Pretransplant Therapy Research Articles

Allogeneic hematopoietic cell transplantation is an effective treatment for patients with Richter syndrome: A systematic review and meta-analysis

Efficacy of conventional chemoimmunotherapy is limited in patients with Richter syndrome (RS) with anticipated median overall survival (OS) of less than 10 months. Allogeneic hematopoietic cell transplantation (allo-HCT) is commonly offered as a consolidative treatment option in RS. To our knowledge, there are no randomized controlled studies that have compared allo-HCT against other therapies in RS; available allo-HCT data are limited to small case series from single-institution or registry studies. We performed a systematic review and meta-analysis to assess the totality of evidence regarding the efficacy (or lack thereof) of allo-HCT for RS. We extracted data on post-allograft outcomes related to benefits (overall response rate [ORR], complete remission [CR], OS, and progression-free survival [PFS]). For harms, data were extracted on non-relapse mortality (NRM) and relapse post-allografting. Our search strategy identified 240 studies, but only four studies (n = 72 patients) met our inclusion criteria. Pooled ORR, CR, OS, and PFS rates were 79%, 33%, 49%, and 30%, respectively. Pooled NRM and relapse rates were 24% and 28%, respectively. Results of this systematic review and meta-analysis indicate that allo-HCT yields encouraging OS in RS, thus remaining a reasonable treatment option in fit patients whose disease demonstrates a chemosensitive response to pre-transplant salvage therapies. Novel strategies are certainly needed to reduce the risk of relapse to further improve outcomes in these patients.

Impact of Treatment Prior to Allogeneic Transplantation of Hematopoietic Stem Cells in Patients with Myelodysplastic Syndrome: Results of the Latin American Bone Marrow Transplant Registry.

It has been suggested that bridging therapy with intensive chemotherapy and/or hypomethylating agents followed by hematopoietic stem cell transplantation (HSCT) can be valuable in the treatment of patients with myelodysplastic syndromes (MDS). However, the influence of this approach on HSCT outcomes remains poorly defined. Therefore, our objective was to investigate the influence of treatment before HSCT in patients with MDS. We retrospectively analyzed data from the Latin American registry of 258 patients from 17 Latin American centers who underwent HSCT from 1988 to 2019. Our data showed that there was pre-HSCT. We detected no significant difference regarding the impact on overall survival of treated and untreated patients before HSCT. Despite these data, the type of previous treatment among treated patients showed a significant difference in overall survival. Treatment with hypomethylating agents together with pre-HSCT chemotherapy seems to result in better survival of the studied population. These data correspond to the first results obtained through cooperative work between various centers in Latin America comparing the different approaches to patients and reflecting their reality and challenges. Therefore, the selection of pretransplant bridge therapy should be analyzed and focus given primarily to those approaches that result in better survival of patients with MDS.

3:36 PM Abstract No. 302 Effect of bridging locoregional therapy on hepatic arterial complications following liver transplant: 3-year, multicenter, retrospective analysis of 608 patients

Recent studies have suggested a relationship between intra-arterial therapy and the development of HAS following orthotopic liver transplant (OLT). This study evaluates the role of pretransplant locoregional therapies on post-OLT HAS. An IRB-approved, multicenter, retrospective analysis was performed on all patients who underwent liver transplant from January 2, 2016, to December 30, 2018 (n = 608). Patients undergoing locoregional therapy were identified, which was determined based on consensus review of a multidisciplinary liver conference for patients with hepatocellular carcinoma (HCC) and included DEB-TACE (100-300μ LC Beads mixed with doxorubicin), Yttrium radioembolization segmentectomy (TheraSphere), and thermal ablation. Additional treatments were performed as deemed necessary, based on incomplete response, with the majority of patients (n = 96) receiving 1-2 treatments. Patients were surveyed with doppler ultrasound at 1 day, 1 week, 1 month, and 3 months following orthotopic liver transplant (OLT). HAS was suspected based on findings of elevated hepatic artery velocity with downstream intrahepatic artery tardus parvus waveforms and low resistive indices and confirmed angiographically in all patients. Of the 608 patients who were transplanted during the 3-year cohort, 145 patients had HCC, and intra-arterial bridging therapy was performed on 126 patients (115 TACE, 5 Y90, and 6 TACE and Y90). Following OLT, 78 patients (13%) developed HAS. Fewer rates of HAS were noted in patients with HCC (12/145 [8.3%] vs. 66/463 [14.3%], P = 0.05). Similarly, fewer rates of HAS were encountered in patients bridged with intra-arterial therapy (10/126 [8%] vs. 68/482 [14.1%], P = 0.06). Additionally, patients who were treated with thermal ablation prior to liver transplant also had lower rates of HAS (1/24 [4%] vs. 77/584 [13%], P = 0.03). However, MELD scores at the time of liver transplant were associated with the development of HAS (P = 0.001). Intra-arterial therapy is not associated with the development of HAS following OLT; however, underlying liver disease appears to be associated with the development of HAS.

Reduced-intensity haploidentical peripheral blood stem cell transplantation using low-dose thymoglobulin for aggressive adult T cell leukemia/lymphoma patients in non-complete remission

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has been accepted as a treatment option for aggressive (acute or lymphoma type) adult T cell leukemia/lymphoma (ATLL) patients with a poor prognosis, when a suitable HLA-matched donor is not available. However, haplo-HSCT carries a potential risk of treatment-related mortality including severe graft-versus-host disease (GVHD). Therefore, we conducted a prospective pilot study in order to evaluate the efficacy and safety of reduced-intensity haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with low-dose thymoglobulin (2.5 mg/kg only on day −2), fludarabine, melphalan, and total body irradiation 4 Gy for aggressive ATLL. Three consecutive acute type ATLL patients, who were ineligible for conventional myeloablative conditioning due to advanced age or comorbidities, were enrolled. One patient received pretransplant mogamulizumab therapy. All the patients were not in complete remission (CR) at the time of transplantation. Our transplantation protocol was safely carried out. CR was achieved in all the patients after transplantation. HTLV-I viral loads became undetectable after transplantation. No severe adverse events such as grade III-IV GVHD or viral/fungal diseases were observed. At a follow-up of 2 years, they were still in CR. However, T cell receptor repertoire diversities were low 1 year after transplantation in next-generation sequencing. Our results show encouraging therapeutic benefits of this pilot approach using reduced-intensity haplo-PBSCT with low-dose thymoglobulin for aggressive ATLL patients.

Self-Reported Changes in the Expanded Disability Status Scale (EDSS) Score in Persons with Multiple Sclerosis after Autologous Stem Cell Transplants: Experience with the “Mexican Method”

<h3>Background</h3> Persons with multiple sclerosis (MS) are sometimes treated with high-dose immune suppressive or cytotoxic drugs and an autotransplant. Therapy-related mortality (TRM) has decreased to <2% because of less intensive pretransplant regimens and better subject selection. Trials have reported a greater proportion of subjects with no evidence of active disease in subjects receiving high-dose therapy and an autotransplant compared with controls. Recent autotransplants use less intensive pretransplant therapy with seemingly similar efficacy and fewer adverse events. We previously reported autotransplants for several haematologic neoplasms can be done in an outpatient setting using refrigerated blood cells. We now report data from 739 subjects with MS receiving autotransplants in an outpatient setting using refrigerated blood cells. <h3>Methods</h3> 739 consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells, on an outpatient basis and conditioning with cyclophosphamide and rituximab (Figure 1). The protocol was registered in ClinicalTrials.gov identifier NCT02674217. Eligibility criteria included all the following: Karnofsky performance score >70%, extended Disability Status Scale (EDSS ≤8 in the 2 w pretransplant), CNS magnetic resonance image (MRI) ≤3 mo pretransplant, no prior bone marrow toxic drugs, normal heart, liver, lung and kidney function, ≥6 mo since exposure to immune suppressive drugs. <h3>Results</h3> 495 females and 244 males were included; median age was 47 years. 310 patients presented with relapsing remitting MS (RRMS), 273 with secondary progressive (SPMS) and 156 with primary progressive (PPMS). All procedures were started on an outpatient basis and only 31 persons needed to be admitted to the hospital during the procedure. In order to obtain at least 1 × 106/Kg viable CD34 cells, one to three apheresis were performed. Total number of viable CD34+ cells infused ranged between 1 and 37.83 × 106/Kg. Patients recovered above 0.5 × 109/L absolute granulocytes on day 8 whereas platelet recovery above 20 × 109/L on day 4. Seven individuals required red blood cells and eight needed platelet transfusions. There were two transplant related deaths and the 30-month overall survival of the patients is 99.7%. All patients had a significant drop in the EDSS 12 and 18-mo after the transplant. The response rate (either drop or stabilization of the EDSS score) were at 12 and 18 months respectively: 85 and 88% for RRMS; 75 and 84% for PPMS and 79 and 85% for SPMS (Figure 2). <h3>Conclusions</h3> Changes in the EDSS score consonant with neurological improvement were observed in persons with all types of MS after HSCT employing the "Mexican method".

Prognosis of Split Liver Transplantation Compared with Whole Liver Transplantation in Adult Patients: Single-center Results under the Korean MELD Score-based Allocation Policy.

BackgroundSplit liver transplantation (SLT) has been occasionally performed in Korea. This study compared the incidence and prognosis of SLT with whole liver transplantation (WLT) in adult patients.MethodsBetween June 2016 and November 2019, 242 adult patients underwent a total of 256 deceased donor liver transplantation operations. SLT was performed in 7 patients (2.9%).ResultsThe mean age of SLT donors was 29.7 ± 7.4 years, and the mean age of recipients was 55.7 ± 10.6 years, with the latter having a mean model for end-stage liver disease score of 34.6 ± 3.1. Mean split right liver graft weight was 1,228.6 ± 149.7 g and mean graft-recipient weight ratio was 1.97 ± 0.39. Of the seven SLT recipients, Korean Network for Organ Sharing (KONOS) status was one in status 1, one in status 2 and five in status 3. The graft (P = 0.72) and patient (P = 0.84) survival rates were comparable in the SLT and WLT groups. Following propensity score matching, graft (P = 0.61) and patient (P = 0.91) survival rates remained comparable in the two groups. Univariate analysis showed that pretransplant ventilator support and renal replacement therapy were significantly associated with patient survival, whereas KONOS status category and primary liver diseases were not. Multivariate analysis showed that pretransplant ventilator support was an independent risk factor for patient survival.ConclusionSurvival outcomes were similar in adult SLT and WLT recipients, probably due to selection of high-quality grafts and low-risk recipients. Prudent selection of donors and adult recipients for SLT may expand the liver graft pool for pediatric patients without affecting outcomes in adults undergoing SLT.

Allogeneic hematopoietic stem-cell transplantation for myelofibrosis.

Myelofibrosis is one of the Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms with heterogeneous clinical course. Though many treatment options, including Janus kinase (JAK) inhibitors, have provided clinical benefits and improved survival, allogeneic hematopoietic stem-cell transplantation (AHSCT) remains the only potentially curative therapy. Considering the significant transplant-related morbidity and mortality, it is crucial to decide who to proceed to AHSCT, and when. In this review, we discuss recent updates in patient selection, prior splenectomy, conditioning regimen, donor type, molecular mutation, and other factors affecting AHSCT outcomes. Relapse is a major cause of treatment failure; we also describe recent data on minimal residual disease monitoring and management of relapse. In addition, emerging studies have reported pretransplant therapy with ruxolitinib for myelofibrosis showing favorable results, and further research is needed to explore its use in the post-transplant setting.

Pretransplant dialysis modality and long-term patient and kidney allograft outcome: a 15-year retrospective single-centre cohort study.

Among factors determining long-term kidney allograft outcome, pretransplant renal replacement therapy (RRT) is the most easily modifiable. Previous studies analysing RRT modality impact on patient and graft survival are conflicting. Studies on allograft function are scarce, lack sufficient size and follow-up. We retrospectively studied patient and allograft survival together with allograft function and its decline in 2277 allograft recipients during 2000-2014. Pretransplant RRT modality ≥60days as grouped into "no RRT" (n=136), "haemodialysis (HD)" (n=1847), "peritoneal dialysis (PD)" (n=159), and "HD+PD" (n=135) was evaluated. Kaplan-Meier analysis demonstrated superior 5-/10-/15-year patient (93.0/81.8/73.1% vs. 86.2/71.6/49.8%), death-censored graft (90.8/85.4/71.5% vs. 84.4/75.2/63.2%), and 1-year rejection-free graft survival (73.8% vs. 63.8%) in PD versus HD patients. Adjusted Cox regression revealed 34.5% [1.5-56.5%] lower hazards of death, whereas death-censored graft loss was similar [HR=0.707 (0.469-1.064)], and rejection was less frequent [HR=0.700 (0.508-0.965)]. Allografts showed higher 1-/3-/5-year estimated glomerular filtration rate (eGFR) in "PD" versus "HD" groups. Living donation benefit for allograft function was most pronounced in groups "no RRT" and "PD". Functional allograft decline (eGFR slope) was lowest for "PD". Allograft recipients on pretransplant PD versus HD demonstrated superior all-cause patient and rejection-free graft survival along with better allograft function (eGFR).

Impact of Somatic Mutations and Pretransplant Strategies on the Outcome of Patients Allografted for MDS or Secondary AML

Introduction: In addition to other disease-, patient- and procedure-related factors, recent studies revealed a strong impact of somatic mutations on the outcome after allogeneic transplantation (allo-SCT) in patients with myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (AML). The choice of pre-transplant strategy (upfront transplantation [Tx] vs. induction chemotherapy [CTX] vs. hypomethylating agent [HMA]) is a matter of debate among experts but may also influence post-transplant outcome. The issue whether there is an interplay between mutational profile and pre-transplant therapies and how this may modulate outcome after allo-SCT has not been investigated so far and was therefore the scope of this analysis. Methods: For this purpose we performed amplicon-based sequencing (TruSight Myeloid 54-gene panel, Illumina®) of pre-transplant samples from 128 patients with MDS (85%) or sAML (15%) who had received an allo-SCT at our institution between 2001 and 2015 from related (46%) or unrelated (54%) donors following standard-dose (39%) or reduced-intensity (61%) conditioning. Seventy-three patients (57%) were directly transplanted (upfront group), while 55 patients (43%) had received pre-transplant cytoreductive therapy (CTX or HMA). Molecular data, pre-transplant therapy and clinical variables were entered into uni- and multivariate analyses to estimate their impact on outcome after allo-SCT and response to salvage therapy in patients relapsing after allo-SCT. Results: Estimated 5-year overall (OS) and relapse-free survival (RFS) of the entire cohort was 56% and 42%, respectively. Corresponding to the presence of at least one mutation in 87% of patients (median 2 mutations per patient, range 0-6) a total of 285 mutations were detected, with RUNX1 (18%), ASXL1 (17%), SRSF2 (15%), DNMT3A (13%), TET2 (13%), TP53 (12%) and SF3B1 (10%) being the most frequently affected genes. Multivariate modeling revealed independent negative prognostic impact of TP53 and SF3B1 mutations on OS, RFS and cumulative incidence of relapse (CIR); NRAS and DNMT3A mutations on OS; as well as NRAS and SF3B1 mutations on non-relapse mortality. Similar to the non-transplant setting, these 4 "poor risk" mutations refined the prognostication of patients with complex karyotype, since those carrying at least one of the "poor-risk" mutations had an even worse prognosis. In addition, pre-transplant cytoreductive therapy negatively influenced not only OS, RFS and CIR after allo-SCT in multivariate analysis, but also interacted with mutations status. Indeed, patients receiving upfront Tx had the best outcome in terms of OS and RFS in the absence of "poor risk" mutations. In the presence of any of these 4 mutations, prognosis of patients receiving upfront TX was worse, but still significantly better compared to patients carrying a "poor risk" mutation who had undergone pre-transplant cytoreduction (Figure 1). The negative impact of these mutations detected prior to transplant was abrogated after transplant in 41 relapsed patients treated with HMA+/-DLI. Pre-transplant strategy also significantly influenced outcome after HMA-based salvage therapy, as patients in the upfront group had a higher likelihood of response and survival. Conclusion: These results confirm and expand previous data on the prognostic impact of mutations in TP53, SF3B1, DNMT3A and NRAS on outcome after allo-SCT. There seems be a prognostic interaction between mutational status and pre-transplant strategy, suggesting that it may be possible to adapt pre-transplant therapy according to the molecular profile of each patient. Figure 1 Disclosures Rautenberg: Jazz Pharmaceuticals: Other: Travel Support; Celgene: Honoraria, Other: Travel Support. Germing:Novartis: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria. Gattermann:Alexion: Research Funding; Novartis: Honoraria; Takeda: Research Funding. Kobbe:Celgene: Honoraria, Other: Travel support, Research Funding; Jazz: Honoraria, Other: Travel support; Medac: Honoraria, Other: Travel support; Roche: Honoraria, Other: Travel support; Amgen: Honoraria, Other: Travel support, Research Funding; Biotest: Honoraria, Other: Travel support; Novartis: Honoraria, Other: Travel support; Neovii: Honoraria, Other: Travel support; MSD: Honoraria, Other: Travel support; Pfizer: Honoraria, Other: Travel support; Takeda: Honoraria, Other: Travel support; Abbvie: Honoraria, Other: Travel support. Schroeder:Celgene Corporation: Consultancy, Honoraria, Research Funding.

Evolution of Moderate Aplastic Anemia into Subclinical PNH/AA and Successful Treatment with Reduced Intensity Haplo-HSCT: A Pediatric Case Report

Introduction: Aplastic Anemia (AA) is diagnosis made after the exclusion of other acquired or inherited disease that can present with pancytopenia. In pediatric AA, there is often overlap with many other diseases including Paroxysmal Nocturnal Hemoglobinuria (PNH) and hypocellular myelodysplastic syndrome (MDS). The diagnosis is often difficult and can evolve. There are new tests and methodologies to guide diagnosis and treatment decision making. Case report: The patient is a previously healthy, 18-year-old Caucasian female referred for pancytopenia. Patient reported progressive fatigue and easy bruising for a month prior to evaluation. Initial white blood count was 2.4 x109/L, hemoglobin 9.7g/dl, platelets 39 x109/L, absolute neutrophil count (ANC) of 590, and absolute retic count 68 x 109/L. A bone marrow exam revealed a hypocellular marrow with 30% cellularity with no dysplasia or blasts on flow cytometry. Viral studies, folate and vitamin B12 levels were normal. Chromosomal analysis, Fluorescent In situ Hybridization (FISH) study for MDS, and telomere length assay were normal. A bone marrow failure (BMF) panel for sixty targeted genes showed no mutations associated with BMF. PNH studies by flow cytometry showed 2.6% erythroid, 2% granulocytes, 2.7% monocytes failed to express GPI associated anchoring proteins (GPI-APs) representing a small PNH clone, not unusual in patients with aplastic anemia (AA). Studies were c/w with moderate AA (mAA). Standard management of mAA is careful observation and treatment if the patient requires transfusions or ANC falls below 500. However, since our patient was soon starting college out of state, we decided to treat with Immunosuppressive Therapy (IST), consisting of equine Anti-thymocyte globulin (eATG) and Cyclosporine. At 24 weeks post IST, no response was observed and the patient was requiring more frequent platelet and red blood cell transfusions. Repeat PNH testing showed 2% erythroid, 5% monocytes and 4% granulocytes that were deficient in GPI-Aps (Table1). BM exam showed 60% cellularity that was consistent with a recovering marrow but there was relative erythroid hyperplasia, without evidence of dysplasia or blasts. At this time, with increasing marrow cellularity but persistent pancytopenia we began to strongly suspect MDS. However, repeat chromosomal analysis and FISH studies were normal and a Foundation One myeloid panel was negative for mutations associated with MDS. At 28 weeks post-IST, repeat BM exam revealed 70% cellularity, again with relative erythroid hyperplasia. At the same time PNH testing, showed that 1.3% erythrocytes, 5.6% granulocytes and 5.4% monocytes were negative for GPI-APs. We concluded that our patient evolved had from mAA to subclinical PNH/AA which accounted for the normocellular marrow. High Disease Activity (HDA) is defined as lactate dehydrogenase (LDH) ≥ 1.5 times upper limit of normal and is associated with large PNH clones. HDA can guide the use of eculizumab as pre-transplant therapy. (DeZern et al, 2012) Throughout the course of the disease, her LDH was normal. She did not have HDA and therefore, was not treated with eculizumab. Because of the normocellular marrow she was not eligible for CTN 1502-CHAMP study. However, the patient underwent reduced intensity conditioning (RIC) and a haplo paternal BMT, followed by post-transplant cyclophosphamide, as per CTN 1502- CHAMP. She tolerated her BMT well without major complications. She is now five months post-transplant, alive and well, fully engrafted with 100% donor chimerism and no signs of GVHD. Post-transplant PNH testing revealed all PNH clones were eliminated. Conclusion: This case illustrates the diagnostic challenges of patients presenting with pancytopenia and the overlap and possible evolution of disease classifications; new diagnostic testing including gene mutation screens to aid in diagnosis; new concepts such as HDA in PNH to help guide treatment decision making; and the successful use of RIC and haplo BMT in a patient with PNH/AA and a normocellular BM Disclosures No relevant conflicts of interest to declare.

Complementary Transplantation Improved Results of Both Peripheral Blood Stem Cells and Unrelated Cord Blood Transplants in Thalassemia: A Multi-Center Study from China

Background: Unrelated cord blood (UCB) transplant (UCBT) is not recommended in patients with thalassemia major (TM) so far. Post-transplant (PT) Cyclophosphamide (PTCy) with long pre-transplant immunosuppression therapy have improved haploidentical peripheral blood (PB) stem cell transplant (haplo-SCT) survival in TM patients but with 2/31 primary rejection. So, we designed a novel dual transplantation of UCBT following haplo-SCTwith PTCy(NF-14-TM-CT protocol). Aim:To improve results of haplo-SCT and UCBT in patients with TM. Patients and method: NF-14-TM -CT protocol was termed as double-insurance dual transplantsincluding a haplo-SCT and an UCBT, in which conditioning regimen consisted of ATG (at -10 to -8 day), Cy (-7), Fludarabine (-6 to -2), Busulfan (-6 to -4) Thiotepa (-3), haplo-PB (0), PTCy (+3, +4) and UCB (+6). PTCy serve as GVHD prophylaxes after haplo-SCT and as conditioning before UCBT. In total 131 patients with TM from three pediatric center in China received NF-14-TM-CT protocolfrom June, 2014 to April, 2019, with a median follow-up of 13 (2-59) months and a median age of 8 (3.5-17) years. Results Final haplo-PB engrafted(group1)in 76 patients with mean PBSC-MNCof 22.49 (±5.36) x108/kgand UCB nuclear cells (NC) of 5.95 (±3.39) x107/kg and final UCB engrafted (group 2) in 55 patients with mean PBSC-MNC of 21.78 (±5.68) x108/kg and mean UCB-NC of. 5.43 (±2.32) x107/kg. The 4-year overall survival (OS), thalassemia-free survival (TFS), graft rejection (GR), and transplant related mortality (TRM) were 97.6%, 96.0%, 1.5%, and 2.4%, respectively (Fig. A), in total. The corresponding rates for group 1 were 98.3%, 96.9%, 1.7% and 1.8% and for group 2 were 95.5%, 93.8%, 4.5% and 1.4%, respectively. No statistic significant difference was found in OS, TFS, GR and TRM, respectively, when comparing group 1 with group 2 (Fig. B. C, D, E).The incidence of grade II-IV acute GVHD, III-IV acute GVHD, mild chronic GVHD, moderate/severe chronic GVHD, VOD, PT cystitisand PT hemolysis of the entire cohort was 16.8%, 6.87%, 9.92%, 1.52%, 4.60%, 31.3% and 14.5, respectively. Summary:Current study proved that the novel CT improved the results of haplo-SCT and UCBT in patients with TM. Disclosures Wing: Miltenyi Biotec: Employment.

Inferior Survival with Use of Autologous Stem Cell Transplant As Second-Line Therapy in Multiple Myeloma

Background: Multiple myeloma (MM) remains incurable with eventual relapse and death occurring despite multiple lines of chemotherapy. Standard frontline therapy for MM has traditionally consisted of combinations of immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and dexamethasone followed by consolidation with high-dose melphalan and autologous stem cell transplantation (ASCT). A randomized trial using IMiD and PI-based induction demonstrated significant progression-free survival (PFS) benefit with upfront ASCT in consolidation compared to ASCT in second-line at relapse, but no OS benefit (Attal et al, NEJM, 2017). Delay of ASCT to second-line or beyond may in part be due to the aforementioned lack of OS benefit shown with upfront ASCT and increase of sustained deep responses, including MRD negativity, to novel frontline 3 and 4-drug regimens and continuation of therapy in the frontline. We performed a chart review comparing PFS1, PFS2, and overall survival (OS) of patients who underwent upfront ASCT as consolidation to those who received ASCT in the second-line after one relapse ('delayed ASCT'). The study was approved by the Institutional Review Board at Weill Cornell Medical College. Methods: 124 MM patients who underwent ASCT either as consolidation in first-line or delayed ASCT after relapsing on one prior treatment between 2010-2016 were included. Demographics and clinical parameters were extracted from the electronic medical record. PFS1, PFS2, and OS were calculated from date of diagnosis to first relapse, second relapse, and death, respectively. Patients were censored if lost to follow-up prior to experiencing the relevant event. PFS1, PFS2, and OS of patients receiving upfront ASCT were compared to those of patients receiving delayed ASCT. Log-rank tests were used to statistically evaluate differences between Kaplan-Meier PFS/OS curves. Cox proportional hazards models were used to calculate hazard ratios (HR) using upfront ASCT as the reference treatment. Results: Among the 124 patients, 93 underwent upfront ASCT as consolidation and 31 underwent delayed ASCT after relapsing on one prior line of therapy (Table 1). Induction regimens and pre-transplant therapies received are detailed in Table 1. Of the delayed group patients, 6 underwent ASCT directly without second-line induction and 25 as consolidation after second-line therapy. Patients receiving upfront ASCT had significantly longer median PFS1 compared to patients who received delayed ASCT (6.45 vs 1.25 years; P&lt;0.001), with a HR of 0.18 (95% CI, 0.11-0.29) (Figure 1A). Median PFS2 in the upfront ASCT group was likewise significantly longer than in the delayed group (9.19 vs 3.69 years; P&lt;0.001), with a HR of 0.31 (95% CI, 0.18-0.55) (Figure 1B). With a median follow-up of 6.0 and 5.8 years in the upfront and delayed groups, respectively, median OS was not reached in either group but trended towards prolonged survival with upfront ASCT (P=0.052), with a HR of 0.46 (95% CI, 0.20 to 1.03) (Figure 1C). Conclusions: In this cohort of 124 MM patients undergoing ASCT as consolidation in the upfront setting or delayed ASCT in second-line after relapse, upfront ASCT was associated with significantly improved PFS1 and PFS2, similar to findings by Attal et al. However, in that study, no difference in OS was seen between upfront and delayed groups, while our data, with longer follow-up, showed median OS trending towards significance. This has important implications as with use of novel induction regimens and maintenance therapy, ASCT is more commonly being delayed to early relapse in second-line or beyond. If transplant is intended to be used in the first few lines of therapy, our data show that delaying ASCT even to second-line has a significant negative impact on PFS. In addition, a shorter OS with delayed transplant was suggested although did not reach statistical significance, possibly due to small numbers or more patients with high-risk MM in the delayed group. It is also important to note the lack of daratumumab-based regimens which may have improved PFS/OS in either or both arms. Thus, our findings should be prospectively validated in a larger trial of ASCT as consolidation in first-line vs second-line or beyond using novel, monoclonal antibody-based regimens. Disclosures Rosenbaum: Janssen: Research Funding; Honoraria Akcea: Other: Accordant Health. Coleman:Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau; Kite Pharmaceuticals: Equity Ownership; Merck: Research Funding; Pharmacyclics: Speakers Bureau. Van Besien:Miltenyi Biotec: Research Funding. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding.

Self-Reported Changes in the Expanded Disability Status Scale (EDSS) Score in Persons with Multiple Sclerosis after Autologous Stem Cell Transplants: Experience with the “Mexican Method”

Background Persons with multiple sclerosis (MS) are sometimes treated with high-dose immune suppressive or cytotoxic drugs and an autotransplant. Use of autotransplants may be substantially more common as many cases are not reported. Therapy-related mortality (TRM) has decreased to &lt;2% because of less intensive pretransplant regimens and better subject selection. Trials have reported a greater proportion of subjects with no evidence of active disease in subjects receiving high-dose therapy and an autotransplant compared with controls. Recent autotransplants use less intensive pretransplant therapy with seemingly similar efficacy and fewer adverse events. Whether the autograft is needed for bone marrow recovery and/or efficacy is uncertain but unlikely to be tested in randomized trials. We previously reported autotransplants for several haematologic neoplasms can be done in an outpatient setting using refrigerated blood cells. We now report data from 739 subjects with MS receiving autotransplants in an outpatient setting using refrigerated blood cells. Methods After June 2015, 739 consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells, on an outpatient basis and conditioning with cyclophosphamide and rituximab. The protocol was registered in ClinicalTrials.gov identifier NCT02674217. Eligibility criteria included all the following: Karnofsky performance score &gt;70%, extended Disability Status Scale (EDSS ≤8 in the 2 w pretransplant), CNS magnetic resonance image (MRI) ≤3 mo pretransplant, no prior bone marrow toxic drugs, normal heart, liver, lung and kidney function, ≥6 mo since exposure to immune suppressive drugs. Results 495 females and 244 males were included; median age was 47 years. 310 patients presented with relapsing remitting MS (RRMS), 273 with secondary progressive (SPMS) and 156 with primary progressive (PPMS). All procedures were started on an outpatient basis and only 31 persons needed to be admitted to the hospital during the procedure. In order to obtain at least 1x106/Kg viable CD34 cells, one to three apheresis were performed (median 1). Total number of viable CD34+ cells infused ranged between 1 and 37.83 x106 / Kg (median 5.62). Patients recovered above 0.5 x109/L absolute granulocytes on day 8 (median, range 2-13), whereas platelet recovery above 20 x109/L on day 4 (median, range 0-10). Seven individuals required red blood cells and eight needed platelet transfusions. There was one transplant related death and the 30-month overall survival of the patients is 99.9%. Patients with RRMS or PPMS had a significant drop in the EDSS before and 15-mo after the transplant, whereas patients with SPMS remained stable (A). The response rate (either drop or stabilization of the EDSS score) at 12 months was 78% for RRMS, 81% for PPMS and 73% for SPMS (B), whereas the relapse-free survival was 84% for all patients (92% for PPMS, 83% for RRMS and 81% for SPMS). Conclusions Changes in the EDSS score consonant with neurological improvement were observed in persons with all types of MS after HSCT employing the "Mexican method". Figure 1 Disclosures Gomez-Almaguer: Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau.

Outcome of Allogeneic Haematopoietic Stem Cell Transplantation in Myeloproliferative Neoplasms-Unclassifiable: A Retrospective Study By the Chronic Malignancies Working Party of EBMT

Introduction Myeloproliferative Neoplasm (MPN) unclassifiable (MPN-U), is a heterogeneous disease that presents with an MPN-type clinical/ histological phenotype yet fails to meet diagnostic criteria for other MPN entities. Incidence is &lt;5% of all MPN when stringent World Health Organisation (WHO) 2016 classification is followed. No well-defined treatment algorithm exists and therapeutic approaches vary, ranging from observation alone, cytoreductive or experimental agents, high dose chemotherapy and in some instances allogeneic Haematopoietic Cell Transplantation (allo-HCT). Outcome analysis for this allo-HCT cohort is lacking.We hereby report on a retrospective, multicentre, EBMT-registry based study of adult patients with a confirmed diagnosis of MPN-U according to updated WHO 2016 criteria that received an allo-HCT. Methods This registry-based analysis was approved by the Chronic Malignancies Working Party of the EBMT. Patient selection was performed by identifying adult patients who underwent first allo-HCT for MPN-U between 2000-2015, using either Reduced Intensity Conditioning (RIC) or Myeloablative conditioning (MAC) as defined by standard EBMT criteria. Further data collection requests (MED-C) forms were sent to centres to improve data completeness. Statistical analyses were performed with SPSS 22 (SPSS Inc./IBM, Armonk, NY) and R. Overall Survival (OS) was calculated from the date of transplant until death or last observation alive. Cumulative incidence functions were used to estimate Non-Relapse Mortality (NRM) and Relapse Incidence (RI) within a competing risk setting. Results A total of 70 patients, 48 (69%) male and 22 (31%) female, with a confirmed diagnosis of MPN-U were analysed. Median age was 57 years (range (r), 22-70 years). Of these patients, 37 (53%) underwent allo-HCT in the period 2001-2010 and 33 (47%) between 2011-2015. MAC regimens were utilised in 31 (44%) patients while 39 (56%) received RIC. Patients were most frequently transplanted within the first two years from diagnosis, with a median time to allo-HCT of 13 months (r, 3-244 months). Diagnostic karyotype was normal in 36 (51%) and abnormal in 23 (33%) patients, with data missing for 11 (16%) patients. A total of 45 (64%) patients had received prior treatment, 23 (33%) patients were untreated and data was incomplete in 2 (3%) patients. Regarding donor type, 27 (39%) patients had a Matched Sibling Donor (MSD) and 43 (61%) an Unrelated Donor (URD). Most frequent conditioning regimens were TBI-based in the MAC cohort and Fludarabine-Busulphan in the RIC cohort. A trend towards higher rates of delayed/failed engraftment was noted in the RIC compared to MAC cohort (p=0.09). Where successful, median time to neutrophil engraftment in both cohorts was similar (18 days for MAC and 17 for RIC) and both platforms demonstrated similar platelet engraftment times (17.5 days). Incidence of grade II-IV aGVHD at 3 months was higher in the MAC (37%) compared to RIC cohort (16%; p=0.05) and the 12-month cumulative incidence of cGVHD for MAC was 52% (95%CI: 32.4, 71.6) and for RIC 32.1% (95%CI: 14.8, 49.4; p=0.117)). Median follow-up was 87 months (minimum and maximum of censored cases: 31 and 196 months). The median OS estimates at 1, 3 and 5-year were 77%, 55% and 42% (MAC) and 59%, 44% and 41% (RIC), respectively (p=0.33). No significant difference existed in OS rates between those who had pre-transplant therapy versus not. Relapse remained significant: cumulative incidences of relapse at 1,3 and 5-years were 10%, 23% and 27% (MAC) and 28%, 36% and 36% (RIC), respectively (p=0.28). NRM probabilities at 1, 3 and 5-years post allo-HCT were also considerable: 19%, 29%, and 34% (MAC) and 28%, 28% and 28% (RIC), respectively (p=0.84). Main causes of NRM were infection and GVHD. Univariate analysis associated use of an URD with a significantly worse OS and NRM compared with MSD. Moreover, the presence of abnormal karyotype at time of allo-HCT was associated with a trend towards a higher risk of relapse (p=0.06). Conclusions This study highlights the potentially curative role of allo-HCT in MPN-U and provides clinicians with robust engraftment, GVHD and outcome data. Both engraftment and OS rates appear acceptable yet NRM and CIR rates in both settings remain high and need to be addressed. The impact of abnormal karyotype at the time of allo-HCT and a trend towards higher risks of relapse requires further elucidation. Disclosures McLornan: Novartis: Honoraria; Jazz Pharmaceuticals: Honoraria, Speakers Bureau. Robin:Novartis Neovii: Research Funding. Chalandon:Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte Biosciences: Consultancy, Honoraria. Beelen:Medac GmbH Wedel Germany: Consultancy, Honoraria. Kröger:Sanofi-Aventis: Honoraria; Riemser: Research Funding; Novartis: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Medac: Honoraria; JAZZ: Honoraria; DKMS: Research Funding; Celgene: Honoraria, Research Funding. Milojkovic:Novartis: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau. Hernandez Boluda:Incyte: Other: Travel expenses paid.

Factors Associated with Subsequent Cancers in Patients with Moderate or Severe Chronic Graft-Versus-Host Disease after Transplant for Hematologic Malignancy

Among patients who survive over two years post-allo-HSCT, cGVHD and subsequent cancers represent a significant source of morbidity and mortality. Long-term treatment with immunosuppressive agents and cGVHD-related immune dysregulation may promote the development of subsequent cancers. The burden of subsequent cancers has not yet been described in patients with the most severe manifestations of cGVHD, who likely represent a high-risk population. 439 patients were enrolled on the prospective NIH Chronic GVHD Natural History Study from 2004 to 2019, underwent one-week evaluation by subspecialists, and were scored in accordance with 2005 NIH criteria. Follow-up data were collected by annual survey in which patients self-reported cancer diagnoses and provided consent for confirmatory medical records. Cumulative incidence was estimated for non-melanoma skin cancer (NMSC) competing with death, relapse, or cancer other than NMSC and for cancer other than NMSC competing with death or relapse using the method of Gooley. Potential predictors of subsequent cancers including demographics, transplant characteristics, and cGVHD-related factors were assessed using Gray's test in univariable analysis and Cox proportional hazards models in multivariable analysis. Patients must have been free of post-transplant relapse, NMSC (for NMSC analyses only), and cancer other than NMSC at evaluation to be included in analysis. 22 NMSC and 19 cancers other than NMSC were observed among 205 eligible patients, with cumulative incidences at 60 months of 11.2% (95% CI: 6.9-16.7) and 7.3% (95% CI 4.1-11.8), respectively. The most common cancers other than NMSC were oral squamous cell carcinoma and melanoma (n=6 each). Factors associated with NMSC in univariable analysis were older age at transplant, older age at evaluation, having received sirolimus for cGVHD, having received extracorporeal photopheresis or psoralen-ultraviolet therapy for cGVHD as well as higher CRP, higher NK cell count, and greater BMI at evaluation. Only older age at transplant (HR=2.12; 95% CI: 1.35-3.31) and higher CRP (HR=9.61; 95% CI: 1.29-71.73) remained associated in the multivariable model. Factors associated with subsequent cancers other than NMSC in univariable analysis were T-cell depletion, lymphoid malignant indication for transplant, and increasing severity of oral cGVHD by NIH score. Only lymphoid malignant indication for transplant (HR=2.58; 95% CI: 1.31-5.07) remained significant in multivariable analysis. The association of CRP with NMSC may represent an effect of cGVHD-related inflammation, with CRP previously associated with cGVHD severity. Interestingly, sirolimus was associated with increased risk of NMSC despite its purported antineoplastic effects. One study has previously reported increased risk of NMSC in allo-HSCT recipients treated with sirolimus, however, numerous studies have reported that sirolimus reduces risk of NMSC in solid organ recipients. In this study population, sirolimus was often prescribed later in patients already with refractory cGVHD and adjustment for measures of disease severity attenuated this association in multivariable modeling. The association of lymphoid indication with cancers other than NMSC may be attributable to age as patients with lymphoid malignancies were older at transplant than those with other indications. Additionally, differences in pre-transplant therapies for lymphoid vs. other indications may also contribute to this observation. Post-transplant patients with cGVHD are at high risk of developing subsequent cancers, with higher incidence of NMSC than other cancers. This study identifies potential risk groups for subsequent cancers, highlights patients who may benefit from increased surveillance, and reiterates the need for effective cGVHD therapy to mitigate risks associated with long-term immunosuppression and immune dysfunction. Disclosures Cowen: UpToDate: Other: Royalties; Elsevier: Other: Royalties.

Outcomes Following Allogeneic Stem Cell Transplantation for AML in First Completion Remission Are Comparable between MRD Negative Patients and MRD Positive Patients Receiving Induction Only and Are Superior to MRD Positive Patients Receiving Induction and Additional Therapy

Background: Data suggests that the presence of measurable residual disease (MRD) at the time of transplant for AML portends a poor prognosis. The timing of MRD assessment and transplant relative to the amount of pre-transplant therapy, however, may affect this prognosis. To examine further the question of optimal timing of transplant in the setting of MRD, we reviewed outcomes in AML patients treated with traditional cytotoxic induction at our center who achieved CR1 and proceeded to transplant. Methods: We analyzed outcomes in patients undergoing first transplant for AML in CR1 between January 2014 and March 2018. CR was defined according to 2017 European Leukemia Network (ELN) guidelines. Non-core binding factor patients were included if they underwent initial therapy with 7+3 chemotherapy (+/- adjunctive inhibitor during induction or as post-transplant maintenance). MRD testing modalities included cytogenetics/FISH (performed in 37 patients, positive in 10), flow cytometry performed by Hematologics Inc (performed in 49 patients, positive in 16), and/or mutation specific droplet digital PCR (ddPCR) performed at our center (performed in 33 patients, positive in 16). For three patients, other molecular methods demonstrated MRD. We compared outcomes in three groups: patients who underwent transplant in CR1 with positive MRD after induction only (MRD positive induction only) (n=15), patients who underwent transplant in CR1 with positive MRD after induction and additional therapy (MRD positive induction plus) (n=19), and patients undergoing transplant in CR1 with no MRD (MRD negative) (n=37). Patient details are summarized in Table 1. Results: CI of relapse was higher among MRD positive induction plus patients than MRD positive induction only patients (p=0.042, HR 0.301 (0.094-0.96)) and comparable among MRD positive induction only patients and MRD negative patients (p=0.987, HR 1.011 (0.29-3.58)). CI of transplant related mortality (TRM) was comparable between MRD positive induction plus patients and MRD positive induction only patients (p=0.165, HR 0.23 (95% CI 0.028-1.81)) and comparable among MRD positive induction only patients and MRD negative patients (p=0.871, HR 1.22 (95% CI 0.12-12.87)). Relapse free survival (RFS) and overall survival (OS) were comparable between MRD positive induction only patients and MRD negative patients and significantly better than for MRD positive induction plus patients (RFS (p&lt;0.0001) and OS (p=0.0008)). (Figure 1) On multivariate analysis including MRD positive induction only, MRD positive induction plus, MRD negative, patient age, Sorror comorbidity index, donor source, conditioning regimen, use of adjunctive therapy, and ELN AML risk status, MRD positive induction plus was associated with a significantly higher risk of relapse than MRD positive induction only (p=0.014, HR 0.231 (95% CI 0.072-0.742)). No other factors were statistically significant. Because multiple strategies were used to assess for MRD, we compared MRD positive induction only to MRD positive induction plus patients using flow cytometry performed by Hematologics Inc as the only MRD assessment technique. CI of relapse trended toward lower in the MRD positive induction only group (p=0.10, HR 0.22, (95% CI 0.036-1.34). OS and RFS were significantly improved in the MRD positive induction only patients (p=0.027 and p=0.026 respectively). Conclusions: For patients achieving CR following induction and moving directly to transplant in spite of MRD positivity, outcomes were comparable to patients going to transplant in an MRD negative state and were significantly improved compared to outcomes of patients in an MRD positive state who received additional therapy following induction. Our series is small, and multiple MRD monitoring strategies were used. However, given the paucity of data on this specific question, uncertainty about whether MRD will clear with additional cytotoxic therapy following induction, and the poor prognosis of patients with persistent MRD in the induction plus group, we consider transplant following induction reasonable in this population regardless of MRD status. Larger series are necessary to more definitively answer this question. Disclosures Loken: Hematologics, Inc: Employment, Equity Ownership. Pollyea:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celyad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Diachii Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Forty-Seven: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees.

R-BEAM versus Reduced-Intensity Conditioning Regimens in Patients Undergoing Allogeneic Stem Cell Transplantation for Relapsed Refractory Diffuse Large B Cell Lymphoma.

