ALBERT

Description: Disease relapse is a major cause of treatment failure after reduced-intensity allografts and while donor lymphocyte infusions (DLIs) can be effective salvage therapy they are associated with severe graft-versus-host disease (GVHD) when administered early after transplantation. We have therefore examined whether imatinib mesylate can delay relapse and postpone the requirement for DLI in 22 patients with chronic myeloid leukemia (CML) allografted using a reduced-intensity regimen. Imatinib was commenced on day + 35 and continued until 1 year after transplantation. Posttransplantation imatinib was well tolerated and abolished the risk of relapse during this period. Twenty-one patients completed 11 months of imatinib therapy, 15 of whom subsequently relapsed and received DLI. Ten patients to date have achieved molecular remission after DLI. Adjunctive targeted therapy allows the kinetics of disease relapse after a reduced-intensity allograft to be manipulated and represents a novel strategy by which outcome may be improved in patients who undergo transplantation for CML and other leukemias.

Description: Introduction Up to 50% of patients with acute GVHD (aGVHD) have a suboptimal response to first line therapy with corticosteroids. Extracorporeal photopheresis (ECP) is one of the recommended second line options. Overall response rates of 60-77% have been reported with ECP as second line therapy for aGVHD. Factors associated with lower response and survival were Grade 〉II at onset and number of organs involved. In a large retrospective study of ECP as second line therapy, 19.5% of patients developed chronic GVHD (cGVHD). Previous studies have included small numbers of patients with aGVHD post T cell depleted transplants or Donor Lymphocyte Infusion (DLI). Methods We conducted a retrospective analysis of outcomes in 40 patients treated with ECP for steroid refractory or steroid dependent aGVHD at 2 UK transplant centres. The aim was to analyse overall survival and long-term outcomes. All patients received 2-3 treatments per week for 8 weeks after which schedules differed according to centre, cessation or gradual taper. Results Between 2006 and 2014, 44 patients had received ECP as second line therapy, 4 were excluded from analysis as they had received less than 4 treatments. The median age was 51years (21-67years). Table 1 illustrates details of conditioning and GVHD prophylaxis. Thirty percent of patients were post DLI: 5 (12.5%) for disease relapse and 7 (17.5%) for mixed chimerism. Transplant conditioning included T cell depletion in 24 (60%): alemtuzumab n=17, ATG n=7. The median duration of steroids pre-starting ECP was 18 days (range 5-56). Using Modified Glucksberg crtieria at the onset of ECP, 5 patients (12.5%) had Grade II, 30 (75%) Grade III (including 6 with stage 4 gut) and 5 (12.5%) Grade IV aGVHD. Nine patients (22.5%) had 1 organ involvement and 31 (77.5%) had 2 or more organs involved. The dominant organ was gut in 21 (52.5%), liver in 10 (25%)and skin in 9 (22.5%). Maximal response rates were CR 57.5%, PR 27.5% and NR 15%. A number of patients received additional immunosuppressive therapy, predominantly anti-TNF antibodies: 14 patients (35%) (etanercept n=11, infliximab n=3). Using Kaplan-Meier analysis, censoring at last follow up, the overall survival from start of ECP at 5 years was 45.1% (95% CI 31.85-63.04%) Figure 1. The median survival was 2 years (27days-7.8yrs). In the DLI group, the 5 year overall survival was 59.8%. In a subgroup log rank Mantel-Cox analysis no significant difference was observed in the 5 year overall survival according to dominant organ involved: 53% skin, 40.6% gut and 50% liver (p=0.77) Figure 2. The cumulative incidence of death was 57.5% (23patients). The leading cause of death was infection 13/23 deaths (56.5%) followed by 5 deaths due to GVHD, 4 due to relapse, 1 from unrelated causes. The incidence of chronic GVHD was 55%. Treatment for cGVHD varied with 8 patients continuing ECP 〉12 weeks on a tapering schedule, 2 patients restarting ECP for cGVHD and the others receiving a variety of therapies including MMF, tacrolimus, Rituximab and imatinib. At last follow up, 17 patients were alive, 9 were off immunosuppression (2 of whom had not developed cGVHD) and 8 were still on immunosuppression. The performance status in the 17 surviving patients was ECOG 0= 8, 1=8 and 2=1. Discussion Our study shows an encouraging 5 year overall survival of 45.1% in a cohort with predominantly severe Grade III aGVHD. The 5 year survival was higher in the DLI group at 59.8%. Fifty three percent had stage 3-4 gut involvement, which