Reduced Incidence Of Relapse Research Articles

Adjunctive Chinese medicine therapy reduces relapse of psoriasis vulgaris after discontinuation of biologics: a prospective registry-based cohort study

Background Biologics have revolutionized psoriasis treatment; however, relapse of psoriasis after discontinuation of biologics remains unresolved. Objective To assess the impact of adjunctive Chinese medicine (CM) therapy on relapse of psoriasis vulgaris (PV) after discontinuation of biologics. Methods We constructed a prospective cohort study through a psoriasis case registry platform that enrolled patients treated with biologics (in combination with or without CM). The endpoint event was relapse, defined as loss of psoriasis area and severity index (PASI) 75. Results A total of 391 patients completed the study and were included in the analysis, of whom 169 (43.2%) experienced relapse during follow-up. To minimize the bias, a 1:1 propensity score matching (PSM) was performed, generating matched cohorts of 156 individuals per group. Adjuvant CM therapy significantly associated with reduced incidence of relapse (HR =0.418, 95% CI = 0.289 ∼ 0.604, p < 0.001), and the protective effect of CM in the subgroup analysis was significant. In addition, PASI 90 response and disease duration were associated with relapse (p < 0.05). Conclusion Adjunctive CM therapy is associated with reduced relapse incidence in PV after discontinuation of biologics.

Real World Outcomes of Patients with Secondary Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation after Induction with Liposomal Daunorubicin-Cytarabine (CPX-351)

Background: Liposomal Daunorubicin-Cytarabine (CPX-351 or Vyxeos), is approved for upfront treatment of adult and pediatric patients with secondary Acute Myeloid Leukemia (sAML) based on results of a randomized phase 3 trial comparing CPX-351 to conventional chemotherapy with 7+3 regimen. The study showed CPX-351 treated patients demonstrated superior complete remission (CR) rates and overall survival (OS) [Lancet et al JCO 2018]. In this study, a higher proportion of CPX-351 treated patients underwent allogeneic hematopoietic cell transplantation (alloHCT), and landmark OS analysis favored CPX-351 treated patients (HR=0.46; 95% CI: 0.24-0.89; p=0.009). Herein, we reviewed City of Hope (COH) and University of California Los Angeles Medical Center (UCLA) database for patients with sAML who underwent allogeneic HCT after CPX-351 induction to investigate OS and disease-free survival (DFS) outcomes of alloHCT in CPX-351 treated patients and to investigate if HCT outcomes are impacted by achievement of pre-HCT measurable residual disease (MRD) negative remission. Methods: We conducted a multi-center retrospective review of 38 consecutive patients who received CPX-351-based induction before allogeneic HCT to treat sAML, at COH (n=10) and UCLA (n=28), between 2017-2021. The primary endpoint was 2-year OS and DFS in all patients. Secondary outcomes included MRD-ve complete remission (CR) after CPX-351 induction. CR was defined as &amp;lt;5% blasts in bone marrow (BM) aspirates. CR with with hematologic recovery (CRh) was defined as absolute neutrophil counts &amp;gt;1000/µL and platelets ≥100,000/µL. Patients without CRh were categorized as CR with incomplete blood recovery (CRi). MRD assessment was done on day-28 BM aspirate using multiparametric flow cytometric (FC) assay with lower limit of sensitivity of 0.01%. OS was defined as the time from the start of therapy to death and patients were censored if alive at the last follow-up, DFS was defined as the time interval from the date of response to relapse or death, whichever occurred first, and patients were censored at the last follow-up if still leukemia free. Descriptive statistics were used to summarize patient demographics, and disease characteristics. Kaplan-Meier curves and log-rank test were used to evaluate OS and LFS. Results: Patients' demographic and disease features are summarized in Table 1. Briefly, the median age at diagnosis was 65 years (range: 14-77) and median blast percentage in BM at diagnosis was 34% (range: 20-69%). Based on ELN criteria, 25 patients (66%) had adverse risk, 12 (32%) had intermediate risk and one (2.6%) had favorable risk AML. sAML was due to antecedent hematologic disorder (AHD) in majority of patients (n=32; 84%), therapy related in four (10%) and MDS-related changes (MRC) in two patients (5.3%). Following Vyxeos treatment, the composite CR rate (CRh+CRi) was 76% (CRh in 25, CRi in 4 patients) and 9 patients (23%) were refractory to upfront therapy. Pre-HCT MRD status was available for majority of patients (n=34; 89%). MRD negative remission by FC was achieved in 58% (20/34) patients (Table 2). The 1- and 2-years OS was 65% (95% CI: 48-78%) and 54% (95% CI: 36-68%), respectively and the 1- and 2-years DFS was 58% (95% CI: 41-71) and 50% (95%CI: 33-64%), respectively (Figure 1). In the 34 patients with available pre-HCT MRD data, no significant difference in OS (50% vs 58%; p=0.4) or DFS (50% vs 48%; p=0.93) was observed based on pre-HCT MRD status. More patients with who were MRD-positive after induction (50%; 7/14) received myeloablative conditioning (MAC) regimen compared to only 15% (3/20) of patients with MRD negative remission. Conclusion: CPX-351 induction in patients with sAML is associated with high MRD negative remission and promising 2-year OS/DFS after allogeneic HCT. In patients with MRD positive remission status after CPX-351 induction, MAC conditioning regimens may be preferred to reduce relapse incidence after alloHCT.

Navigating preemptive and therapeutic donor lymphocyte infusions in advanced myeloid malignancies by high-sensitivity chimerism analysis.

Preemptive and therapeutic donor lymphocyte infusions (preDLI and tDLI) are widely used in relapsing and relapsed hematopoietic malignancies after allogeneic stem cell transplantation (alloSCT) to enhance the graft-versus-malignancy effect. However, in advanced myeloid malignancies, long-term survival after preDLI and tDLI remains low, reflecting our inability to master the double-edged sword of alloreactivity, balancing anti-neoplastic activity versus graft-versus-host disease (GvHD). We previously evaluated a quantitative PCR-based high-sensitivity chimerism (hs-chimerism) based on insertion/deletion polymorphisms instead of short tandem repeats, where increasing host chimerism in peripheral blood predicts relapse more than a month before clinical diagnosis, and declining host chimerism signals anti-host alloreactivity. Here we report 32 consecutive patients with advanced myeloid malignancies receiving preDLI or tDLI “navigated” by hs-chimerism (“navigated DLI”). We compared them to a historical cohort of 110 consecutive preDLI or tDLI recipients, prior to implementation of hs-chimerism at our institution (“controls”). Both groups were comparable regarding age, gender, conditioning, donor type, and time to DLI. With longer median follow-up of the navigated DLI group (8.5 versus 5 months), their landmark overall (64%) and disease-free survival (62%) at 2 years from first DLI compared favorably with controls (23% and 21%, respectively). Improved survival of navigated DLI was due to both reduced relapse incidence (38% versus 60%) and non-relapse mortality (17% versus 44%) at 2 years. Early relapse prediction by hs-chimerism allowed a preemptive approach in 28% of navigated DLI versus 7% in controls. Our results confirm hs-chimerism as a highly valuable tool for monitoring and steering immune interventions after alloSCT.

