weight loss and night sweats. A diagnosis of stage 4B nodular sclerosis Hodgkin lymphoma was made. F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET-CT) and whole-body magnetic resonance imaging with diffusion-weighting (DW-MRI) were performed before and after escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) chemotherapy. The pre-treatment FDG PET-CT (top left) demonstrated extensive nodal disease above and below the diaphragm, including the right supraclavicular fossa. Post-treatment FDG PET-CT (top right) showed physiological FDG uptake only. The pre-treatment DW-MRI (bottom left) showed extensive nodal disease in the same distribution as the pre-treatment FDG PET-CT. DW-MRI revealed a bone lesion (arrow) not diagnosed on the FDG PET-CT, confirmed on the source axial images. Post-treatment morphological MRI (not shown) demonstrated residual nodal disease in the right lower neck and upper abdomen but this was all inactive on DW-MRI (bottom right). FDG PET-CT and DW-MRI independently established a complete response. FDG PET-CT is a recommended imaging method for determining disease activity in residual masses after treatment for Hodgkin lymphoma. There is an increasing body of evidence to support its use in the assessment of early response to chemotherapy and it has been established as reliable for staging Hodgkin lymphoma. However, it involves radiation exposure for both the CT and FDG components of the test. MRI does not use ionizing radiation and offers higher soft tissue contrast compared with CT. The reduction of exposure to ionizing radiation is of particular significance in patients with lymphoma who have a high chance of cure, especially in younger patients. Water diffusion whole body MRI also allows functional assessment of lymphoma response. DW-MRI relies on measuring the random motion of water molecules in tissues. Many malignant tumours, including lymphomas, are more cellular than benign/normal tissue and therefore show more restricted water diffusion, appearing bright on normal images or dark on inverted images such as those shown above. The disadvantages of MRI include the exclusion of patients with pacemakers, implantable defibrillators or significant claustrophobia. In addition, bulk tissue movements and physiological water motion can sometimes affect DW-MRI image quality. In general, FDG PET-CT is accurate for diagnosis of marrow and bone involvement in Hodgkin lymphoma but, in this case, DW-MRI revealed bone disease not diagnosed on FDG PETCT. Further research is needed to compare the relative merits of DW whole-body MRI with FDG PET-CT in the staging and monitoring of lymphoma.