is a recognised poor risk feature. Infection was the leading cause of death, which is of particular relevance in the T deplete setting. Whilst 55% developed cGVHD, over a long follow up period (median of 4years), the cGVHD resolved and performance status was preserved in most of the surviving patients. The incidence of cGVHD was higher than in other studies but the patients had higher grade of aGVHD at onset, were older and had multi-organ involvement. These findings need to be confirmed in prospective studies. Table 1. Pretransplant Characteristics No. of patients (%) Conditioning Regimes Myeloablative 10 (25%) Non-myeloablative 18 (45%) Total post DLI 12 (30%) T cell depletion 24 (60%) Alemtuzumab 17 (42.5%) ATG 7 (17.5%) GVHD prophylaxis CsA 20 (50%) CsA/MTX 9 (22.5%) CsA/MMF Tacro/MMF 8 (20%) 3 (7.5%) Donor Source Matched sibling Matched unrelated donor 10/10 9/10 8/10 Double Cord 9 (22.5%) 21 (52.5%) 3 (7.5%) 1 (2.5%) 6 (15%) Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Radia: Therakos: Other: ASH travel expense, Speakers Bureau. Off Label Use: Extracorporeal Photopheresis (ECP) is not licensed for use in GVHD but is recommended in international guidelines as a therapeutic option.. McLornan:Novartis: Research Funding, Speakers Bureau. Russell:Therakos: Other: shares.

Description: Background: Enteropathy associated T cell lymphoma (EATL) accounts for less than 1% of all Non-Hodgkins lymphomas and ~5% of gastro-intestinal lymphomas, and is strongly associated with Coeliac disease. Treatment has traditionally involved Doxorubicin based combination chemotherapy such as CHOP although there is no consensus on guidelines for treatment. Patients are often emaciated due to malabsorbtion at diagnosis and often tolerate treatment poorly with death occurring due to perforation and gastro-intestinal bleeding. There appears to be a high relapse rate in those who complete treatment, and overall survival rates are agreed to be around 20% at 5 years. Methods: Consecutive patients with biopsy proven Enteropathy associated T cell lymphomas were treated in a single institution. All patients were made nil by mouth, and given intra-venous fluids with oral ciprofloxacin and metronidazole as gut prophylaxis 48 hours prior to chemotherapy. When the risk of perforation was considered to be over continuous NJ feeding was instituted with regular dietetic support. 2 cycles of a combination of Ifosphamide, Etoposide and Epirubicin (IVE) were given 4 weeks apart. Patients had peripheral blood stem cells mobilised with G-CSF support following the second cycle. After stem cell harvest 2 cycles of high dose methotrexate (3g/m2) with folinic acid rescue were given. Following this, patients were admitted for consolidation with autologous stem cell transplantation with BEAM conditioning. Results: The median age of the patients was 56 years (40–59). 5 were diagnosed following laporotomy and small bowel resection and one by lymph node biopsy. All but 1 patient had stage 1E disease. 3 were known to have coeliac disease previously while 3 were diagnosed post-operatively. All 6 patients were able to tolerate the planned treatment with no deviation from protocol and there was no transplant related mortality. There were no episodes of perforation or GI bleeding. One patient was unable to be harvested due to sepsis and was mobilised with G-CSF alone prior to methotrexate being given. All patients suffered with severe diarrhoea and weight loss ranging from 5–11 kilograms during their autograft, despite continuous parenteral feeding. Standard CT restaging showed five patients achieved a complete remission (CR) and one other a very good partial response (VGPR). Of the 6 patients, 2 had florid relapse at 0.21 and 1.71 years post PBSCT and subsequently rapidly died due to intestinal perforation. The other 4 remain alive and in CR at 1.83, 3.35, 3.67 and 4.32 years following transplant respectively. Conclusion: EATL is a rare extra-nodal T cell lymphoma with a very poor prognosis with standard treatment, and large case series take many years to build. EATL is also often added to series of other high-grade T cell lymphomas or GI non Hodgkin’s lymphomas, making it difficult to determine optimal management. In our series of patients there were no serious complications following gut sterilisation and induction and consolidation chemotherapy, and despite marked weight loss all were able to tolerate PBSCT. 4 out of 6 patients (66.7%) remain alive and in a sustained CR, while 2 suffered an early relapse and rapidly died. We conclude that this regimen appears to be extremely efficacious in the treatment of EATL.

