ALBERT

Description: Objectives: In patients with refractory chronic lymphocytic leukemia (CLL), the potential to cure is unique to allogeneic stem cell transplantation (HSCT). Clearance of minimal residual disease by suspected graft-versus-leukemia effects has been described elegantly and documented in several independent patient cohorts. Yet data from large numbers of patients which support the concept of cure by allogeneic transplantation have not been published. With the advent of new targeted therapies for patients with advanced chemo-refractory CLL, this information becomes crucial for clinical decision making and patient counselling. Therefore, we aimed at the description of long-term survival outcomes, and the estimation of excess mortality compared to the age- and sex-matched general population. Patients and Methods: Data from patients with CLL who had received a first allogeneic HSCT from an HLA-identical sibling (SIB) or alternative donor between January 2000 and December 2010, and who were registered with the EBMT database, were analyzed. Patients with Richter's syndrome and with syngeneic donors were excluded from this analysis. Survival probabilities were calculated by means of the Kaplan-Meier estimator both in the total population, and in patients who passed the 2- and 5-year landmark without previous relapse or progression. Excess mortality of the landmark populations compared to an age-, sex- and calendar year-matched general population was estimated with a Cox regression model for relative survival using the R-package relsurv. Results: In total 2589 patients were included into the analysis. The median follow-up of patients alive at the end of follow-up was 4.0 years (range: 1 to 161 months). The median age at HSCT was 55 years (range: 12 to 74 years). One hundred and fifty eight patients (6.1%) were below 40 years of age at the time of transplantation. Seventy-four percent of patients were male. The remission status at the time of transplantation was reported as complete remission in 15%, partial remission in 47%, and stable disease or progressive disease in 32%. Information on the remission status was not available for 6% of the patients. Fifty-one percent of the patients had an HLA-matched sibling donor and seventy-seven percent of patients received reduced-intensity conditioning. For the whole cohort of patients, the 5- and 10-year overall survival (OS), progression-free survival (PFS), and non-relapse mortality (NRM) were 45%, 35%, 36%, and 35%, 28%, 40%, respectively. The cumulative incidence of relapse (CIR) was 21% at two years, 29% at five years, and 32% at ten years. A total of 1023 patients and 394 patients were alive without relapse or progression, and in follow-up at two and five years after HSCT. Five years after patients had passed the 2- and 5-year landmark, OS, CIR and NRM were 73%, 22%, 16%, and 83%, 11%, 10% respectively. Compared to the general population excess mortality of the 5-year landmark population in the subsequent five years was estimated to be 3% for male patients at an age of 45 years, 10% for male patients at an age of 55 years, and 24% for male patients at an age of 65 years (see Figure 1). For female patients in this 5-year landmark population, the corresponding excess mortality rates were 4%, 11%, and 27%. Patients without progression and with CR at any time from HSCT to the two and five-year landmarks had a slightly better outcome than those who had never had CR. Surprisingly, this was not a result of a lower CIR but of a lower NRM. Conclusion: Long-term follow-up data derived from the EBMT registry show a steady decline in hazard of relapse after allogeneic HSCT, yet relapse continues to be a threat. Moreover, even patients alive and disease-free after 5 years are still confronted with substantial NRM. These results show that there is room for improvement of long-term patient care. By comparing mortality of younger patients who passed the 5-year landmark with the general population, only marginal excess mortality was observed, while elderly patients still had substantial excess mortality beyond this landmark. Nevertheless, the results indicate that a significant fraction of patients can be cured by allogeneic HSCT. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Autologous stem cell transplantation (ASCT) leads to induction of molecular remission in mantle cell lymphoma (MCL). A large proportion of the patients, however, relapse after ASCT. Increasing levels of minimal residual disease (MRD) in consecutive BM samples after ASCT have been observed prior to relapse by us and others, whereas patients in continuous clinical remission have remaining low levels of MRD. In the present 2nd Nordic MCL Phase 2 trial we aimed to direct preemptive treatment to patients in clinical remission but with increasing levels of MRD at high risk of relapse after ASCT. We used a combined standard nested and quantitative real-time PCR analysis to estimate MRD levels (Andersen et al, 2002, Exp. Hematol). According to the protocol consecutive BM and PB samples were procured and shipped for central PCR analysis every 3–4 months post-transplant. Preemptive therapy consisted of four weekly doses 375 mg/m2 of Rituximab. Of the 161 MCL cases included in the trial 81 cases underwent ASCT and had PCR markers available. CR-rate after ASCT was 92%. In total 852 post-transplant BM/PB samples were monitored for MRD. 47 of 81 (58%) cases remained standard nested PCR negative after ASCT for a median follow-up time of 2.7 years (range: 0.14–5.7 years). In 4 (8%) of these a clinical relapse was observed without any PCR detectable MRD present in BM or PB after ASCT, including at time of clinical relapse. In 34 (42%) of 81 cases standard nested PCR was positive at least once after ASCT. The majority of the PCR positive cases (26/34 cases, 76%) converted from standard nested PCR negative to positive during post-transplant follow-up, thus, these cases relapsed molecularly. 8 (24%) of 34 cases remained standard nested PCR positive after ASCT. In these, a rising level of MRD was detected by real-time PCR analysis in 4 cases. The remaining 4 cases either had stable low or declining levels of MRD. Of the 30 cases which relapsed molecularly 8 cases simultaneously underwent a clinical relapse leaving no therapeutical window for preemptive treatment. One case refused preemptive treatment. All molecular relapse occurred within 3 years after ASCT, except in 1 case. In total 21 cases have received preemptive treatment. 19/21 (90%) cases became standard nested PCR negative (18 cases) or reduced to low MRD level (1 case). 2/21 cases remained PCR positive and relapsed after 3 and 6 months, respectively. 16/21 cases remain in clinical CR for a median follow-up time of 1.4 years after preemptive treatment (range: 0.25 to 3.8 years) and 5/21 cases have relapsed. Of the latter cases the 3 of the 5 became PCR negative for 6–9 months before relapse. Of note, two cases have received preemptive treatment twice after a second molecular relapse after which they again became PCR negative. Preemptive treatment has not been reported in lymphoma before. Our results in MCL suggest that the large number of cases who remain in molecular remission after intensified ASCT may be followed by MRD monitoring and treated at molecular relapse instead of receiving maintenance therapy. However, 4 of these cases relapsed. Here, more than PCR methods are needed for early stage disease detection. Our results indicate that preemptive treatment using Rituximab can successfully reinduce molecular remission and prolong time to relapse. Finally, more patients may have PCR markers available by applying frozen diagnostic lymph node material.

Description: Background: Minimal residual disease monitoring has been shown to be of relevance in mantle cell lymphoma (MCL) to evaluate quality of remission and predict clinical relapse. The main objectives of the present study were to determine the value of minimal residual disease (MRD) monitoring to guide pre-emptive treatment with rituximab, and to predict clinical relapse in MCL following autologous stem cell transplantation (ASCT) in two prospective trials (MCL2 and MCL3) with long-term follow-up conducted by the Nordic Lymphoma Group. Methods: Patients treated in the two studies received a total of 6 alternating cycles with R-CHOP and R-Ara-C followed by a peripheral blood stem cell harvest and high-dose therapy with ASCT. Additionally, responding patients not in CR before ASCT in the MCL3 trial received yttium-90 ibritumomab tiuxetan (0.4 mCi/kg) as intensification one week prior to the standard conditioning with BEAM/C. Staging included physical examination, blood tests, computed tomography (CT) scans and bone marrow (BM) aspiration and biopsy. Clinical and molecular response evaluation was repeated 2-3 months and 6 months after transplant, and then every 6 months until relapse or 5 years follow-up. A combined standard nested and quantitative real-time PCR assay was used to estimate MRD involvement in consecutive post-transplant BM/PB samples. Molecular relapse after ASCT was defined as; 1. Conversion from standard nested PCR negative to standard nested PCR positive, or 2. For patients who were MRD positive post-ASCT, a significant (〉5 fold) increase of the real time quantitative PCR detectable MRD level in two consecutive BM samples. Patients in clinical remission who developed a molecular relapse in both studies received 4 weekly doses of rituximab (375 mg/m2). This treatment could be repeated in case of recurrent molecular relapses. Results: An MRD marker for Bcl-1 or IgH rearrangement was obtained for 94 out of 160 patients (59%) recruited in the Nordic MCL2 trial, and for 121 out of 160 (76%) in the consecutive MCL3 trial. 183 patients, who had completed induction therapy and autologous stem cell transplantation (ASCT) in the two studies and where a PCR marker in blood or bone marrow was obtained, were included in the current analysis. Median follow-up from inclusion was 8.5 years among survivors. Patients who were MRD negative post-ASCT had significantly longer relapse-free survival (RFS) and overall survival (OS) compared to those who were MRD positive (P