The comparative effectiveness of the homeopathic medicine Bacillinum for ringworm (tinea): A pilot feasibility study

Tinea (ringworm) is a highly infectious and commonly presenting pediatric condition. Standard care in rural Kenya is costly, associated with side effects, becoming less effective, and not always available. The aim of this study was to explore the feasibility of testing and using the homeopathic medicine Bacillinum for tinea. Children were recruited from two rural schools in Kenya. Inclusion criteria were: a clinical diagnosis of tinea and a positive Potassium Hydroxide (KOH) smear test. Children were alternately allocated to receive 28-day courses of standard treatment, or Bacillinum 12C. Outcomes measured were KOH smear test status, and tinea status according to Clinician Assessment Questionnaire (CAQ) completed by the child and the clinician. Tests were performed at baseline, 1, 2, and 6 months. 110 children received clinical diagnoses of tinea, of whom 50 had negative KOH tests, one no show, and 10 were outside the age range. 49 were allocated alternately to standard treatment or Bacillinum. At 56 days, 64% receiving standard treatment and 56% receiving Bacillinum had negative KOH tests. At 6 months, 36% receiving standard treatment and 63% receiving Bacillinum had negative KOH tests. Flexibility was required to accommodate school timetable changes and carers living far away. The KOH smear test and clinical diagnosis frequently disagreed. Bacillinum is a low cost, easily administered intervention which may potentially improve long-term tinea status and reduce relapse incidence. Given tinea prevalence and problems with standard treatment, a randomised controlled trial is warranted. Long-term effects and tinea re-occurrence should be measured. National Commission for Science, Technology and Innovation (NACOSTI) registration number NACOSTI/P/19/78,810/26,078.

Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes

Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age ≥60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose ≤7.2 mg/kg or a low-dose melphalan total dose ≤150 mg/m2. The 2 groups, recipients of FluBu (n=697) and recipients of FluMel (n=448), were comparable in terms of disease- and transplantation-related characteristics except for the more frequent use of antithymocyte globulin or alemtuzumab in the FluBu group (39% versus 31%). The median age was 67 years in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% versus 44%(P ≤ .0001). Transplantation-related mortality (TRM) was higher in the FluMel group (26% versus 16%; P ≤ .0001). Because the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was better at 1 year and beyond with FluMel compared with FluBu (48% versus 40% at 1 year [P=.02] and 35% versus 27% at 3 years [P=.01]). Overall survival was comparable in the 2 groups at 1 year (63% versus 61%; P=.4) but was significantly improved with FluMel compared with FluBu at 3 years (46% versus 39%; P=.03). Our results suggest that FluMel is associated with superior DFS compared with FluBu owing to reduced RI in older patients with MDS patients. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Comparison of Outcome after Allogeneic Stem Cell Transplantation in AML Patients in First or Second Complete Remission Following Either Fludarabin/Busulfan, Flamsa-TBI or Flamsa-Bu Conditioning

