Intensity Conditioning Allogeneic Stem Cell Research Articles

The Easix Score Predicts Overall Survival and Late Relapse in Patients Undergoing Reduced Intensity Conditioned Allogeneic Stem Cell Transplantation for Myeloid Disease

Background Allogeneic hematopoietic stem cell transplantation (alloSCT) is an effective treatment for myeloid malignancies, however outcomes post-transplant are variable and predictive scores limited. The Endothelial Activation and Stress Index (EASIX) measured at key timepoints pre- and post-transplant has been shown to predict outcomes in alloSCT, including overall survival, non-relapse mortality and incidence of sinusoidal obstructive syndrome (SOS). It can be readily calculated using standard biomarkers (LDH (U/L) x creatinine (mg/dL)/platelets (x109/L). We sought to examine its predictive role in a homogenous population of patients. Methods We conducted a retrospective national review of 117 patients undergoing reduced-intensity alloSCT for myeloid disease including AML (n=56), MDS (n=35) and MPN (n=26). All included received fludarabine, busulfan and rabbit anti-thymocyte globulin (Flu/Bu/ATG) conditioning from 2015-2020. We calculated the EASIX score on the day prior to conditioning, on day 0, at onset of acute graft versus host disease and 1 year post transplant. Univariate analysis was conducted in the STATA statistical package. Results At the pre-conditioning time-point the mean EASIX was 3.11 (0.3-17.54). Increased scores correlated with and were reliably predictive of reduced overall survival (p=0.034) (fig. 1). Higher scores at this time-point did not predict chronic GVHD or relapse, however an increased rate of acute GVHD was seen in those with lower EASIX (p=0.012). At day 0 the mean EASIX was 15.38 (1.07-179.02), however we could not demonstrate a predictive effect on SOS as no events occurred in this cohort. Nor did we identify a predictive value at this point for GVHD risk or relapse. At onset of acute GVHD (n=67, mean 3.52, 0.44-51.43), the EASIX score was predictive of overall survival (p=0.027) but did not predict risk of chronic GVHD or relapse. At 1 year post-transplant (n=88, mean 2.09, 0.48-13.59) a higher score showed a trend towards decreased overall survival (p=0.1) but was associated with an increased risk of subsequent relapse (p=0.01)(fig. 2). Conclusions The EASIX score is an easily applicable clinical tool using real world biomarkers readily available at serial time-points in transplant recipients. When applied to our homogenously treated cohort it retains its value in predicting overall mortality at the key time points of pre-conditioning and at onset of GVHD. Adoption of this simple score may be of benefit in risk stratifying the transplant process for reduced intensity conditioned allograft recipients, particularly when combined with established prediction tools for non-relapse mortality such as the HCT-CI. In addition to this, we have shown that the EASIX score may be a useful predictive tool for late relapse in those patients who are alive at 1 year post transplant. We suspect that this effect is primarily reflective of those patients with persistent thrombocytopenia and raised LDH, both markers of potential disease activity. Importantly, the use of this score in the reduced intensity population may be particularly relevant due to the increasing age of transplant eligibility and its use as a surrogate of endothelial dysregulation and potential for end organ complications through the transplant process. To assess the underlying T cell mediated and cytokine secretome effects on endothelial dysfunction, an observational study is ongoing at our institution, examining the interplay of immunomodulatory therapy, graft T cell content, early T and NK cell recovery and the cytokine secretion patterns at various time points before, during and after transplant in reduced intensity conditioned patients with myeloid disease. We plan to correlate these data with serial EASIX assessments to identify the determinants of the underlying biological process and identify potential time-points and biological targets for future study.

RIC Allogeneic Stem Cell Transplantation for High Risk CLL Followed By Preemptive MRD-Based Immunointervention - Final Results from the Phase II ICLL03 Ricac-Pmm Trial (FILO - SFGM-TC French intergroup)

RIC Allogeneic Stem Cell Transplantation for High Risk CLL Followed By Preemptive MRD-Based Immunointervention - Final Results from the Phase II ICLL03 Ricac-Pmm Trial (FILO - SFGM-TC French intergroup)

Safety and Efficacy of Myeloablative Conditioning Autologous Stem Cell Transplantation, Targeted Immunotherapy, and Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation in Children, Adolescents, and Young Adults with Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma

Background Despite high cure rates for children, adolescents and young adults (CAYA) with mature B-cell non-Hodgkin lymphoma (B-NHL) (Cairo, JCO, 2012), the results are dismal in those with relapsed/refractory (r/r) disease following reinduction therapy with myeloablative conditioning (MAC) and autologous stem cell transplantation (AutoSCT) (Cairo, BBMT, 2013). Sequential MAC AutoSCT and reduced intensity conditioning (RIC) allogeneic stem cell transplantation (AlloSCT) has achieved 59% 10-year event-free survival (EFS) in CAYA with Hodgkin (Satwani/Cairo, Leukemia, 2015). The addition of Y-ibritumomab tiuxetan to an RIC based regimen prior to AlloSCT in a cohort of adults with high risk B-NHL was proven to be safe and efficacious (Boubdallah, Annals of Oncology, 2015) and may further improve outcomes. Objective To investigate the safety and efficacy in CAYA with poor risk r/r B-NHL of sequential MAC AutoSCT followed by RIC AlloSCT with or without targeted radioimmunotherapy. Design/Methods CAYA patients with poor risk r/r mature B-NHL who underwent MAC AutoSCT followed by RIC AlloSCT ± targeted radioimmunotherapy are included in this study. Twelve of thirteen patients with chemo-sensitive disease underwent sequential MAC AutoSCT followed by RIC AlloSCT (Fig 1). Six patients received radioimmunotherapy with Yttrium-90 ibritumomab tiuxetan prior to MAC. In addition to EFS, patients were assessed for time to hematological recovery, graft failure, whole blood chimerism, aGVHD ≥ Gr 2 and extensive chronic GVHD. Results Thirteen patients with a mean age of 15.3 years and mean follow-up of 48 months were analyzed. Median time to neutrophil and platelet engraftment is 18.8 and 36.4 days, respectively (Fig. 2). Whole blood chimerism at D+100 is 98.4 ± 1.5 %. Eleven patients are in complete remission with an EFS of 91% (Fig. 3). The transplant-related mortality was 0% and no graft failures developed. Conclusions CAYA with r/r B-NHL receiving MAC AutoSCT, targeted radioimmunotherapy, and RIC AlloSCT can achieve long-term EFS. The combination of radioimmunotherapy comprised of Yttrium-90 ibritumomab tiuxetan with MAC AutoSCT was safe and effective in our cohort. A potential graft versus lymphoma effect may explain the favorable outcomes in this cohort of patients with otherwise dismal outcomes.

