Median Leukemia-free Survival Research Articles

Frontline Azacitidine As a Bridge to Allogeneic Transplantation in Acute Myeloid Leukemia

Introduction: Treatment with the hypomethylating agent (HMA) azacitidine (AZA) has become a standard treatment option for older acute myeloid leukemia (AML) patients thought unfit for standard induction chemotherapy with infusional cytarabine and an anthracycline. AZA is generally well-tolerated, and carefully selected AML patients who achieve complete remission (CR) with frontline HMA therapy may subsequently improve to become suitable candidates for reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) (Lübbert 2009). However, there are very limited data available regarding the use of AZA as a bridge to HCT in AML. The purpose of this study was to evaluate remission status and survival outcomes in patients treated with upfront AZA who undergo HCT.Methods: All AML patients at our institution diagnosed between December 2015 and October 2016 who were initially deemed unfit for intensive chemotherapy and received frontline AZA as a direct bridge to HCT were included in this analysis. Remission statuses after AZA therapy, immediately before transplant, and following transplant were evaluated and categorized as CR, CR with incomplete platelet recovery (CRp), CR with incomplete hematologic recovery (CRi), refractory, or relapsed. Descriptive statistics were used for categorical and continuous variables. The Kaplan-Meier method estimated overall survival (OS) and leukemia-free survival (LFS).Results: Ten patients treated with frontline AZA proceeded directly to HCT; by comparison, during the same period, 17 patients in this age range who received upfront AZA at our institution did not undergo HCT. Of those patients proceeding directly to HCT, there was a male predominance (80%), and median age at diagnosis was 70.5 years (range 60-77; Table 1). Of the 10 patients bridged to HCT, 3 were favorable risk by NCCN guidelines, 3 were intermediate risk, 3 were poor risk, and 1 had an unknown risk status. All patients received 75 mg/m2 of AZA administered daily intravenously on days 1-7 of a 28-day cycle, for a median of 6 cycles (range 4-11), without delays or dose reductions. Four patients received other chemotherapeutic agents concomitantly with azacitidine.During AZA therapy, 5 patients achieved CR, 4 obtained CRi, and 1 was refractory (despite exhibiting a reduction in bone marrow blasts). All patients maintained their respective remission statuses following AZA therapy until immediately prior to HCT. Nine patients underwent haploidentical peripheral blood HCT, and 1 underwent matched related peripheral blood HCT. All patients received a RIC regimen consisting of fludarabine, cyclophosphamide, and total body irradiation as well as post-transplant cyclophosphamide. One patient died from septic shock early during his transplant admission and was included in survival analyses but did not undergo post-HCT disease assessment. At their first disease assessment following HCT, 3 patients achieved CR, 3 obtained CRp, 2 exhibited CRi, and 1 had relapsed. For the aggregate patient cohort, Kaplan-Meier analyses revealed a 1-year OS rate of 86% and a 1-year LFS rate of 75% (Figure 1). Median OS was 19.2 months (95% CI [12.0, N/A]), and median LFS was not reached during the study. Median follow-up time from diagnosis was 14.5 months (range 9.6-19.7).Conclusions: Treatment with AZA was well-tolerated and adequately effective to yield remissions in an older patient population that typically experiences poor outcomes with intensive chemotherapy. Such patients may sufficiently improve while in remission to then proceed with HCT. Frontline AZA can thus be used as a successful bridge to HCT in selected elderly AML patients who were originally considered unfit for standard induction. These results require validation in a larger cohort. [Display omitted] DisclosuresGrunwald:Incyte: Consultancy, Research Funding; Genentech: Research Funding; Alexion: Consultancy; Pfizer: Consultancy; Amgen: Consultancy, Research Funding; Forma Therapeutics: Research Funding; Celgene: Consultancy; ARIAD: Consultancy; Cardinal Health: Consultancy; Janssen: Research Funding. Trivedi:Pharmacyclics: Consultancy, Honoraria.

AcDVP16 Induction Therapy for Acute Myeloid Leukemia

Introduction: The “7+3” regimen, consisting of infusional cytarabine and an anthracycline, has been the mainstay of induction therapy for acute myeloid leukemia (AML) for four decades. With this treatment, complete remission (CR) is achieved in 50-75% of patients (Fernandez 2009). An alternative induction regimen, AcDVP16, is based on the principle of timed sequential therapy (Burke 1977), whereby initial chemotherapy serves to align any residual leukemia cells in S-phase. A subsequent pulse of chemotherapy is then administered for maximum cell kill. AcDVP16 consists of 45 mg/m2/day of daunorubicin and 667 mg/m2/day of infusional cytarabine administered on days 1-3, followed by 400 mg/m2/day of etoposide on days 8-10. As configured, AcDVP16 is an anthracycline-sparing regimen that also obviates the need for a day 14 bone marrow examination. Moreover, with myriad anthracycline and cytarabine dosing options, there is arguably no standard 7+3 regimen currently in use. While AcDVP16 offers the advantage of simplicity, little data exists on outcomes with this regimen. The purpose of the present study is to assess the efficacy and safety of AcDVP16 in adult patients with AML.Methods: We retrospectively analyzed the charts of all newly diagnosed adult AML patients (age ≥ 18 years) treated with AcDVP16 at our institution between August 2013 and April 2017. Responses were defined as follows: CR, CR with incomplete platelet recovery (CRp), CR with incomplete hematologic recovery (CRi), or refractory. Composite CR (CRc) was defined as the aggregate of CR, CRp, and CRi. Survival outcomes were analyzed using the Kaplan-Meier method. Individual predictive factors (age, cytoreduction, and prognostic category) were compared between CRc groups (yes vs. no) using Fisher's exact test. Descriptive statistics were used for categorical and continuous variables.Results: Forty-seven patients received AcDVP16 as initial induction therapy for AML. Ages ranged from 22-65 (median 45) years. By NCCN risk status, 17 patients (36%) were favorable risk, 7 (15%) intermediate risk, and 23 (49%) poor risk. Twelve patients (25.5%) were positive for a FLT3/ITD mutation, and 22 (46.8%) had a NPM1 mutation. Cytoreduction with cyclophosphamide and/or hydroxyurea was administered to 39% of patients prior to initiation of AcDVP16. Of 45 evaluable patients, CRc rate was 89% (CR 74%, CRp 4%, CRi 6%). The CRc rate was not clearly affected by prognostic category (p=0.13), age (p=0.99), or use of cytoreduction (p=0.38).Among the entire cohort, one-year overall survival (OS) was 80.2%, and one-year leukemia-free survival (LFS) was 65.8%. Median OS and LFS were not reached during the study period (Figure 1). Of the 40 patients who achieved CRc, 37.5% relapsed after a median of 6.2 (range 1.9-25.2) months. Of 44 patients who recovered neutrophils following induction, recovery occurred at a median of 35 (range 23-77) days. Median inpatient length of stay was 36 (range 12-63) days. Grade 3/4 non-hematologic adverse events during induction consisted of the following: 7 (14.9%) dermatologic toxicity, 9 (19.2%) mucositis, and 9 (19.2%) hepatotoxicity. Six patients (12.8%) experienced cardiac toxicity, none with grade 3/4. All patients developed febrile neutropenia at some point during hospitalization. Of these, 46.8% had documented bacterial infection, 10.6% viral infection, and 8.5% fungal infection. There was 1 (2.1%) death during the induction hospitalization. Nineteen patients (40.4%) underwent allogeneic transplantation following AcDVP16: 5 (26.3%) with intermediate risk AML and 14 (73.6%) with poor risk disease.Conclusions: This is a single arm cohort analysis examining the efficacy and safety of AcDVP16 induction therapy for AML. AcDVP16 provides an anthracycline-sparing alternative to 7+3 that yields a high survival rate, with a CR rate comparable to the best rates reported for 7+3. Although the time to neutrophil recovery is prolonged with this regimen, the risks are acceptable. Additionally, AcDVP16 avoids the controversy associated with the management of persistent bone marrow disease at day 14 post induction. These findings warrant validation in a larger prospective cohort. [Display omitted] DisclosuresGrunwald:Incyte: Consultancy, Research Funding; Alexion: Consultancy; ARIAD: Consultancy; Pfizer: Consultancy; Celgene: Consultancy; Forma Therapeutics: Research Funding; Genentech: Research Funding; Amgen: Consultancy, Research Funding; Cardinal Health: Consultancy; Janssen: Research Funding. Trivedi:Pharmacyclics: Consultancy, Honoraria.

Combination of Omacetaxine Mepesuccinate (homoharringtonine) and Sorafenib As an Effective Regimen for Acute Myeloid Leukemia (AML) Carrying FLT3-ITD

Objectives: Acute myeloid leukemia (AML) with FMS-like tyrosine kinase-3 (FLT3) internal tandem duplication (FLT3-ITD) is associated with poor response to chemotherapy and prognosis. In vitro drug screening and laboratory mechanistic studies have identified omacetaxine mepesuccinate (OME, also known as homoharringtonine) as an effective agent that demonstrated synergism with FLT3 inhibitors in this AML subtype. We report herein the clinical outcome of the first 40 FLT3-ITD AML patients treated with sorafenib and OME combination (SOME).Methods: Patients with relapsed or refractory (R/R) FLT3-ITD AML were recruited and treated with sorafenib 200-400 mg b.d. continuously and OME [2 mg daily for 7 (first course) or 5 days (second course onwards) every 21 days] until disease progression or allogeneic hematopoietic stem cell transplantation (HSCT). Complete remission (CR) or CR with incomplete hematologic recovery (CRi), leukemia-free survival (LFS) and overall survival (OS) were evaluated. Partial remission (PR) was defined as marrow or circulating blasts ≤ 50% of the pre-treatment state. LFS and OS were evaluated by Kaplan-Meier analysis and compared by log-rank test. Fisher's exact test was used to compare nominal variables. Cox proportional hazard model was used in the univariate and multivariate analyses.Results: Forty patients (16 men, 24 women) were recruited between June 2013 to July 2017. Their clinicopathologic characteristics were shown in Table 1. Thirty patients (75%) achieved CR/CRi, 2 patients showed PR and 7 patients (of whom 5 have had exposure to FLT3 inhibitors) showed no response. One patient was on day 5 of treatment at the time of writing this abstract. The median LFS of the 30 patients who achieved CR/CRi was 4.0 months. Prior exposure to FLT3 inhibitors (p =0.003) and more than one induction chemotherapy before SOME (p <0.001) were associated with a lower rate of CR/CRi. Non-hematological toxicities were minimal and limited to hand-foot-skin reaction and rash associated with sorafenib. Univariate analysis showed that early treatment with SOME (defined as ≤10 months from diagnosis) and HSCT after SOME induced remission were associated with better LFS with a hazard ratio (HR) of 4.1 (1.2-14.1, p =0.026) and 6.1 (1.7-22.0, p =0.005). Achievement of CR/CRi after SOME (HR 4.1, 1.5-11.5 p =0.007), <2 prior induction chemotherapy regimens (HR 3.6, 1.3-9.8, p =0.013), early treatment with SOME (HR 2.8, 1.1-7.2, p =0.031) and HSCT (HR 6.5, 1.5-29.0, p =0.014) were associated with superior OS. In multivariate analysis, HSCT was the only parameter associated with a better LFS (HR 5.4, 1.5-20.0, p =0.012) and OS (HR 6.0, 1.3-27.4, p =0.022).Conclusion: Combination of sorafenib with OME is an effective and safe regimen for R/R FLT3-ITD AML. The molecular features predictive of treatment response as well as the emergence of tyrosine kinase domain mutations at relapse are being evaluated. Further studies testing combination of OME with other FLT3 inhibitors will soon begin. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical effects of administering leukemia-specific donor T cells to patients with AML/MDS after allogeneic transplant

AbstractRelapse after allogeneic hematopoietic stem cell transplantation (HCT) is the leading cause of death in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Infusion of unselected donor lymphocytes (DLIs) enhances the graft-versus-leukemia (GVL) effect. However, because the infused lymphocytes are not selected for leukemia specificity, the GVL effect is often accompanied by life-threatening graft-versus-host disease (GVHD), related to the concurrent transfer of alloreactive lymphocytes. Thus, to minimize GVHD and maximize GVL, we selectively activated and expanded stem cell donor–derived T cells reactive to multiple antigens expressed by AML/MDS cells (PRAME, WT1, Survivin, and NY-ESO-1). Products that demonstrated leukemia antigen specificity were generated from 29 HCT donors. In contrast to DLIs, leukemia-specific T cells (mLSTs) selectively recognized and killed leukemia antigen–pulsed cells, with no activity against recipient's normal cells in vitro. We administered escalating doses of mLSTs (0.5 to 10 × 107 cells per square meter) to 25 trial enrollees, 17 with high risk of relapse and 8 with relapsed disease. Infusions were well tolerated with no grade >2 acute or extensive chronic GVHD seen. We observed antileukemia effects in vivo that translated into not-yet-reached median leukemia-free and overall survival at 1.9 years of follow-up and objective responses in the active disease cohort (1 complete response and 1 partial response). In summary, mLSTs are safe and promising for the prevention and treatment of AML/MDS after HCT. This trial is registered at www.clinicaltrials.com as #NCT02494167.

Early T-Cell Precursor Acute Lymphoblastic Leukemia and T/Myeloid Mixed Phenotype Acute Leukemia Possess Overlapping Characteristics and Both Benefit From CAG-Like Regimens and Allogeneic Hematopoietic Stem Cell Transplantation

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) and T-lymphoid/myeloid mixed phenotype acute leukemia (T/M-MPAL) are closely related entities and remain a therapeutic challenge. In this study, we characterized the clinical features of 43 ETP-ALL and 41 T/M-MPAL patients and compared clinical outcomes and safety between cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CAG)-like regimens in 34 patients and conventional ALL regimens in 50 patients. In our series, ETP-ALL and T/M-MPAL showed similar biological characteristics, immunophenotypes, genomic alterations, and outcomes. The complete remission (CR) rate and minimal residual disease (MRD)-negative CR rate of CAG-like regimens were significantly higher compared with conventional ALL regimens (CAG-like: 80.0% and 59.7%, respectively; P = .039; ALL: 51.4% and 31.3%, respectively; P = .048). Overall, 90.0% of cases (18/20) achieved CR using combined decitabine and CAG-like regimens. Additionally, CAG-like regimens had lower rates of grade 3 or 4 infection (18.8% vs. 38.2%; P = .059) and grade 1 or 2 hepatotoxicity (37.5% vs. 60.0%; P = .043) than conventional ALL regimens. The 38 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the first CR (CR1) had better overall survival (OS) and leukemia-free survival (LFS) than the 11 patients who underwent allo-HSCT in the second CR (CR2) or in no remission (median OS not reached vs. 7.6 months, P = .0004; median LFS not reached vs. 11.6 months, P = .0008). There was a significant difference in 3-year OS (95.7% vs. 52.5%; P = .0039) and LFS (95.8% vs. 43.5%; P = .0003) after allo-HSCT between pre-transplant MRD-negative and MRD-positive patients. The median OS for patients without allo-HSCT was 32.1 months in the CAG-like group compared with 12.1 months in the non-CAG-like group (P = .019). These findings suggest that ETP-ALL and T/M-MPAL possess overlapping characteristics and CAG-like regimens improve their clinical outcomes.

Impact of DNMT3a Status on Post Induction NPM1 MRD Predictive Value on Survival in Elderly AML Patients Treated Intensively

Minimal residual disease is now a powerfull surrogate marker to assess response to chemotherapy in acute myeloid leukemia (AML). In younger adults, NPM1 MRD has recently demonstrated to be a favorable predictive marker for EFS and OS independently of fms-like tyrosine kinase-3 internal tandem duplications (FLT3-ITD) status. However, there is very few datas regarding predictive value of NPM1 MRD in elderly patients treated with intensive chemotherapy. Moreover, numerous studies have suggested the negative impact of DNMT3a mutation in NPM1 AML patients, especially in those with concurrent FLT3-ITD mutation. In this study, we aimed to investigate the impact of DNMT3a status on post induction NPM1 MRD1 predictive value for survival in a retrospective cohort of AML patients aged over 60 years old treated intensively. A total of 138 patients treated for NPM1 mutated AML in two French institutions (Lyon, Lille) were analyzed retrospectively. Median age of the entire cohort was 66.1 years old (range 60-78.2). An FLT3-ITD mutation was evidenced in 52 of 138 patients (37.6%) with a median FLT3-ITD AR of 0.53 (range, 0.05-3). With a median follow-up of 19.61 months (0.07-128.4), the overall CR rate was 89.9% with no influence of DNMT3a or FLT3 mutational status on the probability of CR. In this elderly cohort of NPM1mut patients, a 4log reduction of NPM1 bone marrow (BM) MRD1 was associated with better outcome (median OS: NR vs 13.4 months, HR=0.35, p&amp;lt;0.01)(Figure A). Overall, DNMT3 status did not influence the probability of having a ≥ 4log MRD1 reduction after induction. However, only 9/44 (20.4%) FLT3-ITD patients reached ≥ 4log MRD1 reduction whereas 38/80 FLT3wt (47.5%) were good molecular responders (p&amp;lt;0.001). FLT3-ITD mutated patients who achieved a 4log reduction had a superior outcome compared to those who did not (HR=0.34; 95% CI, 0.16 to 0.70; P &amp;lt;0.001). Similarly, NPM1mut FLT3wt patients with a 4log reduction in NPM1 BM-MRD1 had a longer OS (3-year OS, 68.1%; 95% CI, 48.8 to 82.9) than those without good molecular response (3-year OS, 46.5%; 95% CI, 30.2 to 61.7)(Figure B). DNMT3a negative patients who achieved a 4log reduction had a superior outcome to those who did not reached at least a 4log reduction (HR=0.23; 95% CI, 0.07 to 0.72; P &amp;lt;0.001). However, postinduction NPM1 MRD1 reduction was not predictive of OS and leukemia free survival (LFS) in DNMT3amut patients. DNMT3amut patients has a very poor LFS which was even worst in poor NPM1 MRD1 responders compared to those who reached at least 4log reduction (median LFS: 8.3 months vs 17.4 months, HR = 0.48, 95% CI, 0.25-0.91, p=0.023)(Figure C). In multivariate analysis, only DNMT3a mutational status and a 4-log reduction in NPM1 BM-MRD were significantly associated with survival. Based on these results, we identified among NPM1 positive patients 3 groups with distinct prognosis, based on FLT3-ITD, DNMT3a status and NPM1 BM-MRD post induction response (NPM1 scoring system)(Figure D). When compared to ELN 2017 intermediate risk group (AUC=0.695), NPM1 scoring system (NPM1 SS) was more accurate for OS prediction in patients within intermediate (AUC=0.833) and unfavorable (AUC=0.863) NPM1 SS risk group. However, there was no significant difference in AUC between NPM1 SS favorable and ELN 2017 favorable risk group. These results confirm that post-induction NPM1 MRD1 is a reliable tool to assess disease outcome in elderly AML patients. However, the presence of DNMT3a also identify a subgroup of patients at very high risk of relapase, despite good molecular responses. As hematopoietic stem cell transplantation (HSCT) might improve OS in elderly patients, DNMT3a positive AML elderly patients should be considered for HSCT or post induction maintenance strategies, even within the favorable ELN risk group. Figure Disclosures Sujobert: Gilead/Kyte: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Research Funding.

Outcomes of Therapy with Venetoclax Combined with Hypomethylating Agents in Favorable-Risk Acute Myeloid Leukemia (AML)

Outcomes of Therapy with Venetoclax Combined with Hypomethylating Agents in Favorable-Risk Acute Myeloid Leukemia (AML)

Feasibility, and Efficacy of Donor-Derived cd19-Targeted Car t-Cell Therapy in Refractory/Relapsed(r/r)b-Cell Acute Lymphoblastic Leukemia (b-all) Patients

Backgrounds As CAR T-cell therapy is a highly personalized therapy, process of generating autologous CAR-T cells for each patient is complex and can still be problematic, particularly for heavily pre-treated patients and patients with significant leukemia burden. Here, we analyzed the feasibility and efficacy in 37 patients with refractory/relapsed (R/R) B-ALL who received CAR T-cells derived from related donors. Patients and Methods From April 2017 to May 2020, 37 R/R B-ALL patients with a median age of 19 years (3-61 years), were treated with second-generation CD19 CAR-T cells derived from donors. The data was aggregated from three clinical trials (www.clinicaltrials.gov NCT03173417; NCT02546739; and www.chictr.org.cn ChiCTR-ONC-17012829). Of the 37 patients, 28 were relapsed following allogenic hematopoietic stem cell transplant (allo-HSCT) and whose lymphocytes were collected from their transplant donors (3 HLA matched sibling and 25 haploidentical). For the remaining 9 patients without prior transplant, the lymphocytes were collected from HLA identical sibling donors (n=5) or haploidentical donors (n=4) because CAR-T cells manufacture from patient samples either failed (n=5) or blasts in peripheral blood were too high (&amp;gt;40%) to collect quality T-cells. The median CAR-T cell dose infused was 3×105/kg (1-30×105/kg). Results For the 28 patients who relapsed after prior allo-HSCT, 27 (96.4%) achieved CR within 30 days post CAR T-cell infusion, of which 25 (89.3%) were minimal residual disease (MRD) negative. Within one month following CAR T-cell therapy, graft-versus-host disease (GVHD) occurred in 3 patients including 1 with rash and 2 with diarrhea. A total of 19 of the 28 (67.9%) patients had cytokine release syndrome (CRS), including two patients (7.1%) with Grade 3-4 CRS. Four patients had CAR T-cell related neurotoxicity including 3 with Grade 3-4 events. With a medium follow up of 103 days (1-669days), the median overall survival (OS) was 169 days (1-668 days), and the median leukemia-free survival (LFS) was 158 days (1-438 days). After CAR T-cell therapy, 15 patients bridged into a second allo-HSCT and one of 15 patients (6.7%) relapsed following transplant, and two died from infection. There were 11 patients that did not receive a second transplantation, of which three patients (27.3%) relapsed, and four parents died (one due to relapse, one from arrhythmia and two from GVHD/infection). Two patients were lost to follow-up. The remaining nine patients had no prior transplantation. At the time of T-cell collection, the median bone marrow blasts were 90% (range: 18.5%-98.5%), and the median peripheral blood blasts were 10% (range: 0-70%). CR rate within 30 days post CAR-T was 44.4% (4/9 cases). Six patients developed CRS, including four with Grade 3 CRS. Only one patient had Grade 3 neurotoxicity. No GVHD occurred following CAR T-cell therapy. Among the nine patients, five were treated with CAR T-cells derived from HLA-identical sibling donors and three of those five patients achieved CR. One patient who achieved a CR died from disseminated intravascular coagulation (DIC) on day 16. Two patients who achieved a CR bridged into allo-HSCT, including one patient who relapsed and died. One of two patients who did not response to CAR T-cell therapy died from leukemia. Four of the nine patients were treated with CAR T-cells derived from haploidentical related donors. One of the four cases achieved a CR but died from infection on day 90. The other three patients who had no response to CAR T-cell therapy died from disease progression within 3 months (7-90 days). Altogether, seven of the nine patients died with a median time of 19 days (7-505 days). Conclusions We find that manufacturing CD19+ CAR-T cells derived from donors is feasible. For patients who relapse following allo-HSCT, the transplant donor derived CAR-T cells are safe and effective with a CR rate as high as 96.4%. If a patient did not have GVHD prior to CAR T-cell therapy, the incidence of GVHD following CAR T-cell was low. Among patients without a history of transplantation, an inability to collect autologous lymphocytes signaled that the patient's condition had already reached a very advanced stage. However, CAR T-cells derived from HLA identical siblings can still be considered in our experience, no GVHD occurred in these patients. But the efficacy of CAR T-cells from haploidentical donors was very poor. Disclosures No relevant conflicts of interest to declare.

Long Term Analysis of a Monocentric Cohort of Therapy-Related Acute Lymphoblastic Leukemia

Therapy related Acute Lymphoblastic Leukemia (t-ALL) refers to ALL developed in patients who have received prior cytotoxic therapies, including chemotherapies (CT) and/or radiotherapy (RT). Contrary to therapy-related myeloid neoplasms, t-ALL has not been fully recognized and its clinical and biological features remain poorly described. We reviewed all consecutive cases of adult t-ALL treated at our institution and described their clinical, phenotypic, and genetic characteristics. Between 1998 and 2019, 36 patients were admitted at Institut Paoli-Calmettes for t-ALL which represents 3.5% of all ALL admitted during the same period (n=1036). Median age was 67.5 years (ranges, 20-83). Twenty-eight (78%) patients were females. Thirty-eight (78%) patients of the t-ALL were secondary to a solid cancer. Among the most frequent solid tumors, we found 14 (39%) breast cancers, 5 (14%) pulmonary cancers and 4 (11%) thyroid cancers. Eight patients had a t-ALL secondary to a hematological malignancy (4 Non-Hodgkin lymphomas, 3 Hodgkin lymphomas and one myeloma). Three (8%) patients presented with more than one primary cancer. Primary malignancies were treated with CT in 7 cases (19%), RT in 11 cases (31%) and CT+RT in 16 cases (44%), in association or not with surgery of the primary tumor. Median time between the start of first malignancy treatment and t-ALL diagnosis was 5.4 years (ranges, 0.3-35). Median white blood cell count (WBC) was 15.9 (ranges, 0.6-386). Phenotypic characteristics at diagnosis were consistent with B-ALL for 31 patients (86%), and T-ALL or acute mixed-lineage leukemia for 2 (6%) and 3 (8%) patients, respectively. 9 (22%) cases were Philadelphia chromosome-positive by karyotype or Fluorescent in situ hybridization, 5 (14%) cases had MLL rearrangement, 5 (14%) cases had hypodiploidy, 3 (8%) cases had hyperdiploidy and 3 (8%) cases had normal karyotype. The 11 (30%) other cases had other genetic abnormalities. Thirty-one (86%) patients received intensive CT and 5 (14%) patients received a palliative treatment. For one patient, treatment modalities were missing. Twenty-eight (78%) were in complete remission (CR) after CT and 7 (19%) patients underwent an allogenic hematopoietic stem cell transplantation in first CR. Median follow-up was 52 months. Median overall survival calculated from the time of t-ALL diagnosis was 16 months and median leukemia-free survival was 14.3 months. Multivariate analyses taking age, WBC, MLL alteration, complex karyotype and BCR-ABL rearrangement into account, found that BCR-ABL alteration was associated with a higher OS (HR=4.9; ranges, 1.1-22.6). In conclusion, our results confirm that t-ALL is a rare event. Besides an older age at diagnosis, t-ALL does not display specific phenotypic or genetic characteristics. In our series, the patient outcome was poor. Further genetic studies are needed to better understand the pathogenesis of this ALL subgroup. Disclosures No relevant conflicts of interest to declare.

CD38-Directed CAR-T Cell Therapy: A Novel Immunotherapy Strategy for Relapsed Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

There are few effective therapies for relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which has a poor prognosis. Although CD19-targeted chimeric antigen receptor T cell (CAR-T-19) therapy has achieved remarkable success for B-cell malignancies, few successful CAR-T cell therapies in AML have been reported. In this prospective study, we explored the therapeutic effect and clinical safety of the application of CAR-T-38 in 6 AML patients with relapsed post allo-HSCT and CD38 expression. The decitabine (DAC) + HAAG regimen was used to reduce tumor burden, followed by the fludarabine and cyclophosphamide (FC) regimen for lymphodepletion chemotherapy before CAR-T cell infusion. In total, 8.05 (6.1-10) x 106/kg CAR-T-38 were infused by dose escalation over a 3- to 4-day period. At 1, 2 and 4 weeks after CAR-T infusion, two (33.3%), four (66.7%) and four (66.7%) of six patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), respectively. Five of six (83.3%) patients experienced mild (grade I-II) cytokine release syndrome (CRS), and only one patient presented grade III hepatotoxicity. No neurological toxicities were observed, but all six patients had grade III/IV hematological toxicities. The 6-month overall survival (OS) and leukemia-free survival (LFS) rates were 50% and 50%, respectively, and the median OS and LFS were 12.3 and 10.3 months, respectively. The cumulative relapse rates at 3 and 6 months were 25% and 50%, respectively. Multiparameter flow cytometry (FCM) showed that the percentage of CD38-positive blasts remarkably decreased at day 7 and remained at low levels on day 28 after CAR-T cell infusion, but CD38-positive monocytes and lymphocytes were not depleted. This study is the first to indicate that CAR-T-38 therapy is a promising effective and safe approach for patients with relapsed AML after allo-HSCT. (NCT04351022) Disclosures No relevant conflicts of interest to declare.

Prognostic Prediction with Static-Dynamic Clinical and Pathological Parameters By Machine Learning Algorithm in Acute Lymphoblastic Leukemia

Introduction Current risk stratification of Acute Lymphoblastic Leukemia (ALL) approach has significantly improve the outcome for pediatric and adolescent ALL. However, the outcome for adult ALL remains poor. With the emerging technologies that could drastically increase the parameters and scales of clinical data for treatment strategy formulation and more new therapeutic agents approved for ALL treatment, a better integrated and more systematic risk stratification method is needed for ALL. In our study, we propose to use artificial intelligence to develop an integral outcome prediction models that include all clinical exam and treatment history, aiming to further improve current risk stratification strategies. Method Retrospective clinical data of patients with ALL, including demographic (age &amp; gender), laboratory results including complete blood count (CBC), white blood count (WBC), molecular genetics, cytogenetics, flow cytometry (FC) and treatment history at National Taiwan University Hospital were collected. A total of 513 newly diagnosed ALL from 2005 to 2017 were enrolled this study. The median age at diagnosis was 20 years and the median follow up duration was 49.1 months, 78.9% of them achieved complete remission (CR), 27.5% had relapsed, 31.6% had received HSCT (Table 1). In total, 243,464 CBC &amp; WBC records, 32 types of anti-neoplastic medications in L01, L03 and L04 ATC code category with a total of 20,043 medication records from these 513 patients were utilized in developing the ALL outcome prediction model. A vectorized representation that captures the static-dynamic clinical aspects of an ALL patient can be learned directly from the collected data. The representation includes both static personal attributes (demographic, and genetic) and time-varying progression of patient's clinical assessment across time (laboratory results, HSCT, and medication). The time-dependent representation was derived from training a deep network architecture of bi-directional long short-term memory network (BLSTM). By taking 7 days as a time step, the BLSTM took the input of Fisher-vector encoded time series of a patient's CBC and WBC, medication, and HSCT records separately. The last output layer, which summarized the relapse/mortality risk exhibited in the measurements of patient's clinical conditions over time, of each separately-learned BLSTM was used as the encoded dynamic clinical representation. The concatenation of the ALL patient's static features and the time-dependent representations were fed into a deep neural network followed by a support vector machine to carry out the final prediction. The prediction models were conducted in 5-fold cross-validation experiments and further evaluated using metrics of accuracy (ACC). Results The median leukemia free survival and median overall survival of these 513 ALL patients are 29.3 months and 61.9 months respectively. The outcome prediction models developed achieved accuracy of next 3-month relapse, relapse or mortality, and mortality prediction reached 86.2%, 74.9% and 64.3% respectively (Table 2). Conclusions Our team has demonstrated the BLSTM-DNN model's potential that is capable in taking multiple and longitudinal clinical measurements into integrated relapse or mortality prediction in AML in 2018 (ASH 2018 #2811) and we have observed the same potential in ALL relapse and mortality prediction. More external and multi-national center studies are needed to further improve the performance of such integrated outcome prediction models. Disclosures Ko: Roche: Honoraria.

Obesity-Driven Acceleration of Acute Promyelocytic Leukemia Development in Mice with Inserted PML-RARa

While a number of solid tumors are identified as obesity-associated cancers, multiple myeloma and acute promyelocytic leukemia (APL) are the only hematologic malignancies included in this category. APL is a highly treatable form of AML characterized by maturation arrest at the promyelocyte stage, and frequent cures with combined ATRA and Arsenic Trioxide therapy. APL is initiated by a chromosomal translocation that causes the fusion of thePMLandRARAgenes, leading to the production of PML-RARA protein. To determine if obesity accelerates the development of APL, we used a genetically-engineered knock-in model in which human PML-RARA cDNA was inserted into the 5' untranslated region of the murine cathepsin G gene (Ctsg), which targets expression to early myeloid progenitor cells. This knock-in transgene was extensively backcrossed (&amp;gt;20 generations) into the C57BL/6J (B6) genetic background, which has been consistently shown to render mice susceptible to diet-induced obesity.Ctsg-PML-RARA mice developed on the B6 background generate a lethal APL-like leukemia with a latency of 8-12 months, and a penetrance of about 60%, as cooperating mutations occur and cause clinical disease. We placed cohorts of B6.Ctsg-PML-RARA heterozygous (mCG+/PR) and wild-type (WT) mice, genotyped by PCR, on high-fat (HFD) [57% coconut oil fat] and low-fat (LFD) [10% coconut oil fat] diets, collecting peripheral blood via the retro- orbital sinus at 30 day intervals and performing automated blood counts to observe temporal associations in disease development. HFD feeding significantly accelerated the development of APL in mCG+/PR mice, leading to anemia, thrombocytopenia, leukocytosis of the granulocyte series, and splenomegaly. Survival rate reduction demonstrated sexual-dimorphism, with male HFD-fed mCG+/PR mice displaying a median leukemia-free survival time of 211 days compared to 266 days in the female HFD-fed mCG+/PR cohort. In contrast, LFD-fed mCG+/PR male mice showed a median survival time of 318 days, whereas none of LFD-fed mCG+/PR female group nor any of the WT groups on HFD or LFD have reached median survival as of 325 days. Moreover, no signs of leukemia were observed in either HFD- and LFD-fed WT groups, indicating that adiposity alone had no leukemogenic effect. These studies clearly demonstrate that obesity accelerates leukemogenesis in theCtsg-PML-RARA mouse model of acute promyelocytic leukemia. High density flow cytometry will be applied in the bone marrow of the different groups to evaluate the modulation of multiple hematopoietic cell lineages and cell surface markers. Disclosures No relevant conflicts of interest to declare.

Characteristics and Trends of Adult Acute Lymphoblastic Leukemia in a Large, Public Safety-Net Hospital

BackgroundManagement of acute lymphoblastic leukemia (ALL) in a socioeconomically vulnerable population without ready access to a hematopoietic stem cell transplant (HCT) center and clinical trials is challenging. Data regarding the outcomes of such patients are sparse. Patients and MethodsThis retrospective analysis included 90 consecutive patients with ALL who presented to Harbor-UCLA between 2003 and 2018. The primary objective was overall survival (OS), whereas secondary objectives included leukemia-free survival, toxicities of therapy, and referral for HCT and incidence of successful HCT. ResultsMost patients were male (56.7%) and Hispanic (72.2%). The median age of diagnosis was 36 years (range, 18-63 years). The median OS was 26.8 months (95% confidence interval [CI], 17.4-59.0 months). In patients who achieved complete remission with therapy, the median leukemia-free survival was 16.4 months. Fifty percent of patients experienced at least 1 episode of bacteremia, and nearly 25% of patients developed an invasive fungal infection. Thirty-six percent (n = 32) of patients were referred for HCT. The referral rate increased over time, which led to improved OS in patients who underwent evaluation at a tertiary cancer center (hazard ratio, 0.44; 95% CI, 0.21-0.89; P = .02). Patients who underwent HCT had significantly better OS compared with those who did not (OS not reached vs. 21.9 months; hazard ratio, 0.16; 95% CI, 0.04-0.68; P = .01). ConclusionRisk stratification and evidence-based treatment approaches are important for patients with ALL treated in a resource-limited setting. Most patients can be induced successfully and achieve complete remission with therapy. Partnership with a cancer center with early referral for HCT can facilitate curative HCT to be performed.

Safety and efficacy of blinatumomab: a real world data.

Despite improvement in survival of newly diagnosed adult precursor B-acute lymphoblastic leukemia/lymphoma (B-ALL), the results of relapsed/refractory disease are poor. Blinatumomab, a bispecific monoclonal antibody directed against CD19/CD3 show clinical activity against relapsed/refractory B-ALL and in minimal residual disease (MRD)-positive patients.We report our "real-world" experience with blinatumomab in patients with relapsed/refractory B-ALL.Twenty-one patients, at a median age 52 years with median disease duration of 10 months, were included. Indications for treatment were hematological relapse (n = 17), MRD positivity (n = 2), inability to continue intensive chemotherapy (n = 1), and bridging to a second alloSCT (n = 1). Blinatumomab was given as first salvage in 11 patients and after at least one prior salvage treatment in eight.Complete response (CR) was newly achieved in 47% and was maintained in 75% of patients with baseline CR. At a median follow-up of 12.4 months, 13 patients were alive, and 11 in CR. Median leukemia-free survival was 8.7 months, and median overall survival was 15.2 months. Median leukemia-free survival and overall survival were not reached in patients proceeding to alloSCT compared to 5.1 and 15.2 months, respectively, for patients who did not receive stem cell transplantation.Treatment was well tolerated with neurological events reported in two patients (10%) and GI events in three patients (14%). Cytokine storm was reported in four patients (19%).In conclusion, treatment with blinatumomab is effective and tolerable in adult patients with relapsed/refractory B-ALL outside of a clinical trial stetting.

AML in Saudi Arabia: Analysis According to the European LeukaemiaNet 2017 Cytogenetic Classification

IntroductionTo the best of our knowledge, few studies have addressed the prognosis of patients with acute myeloid leukemia (AML) in Saudi Arabia. The present study retrospectively analyzed the prognostic factors in patients with de novo AML at a single institution owing to the observation of some differences with the reported data from the Western world. Patients and MethodsPatients with de novo AML who had been referred to King Abdulla Medical City were included. All patients had undergone bone marrow aspiration, biopsy, flow cytometry, cytogenetics (conventional and fluorescence in situ hybridization panel performed at Mayo Clinic), molecular tests, and other routine tests. ResultsThe data from 170 patients were reviewed. Of the 170 patients, 26 had had acute promyelocytic leukemia, 16 with AML had received less intensive therapy, 119 had received intensive induction, and 8 had refused treatment. The present analysis was limited to the 119 patients who had received intensive induction therapy. For the major cytogenetic categories, 17 of 27 patients with core binding factor leukemia (62.9%) were reassigned to the intermediate (n = 10; 37%) or unfavorable (n = 7; 25.9%) risk group according to the FLT3-ITD and NPM results. Of the 50 cases of normal cytogenetic findings, 2 (4%) were considered unfavorable, 12 (24%), favorable, 30 intermediate (60%), and 6 (12%) unknown. The median leukemia-free survival was 21.5 months. The median overall survival was 16.4 ± 2.2 months, with a 3-year survival rate of 37.2%. Multivariate Cox regression analysis revealed that the cytogenetics results (P = .002) and the presence of FLT-3 (P = .03) were independent prognostic factors for relapse-free survival. Performance status, response, relapse, and cytogenetics findings were independent prognostic factors for survival. ConclusionsThe results from the present study revealed some differences in patient age and cytogenetic risk groups for patients with AML in our region and those in the Western world, including a younger median age, relevance of core binding factor leukemia, and a greater incidence of monosomies.

High Risk of Relapse with Intermediate Dose Cytarabine for Consolidation in Young Favorable Risk AML Patients Following Induction with 7+3

Introduction CALGB study in 1994 reported improved leukemia free survival (LFS) with sequential courses of high dose cytarabine (HIDAC- 3 gm/m2, q12h on days 1, 3 and 5) compared to lower doses of 100 mg/m2 and 400 mg/m2 per day. Following this study, HIDAC has been commonly used for chemotherapy consolidation in AML patients 60 years or younger. More recently, several groups investigated the role of intermediate dose cytarabine (IDAC-1.5 gm/m2 q12h D 1, 3 and 5 or D 1-3) in this population and reported equivalent outcomes for IDAC compared to HIDAC (Table 1). ELN guidelines published in January 2017 recommend IDAC for consolidation therapy in young (&amp;lt;60 years) favorable risk AML patients. Following these studies and ELN publication, consolidation protocols for AML patients 60 years or younger were changed from HIDAC to IDAC at Singapore General Hospital (SGH) in 2011 and at University of Minnesota Medical Center (UMMC) in February 2017. NCCN continues to recommend HIDAC as category 1 recommendation for consolidation of patients in this setting. We performed a combined analysis of outcomes in young favorable risk AML patients to assess impact of this change in practice on outcomes at our institutions as a quality initiative. Methods Patients 60 years or younger with ELN favorable risk AML between 2004 and 2015 at SGH and between September 2015 and March 2018 at UMMC, who underwent induction therapy with 7+3 regimen (idarubicin 12 mg/m2 D1-3 or daunorubicin 60 - 90 mg/m2 and cytarabine 100 mg/m2 continuous infusion from D1-7) and consolidation with cytarabine monotherapy were identified. These dates were chosen to allow reasonably equal time distribution before and after change in our practice. We extracted relevant outcomes data using chart review. We used Chi-square testing and applied Kaplan-Meier survival analysis to detect differences in relapse and survival outcomes. Results Of 67 ELN favorable risk patients 60 years or younger, 42 received HIDAC and 25 received IDAC. Median age was 39 years (range 16-59). 64 patients received 1 induction cycle and 3 patients received 2 induction cycles to achieve complete remission. Median LFS and overall survival (OS) with HIDAC vs IDAC were not-reached (NR, median time for follow up = 6.9 years) vs 1.35 years (p=0.004) and NR vs 2.27 years (p=0.001) respectively (Figure 1). Cumulative incidence of relapse at 2 years was 23.8% for HIDAC and 60% for IDAC groups (p=0.003). 3-year LFS and OS for HIDAC vs IDAC groups were 71% vs 36% (p=0.06) and 90% vs 48% (p=0.002). Discussion Historical data suggests chemotherapy consolidation with 3-4 cycles of HIDAC achieves long-term LFS of 60 - 70 % in young favorable risk AML patients. While the outcomes in HIDAC group in this study are comparable to historical data with good outcomes, a significantly larger proportion of patients in the IDAC group had early relapse (60%) and death. A major difference between the patients in this study and the other studies which showed similar outcomes with HIDAC and IDAC is the mode of induction. Data from large randomized studies in AML (Table 1) that suggest similar efficacy of IDAC compared to HIDAC used higher intensity induction regimens (frequently double induction therapy) compared to 7+3 and/or used other agents in combination with Ara-C for consolidation. These data are not broadly applicable in patients who receive a single cycle of 7+3 for induction, when selecting dose of Ara-C as monotherapy for consolidation. Furthermore, studies that used 7+3 for induction therapy showed benefit for HIDAC compared with multi-agent chemotherapy that included IDAC (Table 1). Conclusion Using single agent IDAC for post remission therapy is associated with higher rates of relapse and poor overall survival compared to HIDAC among young, ELN favorable risk AML patients who achieve complete remission following 7+3. The large randomized studies that suggested equivalency of IDAC to HIDAC for post remission therapy in AML patients, either used more than one cycle of intensive induction regimen and/or used cytarabine in combination with an anthracycline for consolidation. Hence, ELN guidelines should be cautiously interpreted given the above limitations in generalizability. Our study suggests that HIDAC, rather than IDAC, is the preferred chemotherapy consolidation regimen in young, favorable risk AML patients following standard 7+3 induction. Foot note: BK &amp; NAAH contributed equally. FH &amp; ZL contributed equally. Disclosures Kolla: Amgen: Equity Ownership. Weisdorf:Pharmacyclics: Consultancy; Incyte: Research Funding; Fate Therapeutics: Consultancy.

Successful Treatment of Chimeric Antigen Receptor T Cell Therapy in Refractory or Relapsed Acute Leukemia Patients with TP53 alterations