Description: As part of the randomized MRC Myeloma IX trial, we compared an attenuated regimen of cyclophosphamide, thalidomide, and dexamethasone (CTDa; n = 426) with melphalan and prednisolone (MP; n = 423) in patients with newly diagnosed multiple myeloma ineligible for autologous stem-cell transplantation. The primary endpoints were overall response rate, progression-free survival, and overall survival (OS). The overall response rate was significantly higher with CTDa than MP (63.8% vs 32.6%; P 〈 .0001), primarily because of increases in the rate of complete responses (13.1% vs 2.4%) and very good partial responses (16.9% vs 1.7%). Progression-free survival and OS were similar between groups. In this population, OS correlated with the depth of response (P 〈 .0001) and favorable interphase fluorescence in situ hybridization profile (P 〈 .001). CTDa was associated with higher rates of thromboembolic events, constipation, infection, and neuropathy than MP. In elderly patients with newly diagnosed multiple myeloma (median age, 73 years), CTDa produced higher response rates than MP but was not associated with improved survival outcomes. We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events. This trial was registered at International Standard Randomized Controlled Trials Number as #68454111.

Description: Several studies have established that some chronic myeloid leukaemia (CML) patients with enduring deep molecular responses to tyrosine kinase inhibitor (TKI) therapy can discontinue treatment. However, these studies are confined to patients in stable MR4, i.e. whose BCR-ABL/ABL ratio is consistently below 0.01% (molecular response 4 logs below an arbitrary baseline). Although there are anecdotal reports of successful treatment cessation for a few months in patients in stable MR3 (i.e. BCR-ABL 10,000 ABL control transcripts). Central monitoring was carried out monthly. Molecular recurrence was defined as loss of MR3 (〉0.1%) on two consecutive samples; this prompted resumption of full dose of their entry TKI. Between December 2013 and April 2015, 174 patients (male 98; female 76) were recruited after giving informed consent from 20 UK centres. At entry, 148 patients were receiving imatinib, 16 nilotinib and 10 dasatinib. After 12 months of half-dose therapy (imatinib 200mg daily, nilotinib 200mg twice daily or dasatinib 50mg daily), molecular recurrence was lower in patients with stable MR4 at entry (3 of 125 patients; 2.4%) than in those in MR3 but not MR4 (9 of 49 patients; 18.4%) (p 〈 0.001). The median time to relapse was shorter in the sustained MR3 group than in those in sustained MR4 at entry (4.4 months vs 8.7 months). The probability of molecular recurrence on de-escalation was not related to age, gender, performance status, prior TKI (imatinib vs second generation) or the duration of TKI therapy (median 7.0 years overall). No progression to advanced phase or loss of cytogenetic response was seen; one death and 15 serious adverse events occurred which were all unrelated to CML or TKI treatment. All 12 patients with molecular recurrence regained MR3 within 4 months of resumption of full dose TKI. During the first 3 months of de-escalation but not thereafter, the number of patient-reported common TKI side effects decreased, though interestingly 53 new musculoskeletal symptoms were reported by 36 patients (21%) which were typically mild and transient. In CML patients with stable MR3 or better, decreasing TKI treatment to half the standard dose appears safe, and is associated with improvement in TKI related side effects, implying that many patients with stable responses are being overtreated. Studies of more ambitious de-escalation are warranted. Disclosures Clark: Ariad: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau. Apperley:Novartis: Honoraria, Speakers Bureau; Incyte: Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Ariad: Honoraria, Speakers Bureau. Pocock:Gilead Sciences: Other: Sponsorship to attend the EHA 2016 Meeting; Janssen: Speakers Bureau; Takeda: Honoraria. Smith:Bristol Myers Squibb: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Ariad: Honoraria. Byrne:Bristol Myers Squibb: Consultancy, Speakers Bureau. O'Brien:Ariad: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Copland:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ARIAD: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Description: Objectives.Bosutinib is a second-generation tyrosine kinase inhibitor (TKI) indicated for patients with previously treated Philadelphia chromosome positive chronic myeloid leukaemia (CML) when imatinib, nilotinib and dasatinib are not appropriate. Data describing the use of bosutinib in patients with CML in the real world clinical setting are limited. The objective of this study was to describe the efficacy and safety of bosutinib in patients with CML used under routine clinical practice. Methods.An international, multi-centre, retrospective, non-interventional study in hospitals in the UK (n=7) and the Netherlands (n=2). Fifty-three patients (32 [60%] male) with CML, aged ≥18 years at bosutinib initiation and with ≥3 months data available post-initiation were recruited. Surviving patients provided written informed consent for data collection; data from deceased patients were collected by a member of the direct care team to preserve confidentiality. Data were analysed using descriptive statistics with no imputation of missing values (denominators presented where data are missing). Results.Median age at bosutinib initiation was 63.6 (range: 25.5 to 90.1) years; median time from CML diagnosis to bosutinib initiation was 7.1 (range: 0.5 to 35.7) years; 74% (39/53) of patients had one or more co-morbidities at initiation. Bosutinib was 3rd-line TKI in 32% (17/53) of patients and 4th-line TKI in 53% (28/53) of patients. Fifty-seven percent (30/53) of patients switched to bosutinib due to intolerance and 26% (14/53) due to resistance to a previous TKI. The most common bosutinib starting dose was 300 mg/day (28% [15/53] of patients). Median bosutinib treatment duration was 15.6 (range: 0.4 to 66.0) months. The proportions of patients with cumulative complete cytogenetic response (CCyR), major molecular response (MMR), molecular response 4.0 (MR4.0) and molecular response 4.5 (MR4.5) with bosutinib were 62%, 54%, 34% and 26%, respectively (see figure). At data collection (median follow-up 25.1 [range: 3.0 to 66.0] months), 38% (20/53) of patients had discontinued bosutinib; 2% (1/53) discontinued due to progression, 8% (4/53) due to treatment failure, 15% (8/53) due to adverse events (AE), 6% (3/53) due to loss of response, and 4% (2/53) due to patient request. Ninety-two percent (49/53) of patients experienced ≥1 AE, most commonly diarrhoea (55% [29/53] of patients); 26% (14/53) of patients had grade 3/4 AEs (diarrhoea grade 3/4: 4% [2/53] of patients). Conclusions.Bosutinib used in normal clinical practice in pre-treated patients with CML demonstrates high rates of cytogenetic and major molecular response similar to those seen in clinical trials. Bosutinib is generally well tolerated, with the majority of patients not experiencing grade 3/4 AEs, despite most patients having pre-existing co-morbidities. Disclosures Apperley: Pfizer: Honoraria, Speakers Bureau; Ariad: Honoraria, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Incyte: Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Byrne:Bristol Myers Squipp: Consultancy, Speakers Bureau. Smith:Pfizer: Honoraria, Other: Advisory boards and talks at regional sponsored meetings. Viqueira:Pfizer: Employment. Ferdinand:Pfizer: Employment. Carter:pH Associates: Employment. Nock:pH Associates: Employment. Milojkovic:Ariad: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; Bristol Myers Squibb: Honoraria.