Abstract 4201 Introduction Lenalidomide and dexamethasone is an established treatment for multiple myeloma (MM). We investigated whether changing the dosing schedule reduced treatment costs whilst maintaining efficacy. According to the summary of product characteristics (SPC), the recommended starting dose of lenalidomide is 25mg/day for 21 days every 4 weeks. For grade 3/4 adverse events (AEs), lenalidomide is interrupted until recovery to grade 1 and then dose reduced to 15mg/day. For each subsequent grade 3/4 AE, a further 5mg/day reduction is advised. GCSF is permitted for isolated neutropenia. Within its licensed indication, patients remain on treatment until disease progression (median 10.1 months); however 38% require at least 1 lenalidomide dose reduction due to AEs (Dimopoulos et al. Leukemia 2009). In the UK, the National Institute for Clinical Excellence recommends lenalidomide and dexamethasone at second and subsequent relapse only, with the manufacturer bearing costs after 26 cycles. The incremental cost-effectiveness ratio (ICER) is £43,800 per QALY gained, but at first relapse was deemed too high (more than £69,000 per QALY gained) when compared to bortezomib. The UK price per capsule of lenalidomide (including 20% tax) and the USD equivalent (exchange rate August 2011) is: 25mg £249.60 ($407.56); 15mg £226.80 ($370.25). We therefore investigated the efficacy and costs of alternate day dosing in patients requiring modifications due to grade 3/4 AEs. Methods This was a retrospective review of patients treated with lenalidomide and dexamethasone for relapsed MM in a single UK centre. Treatment commenced with lenalidomide 25mg daily for 21 days per cycle and dexamethasone as per SPC. Upon grade 3/4 AE, lenalidomide was interrupted until recovery to grade 1 toxicity. Dosing was then recommenced at 25mg alternate days instead of 15mg daily. Subsequent dose reductions of 5 mg were made on the alternate day schedule (i.e. down to 15mg, then 10mg, then 5mg on alternate days). The efficacy of this regimen was assessed by IMW response criteria, time to progression (TTP), progression free survival (PFS) and overall survival (OS) according to IMW consensus criteria. Results A total of 42 patients received lenalidomide and dexamethasone of which 39 were evaluable for assessment (2 non-secretory MM, 1 Waldenstroms Macroglobulinaemia). The median age was 68 years (range 37–85) and the median number of prior lines of therapy were 2 (range 1–8). The overall response rate was 85% (PR 59%; VGPR 23%; CR 3%). After a median follow-up of 9.1 months, the median OS was 26.3 months (lower 95% CI of 24.4 months); PFS was 7.7 months (95% CI 4.9–11.6); and TTP was 11.8 months (lower 95% CI of 7.9). The upper 95% values for OS and TTP were not estimated due to few events. The 2 year OS rate was 82.7%. Patients received a median of 6 cycles over 11.7 months with a median duration of response of 7.1 months. These results are comparable to the MM-009/010 phase 3 trials (median TTP 13.4 months; PFS 11.1 months), bearing in mind that our patients were more heavily pre-treated (7% of our patients had 1 prior line compared to 18% in the MM-009/010 trials). 62% of patients required lenalidomide dose modification for AEs (approx. 1.5 times more than MM-009/010). The actual total cost of lenalidomide was £1,450,665.60 ($2,368,901.32) whereas if dose modification according to the SPC was followed, the predicted cost would be £1,914,987.60 ($3,128,254.42). This gives a cost saving of £464,322.00 ($758,615.19) equating to £11,905.69 ($19,455.51) per patient treated. Full cost-effective analysis will be presented at the meeting. Conclusions Whilst lenalidomide and dexamethasone is an effective treatment, dose modifications are required for AEs. Modifying the dosing schedule to alternate days rather than daily dosing at a lower dose resulted in a significant cost saving of £11,905.69 ($19,455.51) per patient treated. Such modifications were more frequent in our dataset due to the heterogeneous characteristics of non-trial patients. Hence this cost-benefit becomes more relevant in those with impaired bone marrow/ renal function and performance status. By making this treatment more affordable this dosing strategy may allow access at an earlier stage in treatment by reducing the ICER per QALY gained. Given the similar efficacy to the conventional dosing scheme, this may represent an alternative and more cost effective way of prescribing. Disclosures: Off Label Use: An alternative method of dosing revlimid.

Treatment for lymph node tuberculosis must be preceded by adequate pathological investigation of the lymphadenopathy

Acute lymphoblastic leukaemia (ALL) with the t(4;11) translocation has a very poor prognosis following conventional chemotherapy. Many patients are offered an allogeneic BMT in first remission. We report on the impact of allogeneic BMT on three patients with t(4;11) ALL in first remission. Median age was 20 years. One patient received marrow from an HLA-identical sibling and the other two from unrelated donors. All three engrafted and none of the patients developed acute or chronic GVHD. Remission status was monitored using a sensitive nested RT-PCR to detect the ALL-1/AF-4 hybrid transcript. All three were PCR-negative at 3 months post-BMT. One of the unrelated recipients died of a fungal infection 4 months post-BMT. The other two are alive and in molecular remission at 21 and 24 months post-BMT. This is the first report of longitudinal follow-up of t(4;11) ALL post-allogeneic BMT by PCR. The early attainment of molecular remission in the absence of GVHD suggests that the conditioning regimen may have been more important than a graft-versus-leukaemia effect in these patients. Follow-up of larger numbers of patients will be required to confirm these preliminary observations.