IntroductionFludarabin/Busulfan (Flu/Bu) is a widely used reduced intensity conditioning (RIC) regimen for allogeneic stem cell transplantation (alloSCT) in AML. As an alternative, the sequential FLAMSA-TBI RIC regimen has been developed and has shown a substantial activity, particularly in relapsed/refractory AML patients (pts). Recently, FLAMSA-Bu with busulfan replacing TBI has also frequently been used. To evaluate their role, the acute leukemia working party (ALWP) of the EBMT conducted a retrospective study, comparing the outcomes of AML pts transplanted in CR1 or CR2 after conditioning with either Flu/Bu or one of the FLAMSA regimens.Patients and MethodsPts were eligible if they had received an alloSCT for AML in CR1 or CR2 between 1/2005 and 6/2016 after conditioning with either Flu/Bu (fludarabine 5x30 mg/m2, busulfan (8x0.8 mg/kg b.w. i.v.)), FLAMSA-TBI (fludarabine 4x30 mg/m2, cytarabine 4 x 2000 mg/m2, amsacrine 4x100 mg/m2)-TBI(4Gy), cyclophosphamide (2x40-60 mg/kg b.w.) or FLAMSA-Bu, in which TBI is replaced by busulfan (8x0.8 mg/kg b.w.). Data were extracted from the ALWP database. Primary endpoint was leukemia free survival (LFS) at two years. Overall survival (OS), relapse incidence (RI), non-relapse-mortality (NRM), graft-versus-host-disease (GVHD) free relapse free survival (GRFS), and rates of acute and chronic GVHD were secondary endpoints. To allow for potential confounding factors between treatment groups, propensity score matching was performed separately for the Flu/Bu group vs. FLAMSA-TBI and FLAMSA-Bu groups using the ‘MatchIt’ package. Factors included in the model were age per deciles, status at transplant, donor type, cytogenetics risk group, sex matching, pt and donor CMV serology and use of in vivo T cell depletion. Then, comparisons were performed using weighted Cox regression.Results1642 pts in the Flu/Bu group were compared to 174 and 318 in the FLAMSA-TBI and FLAMSA-Bu groups, respectively. Median follow-up of survivors was 20.1 months (0.6 - 129.0). Main differences between groups were: pts in the FLAMSA-Bu group suffered more often from secondary AML (25,7% vs.12.6% and 13.9% for Flu/Bu and FLAMSA-TBI, respectively, p<10-4). In addition, they were less often transplanted from a matched sibling donor (29.3 % vs. 46.7% vs. 38.1%, p<10-4) had more wild type NPM1 (79,1% vs. 60.5% vs. 46.2%. p=0.003) and had received more often in vivo T-cell depletion (98.9% vs. 83.8 % vs. 88.6%, p<10-4). Pts in the FLAMSA-TBI group were younger (median: 48y) than in both other groups (59.6y each p<10-4), and had more often a Karnofsky performance status >=90% (81.9%) as compared to the Flu/Bu and FLAMSA-Bu groups (74.0% and 75.8%, respectively, p=0.014).In univariate analysis, LFS at two years was significantly higher in the FLAMSA-TBI group (60.3%) compared to FLAMSA-Bu (48.7%) and Flu/Bu (50.8%), p=0.003. Also, OS and GRFS were highest in the FLAMSA-TBI group (67% and 46% vs. 53.3% and 38.4% vs. 57.1% and 38.3%, respectively p=0.02 and p=0.02). NRM was higher in the FLAMSA-Bu group (26.6%) compared to FLAMSA-TBI (17.1%) and Flu/Bu (17.8%), p=0.02. RI was lower in both FLAMSA groups (FLAMSA-TBI 22.7%, FLAMSA-Bu 24.6%) compared to Flu/Bu (31.4%), p=10-4). Main cause of death in the FLAMSA-Bu group was infection (41.3 %). This rate was lower in the Flu/Bu and FLAMSA-TBI groups with 17.9% and 18.2%, respectively (p=10-5 and p=0.001).Weighted Cox regression revealed that FLAMSA-Bu compared to Flu/Bu was associated with lower RI (HR 0.53 (95% CI 0.33-0.87), p=0.011), whereas NRM was higher (HR 1.88(95% CI 1.17-3.02), p=0.008). LFS, OS, GRFS, aGVHD II-IV, aGVHD III-IV, cGVHD and ext cGVHD were not different. Comparing FLAMSA-TBI with Flu/Bu there was a trend towards reduced relapse incidence for FLAMSA-TBI (HR=0.72 (95% CI 0.51-1.02), p=0.063), better LFS (HR=0.78 (95% CI 0.59-1.04), p=0.085) and GRFS (HR=0.8 (95% CI 0.62-1.03, p=0.081). All other outcome variables were not significantly different.ConclusionsThis retrospective analysis indicates that FLAMSA-Bu compared to Flu/Bu leads to substantial reduction in RI in AML pts transplanted in CR1 or CR2. Higher NRM, mainly due to infections counterbalance this positive effect. Therefore, LFS and OS are not different. Similarly, FLAMSA-TBI was associated with a trend towards reduced RI as compared to Flu/Bu. These data need confirmation in a prospective trial. DisclosuresSchmid:MoilMed: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees. Scheid:Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Socié:Alexion Pharmaceuticals, Inc.: Consultancy. Savani:Jazz Pharmaceuticals: Speakers Bureau.

Reduction of Immunosuppression after Disease-Specific Donor Cell Chimerism Decrease Can Prevent Hematological Relapse Following Allogeneic Stem Cell Transplantation after Non-Myeloablative (NMA) Conditioning — Results of a Prospective Phase II Study. Eudract #: 2007-002420-15

Introduction: Relapse of the disease remains a major burden after stem cell transplantation (HCT) following myeloablative conditioning and even more after reduced intensity and non-myeloablative conditioning. Efforts to reduce relapse incidence involve early immunosuppression withdrawal and prophylactic buffy coat infusion in high risk patients. In this phase II study we analyzed the role of disease-specific chimerism driven immunosuppression.Methods: Between May 2008 and July 2012, 200 consecutive patients (pts) (130 male and 70 female) with a median age of 62.0 (range 26.2-74.8) years (y) with hematological malignancies were transplanted after NMA conditioning. The conditioning regimen consisted of fludarabine 30mg/m2 and total body irradiation (200 cGy) followed by immunosuppression with cyclosporine A (CSA) and mycophenolate mofetil (MMF). The primary objective of the study was to determine the incidence of relapse after a decrease of >10% disease-specific donor cell chimerism (DCC). Furthermore, the incidence of graft vs. host disease (GvHD) and the reconversion of DCC were investigated.Pts were transplanted for acute myeloid leukemia (AML; n=85; 42.5%), multiple myeloma (MM; n=31; 15.5%), myelodysplastic syndrome (MDS; n=26; 13%), chronic lymphocytic leukemia (CLL; n=22; 11%), B-Non-Hodgkin Lymphoma (B-NHL; n=11; 5.5%), T-NHL (n=6; 3.0%), acute lymphoblastic leukemia (ALL; n=7; 3.5%), myeloproliferative neoplasia (MPN; n=6; 3%), MDS/MPN (n=3; 1.5%) and chronic myeloid leukemia (CML; n=4; 2%). Donors were matched-related (MRD)(n=26;13%), matched unrelated (MUD) (n=129; 64.5%) and mismatched unrelated on allele or antigen level (n=45;22.5%).DCC analyses were performed on flow sorted cells on day (d)+ 28, d +56, d+ 84, d + 180 and every 6 months following. As a disease specific DCC line we used CD34 for AML, MDS and MPN pts, CD19 for CLL and B-NHL, CD138 for myeloma pts. The pts with T-NHL were monitored by CD3 chimerism. In addition, engraftment was monitored by CD3 chimerism.Results: Overall survival was 52.9 (95% Confidence Interval (CI) 46.4 - 60.3)% at 2y, and 43.9 (CI 37.3 - 51.6)% at 5y. Relapse incidence was median 28.2 (CI 22.1 - 34.6)% at 2 y and 30.3 (CI 23.9 - 36.9)% at 5 y. Non-relapse mortality (NRM) was 24.3 (CI 18.5-30.5)% at 2y and 30.4 (CI 23.9-37.1)% at 5y.DCC (≥90%) was observed in 116 of the 200 (58.0%) pts, 43 patients (21.5%) showed incomplete disease-specific DCC or reduction of DCC in association with hematological relapse: AML (n=17), MDS (n=4), MM (n=7), CLL (n=7), B-NHL (n=1), T-NHL (n=1), MPN (n=2), ALL (n=2), CML (n=1), MDS/MPN (n=1) and 41 patients (20%) had an isolated line specific DCC decrease after a median of 106 (28-2975) days following HCT.In the 41 pts with decrease in disease-specific DCC without hematological relapse, 1 was off immunosuppression and 3 pts had an active acute or chronic GvHD. In 37 pts CSA and MMF was reduced prematurely. 5 pts showed acute GvHD grade ≥III after reduction and 32 pts GvHD grade 0-II. Of the 37 pts, 27 (73.0%) showed no increase of DCC. 24 (88.9%) pts died, 18 due to relapse, 6 due to non-relapse causes. 3 pts are alive after salvage chemotherapy. 10 of the 37 patients (26.5%) reached full DCC after a median of 29 (21 - 267) days following immunosuppression taper and one recovered from the decrease of DCC and hematological relapse after discontinuing the immunosuppression.43 pts (15.5%) showed no full DCC with (n=12) or without hematological relapse (n=31). Following reduction of immunosuppression 32 pts relapsed, of which 4 are alive after salvage therapy. 2 pts rejected the HCT and are alive after 2nd HCT.85 AML pts were separately analysed, of which 43 experienced a complete DCC at any time point (27 are alive without relapse, 16 died due to non-relapse causes). 25 (29.4%) of which 24 pts were without active GvHD had isolated DCC decreased and were tapered. 7 converted to full DCC. All 17 pts showing no full disease specific DCC with or without simultaneous relapse relapsed. 15 pts died of relapse, 2 are alive after salvage therapy.Conclusion: Decrease of disease-specific DCC was observed in 20% of pts and in 29.4% of the AML pts. Of those 27.7 % in the total population and 29.2 % in the AML group showed recovery of DCC without hematological relapse after tapering of immunosuppression. We conclude that DCC is a useful tool to avoid relapse in the early phase of HCT while the patient is on immunosuppression. [Display omitted] DisclosuresFranke:Novartis: Honoraria, Research Funding; Pfizer: Honoraria; Takeda: Consultancy. Lange:Novartis: Honoraria, Research Funding. Schwind:Novartis: Consultancy.