T Prolymphocytic Leukemia, a rare disease, case presentation with typical pathological findings and review of management

Background: Prolymphocytic leukemia (PLL) is a rare disease, accounting for < 2% of lymphoid leukemias [1].There are 2 quite different entities with distinct pathologic features and different therapeutic strategies, T-cell and B-cell [2]. T-PLL is more common [3]. Although termed ‘prolymphocytic,’ T-PLL is characterized by the proliferation of post-thymic T-lymphocytes. It is estimated that physicians will see a case of T-PLL every five to ten years [4]. Over the last 15 years, 3 cases of T-PLL were diagnosed in our center. We present here the latest case, with typical pathological findings. Case Report: A 63-year-old British gentleman, previously healthy with good performance, presented with fatigue for 6 – 8 weeks with puffiness of face and eyelids and weight loss of 5 kilograms. Physical exam showed periorbital edema and conjunctival injection (Figure 1), cervical lymphadenopathy, and hepatosplenomegaly. Initial complete blood count (CBC): white blood cells (WBCs) 331.9 x109/L (4.0 – 10.0), with 94% lymphocytes, hemoglobin (Hb) 119 gm/L (130 – 170), platelets (Plts) 128 x109/L (150 – 400). Lactate dehydrogenase 10.4 µkat/L (2.1 – 3.7), uric acid 537 µmol/L (210 – 420). Abdomen ultrasound showed markedly enlarged spleen (20.3 cm). The peripheral blood smear showed profound leukocytosis with 94% abnormal lymphoid cells. The cells were small to medium in size with high nucleo-cytoplasmic ratio, moderately condensed chromatin and almost all with prominent nucleolus. Substantial number of the cells show irregular nuclear contour with short indentation. The cytoplasm was basophilic agranular and many cells show irregular cytoplasmic protrusions (Figure 2). Flow cytometry on peripheral blood revealed one homogenous abnormal population positive for cluster of differentiation 45 (CD45) and express the pan T-cell markers (CD3, CD2, CD5 and CD7). All were positive for CD4, T-cell receptor (TCR) alpha/beta, CD43 and BCl2 with partial expression of CD38. These cells were negative for CD56, CD57, CD16, CD25, CD103, CD10, CD117, Terminal deoxynucleotidyl transferase (TdT), CD1a and CD34. (Figure3A) TCRVb region analysis by flow cytometry using IO Test Beta Mark TCR Repertoire kit (Beckman Coulter, Brea, CA, USA) using the panel of 24 monoclonal antibodies to TCR Vb families showed restricted expansion of region 13.1 in 99%. (Figure 3B) Bone marrow aspirate was remarkably hypercellular and extensively infiltrated with abnormal lymphoid cells comprising approximately 75% of total nucleated cells, morphologically similar to those seen in peripheral blood. The biopsy showed extensive diffuse infiltration with small to moderately sized lymphoid cells with prominent nuclear irregularity (Figure 4A&B). The immunophenotype was confirmed by immunohistochemistry and the cells were positive for CD3, CD5, CD7, CD2, CD4, BCL2 as well as for Zap70. BCL6 was uniformly negative. Based on the morphology and the immunophenotypic profile, a diagnosis of CD4+/CD8− T-prolymphocytic leukemia was made. FISH analysis revealed ATM deletion at 11q22 and TRA/D rearrangement in 93% of the cells analyzed and karyotype was complex with multiple numeric and structural abnormalities including inv(14)(q11.2q32); Karyotype: 43,XY,del(11)(q14),add(11)(p15),-13,inv(14)(q11.2q32),der(19)t(13;19)(q11;q13.4),-20,-22[7]/42,idem,-9,add(14)(p11.1),add(17)(p13)[23] After confirming the diagnosis of T-PLL the patient travelled back to his home country. He was started on treatment with alemtuzumab, then pentostatin was added in week 4, after 10 weeks of treatment he achieved complete remission. After that he received reduced intensity conditioned allogeneic stem cell transplant from a matched brother, complicated by mild acute graft versus host disease. Until the time of writing this report he was doing fine.

Current and emerging treatment options for mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with typically aggressive behavior. The genetic signature is the chromosomal translocation t(11;14)(q13;q32) resulting in overexpression of cyclin D1. Asymptomatic newly diagnosed MCL patients with low tumor burden can be closely observed, deferring therapy to the time of disease progression. Although MCL classically responds to upfront chemotherapy, it remains incurable with standard approaches. For patients in need of frontline therapy, the initial decision is whether to proceed with an intensive treatment strategy or a non-intensive treatment strategy. In general, given the unfavorable risk-benefit profile, older MCL patients should be spared intensive strategies, while younger and fit patients can be considered for intensive strategies. The bendamustine and rituximab (BR) regimen is becoming an increasingly popular treatment option among the elderly population, with improved progression-free survival (PFS) and acceptable side-effect profile. Although rituximab maintenance after R-CHOP improves survival outcomes in elderly patients, no clinical trial to date has shown statistical significance to support the use of rituximab maintenance after BR induction in older patients. In young and fit patients with MCL, an intensive strategy to maximize the length of first remission has emerged as a worldwide standard of care. With current high-dose cytarabine-containing immunochemotherapy regimens followed by autologous stem cell transplantation, the median PFS has exceeded 7 years. In the relapsed or refractory (R/R) setting, reduced intensity conditioning allogeneic hematopoietic stem cell transplantation may offer the highest likelihood of long-term survival in young R/R MCL patients, at the cost of increased risk of non-relapse mortality and chronic graft versus host disease. Novel agents targeting activated pathways in MCL cells, such as bortezomib, lenalidamide, ibrutinib and temsirolimus are now available for the management of R/R disease.

Hematopoietic Stem Cell Transplant in Adolescent and Young Adults With Fanconi Anemia Is Feasible With Acceptable Toxicity, With Those Surviving 100 Days Posttransplant Having Excellent Outcomes.