Allogeneic stem cell transplant (alloSCT) is considered in diffuse large B cell lymphoma (DLBCL) patients with chemorefractory disease or who have relapsed after autologous SCT. Here we present the first report of alloSCT using the R-BEAM (rituximab, carmustine, etoposide, cytarabine, melphalan) conditioning regimen in DLBCL patients. We retrospectively compared long-term alloSCT outcomes of DLBCL patients who received either R-BEAM (n=47) or reduced-intensity conditioning (RIC) regimens (n=23). Seventy patients (median age, 53 years) with DLBCL received alloSCT between January 2005 and December 2017. The median number of pretransplant therapies was 3, and 17 patients (24%) received prior autologous SCT. All received rituximab as a frontline or salvage therapy before alloSCT. The donor was unrelated in 42 patients (60%), and peripheral blood stem cells were commonly used (96%). The 6-month cumulative incidence of grades III to IV acute graft-versus-host disease (GVHD) was 36.2% and 8.7% for R-BEAM and RIC, respectively (P=.03). Median follow-up of surviving patients after R-BEAM and RIC was 3.1 and 5.5 years, respectively. Three-year overall survival (OS) after R-BEAM and RIC was 34.4% and 43.4%, respectively (P=.48). At 3 years, R-BEAM was associated with a similar relapse rate (25.5% versus 26.1%, P=.96), nonrelapse mortality (NRM; 39.7% versus 39.1%, P=.98), and relapse-free survival (RFS; 34.8% versus 34.7%, P=.75) compared with RIC. In multivariable analysis lower Karnofsky performance score was associated with lower OS (hazard ratio, .96; P=.05), whereas chemorefractory disease was associated with a higher relapse risk (hazard ratio, 8.8; P=.04). No difference in OS, relapse, NRM, or RFS was noticed between R-BEAM and RIC. R-BEAM regimen seems to be feasible and results in equivalent rates of long-term OS, relapse, NRM, and RFS compared with RIC. However, a significantly higher rate of severe acute GVHD was noticed.

S9GENETIC INFLUENCES ON ANXIETY AND DEPRESSION OUTCOMES FOLLOWING TREATMENTS IN A CLINICALLY RELEVANT POPULATION-BASED COHORT, THE GLAD STUDY

Allogeneic stem cell transplant (alloSCT) is considered in diffuse large B cell lymphoma (DLBCL) patients with chemorefractory disease or who have relapsed after autologous SCT. Here we present the first report of alloSCT using the R-BEAM (rituximab, carmustine, etoposide, cytarabine, melphalan) conditioning regimen in DLBCL patients.We retrospectively compared long-term alloSCT outcomes of DLBCL patients who received either R-BEAM (n = 47) or reduced-intensity conditioning (RIC) regimens (n = 23).Seventy patients (median age, 53 years) with DLBCL received alloSCT between January 2005 and December 2017. The median number of pretransplant therapies was 3, and 17 patients (24%) received prior autologous SCT. All received rituximab as a frontline or salvage therapy before alloSCT. The donor was unrelated in 42 patients (60%), and peripheral blood stem cells were commonly used (96%). The 6-month cumulative incidence of grades III to IV acute graft-versus-host disease (GVHD) was 36.2% and 8.7% for R-BEAM and RIC, respectively (P = .03). Median follow-up of surviving patients after R-BEAM and RIC was 3.1 and 5.5 years, respectively. Three-year overall survival (OS) after R-BEAM and RIC was 34.4% and 43.4%, respectively (P = .48). At 3 years, R-BEAM was associated with a similar relapse rate (25.5% versus 26.1%, P = .96), nonrelapse mortality (NRM; 39.7% versus 39.1%, P = .98), and relapse-free survival (RFS; 34.8% versus 34.7%, P = .75) compared with RIC. In multivariable analysis lower Karnofsky performance score was associated with lower OS (hazard ratio, .96; P = .05), whereas chemorefractory disease was associated with a higher relapse risk (hazard ratio, 8.8; P = .04). No difference in OS, relapse, NRM, or RFS was noticed between R-BEAM and RIC. R-BEAM regimen seems to be feasible and results in equivalent rates of long-term OS, relapse, NRM, and RFS compared with RIC. However, a significantly higher rate of severe acute GVHD was noticed.

Relevance of NANDA-I diagnoses in patients undergoing haematopoietic stem cell transplantation: a Delphi study

Haematopoietic Stem Cell Transplantation ( HSCT) has become the standard of care for some haematological diseases that do not respond to traditional treatments: pre-transplant therapy still causes high mortality and morbidity today. Due to the high risk, patient care requires careful evalua- tion and often complex, intensive and non-risk free interventions; the NANDA-I classification provides a way to classify and standardise areas of nursing interest. A previous consensus among experts had iden- tified 61 diagnoses, according to the classification NANDA-I 2018-2020, relevant in onco-haematolo- gical field. The aim of the study was to identify which of the 61 diagnoses were relevant for patients undergoing HSCT. A Delphi study was conducted in two rounds; a structured questionnaire on a 4 point Likert scale was used to build consensus, involving 57 experienced nurse enrolled in Italian GITMO Centres. The present study has identified 34 relevant NANDA-I diagnoses in patients undergoing HSCT; it also defined 11 as important diagnoses having obtained absolute consensus. Use the NANDA-I diagnoses to know, from a panel of experts, the most important and relevant health problems associated with the toxicity of pre- HCSE treatment, it can direct assistance and resources towards expercied and known outcomes so as to be able to intervene effectively with performances aimed at reducing risks and specific complications.

Staged Biliary Reconstruction After Orthotopic Liver Transplantation: A Practical Surgical Strategy for High-Acuity Adult Recipients.

Background.Biliary complications (BC) following orthotopic liver transplantation (OLT) is strongly associated with inferior patient outcomes and increased healthcare cost. BC in high-acuity patients can be lethal. While the utility of staged biliary reconstruction after liver transplantation (SBRALT) has been reported in adult and pediatric OLT, biliary outcome data are scarce. We sought to evaluate the clinical utility and outcomes of SBRALT in high-acuity transplant recipients.Methods.We conducted an analysis from our prospective database of 149 adult OLT between January 1, 2012, and September 30, 2017. Mean follow-up was 26 months. Variables were compared for Group I: one-stage OLT with biliary reconstruction (N = 58) versus Group II: SBRALT (N = 91).Results.Compared with Group I, patients in Group II had higher acuity of illness: median model for end-stage liver disease scores (19 vs 35 P = 0.002), requirement for pretransplant intensive care unit (29.3% vs 54.9%, P = 0.022), pretransplant renal replacement therapy (15.5% vs 48.4%), estimated blood loss (2000 vs 4750 mL, P < 0.001), and intraoperative packed red blood cells transfusion (4 vs 10 units, P < 0.001). For Group II, biliary reconstruction was performed between 1 and 6 days after OLT. Hepaticojejunostomy was performed in 8.6% (Group I) and 26.4% (Group II), P = 0.010. For Groups I and II, BC rates (8.6% vs 7.7%, P = 0.955) and 1-year graft failure-free survival rates (89.7% vs 88.2%, P = 0.845) were comparable.Conclusions.Graft failure-free survival and biliary outcomes of SBRALT in high-acuity recipients are excellent and comparable to one-stage OLT for low-risk patients. SBRALT is a practical surgical strategy in complex OLT.