Prophylactic Donor Lymphocyte Infusions after Haploidentical Hematopoietic Stem Cell Transplantation for High Risk Hematological Malignancies: A Retrospective Bicentric Analysis of Serial Infusions of Increasing Doses of CD3+ Cells

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative option for hematological malignancies. While many procedures have strongly improved outcome after Allo-HSCT by reducing procedure-related toxicity and mortality, disease recurrence remains the major concern. Prophylactic donor lymphocyte infusion (pDLI) is more and more used after Allo-HSCT, with the goal to reduce relapse incidence but may be limited by the risk of developing Graft versus Host Disease (GVHD). The risk of haploidentical DLI-associated GVHD might be increased as compared to HLA-matched DLI. While curative DLI has been assessed for the treatment of hematological relapse after Haplo-SCT, outcomes related to prophylactic DLI has not been evaluated in the setting of Haplo-SCT using post-transplant Cyclophosphomide.We analyzed all consecutive patients who received pDLI after Haplo-SCT for hematological malignancies with intermediate or high risk of relapse at 2 collaborative centers. pDLI was defined by the infusion of donor lymphocytes in the absence of evidence of hematological relapse or positive minimal residual disease (MRD), the presence of a full donor T-cell chimerism (> 98%) and the absence of previous G 2-4 acute GVHD or chronic GVHD. An escalating dose (CD3+ cells/kg) schedule was used as follow: DLI n°1 = 1x10^5/kg, DLI n°2 = 5x10^5/kg and DLI n°3 = 2.5x10^6/kg.We retrospectively analyzed 36 patients with a median age of 58 years (range 25-75). Patients were mostly transplanted for acute leukemia or myelodysplastic syndrome (75%) or lymphoma (17%); 7 patients (19%) had active disease at the time of Haplo-SCT. Disease risk index was high or very high in 10 patients (28%). Most patients received peripheral blood stem cells as graft source (n=31; 86%), and a conditioning regiment including thiotepa, busulfan, and fludarabine (n = 24; 67%). All patients received post transplantation cyclophosphamide as part of GVHD prophylaxis. Patients received 1 (n = 19; 53%), 2 (n = 13; 36%) or 3 (n = 4; 11%) pDLI at a median time of 109 days (range 70 to 227) between Haplo-SCT and the first prophylactic DLI. Median follow-up after pDLI was 9 months (range 2-56).One-year cumulative incidence of requiring-systemic steroids GVHD was 34%. There were 9 chronic GVHD (6 moderate + 3 severe forms according to NIH classification), and 2 acute GVHD (both grade II according to Glucksberg classification). Only 1 patient relapsed despite the occurrence of acute GVHD. Non-relapse mortality at 1 year after pDLI was 9%. Causes of non-relapse death were GVHD (n=2) and sepsis without GVHD (n=1). The cumulative incidence of relapse at 1 year after pDLI was 14%. One-year overall survival and progression-free survival were 82% and 77%, respectively.We conclude that pDLI is feasible after Haplo-SCT. As previously described in the setting of HLA-matched Allo-HSCT, GVHD after pDLI is frequent, but severe forms are observed only in few patients, leading to very low GVHD-related death. Taking into account the high disease risk of the population, relapse rate and survivals after pDLI are promising, justifying the prospective evaluation of pDLI in further randomized prospective studies. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Silver Lining: Reduced Relapse with Chronic GVHD after Transplant for MDS.

Chronic GVHD following hematopoietic cell transplantation is associated with reduced relapse incidence in patients with leukemias. This impact has been investigated in myelodysplastic syndrome, showing a beneficial impact of limited chronic GVHD on transplant outcomes in a cohort of more than 3,000 patients.See related article by Konuma et al., p. 6483.

Environmental enrichment alleviates the deleterious effects of stress in experimental autoimmune encephalomyelitis.

BackgroundClinical observations support the hypothesis that stressful events increase relapse occurrence in multiple sclerosis patients, while stress-reduction strategies can modulate this effect. However, a direct cause-effect relationship between stress level and relapse cannot be firmly established from these data.ObjectivesThe purpose of this work was to address whether modulation of stress could interfere with symptom relapse in an animal model of multiple sclerosis with relapsing-remitting course.MethodsMice bred in standard or enriched environment were subjected to repeated acute stress during the remission phase of relapsing-remitting PLP-induced experimental autoimmune encephalomyelitis.ResultsWe report that repeated acute stress induced a twofold increase in relapse incidence in experimental autoimmune encephalomyelitis. On the other hand, environmental enrichment reduced relapse incidence and severity, and reversed the effects of repeated acute stress.ConclusionThese data provide the platform for further studies on the biological processes that link stress and multiple sclerosis relapses in a suitable animal model.

Glasdegib as maintenance therapy for patients with AML and MDS patients at high risk for postallogeneic stem cell transplant relapse

Key Points Posttransplantation, glasdegib maintenance therapy in patients at high risk for relapse did not meaningfully reduce relapse incidence. Use of glasdegib in the posttransplantation setting was complicated by adverse events requiring drug holds and occasional discontinuation.

Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Flurabine Improves Transplant Outcomes in Older MDS Patients

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only potentially curative therapy in eligible patients with myelodysplastic syndromes (MDS). Reduced-intensity conditioning (RIC) regimens that have been developed to extend HSCT to older patients resulted in encouraging outcomes. However, several retrospective studies have raised concerns about disease control when RIC is used in MDS and the ideal conditioning regimen has not yet been found. In this study, we aimed to compare two most commonly used RIC regimens; intravenous use of fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel). Study population: Through the CIBMTR, after excluding patients with ex-vivo T cell depletion, we identified 1045 MDS patients aged ≥ 60 years and underwent first HSCT with matched related or matched (8/8) unrelated donor (MRD and MUD) using RIC between 2007-2016. RIC was defined via CIBMTR criteria as a regimen that incorporated an IV busulfan (BU) total dose ≤ 7.2 mg/kg or low-dose melphalan (MEL) total dose ≤ 150 mg/m2. By that, we identified 697 MDS patients who received FluBu (BU 6.4 mg/kg: 87%, BU 3.2 mg/kg: 13%) and 448 receiving FluMel (MEL 140 mg/m2: 80%, MEL 100 mg/m2: 20%). Results: The two groups, FluBu and FluMel, were comparable for disease and transplant related characteristics except the more frequent use of ATG or Campath in FluBu group (39% vs. 31%). The median age was 67 in both groups, and 26% and 19% of FluBu and FluMel groups were aged ³70, respectively. Hematopoietic comorbidity index (HCT-CI) was ³3 in 61% and 59% of FluBu and FluMel groups and MDS risk score by CIBMTR at HCT was high/very high in 34% in both groups. FluMel was associated with a reduced relapse incidence (RI) after HSCT compared with FluBu as presented in Table 1 and Table 2. Adjusted RI at 1-year was 43% with FluBu and 25% with FluMel (p=&amp;lt;0.0001). On the other hand, transplant related mortality (TRM) was higher with FluMel compared with FluBu (27% vs. 15%, p=&amp;lt;0.0001). The difference persisted at 2- and 3-years after HSCT as presented in the figure. Since the magnitude of improvement in RI was greater with FluMel than the improvement in TRM with FluBu, disease-free survival (DFS) was improved at 1-year and beyond with FluMel compared with FluBu (48% vs. 41% at 1-year, p=0.030, and 38% vs 28% at 3-years, p=0.0030). These outcome differences remained significant when sensitivity analyses were performed excluding patients who received RIC with either BU 3.2 mg/kg or Mel 100 mg/m2. FluMel, did not lead to higher incidence of severe grade 3-4 aGvHD (HR=1.2, 95%CI, 0.9-1.6, p=0.3) or chronic GvHD (HR=0.9, 95%CI=0.7-1.06, p=0.2). However, grade 2-4 aGVHD was observed more often with FluMel than FluBu (HR=1.3, 95%CI, 1.1-1.6, p=0.006). This led to inferior outcomes of GRFS within the first 2 months with FluMel (HR=1.9, HR=1.4-2.6, p&amp;lt;0.001) but superior outcomes of GRFS beyond 2 months with FluMel compared with FluBu (HR=0.7, 95%CI=0.6-0.8, p&amp;lt;0.001). Conclusion: Our results suggest that between the two most commonly used RIC regimens in older MDS patients, FluMel was associated with superior DFS and overall survival compared with FluBu due to reduced RI despite higher TRM. Disclosures Oran: AROG pharmaceuticals: Research Funding; Astex pharmaceuticals: Research Funding. Nakamura:Kirin Kyowa: Other: support for an academic seminar in a university in Japan; Alexion: Other: support to a lecture at a Japan Society of Transfusion/Cellular Therapy meeting ; Celgene: Other: support for an academic seminar in a university in Japan; Merck: Membership on an entity's Board of Directors or advisory committees. Scott:Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Agios: Speakers Bureau. Popat:Jazz: Consultancy; Incyte: Research Funding; Bayer: Research Funding.

Early Follicular Lymphoma Progression in Patients Treated with Frontline Immunochemotherapy with/without Rituximab Maintenance: Clinically Meaningful Even in Chemosensitive Individuals

Background: Early events within 24 months (POD24) of initial immunochemotherapy (IC) were repeatedly confirmed to be associated with poor survival in follicular lymphoma (FL). Rituximab maintenance (RM) given to responding patients after IC is effective strategy to reduce relapse incidence and improve survival (Salles, Lancet 2011; Hill, BJH 2019). There is little known about the POD24 incidence pattern in chemosensitive patients, and the impact of subsequent RM application for POD24 reduction has not been studied yet. Aim: To (1) analyze the role of POD24 events in patients with responding FL and (2) describe whether post-induction RM changes the pattern of POD24 incidence and possibly post-POD24 outcome of the patients. Methods: The study comprised patients prospectively enrolled in the Czech Lymphoma Study Group network (ClinicalTrials.gov: NCT03199066) in 2000-2015, with grade 1-3A FL and treated with frontline R-CHOP/R-CHOP-like or R-bendamustine or R-CVP IC. Cases with previous WaW were not enrolled. No frontline stem cell (auto/allo) transplant was allowed. Only patients who achieved complete (CR/CRu) or partial remission (PR) at the end of induction (EOI) and were thus potential candidates for RM were included. Early event was defined as progression, relapse or death within 24 months after the date of EOI response assessment. Overall (OS) and progression-free survival (PFS) were calculated from the date of diagnosis and date of EOI response (OS-EOI). Patients who experienced an event before the median time to RM initiation were excluded from POD24 survival analyses to avoid overestimation of the RM group results. Results: A total of 1089 patients were identified, of whom 729 (67%) received RM (maintenance group) and 360 (33%) were followed without RM (observation group; OBS). When comparing both groups, we found no differences in age (median age 59 yrs for both; P=0.54), sex distribution (males 39% vs. 41% in OBS vs. RM, respectively; P=0.37) and ECOG 0-1 (90% vs. 93% in OBS vs. RM; P=0.10). There was a slightly lower proportion of advanced FL (Ann Arbor III-IV) in OBS (80%) as compared to RM (87%, P=0.01), which translated into a lower proportion of high FLIPI patients (46% vs. 52% in OBS vs. RM, respectively; P=0.003). The induction regimens were as follows: R-CHOP in 70% and 83%, R-COP in 18.6% and 10.7%, R-bendamustine 1% and 4%, R-fludarabine-based in 4% and 1% and others in 5% and 1% in RM and OBS, respectively. The EOI remission status was assessed 61 days (median) after the last IC dose with CR/CRu/PR rates of 65%/9%/26% and 65%/6%/29% in OBS and RM, respectively (P=0.14). The median time from EOI response to the first RM dose was 48 days (range 0-371 days), 89% of the pts have started RM within 120 days. The median number of RM doses given was 8 (range, 1-36), with 85% of patients receiving 8-12 doses of RM. After a median follow-up of 10.4 yrs (OBS) vs. 6.0 yrs (RM); P&lt;0.001, 365 (33.5%) patients progressed or relapsed and 177 (16.3%) died. The 5-year OS and PFS were 84.2% vs. 93.6% (P&lt;0.001) and 54.1% vs. 73.6% (P&lt;0.001) in OBS and RM, respectively. The cumulative incidence of POD24 was higher in OBS (29.7%) than in RM (12.3%; P&lt;0.01). POD24 cumulative incidence correlates with depth of EOI response with 21.8%/35.5%/50.5% and 8.2%/14.6%/21.1% for CR/CRu/PR categories in the OBS and RM groups, respectively. When combining RM application (yes/no) and POD24 incidence (yes/no), survival analysis stratified patients into 4 subgroups with 5-year OS-EOI of 52.4%, 63.4%, 92.0% and 96.9% for POD24-OBS, POD24-RM, noPOD24-OBS and noPOD24-RM patients, respectively (P&lt;0.001); see Figure 1. Patients who developed POD24 on RM had only a 26% lower risk of death, compared to OBS (HR 0.74; P=0.15). POD24-free patients experienced a 50% death reduction after RM (HR 0.49; P=0.002). Conclusion: Early progression of the disease significantly increases the risk of death even in pts who respond well to the initial IC. Application of RM significantly prolonged both OS and PFS and reduced POD-24 incidence by half. However, once patients developed an early event on RM, their outcome remained poor. On the other hand, in the POD-24-free group, RM brought survival benefit that lasted beyond its termination. Large independent validation may enhance the validity of these data since the observation group was mainly of a historical nature. Acknowledgement: Supported by IGA_LF_2019_001, MH CZ - DRO (FNOL, 00098892), and AZV 16-31092A grants. Figure 1 Disclosures Prochazka: Roche: Consultancy; Takeda: Research Funding. Trneny:Morphosys: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Gilead sciences: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria.

Induction chemotherapy followed by allogeneic HCT versus upfront allogeneic HCT for advanced myelodysplastic syndrome: A propensity score matched analysis.

To reduce post-transplant relapse, acute myeloid leukemia (AML) type remission induction chemotherapy has been attempted to reduce disease burden before allogeneic hematopoietic cell transplantation (HCT) in patients with advanced myelodysplastic syndrome (MDS). However, the efficacy of induction chemotherapy before HCT is unclear. We retrospectively analyzed the Japanese registration data of 605 adult patients, who had received allogeneic HCT for advanced MDS between 2001 and 2016, to compare the post-transplant relapse between patients who received induction chemotherapy followed by allogeneic HCT and those who received upfront HCT. Propensity score matching identified 230 patients from each cohort. There were no significant differences in overall survival and non-relapse mortality between the two groups. The cumulative incidence of relapse was significantly higher in patients who received induction chemotherapy than those who received upfront HCT. In the subgroup analyses, upfront HCT had a significantly reduced relapse incidence among patients with poor cytogenetics, those with higher international prognostic scoring system at diagnosis, and those who received reduced-intensity conditioning. Our results suggested that AML type remission induction chemotherapy before HCT did not improve post-transplant relapse and survival for adult patients with advanced MDS. Upfront HCT is preferable for patients with a poor karyotype.

Reduced Relapse Incidence with FLAMSA–RIC Compared with Busulfan/Fludarabine for Acute Myelogenous Leukemia Patients in First or Second Complete Remission: A Study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Busulfan/fludarabine (BuFlu) is a widely used conditioning regimen for patients with myeloid malignancies. The sequential FLAMSA (fludarabine + Ara-C + amsacrine chemotherapy) protocol followed by either cyclophosphamide and total body irradiation (FLAMSA-TBI) or cyclophosphamide and busulfan (FLAMSA-Bu) has shown remarkable activity in high-risk acute myelogenous leukemia (AML) patients. Here we compare the outcomes of AML patients transplanted in first complete remission (CR1) or second complete remission (CR2) after conditioning with BuFlu or FLAMSA. Eligible patients had their first allogeneic stem cell transplantation for AML in CR1 or CR2 between January 2005 and June 2016. Donors were matched related or unrelated with up to 1 mismatch. Conditioning consisted of either BuFlu or FLAMSA. Propensity score matching was applied and comparisons were performed using weighted Cox regression. BuFlu conditioning was used in 1197 patients, whereas FLAMSA-TBI and FLAMSA-Bu were used in 258 and 141 patients, respectively. Median follow-up of survivors was 24.72 months. In univariate analysis, relapse incidence (RI) was 30.3%, 21.9%, and 23.1% in the BuFlu, FLAMSA-TBI, and FLAMSA-Bu groups, respectively (P < .01), and nonrelapse mortality at 2 years was 16.1%, 16.4%, and 26.7%, respectively (P < .01). Leukemia-free survival (LFS) at 2 years was 53.6%, 61.6%, and 50.1%, respectively (P = .03). Weighted Cox regression revealed that FLAMSA-TBI compared with BuFlu was associated with lower RI (hazard ratio [HR], .64; 95% confidence interval [CI], .42 to .98; P = .04) and a trend for better LFS (HR, .72; 95% CI, .49 to 1.06; P = .09). These results suggest that compared with BuFlu, conditioning with FLAMSA-TBI leads to reduced RI at 2 years in AML patients transplanted in CR1 or CR2.

Novel Immunotherapy Agents for Acute Lymphoblastic Leukaemia

Acute lymphoblastic leukaemia (ALL) in adults has a survival rate of 40–50% at 5 years, with a high relapse rate after first-line chemotherapy. After relapse, results with salvage therapy are currently unsatisfactory. Therefore, both the optimisation of front-line therapy to reduce relapse incidence and the search for effective salvage therapies for relapsed/refractory (r/r) ALL have been of great interest to the medical community in recent years. The well-characterised expression of well-defined cell-surface antigens in B cell ALL (B)-ALL and T cell (T)-ALL, such as CD19, CD20, CD22, and CD52, has led to the development of several immunotherapy strategies, comprising ‘nude’ monoclonal antibodies (moAbs), conjugated moAbs, bispeciphic, or highly sophisticated chimeric antigen receptor (CAR)-T cell therapy. Recently, both the bispecific moAb blinatumomab (anti-CD19 coupled with a CD3 recognition subunit) and the conjugated anti-CD22 moAb inotuzumab-ozogamicin have resulted in higher remission rates (44% versus 25%, and 80.7% versus 29.4%, respectively) and survival advantages (median overall survival [OS]: 7.7 months versus 4 months, and 7.7 months versus 6.7 months, respectively) in patients with r/r B-ALL when compared to standard salvage chemotherapy-based regimens. On the other hand, preliminary reports show feasibility and unprecedented response rates of ≤90% in highly refractory children and adults treated with CAR-modified T cells targeting the B cell specific CD19 antigen, which seem to be durable in a significant proportion of patients. Furthermore, the addition of anti-CD20 moAb rituximab to front-line standard chemotherapy in patients with CD20+ B-ALL has resulted in a clinical benefit, with prolongation of response duration and survival (3-year leukaemia-free survival and OS: 70% versus 38%; p&lt;0.001, and 75% versus 47%; p=0.003). In conclusion, immunotherapy is currently providing additional options for high-risk ALL patients both in front-line or advanced phase. Nonetheless, the optimal positioning of these novel agents, specially in relation to allogeneic haematopoietic stem-cell transplantion, needs to be clarified. This article aims to review several of these new therapeutic immunotherapy options available for patients with adult ALL, as well as their specific toxicity profile.

Splenic irradiation before hematopoietic stem cell transplantation for chronic myeloid leukemia: long-term follow-up of a prospective randomized study.

In the context of discussions on the reproducibility of clinical studies, we reanalyzed a prospective randomized study on the role of splenic irradiation as adjunct to the conditioning for hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML). Between 1986 and 1989, a total of 229 patients with CML were randomized; of these, 225 (98%; 112 with, 113 without splenic irradiation) could be identified in the database and their survival updated. Results confirmed the early findings with no significant differences in all measured endpoints (overall survival at 25years: 42.7%, 32.0-52.4% vs 52.9%, 43.2-62.6%; p = 0.355, log rank test). Additional splenic irradiation failed to reduce relapse incidence. It did not increase non-relapse mortality nor the risk of late secondary malignancies. Comforting are the long-term results from this predefined consecutive cohort of patients: more than 60% were alive at plus 25years when they were transplanted with a low European Society for Blood and Marrow Transplantation (EBMT) risk sore. This needs to be considered today when treatment options are discussed for patients who failed initial tyrosine kinase inhibitor therapy and have an available low risk HLA-identical donor.

Addition of Lomustine (CCNU) to Induction and Post-Remission Chemotherapy for Fit Elderly AML Patients without Unfavorable Cytogenetics: Results of the Lamsa-2007 Goelams Trial

Background: The treatment of Acute Myeloid Leukemia (AML) in elderly patients remains unsatisfactory, with an expected survival time of about 1 year post diagnosis. In an attempt to improve outcome for these patients, the prospective open-label phase 3 LAMSA-2007 trial (Clinicaltrial.gov ID, NCT00590837) repeated, at decreasing doses in consolidation and reinduction courses, a standard induction regimen with cytarabine and idarubicin (IC), with or without the randomized addition of lomustine (ICL). This alkylating agent with significant anti-leukemic activity is widely used in France for AML therapy. This study was performed as a confirmatory trial, following our previous report of the French experience in which this compound stood out as a favorable factor of improved outcome for patients with non-unfavorable cytogenetics (Pigneux, JCO 2010).Methods: Eligible patients were adults 60 years old or more, with previously untreated AML, fit to receive intensive chemotherapy (ECOG and SORROR <3), with non-unfavorable cytogenetics. Secondary AML to MDS and MPS were excluded, but not AML secondary to chemotherapy or radiotherapy. As induction therapy, the patients received idarubicin 8 mg/m2/d iv on days 1-5, cytarabine 100 mg/m2/d iv on days 1-7 ± lomustine, 200 mg\\m2 orally at day 1. Patients achieving complete response (CR) or CRi received then a first consolidation with idarubicin 8 mg/m2/d iv on days 1-3 and cytarabine 100 mg/m2/d s/cut on days 1-5 ± lomustine, 80 mg orally at day 1, then 6 courses of reduced doses consolidation with idarubicin 8 mg/m2/d iv on day 1 and cytarabine100 mg/m2/d s/cut on days 1-5 ± lomustine, 40 mg orally at day 1. This was followed by 6 months maintenance therapy with alternating courses of purinethol and methotrexate. The primary objective of the study was overall survival (OS); secondary objectives were response rate, cumulative incidence of relapse (CIR), event-free (EFS) survival, as well as safety.Results: From February 2008 to December 2011, 459 patients were enrolled and 424 were evaluable. The median age of analyzed patients was 68 yo (60-81), 58% were male. Cytogenetics was favorable (5.2%), intermediate (90.3%) or failure (4.5%). Overall, 26% of the patients had a favorable genotype based on NPM, CEBPa and FLT3 ITD mutational status. The two arms were comparable for pre-treatment characteristics. There were 3.7% induction deaths in the IC arm and 7.7% in the ICL arm (p=0.11). The rate of primary resistant AML was 21.4% after IC versus 7.7% after ICL (p<10-4). CR or CRi was achieved in 74.9% of IC patients versus 84.7% in ICL patients (p= 0.01). At two years, OS was much better than expected for such a population, and improved in the ICL arm at 56% versus 48% in the IC arm. As expected at this age, a significant number of events occurred after two years, resulting in the absence of statistical significant difference for OS over the whole period of follow-up. At two years, EFS was improved in the ICL arm at 41% versus 26% in the IC arm (p=0.01). The CIR at two years was 41.2% in the ICL arm versus 60.9% in the IC arm (p=0.003). Grade 3 and 4 toxicities were significantly different between treatment arms after induction and after the first consolidation. Neutropenia <0.5 G/L was prolonged of 2 days in the ICL arm (23 versus 21 for the IC arm, p=0.0001) after induction and of 4 days (11 versus 7 for the IC arm, p<0.0001) after first consolidation. Thrombopenia < 20G/L was prolonged of 5 days in the ICL arm (19 versus 14 for the IC arm, p<0.001) after induction and of 7 days (11 versus 4 for the IC arm, p<0.001) after first consolidation.Conclusion: Thisschedule using the same drugs at decreasing doses during induction, consolidation and reinductions provided unusually good results in the IC arm, further improved in the ICL arm by the addition of lomustine, in fit elderly AML patients without unfavorable cytogenetics, with acceptable toxicity. The higher rate of CR, reduced relapse incidence and improved EFS in the ICL arm support the anti-leukemic effect of lomustine in elderly AML patients, even if it does not translate in a significantly prolonged long term overall survival. New strategies for maintenance therapy remain to be improved in this setting to sustain this positive effect. DisclosuresVey:Janssen: Honoraria; Roche: Honoraria; Celgene: Honoraria.

Prognostic Impact of Recipient and Donor CMV Serostatus in Acute Leukemia Patients After Allogeneic Stem Cell Transplantation At the Era of Preemptive Therapy.

AbstractAbstract 3110 Background:Monitoring and (preemptive) treatment of cytomegalovirus (CMV) infection or disease have been implemented in clinical routine algorithms in patients after allogeneic stem transplantation (allo-SCT) in the early nineties and resulted in a dramatic decrease of CMV disease from 20–30% to less than 5% in recent years. However, a significantly reduced relapse incidence (RI) in acute myeloid leukemia (AML) patients with vs. without early CMV replication has been reported just recently. Larger analyses evaluating the prognostic impact of recipient and donor CMV serostatus - as one of the most important risk factors for CMV infection and disease - are lacking at the era of preemptive treatment of CMV infection. Design and methods:We analyzed the prognostic impact of the (pretransplant) recipient and donor CMV serostatus in 16 628 adult de novo acute leukemia patients who underwent allo-SCT between 1998 and 2009 and are documented in the European Bone Marrow Transplantation (EBMT) database (Cohort I). Additionally, 544 patients with secondary AML (e.g. following myeloproliferative neoplasms) who underwent allo-SCT and were reported to the German Registry for Stem Cell Transplantation (DRST) were analyzed according to the prognostic impact of the CMV serostatus (Cohort II). Finally, 97 acute leukemia patients allografted at the Charité University Hospital (Berlin, Germany) were studied more in detail including other parameters such as kinetics of CMV infection and hematopoietic recipient/donor chimerism (Cohort III). Results:Recipient and/or donor CMV seropositivity was associated with a reduced 2-year leukemia-free survival (LFS) (44% vs. 49%, p<0.001) and overall survival (OS) (50% vs. 56%, p<0.001) in de novo acute leukemia patients (Cohort I). These observations were mainly due to an increased non-relapse mortality (NRM) (23% vs. 20%, p<0.001) and strongest in recipients allografted from a non-HLA identical sibling. However, also higher RI was noted especially for acute lymphoblastic leukemia (ALL), resulting in a markedly decreased 2-year OS (46% vs. 55%, p<0.001) in these patients. The negative prognostic impact of recipient and/or donor CMV seropositivity with respect to LFS, OS, NRM and RI remained in a multivariate Cox regression model including different other parameters (e.g. conditioning type). Conversely, the donor CMV serostatus had no significant prognostic impact among CMV seropositive recipients. Recipient CMV seropositivity was further associated with a significantly increased frequency of death due to interstitial pneumonitis, but decreased incidence of both chronic and II-IV° acute graft-versus-host disease (28% vs. 31%, p<0.001). However, it had no significant impact on the incidence of graft failure. Also in secondary AML (Cohort II) recipient and donor CMV seronegativity was associated with a superior 2-year LFS (48% vs. 41%) and OS (54% vs. 44%), but decreased RI (27% vs. 30%) and NRM (25% vs. 31%). The negative impact of CMV seropositivity of the recipient and/or the donor with respect to OS likewise remained in this cohort of secondary AML in a multivariate Cox regression model (Hazard ratio 1.4, p=0.03). Finally, analysis of cohort III showed that CMV seropositive vs. CMV seronegative patients had a significantly reduced OS even in the absence of CMV antigenemia and less frequently had a complete day +30 hematopoietic chimerism (68% vs. 92%, p=0.02). Conclusion:The recipient and donor CMV serostatus still has an important prognostic effect in acute leukemia patients after allo-SCT - particularly in ALL and those allografted from a non-HLA identical sibling - despite the implementation of most sophisticated techniques for monitoring and (preemptive) treatment of CMV in recent years. The increased RI in cases with CMV seropositivity of the recipient and/or the donor argues against a clinically important ‘virus-versus-leukemia effect′ which has been suggested just recently. Disclosures:No relevant conflicts of interest to declare.

Clinical studies of acute myeloid leukemia in the Japan Adult Leukemia Study Group

Acute myeloid leukemia (AML) is the most common adult leukemia in Japan. The treatment for AML consists of induction, consolidation, and maintenance therapies. To improve outcomes in the treatment of AML, the Japan Adult Leukemia Study Group has conducted six studies in AML patients aged 15-64 years since 1987. In AML201 study, IDR (12 mg/m(2)/day for 3 days) or DNR (50 mg/m(2)/day for 5 days) in combination with Ara-C (100 mg/m(2)/day continuous infusion for 7 days) was established as the standard induction therapy, and four courses of combination chemotherapy using non-cross-resistant agents for non-core binding factor (CBF) AML or three courses of high-dose Ara-C for CBF AML was established as the standard consolidation therapy. The AML97 study showed that allo-HSCT from an HLA-identical sibling donor reduced relapse incidence and improved disease-free survival (DFS), but did not significantly impact overall survival (OS) in poor or intermediate risk patients. Despite these studies by JALSG, only about one-third of AML patients remain free of disease for more than 7 years. The JALSG is now conducting the AML209 study to adapt individual therapies according to genetic alterations.