Description: Donor leucocyte infusions (DLI) are frequently required following reduced intensity conditioned (RIC) allografts to convert mixed donor chimerism (MC) to full donor chimerism (FDC). The rationale is to prevent tolerance developing and therefore to maximise the graft versus tumour (GvT) responses. However, the impact that the chimeric state has on disease relapse and transplant outcome remains controversial. To address this we analysed the impact of the complete (global) chimerism pattern in 125 recipients of RIC transplants. The transplants were performed for a broad range of malignant haematological diseases. Conditioning regimens consisted of fludarabine, melphalan, campath (65), fludarabine, busulphan, campath (13), BEAM, campath +/− fludarabine (38) and other (9). The donors were HLA matched siblings (62, 50%), HLA mismatched siblings (6, 5%), matched unrelated (29, 23%) and mismatched unrelated (28, 22%). The median patient age was 52 and donor age was 42. The median follow up was 823 days (range 99–2674). Four patterns of chimerism were seen: A. always 100% donor chimerism (68, 54%), B. persisting MC post transplant including cases refractory to DLI (27, 22%) C. MC post transplant with subsequently development of FDC either spontaneously or post DLI (22, 18%), D. lost DC and had autologous reconstitution (8, 6%). A number of patients in both groups B and C had FDC early post transplant. In group A 18 (26%) patients received DLI for relapse or residual disease. A complete response was achieved in 6 (35%). In group B 10 (37%) patients had DLI: 4 for MC, 1 for residual disease, 2 for relapse and 3 for both MC and relapse; only partial responses were seen (20%). In group C DLI was given in 14 (64%) patients: 4 for MC, 5 for residual disease, 3 for relapse and 2 for both MC and relapse. A complete response was achieved in 12 (86%). The risk of relapse at 2 years was significantly associated with the pattern of chimerism (p=0.012) and was greatest for group D (75%). Patients in group C (DLI responders) had a relapse rate of 24% compared to 61% in group B (DLI non-responders). In group A it was 37%. This resulted in a significant survival advantage for patients in group C as compared to all other groups (p=0.009). Predicted overall survival at 2 years was 95% in group C, but 54% in group A, 57% in group B, and 58% in group D. We conclude that patients with MC who later achieve FDC have a lower incidence of disease relapse than those with persistent MC, supporting the use of DLI in this group. However the observation that the patients receiving DLI to achieve FDC have a superior outcome to those patients with persistent FDC (group A) suggests that this group may have benefited from a GvT effect against minimal residual disease. The use of pre-emptive DLI in this group (despite FDC) may reduce the risk of relapse and improve transplant outcome.

Description: Following reduced intensity conditioned (RIC) transplants, donor leukocyte infusions (DLI) are frequently used either to convert mixed chimerism (MC) to full donor chimerism (FDC) or for residual or relapsed disease. Unfortunately, DLI are not universally successful and few factors are known (e. g disease type and level of pre-DLI chimerism) which predict for good responses. We analysed the impact of the chimerism pattern in 125 recipients of (CAMPATH containing) RIC transplants for malignant diseases. Of these, 68 (55%) had FDC (group A), 49 (39%) developed MC and 8 (6%) lost DC and had autologous reconstitution (group D). The patients who developed MC could be further subdivided into those with persisting MC post transplant (27, 55%; group B: non-responders) and MC post transplant with subsequently development of FDC (22, 45%; group C: responders). These two groups were analysed further. The median patient age was 55 (range: 19–71). The donors were siblings (22) or unrelated (27). The diseases were as follows: AML/MDS 14, CML 4, Myeloma, 4, lymphoma/CLL 26, MF 1. Stem cell source was PBSC (38) and bone marrow (11). Conditioning consisted of fludarabine, melphalan and campath (fmc) in 24 patients; fludarabine, busulphan and campath (fbc) in 5; BEAM, campath +/− fludarabine in 18 and FLAG in 2. There were no significant differences in any of these features between groups B and C. 25/49 patients received DLI. This was for disease relapse in10 patients, residual disease in 6 and