Backgrounds: Refractory or relapsed(R/R) acute leukemia (AL) patients with TP53 alterations have a dismal outcome with current therapy. Recently, chimeric antigen receptor T cells (CAR-T) therapy has emerged as a novel immunotherapy modality in treating patients with R/R acute B lymphocytic leukemia (B-ALL) patients, with consistently high response rates and durable remissions and even cures across multiple studies. However, successful treatment of CAR-T therapy in R/R AL with TP53 alterations has been a challenge. Here, we conducted a phase II trial testing efficacy and toxicities of CAR-T therapy in R/R AL patients with TP53 alterations. Methods: The second generation CAR-T cells were successfully made from 9 patients' autologous lymphocytes and 2 donors' allogeneic lymphocytes and qualified tests were done before infusion to patients. CAR constructs used were humanized CAR targeting CD19, CD22 or tandem CD19 and CD22 according to the expression levels of each target on blasts. In this ongoing trial, 11 R/R AL patients with TP53 alterations (10 with TP53 mutations and 1 with TP53 deletions) including 2 relapsed after allo- allogeneic hematopoietic stem cell transplantation were included to evaluate the efficacy and safety of CAR-T therapy. Among the enrolled 11 R/R patients, 9 patients were diagnosed with B-ALL, 1 was diagnosed with acute myeloid leukemia (AML) and 1 was diagnosed with mixed phenotype acute leukemia (MPAL) (B-ALL and AML). After leukapheresis, all patients received fludarabine-based lymphodepletion chemotherapy with FLAG regimen (Fludarabine 30mg/m2 × 5d, Cytarabine 2g/m2 × 5d and Granulocyte-colony stimulating factor 300ug ×6d) in two cases, FC regimen (Fludarabine 30mg/m2 × 3d and Cyclophosphamide 300mg/m2 × 3d) in five cases, and FC+DAC regimen (Decitabine 50mg × 3d, Fludarabine 30mg/m2 × 3d and Cyclophosphamide 300mg/m2 × 3d) in four cases. Two days after chemotherapy, autologous/allogeneic CAR-T cells were infused within 2 to 4 days in a dose-escalation. Results: With a median (range) dose of 1×107/kg (0.1-1.5×107/kg) CAR-T cells, we observed a high response rate with 10/11 (90.9%) evaluated R/R patients achieved complete remission (CR) and 9/11 (81.8%) patients achieved molecular CR (mCR). Moreover, Most cases (8/11, 72.7%) only experienced mild to moderate cytokine release syndrome (CRS) and no neurological toxicity were observed. With a median follow-up of 10 months, 3 cases died of progressive disease including 1 case failed to response to CAR-T therapy, 1 case achieved CR and relapsed after CAR-T therapy and 1 case achieved mCR after CAR-T therapy and relapsed after the following allo-HSCT, and the left 8 cases still kept in mCR and alive. The one-year overall survival (OS) and leukemia-free survival (LFS) rates were 68.4% and 78% respectively. The 2-year cumulative incidence of relapse was 22.2%, and the non-relapse mortality rate was 0%. Further subgroup analysis showed that all 6 cases who received decitabine therapy (DAC group) achieved and maintained in mCR, while only 2 cases achieved and kept in mCR and 3 cases died from progressive disease in the cases without receiving decitabine therapy (Non-DAC group). The median OS and LFS for Non-DAC group was 10 and 16.375 months respectively, while the median OS and LFS for DAC group were unreached. Relative IL-6 and CRP levels increased dramatically in DAC group than that in Non-DAC group. However, there were no significant difference on treatment related toxicities between cases in DAC group and Non-DAC group. Conclusions: Our trial indicates that CAR-T therapy is a safe and powerful salvage approach to R/R AL patients with TP53 alterations and application of decitabine may fuel CAR-T therapy and reduce the relapse rate without increasing therapy related mortality incidences in this high risk population. Disclosures No relevant conflicts of interest to declare.

The Prognostic Significance of Monocytopenia in Patients with Myelodysplastic Syndrome

The Prognostic Significance of Monocytopenia in Patients with Myelodysplastic Syndrome

Long Term Effects of Eltrombopag Treatment Versus Placebo for Low-Risk Myelodysplastic Syndromes with Thrombocytopenia (EQoL-MDS): Interim Results of a Single-Blind, Randomised, Controlled, Phase 2 Superiority Trial

Long Term Effects of Eltrombopag Treatment Versus Placebo for Low-Risk Myelodysplastic Syndromes with Thrombocytopenia (EQoL-MDS): Interim Results of a Single-Blind, Randomised, Controlled, Phase 2 Superiority Trial

PB2350 EFFICACY AND SAFETY OF POST HEMATOPOIETIC STEM CELL TRANSPLANTATION DONOR LYMPHOCYTE INFUSION IN PATIENTS WITH ACUTE LEUKEMIA. RETROSPECTIVE ANALYSIS IN OUR CENTER

Background:Relapse of acute leukemia (AL) after allogenic hematopoietic stem cell transplantation (alloHSCT) worsens patients’ prognosis. Donor lymphocyte infusion (DLI) may be an effective therapy in these patients.Aims:Our objective was to asses the efficacy and safety of DLI in three different settings after alloHSCT: therapeutic (relapse or progression), pre‐emptive (positive minimal residual disease or mixed chimerism) and prophylactic (patients at high risk of relapse).Methods:Retrospective analysis of 30 patients with AL who received DLI after alloHSCT from 2000 to 2018. Patients in 2nd or further complete remission (CR), positive MRD or adverse cytogenetics were considered at high risk for relapse. Median age was 37 years (5‐71). Twenty one patients were males. The baseline characteristics of the patients are shown in table 1.Twenty two patients had a matched donor (14 related, 8 unrelated), 5 patients received a mismatched graft and 3 patients a haploidentical graft. Fourteen patients received DLI therapeutically, 11 pre‐emptive and 5 as prophylaxis. At DLI, only one patient had mild chronic graft versus host disease. All patients were off immunosuppresive therapy at DLI. Seven patients received reinduction chemotherapy before the DLI.Fifty eight doses of DLI were administered, with a median of 1 (1‐5) dose per patient. The maximum infused dose varied, depending on the type of donor and degree of HLA disparity: 5,4 (1 ‐15,3), 4,2 (1‐10), 1,9 (0,2‐4,6) and 0,5 (0,2‐1) × 10^7/kg in matched related donor, matched unrelated donor, missmatch and haploidentical, respectively. The dose was higher in the therapeutic group. Median time until triggering event of DLI (relapse, appearance of MRD or loss of chymerism) was 132 days (21‐547) and median time from alloHSCT until first DLI was 179 days (38‐771)Leukemia Free Survival (LFS) and overall survival (OS) were calculated using de Kaplan‐Meier (KM) method and compared using the log‐rank test. The median follow‐up was calculated with the inverse of KM. SPSS software was used for the data analysis.Results:Nine out of 14 patients in the therapeutic group reached CR and 1 PR. Among 11 patients in pre‐emptive group, 5 reached CR. Four out of 5 patients in the prophylactic group remained in CR. The median follow up after DLI was 65 (IC 95% 16,3 to 113,6) months. Median OS and LFS for the entire cohort were 14 (IC 95%, 3, 9 to 24,1) and 9 (IC 95%, 1,1 to 16,9) months, respectively.Median OS and LFS in the therapeutic group were 7 (CI 95%, 1, 5‐12,5) and 4 (CI 95%, 0‐12,5) months, respectively. Median OS and LFS in the pre‐emptive group, were 14 (CI 95% 7, 7‐20,3) and 5 (CI 95%, 0‐38) months, respectively. In the prophylactic group, the median OS (p = 0,029) and LFS (p = 0,01) were not reached. The LFS probability at 1, 2 and 3 years was 80% (IC 95%, 77 to 82).Patients in CR after DLI (n = 14) had a median LFS of 17 months (IC 95% 5,5 to 28)After DLI, 14 (46,7%) patients developed GvHD: grade III‐IV acute GvHD in 2 (6,7%) and moderate‐severe chronic GvHD in 5 (16,6%). Two patients with chronic GvHD died of related complications. The causes of death were: relapse (n = 13), severe infection (1), demyelinizing neuropathy (1) and 2 unknown.Summary/Conclusion:Our data suggest that prophylactic DLI could improve LFS in high risk patients. Therapeutic and pre‐emptive DLI was useful in a subgroup of patients with relapsed leukemia or positive MRD. More than half of relapsed patients reached CR after DLI. DLI was a safe treatment, GVHD being the most frequent complication but with a low incidence of severe forms.image