Description: Introduction:Even in the era of novel targeted therapies for the treatment of Chronic Lymphocytic Leukemia (CLL) patients, such as BTK, PI3K and BCL2 inhibitors, allogeneic hematopoietic stem cell transplantations (alloHCT) will remain an important treatment option for a subset of patients with very high risk CLL. The current study focused on the impact of center and procedure-related factors on outcomes after alloHCT, taking into account the impact of patient- and disease-related risk factors. Patients and Methods:Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analyzed. Their data were collected as part of the EBMT CLL Data Quality Initiative. Outcomes of interest were Event-Free Survival (EFS) up to 5 years after transplantation and mortality in the first 100 days after alloHCT. Outcomes were analyzed by means of the Kaplan-Meier method and Cox proportional hazards models with a frailty (random effects) component to take into account unexplained center heterogeneity. The following factors describing center characteristics or the transplant procedure were analyzed: experience in alloHCT in general and, for CLL specifically, accreditation by the Joint Accreditation Committee-ISCT & EBMT (JACIE), Gross National Income (GNI)/capita based on purchasing power parity (PPP) (GNI/cap), donor type, donor-patient sex-match, type of conditioning, stem cell source and T-cell depletion (TCD). Results:Five-year EFS of the whole cohort was 37% (95% Confidence Interval, 33%-42%), Day-100 survival was 90% (88%-92%). Experience of the transplant center was measured by the number of all alloHCTs, and alloHCTs for patients with CLL respectively. The median total number of alloHCTs per center per year was 45 (range 0-169) and the median number of CLL alloHCTs was only 2 per center per year (range 0-19). Greater experience with transplantation of patients with CLL (Hazard Ratio (HR) 0.96 per additional transplant, p=0.002), JACIE accreditation (HR 0.7, p=0.045) and a higher GNI/cap (HR 0.4, 95% CI 0.2-0.96, p=0.04) showed a protective impact on 5-year EFS in the Cox model. In vivo TCD with alemtuzumab (HR 1.5 compared to no TCD, p=0.03) and a female donor for a male patient (HR 1.4 compared to a male donor for a male patient, p=0.02) were the only procedure-related factors significantly associated with EFS. Event-Free Survival after in vivo TCD with Anti-Thymocyte-Globulin or after ex vivo TCD was comparable to EFS without TCD (HR 0.9, 0.7-1.3, p=0.6; HR 0.9, 0.5-1.6, p=0.8). Non-myeloablative conditioning did not have a negative impact on 5-year EFS, and exposed patients to a lower risk of non-relapse mortality. Measured and unmeasured center characteristics did not have a significant impact on 100-day mortality. Even when correcting for patient-, procedure- and center-related characteristics, there was still significant variation in center outcome, expressed by center-specific HRs derived from the frailty models, ranging from 0.6 to 1.2. Their impact is illustrated in a model-based plot for EFS (see Figure) which shows outcomes for three reference patients with the same characteristics who would be transplanted in three centers with the same measured characteristics but with the highest, average and lowest HRs in the dataset. These unexplained center effects likely represent a mixture of differences which could apply to the location of the transplant center, unmeasured characteristics of the patient population transplanted at this center, selection criteria which were not reported and factors determining the success of the transplant procedure which might differ between centers. Conclusion: We have confirmed that both center- and procedure-related factors have a significant impact on the EFS of patients with CLL undergoing alloHCT. Our results may help to interpret outcomes of single or multicenter studies better. Since non-myeloablative conditioning did not have a negative impact on EFS and exposed patients to a lower risk of non-relapse mortality, this approach should be favored for future alloHCT for CLL. Probability of Event-Free Survival up to Five Years Post-HCT for three Reference Patients Contribution: J.S. designed the research and wrote the paper. L.C.d.W conducted the statistical analysis and produced the figure. Figure Figure. Disclosures Schetelig: Sanofi: Honoraria. Gramatzki:Janssen: Other: Travel/Accommodation/Expenses, Research Funding. Dreger:Gilead: Consultancy; Gilead: Speakers Bureau; Janssen: Consultancy; Novartis: Speakers Bureau; Novartis: Consultancy; Roche: Consultancy.

Description: BACKGROUND: The advent of the Bruton's tyrosine kinase inhibitor ibrutinib has improved the outlook of patients with CLL and MCL failing chemoimmunotherapy (CIT). However, the impact of ibrutinib on the feasibility and safety of a subsequent alloHCT is unknown. Here we present results of the ibrutinib cohort of an ongoing EBMT survey on the outcome of alloHCT following prior exposure to pathway inhibitors (PI) in patients with CLL or lymphoma (EBMT study code LWP 2013-N-03/CMWP 44204425). DESIGN: Eligible were patients aged 〉18 years registered with the EBMT data office for a planned alloHCT for CLL or lymphoma after pre-exposure to ibrutinib at any time before transplant. Baseline patient, disease, and transplant data were collected from MED-A forms. Centers were requested to provide additional treatment and follow-up information. Statistical analysis used Gray's test to assess the impact of baseline characteristics on the cumulative incidence of relapse (REL) in a competing risk framework. RESULTS: As of July 4, 2016, 38 patients (84% male) were evaluable in the ibrutinib cohort. Diagnosis was CLL in 28 patients, MCL in 9 patients, and follicular lymphoma (FL) in 1 patient. The median age was 51 (33-68) years and the median number of treatment lines prior to ibrutinib 2 (1-9). Eight of the 9 patients with MCL but none of the other patients had a prior autoHCT. Patients had been on ibrutinib for a median of 190 (39-432) days. In 2 patients, ibrutinib had been stopped because of disease progression 〉100d before transplant, whereas the interval between ibrutinib withdrawal and alloHCT was 15-100d in 30%, 4-14d in 51%, and 0-1d in 14% of the patients. Of the CLL patients, 43% had a TP53 lesion, and 87% and 79% met at least one of the 2007 and 2014 EBMT criteria for high-risk CLL, respectively, including PI failure in 29%. Disease status at alloHCT was sensitive in 78% of the CLL patients, and in 60% of the patients with lymphoma. Conditioning was reduced-intensity in 60% of the transplants and included in-vivo T cell depletion with ATG (71%) or alemtuzumab (11%) in the majority of cases. Donors were identical siblings in 26%, matched unrelated in 66%, and partially matched unrelated in 8%, with PBSC (89%) being the predominant stem cell source (bone marrow 8%, cord blood 3%). The median time to reach neutrophils of 〉0.5/nl and platelets of 〉20/nl was 17 (10-26) and 15 (10-46) d post transplant, respectively. Acute GVHD grade 2-4 (3-4) was observed in 37% (10%) of 30 evaluable patients, and limited and extensive chronic GVHD occurred in 24% and 16% of 25 patients at risk. With a median observation time of survivors of 8 (1-24) months, there were only 2 non-relapse deaths, translating into a 1-year non-relapse mortality (NRM) of 6% (95%CI 0-15%). 1-year REL, progression-free survival, and overall survival was 36%, 61%, and 73% for CLL, and 14%, 75%, and 75% for lymphoma. In the 25 evaluable patients with CLL, PI-sensitive compared to refractory disease status at alloHCT tended to be associated with a lower 1-y REL (29% vs 60%; p 0.071), whereas prior PI failure, TP53 status, duration of ibrutinib exposure, interval between ibrutinib withdrawal and alloHCT, and conditioning intensity had no significant impact on REL. CONCLUSIONS: Ibrutinib for bridging to alloHCT for CLL and MCL does not appear to adversely affect engraftment, GVHD risk, and NRM. Patients with CLL still responding to ibrutinib at the time of alloHCT might benefit from ibrutinib bridging as our preliminary results indicate that also after PI exposure sensitive disease translates into a lower risk of relapse. Therefore, ibrutinib may improve the perspective of CIT-refractory patients scheduled for alloHCT. The optimum timing of ibrutinib administration in the interrelation to alloHCT in CLL and MCL needs to be defined by additional studies. Disclosures Dreger: Gilead: Consultancy; Janssen: Consultancy; Novartis: Speakers Bureau; Gilead: Speakers Bureau; Novartis: Consultancy; Roche: Consultancy. Michallet:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas Pharma: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria. Berg:Celgene: Other: Travel Funding; Astellas: Other: Travel Funding; Alexion: Other: Travel Funding. Niederwieser:Novartis Oncology Europe: Research Funding, Speakers Bureau; Amgen: Speakers Bureau. Montoto:Gilead: Research Funding; Roche: Honoraria. Schetelig:Sanofi: Honoraria.