MC alone in 8 (Unknown in 1). A complete disease response (CDR) was seen in 9/14 (64%) evaluable cases. There was a highly significant difference in CDR between the two groups (group B: 0/4, group C: 9/10, p=0.005). The reason for the difference in response rate was investigated. Median time to DLI was 196 days (range: 57–2123), not significantly different between the groups (p=0.561). The indication for and total number of DLI, the underlying disease and the degree of pre-DLI donor chimerism were not significantly different. In addition there was no significant difference in the incidence of post DLI GvHD (p=0.137), although this was 10/13, 77% in those who responded and 2/5, 40% in those who did not. Conversely, there was a significant difference in the pre-DLI lymphocyte counts (p=0.036). The median count was 2.24 × 109/l. In group B 3/11 (27%) were below this while 10/14 (71%) in group C were below this. The pre-DLI lymphocyte count was not significantly correlated with the time post transplant at which DLI was given, the type of donor, the indication for DLI or the disease, conditioning or post transplant immunosuppression regimen. The predicted overall survival at 2 years was significantly better in group C than in group B (95% versus 57%, p=0.002). This was largely due to the higher relapse risk in group B (77%) compared to group C (32%) (p=0.043). In conclusion, in patients with MC, the development of FDC was significantly associated with a superior OS. In those receiving DLI, the factor most significantly predictive for a ‘responsive’ (C) versus ‘non-responsive’ (B) pattern was the presence of a low pre-DLI lymphocyte count, suggesting that a lack of ‘space’ for expansion or increased suppressor cells in the lymphoid compartment mediate DLI resistance. We postulate that DLI ‘non-responders’ (those with higher lymphocyte counts) may be converted to ‘responders’ by the addition of pre-DLI lymphoreduction, thus reducing relapse and improving outcome.

Description: Allogeneic HSCT is increasingly being performed for lymphoproliferative disease, particularly with reduced intensity conditioning (RIC). DLI are an important part of this strategy however there is a paucity of information in this setting although responses have been reported in Hodgkin’s disease and follicular lymphoma. We have treated 17 patients (median age 51 year; 30–62yr) with refractory disease (n=7) or disease relapse (n=10) following allogeneic HSCT for lymphoma with a DLI based strategy. The diagnosis was CLL, including 1 Richter’s (n=5); mantle cell lymphoma (n=4); high grade NHL (n=4) and follicular NHL (n=4). 15 patients received RIC transplants with either Beam/Alemtuzumab (n=11), or fludarabine/melphelan/alemtuzumab (n=4). Two patients received myeloablative conditioning with TBI and cyclophosphamide. The median time to DLI was 0.96 years (0.23 to 4.58yr) and in 15/17 the donor was a matched sibling (n=13) or 1 antigen mismatched sibling (n=2) and in 2 cases was an unrelated donor. At DLI, 6 patients had mixed chimaerism (20–95%) and 8 had full donor chimaerism with the chimaerism status being unknown in 5 cases. Patients with low grade disease received DLI either alone (n=7) or following initial radiotherapy (n=1). Patients with high-grade NHL, MCL or Richter’s transformation of CLL (n=11) all received chemtherapy pre-DLI. For the 15 sibling donors the median first dose of CD3+ cells infused was 2.0 x 10 7/kg ( range 0.5–6 x 10 7/kg) following which 6 achieved CR. 6 patients received a 2nd infusion (median dose 5 x 10 7/kg) with 2 achieving CR and 1 patient receiving a 3rd DLI and achieving CR. Both MUD DLI recipients achieved a CR after 2 and 3 infusions. Overall 10 out of 17 patients achieved a CR including 3/4 patients with CLL, 4/4 with MCL; 3/4 with follicular NHL but none of the 5 patients with high-grade NHL/Richter’s transformation responded. The median CD3 cell dose required to achieve CR for sibling donors was 2x 107/kg whereas non-responders received a median of 5.0 x 107/kg. An additional patient with CLL who developed aplasia following the first DLI had a second transplant from the same donor and is in CR at 14m giving a final overall CR rate of 70%. Response to DLI was independent of chimaerism status at relapse. Acute GvHD developed in 11 patients and was grade II in 8/10 and grade 111/IV in 3 cases. 