Fanconi anemia is a congenital bone marrow failure syndrome that is associated with congenital anomalies and increased risk of cancer. Hematopoietic stem cell transplant is a potentially curative modality for bone marrow failure in Fanconi anemia patients. Here, we report our center's experience regarding adolescent and young adult patients with Fanconi anemia and hematopoietic stem cell transplant. We conducted a retrospective patient record analyses of patients who presented at our center from 1988 to 2014. We included patients greater than 14 years old with confirmed Fanconi anemia based on positive chromosome breakage study and who underwent hematopoietic stem cell transplant at our institution. Our study group comprised 12 patients with Fanconi anemia who underwent hematopoietic stem cell transplant at our institution. The median age was 20 years (range, 14-31 y) with a female predominance of 83%. Low-dose cyclophosphamide (20-80 mg/kg)-based conditioning regimens were used with different combinations that included fludarabine, antithymocyte globulin, or total body irradiation. All patients had HLA-matched sibling grafts. In all patients, stem cell source was the bone marrow. All patients showed engraftment. Four patients (33%) developed acute graft-versus-host disease. Three patients (25%) died early before day 100 after hematopoietic stem cell transplant due to infectious complications, with 1 patient having steroid refractory acute graft-versus-host disease. Overall survival was 75% at a median follow-up of 43 months. All patients who survived are well and remained transfusion independent without evidence of secondary malignancy. Our findings support the feasibility of reduced intensity conditioning allogeneic hematopoietic stem cell transplant in older and more heavily pretreated patients with Fanconi anemia, especially for those who are engrafted.

Reduced intensity conditioning allogeneic hematopoietic stem cell transplantation in chronic lymphocytic leukemia (CLL) patients with the aberration of p53 gene

目的探讨减低强度预处理的异基因造血干细胞移植（RIC-allo-HSCT）治疗伴p53缺失的超高危慢性淋巴细胞白血病（CLL）的疗效及安全性，并提高allo-HSCT在CLL治疗中的认识。方法回顾性分析2012年7月至2014年1月进行同胞全相合供者RIC-allo-HSCT且伴p53缺失的4例超高危CLL患者资料，移植方式采用RIC方案，观察造血重建、移植相关并发症、总体生存（OS）、无进展生存（PFS）等临床指标。结果4例CLL患者中男3例，女1例，中位年龄56（49~61）岁。输注的中位单个核细胞（MNC）数为6.54（2.85~14.70）×108/kg，中位CD34+细胞数为5.81（2.85~7.79）×106/kg。4例患者移植后均获得快速而持久的造血重建，中性粒细胞和血小板植入时间分别为11（9~12）和5.5（0~11）d。造血重建后植活细胞嵌合鉴定证实3例为供者完全植入，1例为供受者混合植入。2例发生Ⅰ度急性移植物抗宿主病（GVHD），2例出现CMV感染，1例发生带状疱疹病毒及EB病毒血症，对症支持治疗后均好转；无移植相关死亡。中位随访时间为26.5（21~39）个月，3例完全缓解期行RIC-allo-HSCT的患者均无病生存，1例部分缓解期行移植的患者于移植后5个月发生疾病进展。结论伴p53缺失的超高危CLL患者对临床常规化疗敏感性差，生存期短；RIC-allo-HSCT对此类患者不良反应小并耐受性良好，临床缓解期长，值得进一步观察、推广。

Research progress of reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation in treatment of myelodysplastic syndrome

Allogeneic hematopoietic stem cell transplantation(allo-HSCT) is likely to be the optimum method to cure international prognostic scoring system (IPSS) intermediate and high-risk patients with myelodysplastic syndrome(MDS). However, patients suffered with MDS are usually too old to undergo myeloablative conditioning allogeneic stem cell transplantation(MAC-HSCT). On account of its advantages of higher efficiency and lower toxicity, reduced intensity conditioning allogeneic stem cell transplantation(RIC-HSCT) is widely applied in the treatment of MDS patients. Currently, fludarabine plus alkylating regimens are widely applied, but the clinical outcomes are different from each regimen. Although RIC-HSCT has unique advantages in treating intermediate and high-risk elder MDS compared with MAC-HSCT and non-HSCT therapy, whether the outcome is influenced by factors such as tumor burden, recipient age, IPSS risk stratification, type of allo-HSCT, and comorbidity before transplantation is still unclear. In this article, we review literatures on RIC-HSCT in treatment of MDS. Key words: Myelodysplastic syndrome; Transplantation conditioning; Hematopoietic stem cell transplantation

Antithymocyte Globulin (ATG) 4.5 Vs. 6.0 Mg/Kg in Reduced Intensity Conditioning (RIC) Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT)

Antithymocyte Globulin (ATG) 4.5 Vs. 6.0 Mg/Kg in Reduced Intensity Conditioning (RIC) Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT)

The Use of Busulphan As Compared to Melphalan in Combination with Fludarabine in the Reduced Intensity Conditioning Improves Overall Survival in Patients with Lymphoma

Background: While many studies have attempted to compare different GVHD prophylaxis within the reduced intensity conditioning allogeneic stem cell transplant setting (RIC SCT), few studies have been performed comparing different conditioning regimens. Due to the lack of evidence on the best RIC, the selection of the conditioning regimen is mainly based on the experience from each institution. In this study, we compared the outcomes of patients undergoing RIC SCT in 2 different settings: the Spanish Group of Transplantation (GETH), where fludarabine + melphalan (FluMel) has been the standard RIC in patients with lymphoid malignancies and Dana-Farber Cancer Institute/Brigham and Women's Hospital (DFCI/BWH), where fludarabine + busulphan (FluBu) is the standard RIC.Patients and methods: We analyzed the outcomes of 136 patients diagnosed with lymphoma undergoing RIC with either FluBu (n=61) or FluMel (n=75) in the GETH or at DFCI/BWH between 2007 and 2014. Patient characteristics are shown in table 1. The following variables were included into the multivariable analysis: type of conditioning, GVHD prophylaxis, type of donor, age, previous transplant, and disease risk index (DRI) based on diagnosis and disease status at transplant. Median follow-up was 36 months.Results: The cumulative incidence of grades 2-4 acute GVHD was 13% vs 36% among patients receiving FluBu vs FluMel, respectively (p=0.002). In multivariable analysis only the type of conditioning significantly influenced the risk of grades 2-4 aGVHD [HR with FluMel 7.35, (95% CI= 2.27-23.8), p=0.0008]. The cumulative risk of non-relapse mortality at 1 year was 3.3% vs 31% for FluBu vs FluMel, respectively (p<0.001). In multivariable analysis again only type of conditioning significantly influenced the risk of NRM [HR with FluMel 5.61, (95% CI= 1.57-20.03), p=0.007]. The 1y cumulative incidence of relapse was 29% with FluBu vs 10% with FluMel (p=0.08). In multivariable analysis, only prior transplantation and donor type were associated with the risk of relapse. The 3-year disease-free survival in patients receiving FluBu was 55%, vs 40% for those receiving FluMel (p=0.24). Only donor type was significant in the DFS in multivariable models. Finally, the 3y OS in the BuFlu group was 72% vs 50% for those receiving FluMel (p=0.01) (fig 1). Conditioning regimen was the only factor significantly associated with OS in multivariable analysis, HR with FluMel 2.87, (95% CI= 1.28-6.43), p=0.01].Conclusion: In this retrospective study of patients who received a RIC SCT for lymphoma, the use of FluBu as compared to FluMel was associated with a significant decrease in non-relapse mortality and an improvement in overall survival. Acknowledging the limitations associated a retrospective study, but in the absence of prospective randomized data, our results lend support to the choice of FluBu as a conditioning regimen in this setting.Table 1N= 136Flu-Bu (n= 61)Flu-Mel (n= 75)PSex (male)41 (67.2%)49 (65.3%)0.081Age42 (SD: 12.3)48.2 (SD: 12.3)0.073Diagnosis:- Hodgkin- NHL9 (14.8%) 52 (85.2%)26 (34.7%) 49 (65.3%)0.008Type of donor:- Related- Unrelated25 (41.0%) 36 (59.0%)36 (48.0%) 39 (52.0%)0.413Source of stem cells:-BM-PB-- 61 (100%)2 (2.7%) 73 (97.3%)0.502Dis status at trx:- CR- PR or active dis31 (50.8%) 30 (49.2%)38 (50.7%) 37 (49.3%)0.986GVHD prophylaxis:- CNI-MTX- SIRO-TKR42 (68.9%) 19 (31.1%)34 (45.3%) 41 (54.7%)0.006Cause of death:- GvHD- Infection- Relapse- Others3 (15.8%) 2 (10.5%) 12 (63.2%) 2 (10.5%)11 (28.9%) 8 (21.1%) 10 (26.3%) 9 (23.7%)0.114 [Display omitted] DisclosuresAntin:Gentium SpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Armand:BMS: Research Funding; Sequenta, Inc.: Research Funding; Merck: Consultancy, Research Funding; Infinity: Consultancy, Research Funding.

Post-Transplant Cyclophosphamide (PTCY) Versus Anti-Thymoglobulin (ATG) As Part of the Gvhd Prophylaxis for Fludarabine/Clofarabine/Busulfan Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT): Influence on Early Outcomes

Introduction: Recently, theuse of high-dose post-transplant cyclophosphamide (PTCY) has contributed to reconsider T-replete haplo-identical allo-SCT because of the lower incidence of severe graft-versus-host disease (GVHD) observed in patients. However, the influence of PTCY on early outcomes has been poorly studied so far, especially in comparison to the standard use of anti-thymoglobulin (ATG) as GVHD prophylaxis.Patients and Methods: This retrospective study was conducted at the University Hospital of Nantes with the aim to compare the incidence of early outcomes (engraftment, neutrophils and platelets recovery, viral infections (HHV-6, CMV, EBV, BKv, ADV), acute GVHD, relapse or deaths and day+100 non-relapse mortality (NRM)) between patients receiving either PTCY (n=30) or ATG (n=46) as part of GVHD prophylaxis for a RIC allo-SCT. In the PTCY group, RIC was the Baltimore regimen (Luznic, BBMT 2008) in 17 patients while 9 patients received clofarabine instead of fludarabine because of a myeloid malignancy and 4 patients a sequential approach. In this group, 6 and 24 patients received 1 or 2 days of PTCY, respectively, while donors were matched (sibling n=2, unrelated n=5) in 7 cases and haplo-identical in 23, respectively. All patients received cyclosporine + MMF with PTCY as GVHD prophylaxis. In the ATG group (2 days of ATG for siblings and 10/10, 3 days for 9/10), 13, 11 and 22 patients received respectively a FB2, FB3 or CloB2 RIC regimen (Chevallier, Haematologica, 2014). Donors were siblings in 18, matched unrelated in 23 and mismatched unrelated (9/10) in 5. GVHD prophylaxis was cyclosporine alone in case of sibling donors and cyclosporine +MMF for all other cases. The characteristics of both groups (PTCY vs ATG) were similar in terms of gender (male: 63% vs 54%), type of disease (myeloid: 67% vs 63%) and disease status at transplant (complete remission: 43% vs 67%). PTCY patients were significantly younger (median age: 55.5 vs 63 years, p=0.01) and had been previously allografted in a significantly higher proportion (40% vs 4%, p=0.003). Patients were transplanted between March 2012 and April 2015 and were considered up to day+100 post-transplant. All patients received peripheral blood stem cells as stem cell source except one patient in the PTCY group who received bone marrow.Results: All patients engrafted except one in the ATG group. The median time of neutrophils recovery was similar between both groups (PTCY 18 days vs ATG 19 days, p=0.9). Conversely, median time of platelets recovery was significant higher for the PTCY group (27 vs 13 days, p<0.0001). Median donor chimerism was significantly higher in the PTCY group at day +30 on whole blood (99.9% vs 99.1%, p=0.01), and at day +60 and +90/100 on CD3+ T cells (100% vs 95.4%, p<0.0001; and 100% vs 87.4%, p=0.0002, respectively). At day+100, PTCY and ATG patients shared similar rates of acute GVHD (20% vs 26%, grade 2-4: 13% vs 22%, p=0.7), relapses (3% vs 2.1%, p=0.7), deaths (3% vs 0%, p=0.7) and NRM (3% vs 0%, p=0.7). Also similar incidences of CMV (20% vs 37%, p=0.19), BKv (33% vs 19.5%, p=0.3) and ADV (7% vs 4%, p=0.9) infections were observed between both groups. Incidence of HHV-6 reactivations was higher in the PTCY group (53% vs 19.5%, p=0.7) while ATG patients developed significantly more EBV infections (79% vs 27%, p<0.0001). Interestingly, in the PTCY group, patients who were transplanted with a matched donor did not develop any HHV-6, CMV or ADV reactivation compared to 79% (p=0.004), 21% (p=NS) and 8% (p=NS) of the patients with haplo-identical donors, respectively. Also, among patients who received 1 day of PTCY, none developed HHV-6, CMV or BKv reactivation compared to 67% (p=0.007), 25% (p=NS) and 8% (p=NS), respectively, for the patients who received 2 days of PTCY.Conclusion: When considering early outcomes, PTCY is associated with a longer time to platelets recovery and higher early median donor chimerism compared to the use of ATG for GVHD prophylaxis after allo-SCT. The dosage of PTCY and type of donor when using PTCY may also influence the occurrence of viral infections. Prospective larger studies are warranted to confirm these results in the future. DisclosuresMoreau:Celgene, Janssen, Takeda, Novartis, Amgen: Membership on an entity's Board of Directors or advisory committees.

RIC Allogeneic Stem Cell Transplantation for High Risk CLL Followed By Preemptive MRD-Based Immunointervention - Intermediate Results from the Phase II ICLL03 Ricac-Pmm Trial (FILO & SFGM-TC French intergroup)

Introduction Reduced intensity conditioning (RIC) allogeneic stem cell transplantation (ASCT) remains a valuable and potentially curative strategy in high-risk CLL. Post-ASCT relapse remains an important (30-40%) cause of failure, predicted by persisting positive minimal residual disease (MRD) at 12m post-ASCT. ASCT is also associated with a toxic mortality and with the burden of chronic graft versus host disease (cGVHD). We evaluated the efficacy and safety of a preemptive immunointervention (PrIm) based on serial MRD assessment in high-risk CLL. (NCT01849939)Methods Main inclusion criteria were (1) EBMT criteria for ASCT, (2) CLL in PR/CR, (3) mass ≤5cm, (4) age ≤70, (5) SORROR score ≤2 and (6) HLA donor (10/10). RIC regimen included fludarabine 120 mg/m2, IV busulfan 6.4 mg/kg, rabbit ATG 5mg/kg and CsA prophylaxy. Centralized 10-color flow cytometry blood MRD was assessed before and at M1, M2, M3, M4, M5, M6, M9 and M12 post-ASCT. MRD[-] was defined by blood detection <10e-4 at 2 consecutive time-points, confirmed (if possible) on bone marrow aspiration. PrIm algorithm, applied from D30 to M12, considered IWCCL response criteria, blood MRD and GVHD occurrence/severity. PrIm comprised tutored CsA early (≤4-5m), standard (6m) or late (7m) tapering and discontinuation (T&D). Early CsA T&D was followed in case of failure to achieve MRD[-] by 1-3 increasing DLI doses (1, 5 or 10x10e6 CD3/kg). Primary end point was the rate of MRD[-] at M12. Chimerism was assessed in parallel on full blood and on sorted CD3+ cells and was not a part of PrIm decision.Results As of 2015, August the 1st, the 43 planned inclusions have been done. Before their last line prior to ASCT, pts had: (a) presence of a del(17p) in 1st line (n=24) or in relapse (n=3), (b) absence of del(17p) but relapse ≤2y post fludarabine-based combination (n=14) or post-autologous transplantation (n=1). At time of transplantation, 11/43 (26%) had achieved CR, 28/43 (65%) had achieved PR, 2/43 (5%) had SD with 2 unknown status. Six patients had undetectable MRD (limit of detection: 5x10-6). For the 37 other patients, the median pre-ASCT MRD level was 2.35%(0.014 to 70%).The results of these 43 pts will be available in December 2015. This abstract describes the outcome of the 30 first consecutive pts including 26 pts evaluable [alive with ≥12m post-ASCT follow-up] and 4 pts non evaluable [death at M10 (n=1; sepsis) and at M8 (n=1 GVHD), EBV induced lymphoproliferation (n=1) and immediate graft rejection (n=1)], all included in the ITT analysis. In the 29 pts with full engraftment, the full blood chimerism at 3m and 12m was 99.1[62.1 ;99.8] and 99.5[59.4 ;99.9], and the T-cell specific chimerism was 99.2[5.2;99.8] and 99.6[21.1;99.8], with 30% and 25% >95% donor derived CD3+ cells respectively. MRD evolution followed different patterns (Table 1). At the M3 checkpoint, among evaluable patients, 10 were already MRD[-], and 16 were still MRD[+]. Then 10 pts became MRD[-] and 6 remained MRD[+]. This approach achieved 67% blood MRD[-] at M12 (ITT). When early CSA T&D had failed DLI done in 6 pts did not achieve MRD negativity. Finally, 6 pts (20%) remained MRD[+] at 12m.At 12m FU, the rate of Gr≥2 aGVHD was (11/30) 37% (consecutive to early CsA T&D in 2 pts and to early CsA T&D followed by DLI in 1 pt) and the rate of extensive cGVHD was (5/29) 17% (consecutive to CsA T&D in 1 pt). Hence we observed the occurrence of Gr≥2 aGVHD and extensive cGVHD in 2/8 and 1/8 pts after early CsA T&D. We also observed one case of Gr≥2 aGVHD among the 6 pts who had early CsA T&D followed by DLI. Eighteen severe adverse events were reported, including the 2 aforementioned deaths. These events were not related to the study procedure (PrIm).Discussion These preliminary data highlight the feasibility, safety and efficacy of a standardized PrIm strategy in high-risk CLL. As DLI appears to have limited impact when CsA T&D fails, the preemptive use of new agents should be considered at this point for persistent MRD[+] after 3-6m post-ASCT.Table 1Table 1M12 MRDN%MRD[-] pre-ASCT remaining MRD[-][-]27MRD[+] (M1-2) spontaneously translating to MRD[-] within 3m[-]827MRD[+] (M1-3) translating to MRD[-] after early CsA T&Dconcomitant of severe GVHD (≥G2 aGVHD and/or ext cGVHD)[-]108233MRD[+] (M1-3) remaining MRD[+] despite early CsA T&D followed by DLIdespite early CsA T&D, transient MRD[-], relapse and DLI[+]65120Non evaluable: toxic deaths (2), EBV LPD (1), graft rejection (1)NE413 DisclosuresTournilhac:GSK: Other: Travel Support, Research Funding; Mundiphrama: Honoraria, Other: Travel Support, Research Funding; Celgene: Other: Travel support; Roche: Other: Travel support, Research Funding; Janssen Cilag: Honoraria, Other: Travel support; Gilead: Other: Travel Funding.

Comparison of Two Doses of Antithymocyte Globulin (ATG) in Reduced Intensity Conditioning (RIC) Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT)

Introduction: The appropriate dose of antithymocyte globulin (ATG) to be used in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) is yet to be determined. In our previous retrospective analysis we compared two dosing schedules of ATG (7.5 mg/kg vs 6 mg/kg) in 136 patients who had undergone RIC allo-HSCT, and found no significant differences in the incidence of acute or chronic graft-versus-host disease (GVHD), non-relapse mortality (NRM), relapse, progression-free survival (PFS) or overall survival (OS). As of October 2013, our ATG dosing was lowered from 6.5 to 4.5 mg/kg. We now compare the outcomes of patients who received ATG at a dose of 4.5 mg/kg (r-ATG) to 6 mg/kg (R-ATG)Methods: We retrospectively analyzed the outcomes of patients who underwent unrelated or mismatch related RIC allo HSCT for hematologic malignancies and received r-ATG (40 patients) vs R-ATG (216 patients) at The Ohio State University Comprehensive Cancer Center between October 2007 and September 2014. Cumulative incidences of GVHD, infection, NRM, and relapse were analyzed using Gray's test, accounting for competing risks. PFS and OS were analyzed using the log-rank test.Results: Patients with hematologic malignancies included AML/MDS (53%), NHL/Hodgkin's (19%), CLL (12%), and other hematologic malignancies including ALL (16%). There was a significant association between disease group and ATG dose (p<0.001), with none of the patients diagnosed with CLL receiving r-ATG and a higher percentage of those with other malignancies receiving r-ATG vs R-ATG than expected. Secondary to the imbalance in disease groups, those receiving r-ATG were younger (median 50 vs 59 yrs, p=0.01) and more likely to have bone marrow stem cell source (18% vs 5%, p=0.008). There were no significant differences in recipient or donor sex, degree of HLA match, prior autografts, comorbidity index, donor/recipient CMV status and CD34 cell dose between the two groups. The cumulative incidences of acute GVHD grade II-IV at day 180 in the r-ATG and R-ATG groups were 63% and 44% (p=0.009), and of grade III-IV 18% and 11% (p=0.25) respectively (Figure 1A and B). When controlling for differences in underlying disease, the estimated risk of acute GVHD grade II-IV was 1.6 times higher with r-ATG (p=0.04). The respective cumulative incidences at 6 months of chronic GVHD were 14% and 16% (p=0.65), and of extensive chronic GVHD 14% and 13% (p= 0.29). With limited follow-up in patients receiving r-ATG (median 10 months), significant differences were not observed in longer-term outcomes between the two groups including relapse rate (p=0.83), NRM (p=0.91), PFS (p=0.92), and OS (p=0.996). The incidence of CMV reactivation at day 180 was lower in the r-ATG group (5% vs 26%, p=0.005), though the incidence of competing risks including GVHD, relapse and death prior to documented reactivation was higher in the r-ATG group (p<0.0001). No statistically significant differences were seen in Epstein-Barr virus reactivation (p=0.74), BK-virus associated hemorrhagic cystitis (p=0.79), bacterial infections (p=0.11), or Clostridium Difficile infections (p=0.22).ConclusionsWhile there was an increase in grade II-IV acute GVHD with r-ATG, there was no significant difference in acute GVHD grade III-IV, relapse, NRM, PFS and OS between the two cohorts. r-ATG resulted in a lower proportion of CMV reactivation, but in a higher proportion of other competing risks. Given the increasing use of RIC allo-HSCT for treating malignant hematologic conditions, the correct dose and schedule of ATG administration should be defined by prospective randomized controlled trials. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Efficacy of immune suppression tapering in treating relapse after reduced intensity allogeneic stem cell transplantation.

For patients who relapse after allogeneic hematopoietic stem cell transplantation while still on immune suppression, there is anecdotal evidence that tapering the immune suppression may result in graft-versus-tumor activity. We reviewed the medical records of all patients with documented histological or radiographic disease recurrence within 1 year of stem cell transplantation while on immune suppression at our institution. The median time to relapse was 110 days (range, 18-311) after transplant. Among 123 patients with relapse treated with immune suppression tapering without chemotherapy, radiation, or donor lymphocyte infusion, 34 responded (33/101 reduced intensity conditioning transplant and 1/22 myeloablative conditioning transplant, 32.7% and 4.5% respectively; P=0.007). The median time to response after initiation of immune suppression tapering was 82 days (range, 16-189). Thirty-three patients (97.1%) had development or progression of acute or chronic graft-versus-host disease as a consequence of immune suppression tapering, at a median time of 39 days (range, 16-98). Six patients subsequently relapsed late after initial response to immune suppression tapering at a median time of 2 years (range, 0.9-3.8). The median overall survival from immune suppression tapering for responders was 5.1 years (range, 1.9-not estimable). When clinically feasible, immune suppression tapering alone in patients who relapse early after reduced intensity conditioning allogeneic stem cell transplantation can produce durable remissions, but is almost always associated with graft-versus-host disease.

Alemtuzumab As Pre-Conditioning Is Safe and Feasible in Patients with T-Cell Lymphoid Neoplasms Undergoing Allogeneic Stem Cell Transplantation

▪Background: In vivo T-cell depletion with Alemtuzumab reduces the incidence of acute and chronic graft-versus-host disease (GvHD) and graft failure, yet it results in an increase of opportunistic infections and delayed immune recovery. In addition, Alemtuzumab has considerable anti-lymphoma activity in T-cell neoplasms.We report on a pilot study analysing the safety and feasibility of Alemtuzumab as pre-conditioning prior to reduced intensity conditioning allogeneic stem cell transplantation (RIC-alloSCT) in patients diagnosed with T-cell non-Hodgkin lymphoma.Methods: Six consecutive patients diagnosed with a T-cell lymphoid malignancy underwent RIC-alloSCT from a HLA-identical sibling (n=5) or a matched unrelated donor (n=1). Diagnosis were Angioimmunoblastic T-cell lymphoma (n=3), hepato-splenic gamma-delta T-cell lymphoma (n=1), T/NK cavum lymphoma (n=2) and Sèzary Syndrome (n=1). All received unmanipulated peripheral blood stem cells; At transplantation 2 patients were in CR, and 4 in PR. Median number of prior regimens was 2 (range 2-5). Conditioning regimen included Fludarabine (5 x 30mg/m2) and Melphalan (2 x 70mg/m2) in all cases. GvHD prophylaxis comprised Cyclosporine A and Methotrexate.The pre-conditioning protocol consisted on 6 escalating doses of intravenous Alemtuzumab starting on day -28 (3 mg on day -28, 10 mg on day -26 followed by four doses of 30 mg on days -24 to -17) given 3 times a week (MWF) on an out-patient basis.Results: Five patients received all six doses of Alemtuzumab as planned whereas one patient received only four doses for logistic reasons related to donor availability. Acetaminophen, Hydrocortisone and Dexchlorpheniramine were administered as pre-medication in all cases with no severe infusional reaction observed. There were no delays in proceeding to SCT conditioning and patients develop no infectious complications during the Alemtuzumab - alloSCT interval.All patients engrafted with a median time to neutrophil engraftment of 23 days (range 14-27). Acute skin GvHD (grade I and III) was observed in 2 patients (33.3%), both obtaining a CR with topical and systemic corticosteroids respectively. Two patients developed mild ocular chronic GvHD (one after subsequent infusions of donor lymphocytes - DLI) but none has suffered from extensive chronic GvHD. No opportunistic infection was observed apart from CMV reactivation that developed in 3 out of 4 seropositive patients (no CMV disease was observed). All patients experienced delayed immune reconstitution (CD4 >200/ul) at a median of 321 days (range 229-518). All 4 patients in PR prior to alloSCT achieved a complete remission. Only one patient (diagnosed with Sèzary Syndrome) experienced a relapsed and responded to DLI. With a median follow-up of 42 months, all patients remain alive and in CR.Conclusions: Our preliminary results suggest that administration of Alemtuzumab prior to reduced intensity conditioning is feasible and safe. In addition to providing T-cell depletion, Alemtuzumab may improve the response rate in T-cell lymphoid malignancies without increasing the risk of infectious complications. These results require further validation in larger phase II studies. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Similar Outcome Using Sibling, Unrelated Donor, and Cord Blood Grafts after Reduced-Intensity Conditioning in Children: A Retrospective Study from the SFGM-TC

Reduced intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) is increasingly used in children, especially in those who have been heavily pre-treated or who have received prior autologous or allo-SCT. Of note, use of cord blood as stem cell source is currently a standard of care in pediatric patients lacking a sibling or an unrelated donor. Currently, comparison between matched siblings (SIB), unrelated donors (URD), or umbilical cord blood (UCB) allo-SCT has not yet been reported in the RIC setting in children.Here, we compared reduced-intensity conditioning allo-SCT performed between January 1998 and December 2012 in 124 consecutive children (<18 years) with a median age of 12.8 years (males, n=69). Disease included acute leukemia (n=78), myelodysplastic syndrome (MDS)/myeloproliferative disorder (MPD)/chronic myeloid leukemia (CML) (n=22) and lymphoma (n=24). Status at transplant were as follows: complete remission (CR), n=84, (CR1 n=22, CR2 n=35, CR3 n=20, missing n=7); partial response n=6; primary induction failure n=8; relapse or progression n=19, up-front (MDS) n=2, chronic phase (CML) n=2, missing n=3. Twenty-five patients had received a previous auto-SCT and 44 a previous allo-SCT. Clinical data were prospectively collected using ProMISe (Project Manager Internet Server), an internet-based data registry system shared by all SFGM-TC centres. Type of donor included SIB (n = 32), URD (n = 56), or UCB (n = 36, single n=23; double n=13). The three groups were well balanced in terms of gender, diagnosis, status at transplant, median follow-up, previous transplant status, median time interval between disease diagnosis and allo-SCT, period of transplant, patients aged < or >= 10 years at time of transplant. Regarding RIC regimen, fludarabine and iv busulfan was the most commonly used regimen for SIB and URD cases while it was fludarabine + low-dose total body irradiation (Minneapolis approach) for UCB patients. The use of in-vivo T cell depletion (ATG) was significantly less frequent in the UCB group (16.7% vs 53.1% (SIB) vs 66.1% (URD), p<0.0001). Considering the whole cohort, cumulative incidence of engraftment was 81.4%. With a median follow-up of 49 months (range: 7-163), 5-year overall (OS) and disease free (DFS) survival rates were 40% (31-50) and 39% (31-48), respectively. 5-year cumulative incidences of relapse (RI) and non-relapse mortality (NRM) were 43% (34-52) and 17% (11-24), respectively, while 2-year incidence of chronic GVHD was 20% (12-29).Engraftment rates were similar between the three groups: 93.3% (SIB) vs 86.8% (URD) vs 77.1% (UCB), p=0.10. The 5-year cumulative incidences of NRM were 13%, 18%, and 19% with SIB, URD, and UCB transplantation, respectively (p=0.73). The 5-year DFS rates were 42% (24-59), 36% (23-48), and 43% (27-60) with SIB, URD, and UCB transplantation, respectively (p=0.70). The 5-year OS rates were 40% (22-59), 40% (27-53), and 38% (17-60) with SIB, URD, and UCB transplantation, respectively (p=0.94). Finally, grade 2-4 acute GVHD and 2-year incidence of chronic GVHD were similar between the three groups: 29.6% (SIB) vs 32.1% (URD) vs 38.2% (UCB), p=0.75; and 10% (SIB) vs 23% (URD) vs 24% (UCB), p=0.51.In multivariate analysis, donor type had no significant impact on overall survival (SIB vs URD, HR: 1.19; 95%CI: 0.61-2.33, p=0.61; SIB vs UCB, HR: 1.28; 95%CI: 0.69-2.37, p=0.43) while a diagnosis of MDS/MPD/CML was independently associated with better OS (HR: 2.49; 95%CI: 1.17-5.29, p=0.02).In conclusion, despite evident limitations due to the retrospective setting of this study, results from this national survey support the recommendation to consider any stem cell source (SIB donor, URD, or UCB) in children candidate for a RIC allo-SCT. DisclosuresBeguin:Amgen: Consultancy, Speakers Bureau; Vifor: Consultancy, Speakers Bureau.

Split Mixed Donor Chimerism Early after T-Cell Depleted Reduced Intensity Conditioned Allogeneic Haematopoietic Stem Cell Transplantation Predicts Survival