Description: This trial aimed to evaluate the efficacy of sirolimus in addition to cyclosporine (CSP) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis after nonmyeloablative conditioning for HLA class I or II mismatched hematopoietic cell transplantation (HCT). Eligible patients had hematologic malignancies treatable by allogeneic HCT. Conditioning consisted of fludarabine (90 mg/m2) and 2 to 3 Gy total body irradiation. GVHD prophylaxis comprised cyclosporine, mycophenolate mofetil, and sirolimus. The primary objective was to determine whether the cumulative incidence of grade 2 to 4 acute GVHD could be reduced to

Description: Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy with stem cell support has not been tested in large, prospective series. In the 2nd Nordic MCL trial, we treated 160 consecutive, untreated patients younger than 66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy with rituximab (R) + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP), alternating with R + high-dose cytarabine. Responders received high-dose chemotherapy with BEAM or BEAC (carmustine, etoposide, cytarabine, and melphalan/cyclophosphamide) with R-in vivo purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progression-free survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole independent predictor of event-free survival. The nonrelapse mortality was 5%. The majority of stem cell products and patients assessed with polymerase chain reaction (PCR) after transplantation were negative. Compared with our historical control, the Nordic MCL-1 trial, the event-free, overall, and progression-free survival, the duration of molecular remission, and the proportion of PCR-negative stem cell products were significantly increased (P 〈 .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression-free survival of MCL and perhaps cure. Registered at www.isrctn.org as #ISRCTN 87866680.

Description: Abstract 932 The Nordic Lymphoma Group has since 1996 conducted three consecutive phase II trials for front-line treatment of MCL patients ≤ 65 years of age. The first protocol (MCL1) 1996-2000 introduced high-dose chemotherapy with autologous stem cell support (unpurged or ex vivo purged) as consolidation after 4 cycles of intensified CHOP (maxi-CHOP). The results were disappointing, as the majority of patients relapsed. 1 Being in CR pre-transplant was the most important factor for outcome. Hence, in the second trial (MCL2) 2000-2006 induction therapy was intensified by adding high-dose Ara-C and rituximab to the regimen. Compared to MCL1 this led to significant improvement of event-free and overall survival, and the rate of PCR negative stem cell grafts and bone marrow samples.2 Again, responders in less than CR pre-transplant had a significantly poorer outcome. We therefore made a further intensification for the MCL3 study (2006-2009) by adding 90Y-Ibritumomab tiuxetan (Zevalin®) to the high-dose BEAC/BEAM to responders not in CR. Methods: As in the MCL1 and 2 studies newly diagnosed stage II-IV MCL patients ≤ 65 years were included. Induction treatment was identical to that of the MCL2 study with alternating cycles of maxi-CHOP-rituximab (3 cycles) and Ara-C-rituximab (3 cycles). Response evaluation was done after cycle 5. PET/CT was recommended, but could not influence the response evaluation, which was done according to the International Workshop criteria. Responders underwent in vivo purged harvest of stem cells after cycle 6 (Ara-C + 2 doses of rituximab). Patients in CRu or PR received a standard dose 90Y-Ibritumomab tiuxetan (0.4 mCi/kg) one week prior to the BEAM/BEAC, CR patients received BEAM/BEAC alone. Patients are followed by CT-scans, bone marrow and blood samples, including PCR for minimal residual disease or molecular relapse. For molecular relapse preemptive treatment with 4 standard doses of rituximab, as in the MCL2 study3, is given. Results: The planned accrual of 160 patients was reached in June 2009. The patient characteristics are similar to those of the MCL2 trial with a median age of 57 years (28-65), the majority male (80%) and in stage IV (89%) with bone marrow involvement (74%). The response rates pre-transplant so far compare favorably with data from MCL2 with 50% in CR, 18% in CRu, and 28% in PR. Only 4 out of 128 evaluable patients did not respond (3%) and there was one case (1%) of treatment-related mortality during induction therapy. While it is still too early to assess the impact of the 90Y-Ibritumomab tiuxetan on the progression-free survival, the side effects were similar to those of the MCL2 study including a treatment related mortality of 4%. Fifty-five patients in CRu or PR have so far been treated with 90Y-Ibritumomab tiuxetan, with no indication of any added toxicity. Only 12 out of 133 patients (10%) have not undergone transplant, 5 due to stem cell harvest failure, 3 due to toxicity and 4 due to non response to induction treatment. PET-scan prior to transplant was positive in 2% of CR patients, 20% of CRu patients and 54% of PR patients. Patients with a positive PET-scan pre-transplant had a 36% chance of achieving a molecular remission post-transplant, compared to 92% of cases with a negative PET-scan (p

Description: Chronic Graft-versus-Host Disease (cGVHD) has a negative impact on transplant related death and quality of life after hematopoietic stem cell transplantation. In an attempt to thoroughly assess cGVHD after double umbilical cord blood transplantation (dUCBT), we used the major revised consensus criteria (NCC 2005) proposed by the National Institutes of Health (NIH) in 2005. Material and methods: This is a retrospective study using Eurocord-EBMT database. A specific questionnaire including the NCC 2005 characteristics and features was sent to each transplant centers for collecting data. Eligible pts were adults 〉18years, who received dUCBT for hematological malignancy in an EBMT center between 2006 and 2014, achieved neutrophil engraftment, survived ≥100 days and developed cGVHD. Results: A total of 154 pts were included. Median age at dUCBT was 43 years (18-70). The primary diagnosis was acute myeloid leukemia in 40%, acute lymphoblastic leukemia in 21%, myelodysplastic/myeloproliferative disease in 19%, and other hematological disorders in 20%. The majority of pts was transplanted in CR, including 51% in CR1, 37% in CR2. Reduced intensity conditioning regimen (mainly with low dose total body irradiation) was used in 60% of cases. 24% pts received anti-thymocyte globulin before transplant. Cyclosporine and mycophenolate mofetil (MMF) was the most common (79%) combination for GVHD prophylaxis. 70% (n=107) of pts received gender mismatched grafts, and 59% had 1-2 major ABO incompatibility. Most (〉80%) grafts had 2 HLA mismatches with the recipients. Median number of total nucleated cells at cryopreservation was 5.1(2.3-13.3) ×107/Kg. All pts achieved neutrophil engraftment in a median of 25 days and 89% had full donor chimerism at day 100. Median follow-up was 27.5 (3-103) months, 45 pts relapsed and 60 pts died (28 of relapse, 12 of GVHD and 20 of other TRM). Grade II-IV acute GVHD occurred in 88 pts in a median time of 24 (6-106) days. Grade III-IV aGVHD was reported in 43 pts, mainly with skin and gastrointestinal (GI) tract involvement. Median time for cGVHD onset was 219 (47-2056) days, and most of these were reported within the first 1.5-2 years. Based on Seattle criteria, cGVHD was limited in 73 (47%) pts and extensive in 81 (53%) pts. According to NIH criteria (NCC2005), global cGVHD severity was scored as mild in 67 (44%), moderate in 53 (35%) and severe in 33 pts (21%). cGVHD presented mainly as one or two organs involvement, with skin being the most common site. 56% pts (n=86) had a single organ involvement (mainly skin n=60; 38%). Skin, GI tract, and oral mucosa were the top three affected sites (93%; n=143), both in solo and multiple involvements. 23 patients had 〉 3 affected organs, skin being most common (n=20; 87%). No joint or fascia involvement was reported as a single organ involvement in any grade. Mild and moderate cGVHD presented as one or two organs involvement, mainly affecting skin, GI and oral mucosa. Severe cGVHD often involved skin, GI, lung and liver. Severe GI tract cGVHD was mostly reported as a single organ involvement. Severe lung involvement was reported in 12 pts (8%). Major functional impact by scoring grade 3 was observed in skin (n=7), GI (n=8), liver (n=5), eye (n=3), oral mucosa (n=2), and lung (n=5). Twenty %pts (n=31) received only topical or no treatment, for 1 or 2 organs involvement and mild to moderate grade cGVHD. The first line treatment of cGVHD included systemic steroids +/- calcineurin inhibitors (CNI) or MMF based regimen, and was used in 72% pts (n=111). cGVHD resolved in 94 pts (61%), and remained clinically significant in 57 pts (mild, n=14; moderate, n=20 and severe, n=23). Among the 12 pts who died of cGVHD, there was multiple organs involvement in most cases; and 6 pts had severe lung cGVHD. Conclusion: According to NCC 2005 criteria, we report that, after dUCBT, cGVH was usually mild with skin being the most common site resulting, in this small group of patients, in a relatively low incidence of severe cGVH with as a consequence a better survival and quality of life. Disclosures Michallet: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas Pharma: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria.

Description: Introduction 17p-/TP53-mutated CLL (17p- CLL) represents approximately 5 to 10% of newly diagnosed CLL cases. Patients with this abnormality have a poor prognosis after chemo-immunotherapy. According to current guidelines, allogeneic hematopoietic cell transplantation (HCT) is recommended in 17p- CLL cases as part of the first- or second-line treatment. In 2010, the European Society for Blood and Marrow Transplantation (EBMT) and the European Research Initiative on CLL (ERIC) started a non-interventional study, to evaluate the outcome of allogeneic HCT in 17p-CLL. Here we report first results from this study. Patients & Methods Major eligibility criteria were 17p- CLL in complete or partial remission after first-line therapy or treatment of relapse, age below 70 years, availability of an HLA-compatible related or unrelated donor with up to one HLA-mismatch at HLA-A, -B, -C or DRB1. The primary objective was to determine relapse-free survival. Results Forty-one patients (30 males, 11 females) from eleven transplant centres were registered for this study between June 2010 and September 2012. The median age was 59 years (range, 28 to 70 years). Twelve patients (29%) were transplanted in first remission. The median number of pre-treatments was 2 (range, 1 to 7) and included alemtuzumab in 31 patients (76%). The remission status at HCT was reported as partial remission in 31 patients (76%) and as complete remission in 10 patients (24%). The median time between diagnosis and HCT was 35 months (range, 4 to 229 months) and the median time between first treatment of CLL and HCT was 12 months (range, 2 to 227 months). Myeloablative conditioning was administered in 3 patients (7%), fludarabine-based reduced-intensity conditioning in 25 patients (61%) and non-myeloablative conditioning, based on 2 Gray TBI, in 13 patients (32%). Donors were HLA-identical siblings for 11 patients (27%), well-matched HLA-compatible unrelated donors for 25 patients (61%) and partially matched unrelated donors for 5 patients (12%). Thirteen patients received ATG. Fifteen patients experienced grade II to IV graft-versus host disease. By July 2014, 27 patients were alive and 14 patients had died. From the deceased patients, 4 patients died subsequent to relapse and 10 patients died without relapse. Causes of death were GVHD in 7 patients, infection in one patient and other causes in 2 patients. The median observation time for living patients was 16 months (range, 3 to 36 months). The probability of relapse-free survival (see also Figure 1) and overall survival at 2 years was 56% (95% CI, 42% to 74%) and 67% (95% CI, 51% to 83%). At two years the cumulative incidences of relapse and non-relapse mortality were 20% (95% CI, 6% to 34%) and 24% (95% CI, 10% to 39%). Conclusions When considering the high disease-specific risk and the median age of 59 years at transplantation of this cohort of patients, we present favourable early results after allogeneic HCT for patients with 17p- CLL. Non-relapse mortality, mainly caused by GVHD, compromised relapse-free survival. The data suggests that allogeneic HCT remains an attractive treatment option, especially for patients with a low transplant risk and a high disease-specific risk of mortality. These results may serve as benchmark for new drugs which are currently under clinical development or have recently received approval for this indication. Figure 1) Relapse-free Survival in 41 patients with del(17p) CLL after HCT Figure 1). Relapse-free Survival in 41 patients with del(17p) CLL after HCT Disclosures No relevant conflicts of interest to declare.