Cancer patients frequently suffer with anxiety, fatigue, loss of well-being and functionality. In myeloma patients this is compounded by the effects of lytic bone disease, causing chronic pain and impaired mobility. The result is a decrease in physical fitness and loss of confidence in carrying out day-to-day activities, contributing to a reduced QoL. The development of novel therapies has extended the survival of these patients, hence such issues are of increasing importance and effective rehabilitation programmes are urgently needed. We carried out a pilot study of a tailored exercise training programme in patients in stable plateau phase. The primary aims were to determine the feasibility, adherence rate, and the effects on QoL, physiological and cardiorespiratory functions. Eligible patients underwent radiological and cardiac screening prior to study entry. There was a 25% screening failure rate due to disease progression or fracture risk, these patients proceeding to prophylactic surgery or radiotherapy. Twenty-five patients were given a programme based on their current exercise capacity, level of functioning and individual rehabilitative needs. Patients undertook exercise training 3 times a week for 6 months, with 1 supervised exercise session each week in the hospital outpatient gym. Each session comprised stretching and mobility, aerobic (treadmill, cycle ergometer or walking to 50–60% of heart rate reserve and 15–30 minutes duration) and resistance training (theraband, ankle, hand weights and body-weight) in order to improve flexibility, cardiorespiratory fitness and muscle strength. QoL and physiological outcomes were assessed at baseline, 4-weekly for 3 months, then 6 weekly for 3 months during the 6-month study period. A preliminary analysis of 17 patients who completed 3 months on the programme has been performed. Average attendance at the weekly exercise class was 84%. Adherence to the exercise programme, as assessed by inspection of a log-book was >50% in all patients; 35% achieved >90% adherence. Significant improvements were found in the FACT G (baseline: median 85; range 62 – 104, 3 months: 90; range 70 – 108, p

Lymphoplasmacytic Lymphoma (LPL) is a relatively rare low-grade lymphoma which primarily affects elderly patients. Standard doses of alkylating agents, purine analogues and anti-CD20 monoclonal antibody effect response rates of up to 60%. However, complete response is infrequent and there is no cure. Due to indolent nature of the disease and older patients with comorbidities, evaluation of the role of high dose therapy with transplant has been infrequent in the past. Here we report a retrospective multicentre study of 146 LPL patients (94 male, 52 female), who underwent autologous stem cell transplantation (ASCT) between 1992 and 2004. The median age was 60 years (54–67) and median time from diagnosis to transplant was 62 months (5–119). Twenty-six patients (18%) were in CR1, 35 (24%) in CR2, 30 (20%) in ≥CR3, 45 (31%) in PR, 10 (7%) primary refractory at transplant. Combination of GCSF with either Cyclophosphamide, ESHAP or AraC were mainly the stem cell mobilisation regimens used, and 18 patients with extensive prior use of purine analogues, required second attempt for harvesting. The conditioning regimens used were BEAM, Cyclophosphamide/TBI or Melphalan/TBI. The source of stem cells was PBSC in 129, BM in 11 and both in 6 patients. All patients except one had successful engraftment. With a median follow-up of 12 months (2–126), 131 (90%) patients are alive and 15 (10%) dead. Thirteen patients died from disease progression and 2 from regimen toxicity. Actuarial non- relapse mortality was 2.4% at 1 and 2 years. The actuarial OS was 90% at 1 year, 79% at 3 years and 69% at 5 years. The probability of relapse was 80% at 1 year, 53% at 3 years and 39% at 5 years. Relapse rate was not statistically significant for patients with chemosensitive disease. In conclusion this study shows that ASCT is safe, and a significant proportion of previously multitreated LPL patients can be salvaged and sustain prolonged DFS.

BackgroundPrompt diagnosis and early treatment prevents disability in Polyneuropathy Organomegaly Endocrinopathy Monoclonal-protein and Skin Changes (POEMS) syndrome. Delay in diagnosis is common with 55% of patients initially incorrectly diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients are often treated with intravenous immunoglobulin which is both expensive and ineffective in the treatment of POEMS. Testing patients with acquired demyelinating neuropathy with serum vascular endothelial growth factor (VEGF) more accurately identifies POEMS syndrome than the current standard of care. Incorporating VEGF testing into screening could prevent misdiagnosis and reduce costs.MethodsWe used observed treatment information for patients in the University College London Hospital’s POEMS syndrome database (n=100) and from the National Immunoglobulin Database to estimate costs associated with incorrect CIDP diagnoses across our cohort. We conducted a model-based cost-effectiveness analysis to compare the current diagnostic algorithm with an alternative which includes VEGF testing for all patients with an acquired demyelinating neuropathy.ResultsTreatment associated with an incorrect CIDP diagnosis led to total wasted healthcare expenditures of between £808 550 and £1 111 756 across our cohort, with an average cost-per-POEMS-patient misdiagnosed of £14 701 to £20 214. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy would lead to annual cost-savings of £107 398 for the National Health Service and could prevent misdiagnosis in 16 cases per annum.ConclusionsMisdiagnosis in POEMS syndrome results in diagnostic delay, disease progression and significant healthcare costs. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy is a cost-effective strategy allowing for early POEMS diagnosis and potentially enabling prompt disease-directed therapy.