▪The significance of mixed donor chimerism as a hallmark of an unsuccessful graft versus leukaemia effect and disease relapse is unclear. Whilst some studies have described changes in PBMC and T cell chimerism that may predict relapse, patients at high risk are not identifiable at a stage to permit early intervention.In this retrospective study, the prognostic impact of early “split” PBMC and T cell chimerism in 212 patients who underwent T cell depleted RIC-SCT at 2 UK centers is described. 118 and 94 patients were transplanted using PBMC grafts from matched unrelated or sibling donors respectively. 169 received fludarabine and melphalan, 24 other fludarabine containing regimes, 17 BEAM, and 2 TLI. 203 underwent TCD with alemtuzumab, whilst 9 received ATG. Overall survival by day 3773 days post-SCT was 67.1%, and relapse-free survival was 58.9%. 28.7% experienced acute GvHD (grade 2 or above), and 22.8% developed chronic GvHD.Patients were grouped according to percentage donor PBMC and T cell chimerism at a median of 49 days post SCT (25% and 75% percentiles, 31 and 61 days respectively). 68 Patients exhibited “split” chimerism (SC) in whom PBMC chimerism was >99%, but T-cell chimerism <98%. SC patients demonstrated comparable overall survival to the 81 patients with full donor chimerism (FC) in whom both haematopoietic compartments displayed donor chimerism >99% (HR 1.36, 95% CI 0.697 - 2.638, log-rank p= 0.3698). In contrast, 63 patients with chimerism of <98% in both compartments (MC) exhibited significantly worse overall survival, than the SC cohort (HR 2.10, 95% CI 1.13 - 3.92, log-rank p=0.019). Of that MC cohort, those entering HSCT with intermediate or high risk disease had 3 times the relative risk of relapse compared to MC patients with low risk disease.Multivariate analysis confirmed the predictive value of early SC versus MC status.Despite differences in overall survival SC and MC patients displayed comparable relapse free survival. It was therefore hypothesised that SC patients experienced improved OS compared to MC patients by responding to donor lymphocyte infusion (DLI). In this cohort, 11 original FC, 28 SC, and 33 MC patients underwent DLI at medians of 808, 325 and 227 days post SCT respectively. There were no differences between the groups in the proportion of patients receiving DLI for molecular relapse versus the presence of residual host haematopoiesis. SC patients displayed significantly improved OS after DLI than MC patients (HR 0.37 95% CI 0.15 - 0.91, log-rank p= 0.03), where all deaths were due to disease.To conclude, this is the first study to show that early “split” chimerism post SCT predicts overall survival after HSCT in a T deplete setting, and identifies patients with mixed PBMC and T cell donor chimerism at day 50 to be at significantly greater risk of relapse. This data supports a rationale to intervene early in MC patients post SCT, particularly those with an intermediate or high pre-SCT disease risk. Work to elucidate targetable mechanisms is underway. DisclosuresNo relevant conflicts of interest to declare.

Lifting the mantle: Unveiling new treatment approaches in relapsed or refractory mantle cell lymphoma

The management of relapsed/refractory mantle cell lymphoma (MCL) remains a clinical challenge. A standard second-line treatment for relapsed/refractory MCL does not exist. Management of relapsed/refractory MCL requires an individualized treatment approach, incorporating factors such as: functional status, prior treatments, response to prior therapies, and disease biology. Generally, there are two categories of salvage therapy; the first, non-cross-resistant cytotoxic chemotherapeutic agents and, the second, pathway-targeted agents. For transplant eligible patients, the optimal therapy usually consists of salvage, remission re-induction phase followed, whenever possible, by a consolidation phase. Bendamustine and/or high dose cytarabine plus rituximab based chemotherapy represent the most common salvage therapy with an overall response rate of 70–80%. Consolidation with a reduced intensity conditioning allogeneic stem cell transplantation represents the only potentially curative treatment. Overall survival ranges from 30% to 50% at 5years with this approach. For transplant ineligible patients, ibrutinib is the most effective treatment with an overall response rate of almost 70% and median response duration of 17.5months. Lacking an effective consolidation, this approach is not considered curative. In this review we characterize the main therapeutic approaches available in this setting and summarize our preferred clinical treatment approach.

Geriatric assessment before reduced intensity conditioning allogeneic hematologic stem cell transplantation in elderly patients

Introduction: A growing number of patients with hematological malignancies over the age of 65 years are considered for more intensive treatment. Elderly patients represent a heterogeneous population in which the decision to proceed to a reduced intensity conditioning allogeneic hematologic stem cell transplantation (RIC-AHSCT) is often difficult to assess because of more comorbidities and frailty. Objectives: The present studydescribes a population of patients older than 65 years who received a geriatric assessment before a RIC-AHSCT. Methods: During 2013 we have systematically carried out geriatric consultations, usingwell-validated international scales for elderly patients whowere considered for RIC-AHSCT by the transplant physician. Patients were evaluated before the start of the conditioning regimen by functional ability (ADL, IADL), nutritional status (weight loss, Mini Nutritional Assessment, albuminemia), socio environmental circumstances, cognition and mental health (minCOG and/or Mini Mental State Examination), mobility and pain. Comorbidities were also listed for each patient. Results: From February to December 2013, 28 patients over the age of 65 years (19 men, 9 women) with a median age of 68.5 years (range 65– 73 years) were considered for RIC-AHSCT. All patients had hematological malignancieswithmostly diagnoses of acute leukemiamyeloproliferative and myelodysplastic syndromes and were evaluated by a geriatric physician. The geriatric assessment resulted in functional disability in 28.6%of patients,malnutrition in 46%of patients anda risk ofmalnutrition in 25% of patients, a socio environmental risk in 18% of patients, cognitive impairment in 3.6% of patients and suspicion of cognitive impairment in 14% of patients, mobility impairment in 35% of patients, pain in 25% of patients, and thymic disorders in 35.7% of patients. Conclusion: In our knowledge, this is the first study that evaluates elderly patients who pretend to RIC-AHSCT. In this descriptive study 75% of patients with hematological malignancies considered for RIC-AHSCT were fit, 18% were vulnerable and 7% were frail. Up to now, for our knowledge the geriatric assessment has no impact on the decision of the transplant physician. With regard to the growing age of patients, the advances in treatment and supportive care will need a better collaboration between geriatrician and hematologist to optimize patient care. Further studies are necessary to assess the impact of geriatric assessment before RIC-AHSCT. Disclosure of interest: None declared.

Prediction of non-relapse mortality in recipients of reduced intensity conditioning allogeneic stem cell transplantation with AML in first complete remission.

Non-relapse mortality (NRM) after allogeneic hematopoietic stem cell transplantation (alloHSCT) can be predicted by the hematopoietic cell transplantation comorbidity index (HCT-CI) and the European Group for Blood and Marrow Transplantation (EBMT) score, which are composed of different parameters. We set out to integrate the parameters of both scores in patients with acute myeloid leukemia (AML) in first complete remission (CR1) receiving reduced intensity conditioning (RIC) alloHSCT. All parameters from the HCT-CI and the EBMT-score with the addition of patient and donor cytomegalovirus serology were evaluated in 812 patients by multivariable analysis with end-point NRM at 2 years. Subsequently, 16 parameters were selected based on hazard ratio >1.2, and were incorporated into a novel score, which was further internally validated by bootstrapping. Both the HCT-CI and the EBMT-score showed relatively weak predictive value, whereas the integrated score allowed to identify three clearly distinct risk groups with 2-year NRM estimates of 8±2% (low-risk), 17±2% (intermediate-risk) and 38±4% (high-risk), which also translated in prediction of overall survival. Collectively, integration of the most dominant parameters from the HCT-CI and the EBMT-score allowed to develop a simple and robust, integrated score with improved prediction of NRM for AML patients proceeding to RIC alloHSCT in CR1.