1 patient died in CR of acute GvHD. Chronic GvHD developed in 9 of 11 surviving patients. Only 1 patient with mantle cell lymphoma has relapsed at 18m post-DLI. The median follow-up for the surviving patients is 34m (range 6m–60m). The overall survival at a median of 30 months post DLI is 58%. We conclude that lymphoma patients, particularly those with low grade NHL including mantle cell lymphoma relapsing following an allogeneic transplant have a high response rate to DLI based strategies,superior to that seen in myeloma and comparable to that seen in CML. Furthermore these responses appear durable with a low risk of relapse. Patients with high-grade disease appear to have a poor response rate despite using pre-DLI chemotherapy

Description: Background: Imatinib and dasatinib are established drugs in the first-line treatment of chronic myeloid leukemia (CML). Several studies, including SPIRIT2 have shown that first-line dasatinib (100mg once daily) has a superior complete cytogenetic and major molecular response rate compared to imatinib (400mg once daily), but no significant differences in progression-free or overall survival have been shown in any study. To date, there has been no direct comparison of quality of life (QoL) using generic and cancer-specific instruments for first-line treatment of chronic-phase CML with imatinib and dasatinib. SPIRIT2 (STI571 Prospective International Randomised Trial 2) is the first randomized clinical trial to incorporates generic and cancer-specific QoL measurement for first-line therapy. Methods: Quality of life is a secondary endpoint in the SPIRIT2 trial and has been assessed at baseline, and at 1, 2, 3, 6 and 12 months post trial entry and thereafter annually. The EQ-5D, FACT-G, FACT-BRM and the FACT-TOI have been used as QoL measures in this trial. The FACT-G covers cancer-specific QoL measure dimensions such as physical well-being, functional well-being, social and family well-being, emotional well-being and the FACT-BRM and the FACT-TOI different subsets of them. The QoL scores (EQ-5D, FACT-G, FACT-BRM, FACT-TOI) were calculated at different time points and comparison of the mean scores for both treatment groups was made. Results: A comparison between imatinib and dasatinib shows no significant difference in QoL in generic instruments and also in cancer-specific instruments. EQ-5D was 0.77 and 0.79 at baseline and 0.80 and 0.82 at one year for dasatinib and imatinib, respectively (2-3 basis points increase over 1 year). Similar results were obtained for the FACT-G, FACT-BRM and the FACT-TOI. There was a slight increase for the FACT-G (4-5 basis points), FACT-TOI (3-4 basis points) and FACT-BRM (8-10 basis points) after 1 year for both treatments, but this difference was not significant. The effects on the well-being and the emotional dimensions have been analysed for both drugs and there was no change over time, demonstrating results similar to the imatinib arm of the IRIS trial. Conclusions: Standard dose imatinib and dasatinib are both used as first-line treatments for CML and, despite different side effect profiles, there is no significant difference in QoL using the instruments described here between these two drugs over time. These data will allow the derivation of utility values to contribute to future health economic/technology appraisals. Additional analyses of how generic and cancer-specific measures of different QoL instruments change in CML patients over time in those patients that develop side effects, e.g. fluid retention with imatinib or pleural effusion with dasatinib will be presented. Disclosures Copland: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cork:BMS: Research Funding; Novartis: Research Funding; Roche: Research Funding; Ariad: Research Funding. Hedgley:Ariad: Research Funding; Roche: Research Funding; BMS: Research Funding; Novartis: Research Funding. Gills:Novartis: Research Funding; Ariad: Research Funding; BMS: Research Funding; Roche: Research Funding. Holyoake:Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Bescoby:Roche: Research Funding; Ariad: Research Funding; BMS: Research Funding; Novartis: Research Funding. Pocock:Janssen: Honoraria. Clark:Novartis: Honoraria, Research Funding, Speakers Bureau; Pzifer: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding. O'Brien:Novartis: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding; Pzifer: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding.