Outcome Of Acute Lymphoblastic Leukemia Patients Research Articles

Evaluation of the Effectiveness of Antifungal Prophylaxis in Adult Acute Lymphoblastic Leukemia during Induction Chemotherapy

Background and Objectives: Due to immune suppression, patients with hematological malignancies are at a high risk of invasive fungal disease (IFD) during chemotherapy. For patients with myeloid tumors, antifungal prophylaxis is generally recognized. However, there are evident interactions between agents used in acute lymphoblastic leukemia (ALL) remission-induction and antifungal agents, resulting in most clinical trials excluding ALL patients. The need for primary antifungal prophylaxis in ALL patients during chemotherapy is still under debate. This study analyzed the efficacy of primary antifungal prophylaxis (PAP) and the incidence of IFD during the first remission induction in the PDT-ALL-2016 cohort, as well as evaluated the impact of PAP on the outcomes of ALL patients. Methods: The PDT-ALL-2016 cohort consists of 408 newly diagnosed ALL patients aged ≥ 14 years, treated between January 2016 and December 2021. All patients were treated using the GRAALL-2003 backbone, a pediatric-like regimen. This study included 280 patients, with a total of 128 exclusions. Excluded patients consisted of 103 individuals who received initial induction treatment in other hospitals, 12 individuals who died without IFD during the induction period, 9 individuals who experienced fungal infection before induction treatment, 2 individuals who did not complete induction remission treatment and were discharged, and 2 individuals who had lost their cases. PAP was defined as the administration of any systemic antifungal agent for two or more consecutive days to a patient without any evidence or history of IFD during the neutropenic period. The diagnosis of IFD was based on the European Organization for Research and Treatment of Cancer/Mycosis Study Group criteria. Results: Among the 280 patients, 232 received PAP, with caspofungin (n=104), voriconazole (n=59), micafungin (n=44), and others being used as prophylaxis. The baseline characteristics of patients who did or did not receive PAP were similar, except for the age difference (prophylaxis group median age 28.7 versus without prophylaxis group 23.0, P<0.01). In the cohort, 11 proven/probable and 21 possible IFD cases were identified. The incidence of IFD in patients who did or did not receive PAP was 8.6% and 25.0%, respectively. The cumulative incidence of IFD was significantly lower in patients receiving PAP compared to those who did not (HR 0.3, 95% CI 0.1-0.6; P=0.001). In the cohort, the infections of IFD negatively affected overall survival (HR 1.6, 95% CI 0.9-2.7, P=0.093). Conclusions: Our study demonstrates, in a real-life setting, that IFD is a poor prognostic factor for adult ALL and that PAP significantly reduces the incidence of IFD during induction chemotherapy, thereby improving patient survival. Furthermore, compared to published studies (4.3%-18.3%), the incidence of IFD in the prophylaxis group within our cohort is relatively lower. This research was supported by the National Natural Science Foundation of China(NFSC82170163, 81970147), Clinical Study of Nanfang Hospital(LC2016ZD009/2019CR012).

Risk Factors Influencing Transplant Outcomes of Adults with Acute Lymphoblastic Leukemia in First Complete Remission: A Retrospective Analysis from the ALWP of the EBMT

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) remains a standard of care for adult patients with acute lymphoblastic leukemia (ALL) at high risk of relapse, i.e. high-risk features at time of diagnosis (ex. Philadelphia (Ph) positive ALL), or detectable minimal residual disease (MRD+). The aim of our study was to identify risk factors influencing transplant outcomes in ALL patients transplanted between 2015 and 2021. Methods: We included adults undergoing allo-HSCT for ALL in CR1 with available data of ALL phenotype, Ph-status, and MRD pre-transplant. All donor types and stem cell sources were eligible, except cord blood. Ex-vivo T-cell depletion (TCD) represented an exclusion criterion. Results: We identified 2349 transplanted patients including 870 from HLA-matched sibling (MSD), 1150 from unrelated (79% 10/10 and 21% 9/10 UD), and 329 from haploidentical donors (Haplo). Median age was 42.6 (range 18-76.1) years. Median follow-up was 23.5 (95% CI 21.8-24.2) months. The entire cohort was composed of 667 patients (28.4%) with Ph-negative B-ALL, 1325 (56.4%) with Ph-positive B-ALL and 357 (15.2%) with T-ALL. Median time from diagnosis to allo-HSCT was 5.8 (range 1.3-18) months. Stem cell source was peripheral blood (PB) in 85.3% of cases. Conditioning regimen was reduced-intensity (RIC) in 21% and myeloablative (MAC) in 79% of cases. Total body irradiation (TBI) was used in 65.8% of patients, mostly as a MAC (93.9%). Pre-transplant MRD+ was reported in 35.4% while in-vivo TCD was used in 51.5% of cases. At 180 days, cumulative incidence of grade II-IV and grade III-IV acute graft-versus-host disease (aGVHD) were 29.2% (95% CI 27.3-31.1) and 10.1% (95% CI 8.9-11.4), respectively. Two-years overall and extensive chronic GVHD (cGVHD) were 34% (95% CI 31.7-36.3) and 15% (95% CI 13.2-16.8), respectively. At two years, relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival (OS) and GVHD-free/relapse free survival (GRFS) were 22.2% (95% CI 20.3-24.2), 15.4% (95% CI 13.8-17.1), 62.3% (95% CI 60-64.6) 73.9% (95% CI 71.7-76) and 48% (95% CI 45.6-50.3), respectively. By multivariate analysis, MSD (reference group) was associated to higher RI compared to 9/10 UD (HR 1.47, 95% CI 1.01-2.12; p<0.05) and Haplo (HR 1.64, 95% CI 1.15-2.27; p<0.01) but lower NRM and grade II-IV aGVHD compared to both 9/10 and 10/10 UD (for NRM HR 0.54, 95% CI 0.36-0.81; p<0.01 and HR 0.65, 95% CI 0.48-0.88; p<0.01; for aGVHD: HR 0.58, 95% CI 0.44-0.78; p<0.01 and HR 0.70, 95% CI 0.56-0.87; p<0.01). Compared to Ph-negative ALL (reference group), Ph-positive ALL was associated with a lower RI (HR=0.61, 95% CI 0.49-0.77; p<0.01) and higher LFS (HR=0.71, 95% CI 0.60-0.85; p<0.01), OS (HR=0.59, 95% CI 0.48-0.72; p<0.01) and GRFS (HR=0.81, 95% CI 0.70-0.94; p<0.01), while T-ALL was associated to lower NRM (HR 0.58, 95% CI 0.37-0.91: p<0.02) and cGVHD (HR 0.73, 95% CI 0.54-0.98; p<0.04). MRD+ group faced higher RI (HR=1.74, 95% CI 1.42-2.12; p<0.01), lower LFS (HR=1.41, 95% CI 1.21-1.65; p<0.01), OS (HR=1.31, 95% CI 1.08-1.58; p<0.01) and GRFS (HR=1.31, 95% CI 1.14-1.49; p<0.01). Use of TBI enabled lower RI (HR 0.78, 95% CI 0.61-0.99; p=0.04), higher LFS (HR=0.80, 95% CI 0.67-0.96; p<0.02) but higher grade II-IV aGVHD (HR 1.54, 95% CI 1.23-1.92; p<0.01) and cGVHD (HR 1.47, 95% CI 1.16-1.87; p<0.01) compared to chemotherapy. Patients receiving a RIC had a higher RI (HR=1.52, 95% CI 1.17-1.98; p<0.01) and a lower NRM (HR=0.55, 95% CI 0.39-0.77; p<0.01). In vivo TCD allowed lower risk of cGVHD (HR=0.69, 95% CI 0.55-0.85; p<0.01) and higher GRFS (HR=0.78, 95% CI 0.66-0.91; p<0.01). PB stem cells and female-donor to male-recipient were independently associated to higher risk of cGVHD. Elderly patients faced lower LFS, OS and GRFS. Conclusions: Our study reported overall favorable outcomes in the population of recently allografted patients with ALL in CR1 (LFS> 60% et OS> 70% at 2 years). Prognostic role of pre-transplant MRD is confirmed. Results in Ph-positive ALL are not inferior compared to Ph-negative ALL, most probably due to the use of tyrosine kinase inhibitors. Whether incorporation of novel agents will change the role of allo-HSCT in Ph-positive ALL is under investigation. Use of TBI and HLA mismatches are both associated with lower RI despite a higher risk of GVHD, highlighting the importance of tailoring GVHD prophylaxis in these settings.

Prognostic Observational Analysis of BMI, Leptin, and Adiponectin in Children With Acute Lymphocytic Leukemia Undergoing Remission-Induction Chemotherapy.

BackgroundThe survival rate of children and adolescents with acute lymphoblastic leukemia (ALL) has progressively improved. However, ALL survivors often have adverse effects after treatment, such as an increased risk of obesity. Obesity has been associated with reduced survival.ObjectiveWe investigated the relationship between obesity, adipocytokine levels, and ALL short-term outcomes.MethodsWeight and height were measured, and body mass index (BMI) was calculated at patient diagnosis and discharge. Leptin and Adiponectin levels and Minimal Residual Disease (MRD) were measured before therapy, at days 19 of remission-induction therapy, and at the end of remission-induction therapy (days 46). The relationship between BMI, adipocytokine levels, and MRD was then determined.ResultsCompared to the normal BMI group, children with an abnormal increase in BMI had an increase in MRD at day 19 and 46 (P = 0.04 and P = 0.008), and showed a positive correlation (P = 0.014). In addition, we found a positive correlation between weight, hip circumference at diagnosis and at day 19, and MRD at day 46. Both BMI and fat concentric distribution affected the outcome of ALL children. A higher BMI was also associated with a significant increase in Leptin levels at diagnosis. Leptin resistance should be considered in ALL children with high BMI.ConclusionBMI affects the outcome of ALL patients. Early interventions such as regular weight, height monitoring, and dietary assessments should be preferably initiated during remission-induction chemotherapy.

Retrospective Comparison between 12-Gray and 8-Gray Total Body Irradiation (TBI) before Allogeneic Hematopoietic Cell Transplantation in Patients with Acute Lymphoblastic Leukemia in First Complete Remission

Retrospective Comparison between 12-Gray and 8-Gray Total Body Irradiation (TBI) before Allogeneic Hematopoietic Cell Transplantation in Patients with Acute Lymphoblastic Leukemia in First Complete Remission

The association of hyperglycemia with the development of infectious complications in adult Filipino patients with acute lymphoblastic leukemia

IntroductionHyperglycemia occurs in Acute Lymphoblastic Leukemia (ALL) due to chemotherapeutic agents and may be stress-induced. Given the potential impact of hyperglycemia on the clinical outcomes of ALL patients, we sought to determine the association of hyperglycemia with the development of infectious complications. MethodsThis is a retrospective cohort involving adult Filipino ALL patients admitted at a tertiary referral center. Patients were stratified according to blood glucose levels and infections were classified into microbiologically and clinically defined infections. Logistic regression was performed to determine whether hyperglycemia was associated with the development of infectious complications. ResultsOf the 174 patients admitted for ALL, only 76 patients (44%) underwent blood glucose monitoring and were thus included in this study. Hyperglycemia was observed in 64 patients (84.21%). Infectious complications were seen in 56 patients (73.68%), of whom 37 patients (48.68%) had microbiologically defined infections and 19 (25%) had clinically defined infections. The respiratory tract was the most common site of infection and gram-negative bacteria were the predominant isolates. Hyperglycemia significantly increased the likelihood of infectious complications, particularly at blood glucose levels ≥ 200 mg/dL. ConclusionHyperglycemia is associated with an increased likelihood of infectious complications in Filipino ALL patients. With sepsis being one of the main causes of mortality in this population, our study provides compelling evidence for us to consider routine blood glucose monitoring in order to manage and potentially decrease the occurrence of infections in these patients.

Busulfan-containing conditioning regimens in allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia: A Taiwan observational study.

BackgroundAllogeneic stem cell transplantation (allo‐HSCT) is the ultimate cure for acute lymphoblastic leukemia (ALL).AimThis study was performed to compare the outcomes of ALL patients receiving busulfan (Bu) with cyclophosphamide (Cy)‐based or total body irradiation (TBI)‐based regimen in a Chinese population.MethodsWe enrolled 224 adult patients with ALL who received allo‐HSCT at National Taiwan University Hospital between 1997 and 2016.ResultsThe median age at transplantation was 33 years. Before allo‐HSCT, 75.9% of patients attained first or late complete remission. A total of 141 patients (62.9%) received Bu/Cy‐based conditioning, either myeloablative (MA) or reduced‐intensity stem cell transplantation (RIST), and 83 patients received a TBI‐based regimen (MA‐TBI). Patients receiving the MA‐Bu regimen had longer relapse‐free survival (RFS) than those receiving the MA‐TBI regimen (median, 24.1 vs. 6.7 months, p = .044). There was no difference in overall survival (OS, MA‐Bu vs. MA‐TBI vs. RIST‐Bu: 39.4 vs. 28.2 vs. 13.1 months, p = .276), treatment‐related mortality (TRM), or incidences of grade 3–4 acute graft‐versus‐host disease (GvHD). Among patients receiving identical GvHD prophylactic regimens, there was no difference between MA‐Bu and MA‐TBI groups regarding the incidence of grade 3–4 acute GvHD, grade 2–4, and all‐grade chronic GvHD. In subgroup analysis, patients receiving oral busulfan had comparable RFS and OS to the intravenous busulfan group (p = .436 and p = .236, respectively), but a higher TRM (25% vs. 9.8%, p = .016). In the multivariable analysis, disease status before allo‐HSCT was the only risk factor impacting RFS and OS.ConclusionIn summary, patients receiving Bu/Cy‐based or TBI‐based regimens as conditioning had similar results in terms of OS, TRM, and acute GvHD, whereas the use of myeloablative Bu/Cy resulted in a better RFS. A Bu‐based regimen could be an alternative conditioning choice for patients who are ineligible to receive TBI. Prospective and randomized controlled trials are warranted to validate the long‐term outcomes.

Long-Term Outcomes of Total Body Irradiation Plus Cyclophosphamide Versus Busulfan Plus Cyclophosphamide As Conditioning Regimen for Acute Lymphoblastic Leukemia: A Comparative Study

Introduction: Total body irradiation-Cyclophosphamide (TBI-Cy) and Busulfan-Cyclophosphamide (Bu-Cy) are the most commonly used conditioning regimens in allogeneic hematopoietic stem cell transplantation (allo-HCT) for acute lymphoblastic leukemia (ALL). TBI-based conditioning regimens may have a better antitumor effect at sanctuary cites compared to chemotherapy regimens. However, some controversy still remains concerning the role of TBI in adult ALL. Therefore, we aimed to retrospectively investigate long-term treatment outcomes of ALL patients post allo-HCT and identify prognostic factors and the impact of the conditioning.Methods: We enrolled consecutive patients with ALL who underwent alloHCT from 1990 to 2016 in our center, following a TBI- or a Busulfan (Bu)-based conditioning regimen. TBI at 14.4Gy was divided at 6 fractions over 3 days and Bu (mainly oral) at 4mg/kg/day. Both regimens included 120mg/kg Cy. Graft source was mainly mobilized peripheral blood stem cells.Results: We studied 151 ALL (114 B-ALL, 35 T-ALL and 2 biphenotypic) patients aged 28±12 years, transplanted in CR1 (60), other CR (33) or relapsed/refractory disease (58) from sibling (87), HLA matched (42) or mis-matched (17) unrelated and alternative donors (5). TBI-based conditioning was administered in 84, whereas non-TBI in 67. No differences were observed in baseline characteristics, except for disease phase, disease risk index (DRI) and graft source. The majority of non-TBI patients had relapsed/refractory disease at transplant (50.7% versus 28.6% in TBI-conditioning, p=0.043) and subsequently significantly higher DRI (p=0.025). Furthermore, bone marrow was the graft source in significantly higher number of non-TBI patients (28.4% versus 8.3% in the TBI group, p=0.001).With a follow-up of 19.0 (0.5-170.5) in TBI and 14.5 (1.2-319.1) months in the non-TBI group, there was no difference in the incidence of acute (Grade 2-4) or chronic GVHD, thrombotic microangiopathy, bacterial or fungal infections. Only viral infections were significantly increased in the non-TBI group (59% versus 41% in the TBI group, p=0.03). Therefore, there was no significant difference in the cumulative incidence (CI) of treatment-related mortality (5-year CI of 24.1% in non-TBI versus 27.7% in the TBI group, p=0.678) or relapse mortality (5-year CI of 29.2% in non-TBI versus 37.1% in the TBI group, p=0.283).Overall survival (OS) was similar in the TBI and non-TBI group (5-year 46.7% compared to 35.8%, p=0.201). In the multivariate analysis, unfavorable pre-transplant predictors of OS were age (p=0.024), higher disease risk index (DRI) (p=0.007) and female to male donor (p=0.006). Disease-free survival (DFS) was similar in the TBI and non-TBI group (5-year 47.1% compared to 35.4%, p=0.134), with age, higher DRI and female to male donor being unfavorable predictors. When the analysis was limited to patients transplanted in CR1 (40 in the TBI versus 20 in the non-TBI group), there were also no significant differences.Interestingly, age predicted OS and DFS only in the TBI group. TBI patients younger than 40 years had significantly high OS (55.1%, p=0.023) and DFS (55.5%, p=0.02) versus the older ones. Older TBI patients had higher TRM (43.3% versus 20.1%, p=0.135) and relapse mortality (45.8 versus 24.7, p=0.238) that did not reach levels of statistical significance. However, the same was not true for the non-TBI group (p=0.233 for DFS, p=0.326 for OS).Conclusion: In our retrospective data of the last 3 decades, the type of conditioning regimen did not influence the outcome of transplantation. Based on our results, high dose TBI is a feasible conditioning in terms of a prolonged DFS and OS for younger patients and seems an efficient tool to cure high-risk ALL in CR1. It should be kept in mind that intravenous BU is also used with stable pharmacokinetics. Since our data were not powered to appraise superiority of one regimen in terms of efficacy and toxicity, the choice between TBI or Bu conditioning regimens is still under consideration. Treatment is complex for adult ALL patients and remains a field of debate and a challenge for prospective studies in the future. DisclosuresGavriilaki:European Hematology Association: Research Funding.

Genetic Determinants of Blood Cell Traits Play a Role in Susceptibility to Acute Lymphoblastic Leukemia

Background: Genome-wide association studies (GWAS) have identified several genes associated with childhood acute lymphoblastic leukemia (ALL) that are also implicated in variation in hematological traits. We performed a comprehensive study of the shared heritability of blood cell traits and ALL, and investigated whether genetic variation in blood cell traits may underlie ALL risk. Methods: We leveraged genome-wide single nucleotide polymorphism (SNP) data from: 1) 335,332 European ancestry, cancer-free subjects without immune deficiencies or hematopoietic disorders in the UK Biobank (UKB); and 2) a childhood ALL GWAS meta-analysis including 2,121 cases and 59,965 controls of European ancestry, to investigate the shared genetic basis of blood cell trait variation and ALL susceptibility. Co-heritability between blood cell profiles and ALL susceptibility was evaluated by LD score regression. To formally test variation in blood cell traits as potential causal pathways in ALL development, we conducted Mendelian randomization (MR) analyses, which use genetic predictors of blood cell phenotypes to overcome potential confounding and reverse causation in directly measured blood counts. Genetic instruments for MR were developed using a two-stage GWAS of 6 cell types (lymphocytes, monocytes, neutrophils, eosinophils, basophils, platelets), and their ratios (lymphocyte/monocyte - LMR; neutrophil/monocyte - NLR; platelet/lymphocyte - PLR) in the UKB. Next we applied multi-trait analysis of GWAS (MTAG) to improve power for identifying trait-specific loci by exploiting the correlated nature of blood cell traits. Causal odds ratios (OR) for ALL were estimated per 1 standard deviation increase in normalized cell counts (109cells/L) or 1-unit increase in cell type ratios. Results: Using genome-wide SNP data, we found that ALL has a heritability of hg=0.235 (95% confidence intervals, CI:0.203-0.268) in European ancestry individuals. In LD score regression, ALL susceptibility was correlated at the genetic level with overall blood cell counts (rg=0.070, P=0.003), lymphocyte counts (rg=0.088, P=0.004), LMR (rg=0.065, P=0.012), and PLR (rg= -0.072, P=0.001). Genetic instruments for MR were selected from independent (LD r2&amp;lt;0.05) variants with P&amp;lt;5×10-8 in the discovery blood cell trait GWAS/MTAG (N=234,778) and P&amp;lt;0.05 in the replication analysis (N=100,554). The resulting genetic predictors explained between 4.0% (basophils, NSNP=144) and 23.9% (platelets, NSNP=661) of trait variation. Our findings lend support to a modest but significant causal effect of variation in lymphocyte counts (OR=1.16, 95% CI:1.01-1.33), LMR (OR=1.23, 95% CI:1.07-1.41), NLR (OR=0.67, 95% CI:0.54-0.83), and PLR (OR=0.80, 95% CI:0.70-0.92) on ALL risk. There was no evidence of directional pleiotropy based on the MR Egger intercept test (P&amp;gt;0.05). However, significant heterogeneity among SNP-specific causal effects (Cochran's Q P&amp;lt;0.05) indicated potential for confounding due to balanced pleiotropy. In sensitivity analyses using MR-PRESSO framework, which corrects for distortion in causal effects due to pleiotropy, the associations with ALL risk became attenuated for lymphocytes (OR=1.14, 95% CI:0.98-1.32), but persisted for LMR (OR=1.18, 95% CI:1.01-1.38), NLR (OR=0.76, 95% CI:0.60-0.97), and PLR (OR=0.82, 95% CI:0.70-0.95). Next, we searched for individual variants that may underlie the effects on ALL risk using heterogeneity-based clustering of genetic instruments. This analysis confirmed that regulation of blood cell traits partially mediates the effects of known ALL risk variants: rs4948492, rs4245597 (ARID5B), rs2239630 (CEBPE), and rs78697948 (IKZF1). We also identified putative novel ALL risk loci at chromosome 2q22 (OR=1.28, P=2.5×10-6), chr6q23 (OR=1.21, P=9.3×10-6), and chr13q12 (OR=1.79, P=3.2×10-5), though further analyses are required to confirm these associations and identify likely causal variants and genes at these loci. Conclusions: Our findings suggest that dysregulation of blood cell profiles characterized by a genetic predisposition to increased lymphocyte counts, particularly in relation to neutrophils, monocytes, and platelets, confers a modest but significant increase in ALL risk. Additional research is required to determine whether a genetic propensity to higher lymphocyte levels is associated with ALL subtypes or clinical outcomes in ALL patients. Disclosures Ma: Celgene/BMS: Research Funding; BMS: Consultancy.

MicroRNA Signatures in Blood or Bone Marrow Distinguish Subtypes of Pediatric Acute Lymphoblastic Leukemia

OncomiRs are microRNAs that are associated with early onset of specific cancers. To identify microRNAs involved in pediatric acute lymphoblastic leukemia (ALL) subtypes T-ALL and B-ALL, peripheral blood and bone marrow samples were independently subjected to microarray analysis using two different high-fidelity array platforms. The unique and common gene signatures from both arrays were validated by TaqMan individual assays in 100 pediatric ALL samples. Survival studies were carried out in the test set and validation set with 50 randomly selected samples in each set. MicroRNA expression profile revealed characteristic signatures for distinguishing T and B lineages and identified 51 novel microRNAs in pediatric ALL. Interestingly, the present study also revealed endogenous similarities and differences between blood and bone marrow within each ALL subtype. When Cox regression analysis was carried out with these identified microRNAs, 11 of them exhibited expression levels significantly correlated with survival. Validation of some of the common and relevant microRNAs from both arrays showed that their targets are involved in key oncogenic signaling pathways. Thus, this study suggests that microRNAs have the potential to become important diagnostic tools for identification and monitoring clinical outcomes in ALL patients.

Comparing transplant outcomes in ALL patients after haploidentical with PTCy or matched unrelated donor transplantation

AbstractWe compared outcomes of 1461 adult patients with acute lymphoblastic leukemia (ALL) receiving hematopoietic cell transplantation (HCT) from a haploidentical (n = 487) or matched unrelated donor (MUD; n = 974) between January 2005 and June 2018. Graft-versus-host disease (GVHD) prophylaxis was posttransplant cyclophosphamide (PTCy), calcineurin inhibitor (CNI), and mycophenolate mofetil (MMF) for haploidentical, and CNI with MMF or methotrexate with/without antithymoglobulin for MUDs. Haploidentical recipients were matched (1:2 ratio) with MUD controls for sex, conditioning intensity, disease stage, Philadelphia-chromosome status, and cytogenetic risk. In the myeloablative setting, day +28 neutrophil recovery was similar between haploidentical (87%) and MUD (88%) (P = .11). Corresponding rates after reduced-intensity conditioning (RIC) were 84% and 88% (P = .47). The 3-month incidence of grade II-IV acute GVHD (aGVHD) and 3-year chronic GVHD (cGVHD) was similar after haploidentical compared with MUD: myeloablative conditioning, 33% vs 34% (P = .46) for aGVHD and 29% vs 31% for cGVHD (P = .58); RIC, 31% vs 30% (P = .06) for aGVHD and 24% vs 29% for cGVHD (P = .86). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 44% and 51% with haploidentical and MUD (P = .56). Corresponding rates after RIC were 43% and 42% (P = .6). In this large multicenter case-matched retrospective analysis, despite the limitations of a registry-based study (ie, unavailability of key elements such as minimal residual disease testing), our analysis indicated that outcomes of patients with ALL undergoing HCT from a haploidentical donor were comparable with 8 of 8 MUD transplantations.

T315I mutation exerts a dismal prognosis on adult BCR-ABL1-positive acute lymphoblastic leukemia, and salvage therapy with ponatinib or CAR-T cell and bridging to allogeneic hematopoietic stem cell transplantation can improve clinical outcomes.

A single-center retrospective was performed with consecutive de novo BCR-ABL1-positive acute lymphoblastic leukemia (ALL) patients who received TKI-containing therapy between January 2010 and December 2018 to review the incidence, treatment, and outcome of the T315I mutation. A total of 38 (18%) patients harbored the T315I mutation in this period. According to the type of salvage therapy, patients were divided into subgroups of hematopoietic stem cell transplantation (HSCT) recipients (n = 9) and HSCT nonrecipients (n = 29). In the latter subgroup, there were 7 patients who newly acquired the T315I mutation after HSCT, and the median time was 10.8months. In addition to these 7 cases, 5 out of 22 patients were managed with chimeric antigen receptor (CAR) T cells and ponatinib. There were 4 patients in the HSCT recipient subgroup who were treated with CAR-T cells or ponatinib before HSCT. The complete molecular remission (CMR) and recurrence rate of HSCT recipients were both 67%, and the median recurrence time was 3.6months. A better overall survival (OS) was observed in the HSCT recipient subgroup than in the HSCT nonrecipient subgroup (median of 12.3months vs 3.3months, respectively; p = 0.004). Compared with patients who were not bridging to HSCT, the patients who were treated with CAR-T cells and/or ponatinib and bridged to HSCT tended to have a better OS (median of 3.3months vs 13.3, respectively; p = 0.09). In conclusion, the outcomes in ALL patients with the T315I BCR-ABL1 mutation were poor. A better OS can be achieved through ponatinib, CAR-T cells, and bridging to HSCT, but it also has a higher risk of recurrence.

Most Variable Genes and Transcription Factors in Acute Lymphoblastic Leukemia Patients.

Acute lymphoblastic leukemia (ALL) is a hematologic tumor caused by cell cycle aberrations due to accumulating genetic disturbances in the expression of transcription factors (TFs), signaling oncogenes and tumor suppressors. Though survival rate in childhood ALL patients is increased up to 80% with recent medical advances, treatment of adults and childhood relapse cases still remains challenging. Here, we have performed bioinformatics analysis of 207 ALL patients' mRNA expression data retrieved from the ICGC data portal with an objective to mark out the decisive genes and pathways responsible for ALL pathogenesis and aggression. For analysis, 3361 most variable genes, including 276 transcription factors (out of 16,807 genes) were sorted based on the coefficient of variance. Silhouette width analysis classified 207 ALL patients into 6 subtypes and heat map analysis suggests a need of large and multicenter dataset for non-overlapping subtype classification. Overall, 265 GO terms and 32 KEGG pathways were enriched. The lists were dominated by cancer-associated entries and highlight crucial genes and pathways that can be targeted for designing more specific ALL therapeutics. Differential gene expression analysis identified upregulation of two important genes, JCHAIN and CRLF2 in dead patients' cohort suggesting their possible involvement in different clinical outcomes in ALL patients undergoing the same treatment.

Busulfan-Containing Conditioning Regimens in Allogeneic Hematopoietic Stem-Cell Transplantation for Acute Lymphoblastic Leukemia: Single Tertiary Center Experience in Taiwan

The allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is viewed as the ultimate cure for acute lymphoblastic leukemia (ALL). An essential component of allo-HSCT is the conditioning regimen administered before the hematopoietic stem-cell infusion. This study is aimed to compare outcomes of ALL patients receiving either a busulfan with cyclophosphamide (BuCy) or a total body irradiation(TBI)-based regimen. We retrospectively analyzed data from National Taiwan University Hospital institute registry. We enrolled 224 adult patients with ALL who received allo-HSCT between 1997 and 2016 and compared outcomes of patients receiving either a BuCy-based or a TBI-based regimen. There were more B-cell ALL than T-cell ALL (67.8% vs 32.2%). A total of 41 patients (22.5%) carried the Philadelphia chromosome (Ph) while 38 patients (20.9%) carried complex karyotype. Before the allo-HSCT, 164 (73.2%) patients achieved first or late complete remission (CR). The main source of stem-cell was from peripheral blood (71%), followed by bone marrow (22.3%). Siblings comprised 54.9% of the donors. A total of 141 patients (63%) received BuCy-based conditioning, either myeloablative (MA) or reduced intensity stem cell transplantation (RIST) and 83 patients (37%) received TBI-based regimen. The mean dose of stem cell was 4.96 ± 2.42 × 106/Kg CD34+ cells. We use cyclosporine and mycophenolate mofetil for prophylaxis of graft-versus-host disease (GvHD). In results, patients received BuCy-based regimen performed as well as TBI-based group in terms of 5-year overall survival (47.5% vs 37.3%, p=0.115). As to 5-year relapse-free survival (RFS), BuCy group had slightly better result, especially the group received myeloablative conditioning (MA, Bu-based vs. MA, TBI-based, p=0.059), albeit the p value didni¦t reach significance, the curves went on departing ways. In this study, all regimen groups yielded similar treatment-related mortality (TRM), (MA, Bu-based vs RIST, Bu-based vs MA, TBI-based: 17% vs 10.9% vs 21.7%, p=0.308) and incidences of grade 3-4 acute GvHD at day+100, (p=0.445). Further, in patients with extramedullary disease, there was no difference among groups; and interestingly, BuCy group with MA conditioning seemed to yield better result than TBI group (p=0.072). By multi-variate analysis, disease status before allo-HSCT is the only risk factor impacting OS and RFS. In conclusion, patients received BuCy-based regimen or TBI-based regimen as conditioning had similar results in terms of OS, RFS, TRM, and GvHD.

Venetoclax and Navitoclax in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Background: Patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma have an unmet need for new treatment strategies. Navitoclax (Nav), a BCL-2/BCL-XL/BCL-W inhibitor, has shown promising effects in hematologic malignancies, however its usage is limited by prolonged thrombocytopenia mediated by inhibition of BCL-XL in platelets (J Clin Oncol. 2012;30:488). Venetoclax (Ven) is a highly selective BCL-2 inhibitor with similar anti-tumor efficacy. The addition of Nav to Ven has shown synergistic effects in preclinical models and might mitigate the dose-limiting thrombocytopenia associated with Nav monotherapy (Blood. 2016;128:1382). We report updated outcomes for ALL patients treated with Ven, Nav, and chemotherapy. Methods: R/R ALL patients aged ≥4 years were enrolled in this phase 1, multicenter, open-label, dose escalation study (NCT03181126). Patients received the weight-adjusted equivalent of 200 mg Ven on day 1, and a 400 mg equivalent daily thereafter. Daily oral Nav was administered on day 3 onward with up to three dose levels for patients ≥45 kg (25, 50, 100 mg) and up to two dose levels for patients Results: Nine adult patients, ≥45 kg (5 with B-cell ALL and 4 with T-cell ALL) have been enrolled as of the data cutoff of June 1, 2018. All patients treated thus far have received 400 mg QD Ven and 25 mg QD Nav (Dose Level 1). Chemotherapy was started on day 9 for 7 patients; patient A began chemotherapy on day 169 and patient H began on day 10. Baseline characteristics of the first 9 patients are shown in Table 1. The most common adverse events (AEs) of any grade are shown in Table 2. Serious AEs included nausea, vomiting, febrile neutropenia (n=2 each), abdominal pain upper, pseudomonal sepsis, somnolence, septic shock, acute pancreatitis, and pulmonary embolism (n=1 each). Of the serious AEs, only febrile neutropenia was considered possibly related to Ven + Nav. AEs led to dose interruptions in 4 patients. No dose-limiting toxicities (DLTs) have occurred. As of the data cutoff, 2 patients have died. Patient B died due to disease progression on day 148 and Patient E died due to an event of sudden death on day 38 not related to study drug (event was associated with not wearing a LifeVest personal defibrillator). Preliminary efficacy for these 9 patients is shown in Table 3. All 9 patients were evaluated at day 8 after Ven + Nav therapy alone. One patient had a complete response with incomplete marrow recovery (CRi) and 1 patient had a partial response (PR); the remaining patients had stable disease (SD). Five patients had assessments at day 36 or later, including 4 patients who had completed 1 cycle of chemotherapy combined with Ven + Nav, and 1 who had received Ven + Nav only; 3 patients achieved CR, and 1 patient each achieved CRi and CRp as their best response. Patient A achieved CRi after Ven + Nav therapy without chemotherapy on day 8, had a duration of response of 5.1 months before developing progressive disease and is now also receiving chemotherapy. Patient C achieved CR on day 36, stopped all therapy on day 38, and maintains ongoing response at 3.5 months. Overall, in this heavily pretreated group, 5 patients achieved a complete response (CR/CRi/CRp). Two patients with CR had no detectable MRD. The remaining 4 patients have not reached the day 36 assessment as of the data cutoff; of these patients, 1 patient had PR and 3 patients had SD. Conclusions: Ven + Nav in combination with chemotherapy is well tolerated, without any unexpected side effects and no DLTs observed to date. Preliminary data suggest that Ven + Nav with chemotherapy is efficacious in some patients with R/R ALL who have had multiple lines of therapy, including prior stem cell transplant. Enrollment, clinical follow-up, and correlative biology studies are ongoing. Disclosures Alexander:Abbvie: Other: travel expenses. Jabbour:Bristol-Myers Squibb: Consultancy, Research Funding; Abbvie: Research Funding; Takeda: Consultancy, Research Funding; Novartis: Research Funding; Pfizer: Consultancy, Research Funding. Khaw:Abbvie: Research Funding; Amgen: Other: travel expenses, Research Funding; Bristol Myers Squibb: Research Funding; Jazz Pharmaceuticals: Research Funding; Novartis: Other: travel expenses. Mullighan:Cancer Prevention and Research Institute of Texas: Consultancy; Abbvie: Research Funding; Amgen: Honoraria, Speakers Bureau; Loxo Oncology: Research Funding; Pfizer: Honoraria, Research Funding, Speakers Bureau. Leonard:Amgen: Research Funding. Schmidt:Abbvie: Employment, Equity Ownership. Tong:Abbvie: Employment, Equity Ownership. Zhou:Abbvie: Employment, Equity Ownership. Ross:AbbVie, Inc: Employment, Equity Ownership. Rosenwinkel:Abbvie: Employment, Equity Ownership. Jacobson:Abbvie: Employment, Equity Ownership. Kim:Abbvie: Employment, Equity Ownership. Stock:Jazz Pharmaceuticals: Consultancy.

P006 NK KIR receptor genotypes are associated with relapse in mexican HLA matched sibling patients with acute lymphoblastic leukemia (ALL)

Aim The outcome of Hematopoietic Stem Cell Transplantation (HSCT) is strongly associated with the HLA identity of donor/recipient, and GVHD remains the most frequent associated factor with mortality and impact on the quality of life. A successful HSCT depends also on T-cell mediated graft vs. leukemia (GvL) effect. Relapse is a major important challenge. NK cells, KIR and their HLA ligands are involved with an increase in overall survival, as well as better engraftment and reduced incidence of GVHD in patients with AML. The aim of the study was to determine the KIR gene content, their HLA ligands and their association on the outcome of ALL patients transplanted with HLA-identical sibling donors. Methods Twenty-seven Mexican patients with their HLA-identical siblings were included. Of these, 20 had ALL and 7 AML. KIR gene content was determined with the LinkSēq™ KIR kit and was run on an ABI 7500 Real-Time PCR instrument. Analysis was done with SureTyper 5. HLA intermediate resolution typing was performed by SSOP on a Luminex. HLA alleles were analyzed with the Match it DNA 1.2.0 software. KIR haplotypes and HLA ligands were assessed using https://www.ebi.ac.uk/ipd/kir/ligand.html . Allele Frequency (AF) and multiple parameter comparison analysis was performed using the SPSS17 software. Results We looked if activating or inhibitory KIR genes had any effect on relapse, long term disease free survival (DFS), GVHD or mortality. An association with relapse was observed in ALL patients, when the matched sibling donor carried the 3DL1 -Bw4 ligand (50% of ALL patients were carriers); (Chi2 = 5.93; p = 0.03) with no differences in Bw4 80I and 80T ligand. The AA and Bx haplotypes did not have any association with mortality, GVHD, relapse or DFS. Conclusions The results in ALL regarding relapse show that the presence of 3DL1 -Bw4, conveys higher susceptibility for relapse, as shown for AML. Contrary to AML, no effect was detected with 80I or 80T with intermediate relapse and mortality, implying a non benefit of education and sensitivity to inhibition as reported for AML. More cases of ALL are being analyzed to confirm if HLA and KIR allele typing in donor selection, enables the antileukemic benefits of NK alloreactivity in HSCT, in ALL, as it has been pointed out in AML, since the affected cell population in ALL, is totally different of the latter.

Long-term results of the risk-stratified treatment of childhood acute lymphoblastic leukemia in China.

Long-term follow-up data for childhood acute lymphoblastic leukemia (ALL) are scarce in China because of lacking population-based and hospitalized registry system. This retrospective study, conducted at Shanghai's Children's Medical Center in China (SCMC), aimed to investigate the long-term results of childhood ALL and to identify prognostic factors. The Pediatric Oncology Network Database, designed by St. Jude Children's Research Hospital, USA, were used to collect data for the enrolled patients starting in 2005. From 2005 to 2014, 1085 evaluable patients with ALL aged 1 to 18years old were enrolled and treated using SCMC-ALL-2005 risk-stratified protocol. Complete remission was achieved in 95.6% of patients. At 5 and 10years, the event-free survival rate was 68.3±1.4% and 64.6±1.6%, and the overall survival rate was 80.0±1.2% and 76.3±1.6%, respectively. The 5-year event-free survival rates were 81.8±2.0%, 67.0±1.9%, and 14.3±4.0% for patients in low-risk, intermediate-risk, and high-risk groups, respectively. The cumulative risk of relapse was 24.5% at 10years. Induction failure conferred worse prognosis. Patients younger than 1year of age at diagnosis, intermediate-risk/high-risk group, male gender, and positive minimal residual disease (MRD) results at day 55, both in the univariate and multivariate analysis, were associated with significantly worse prognosis (P<.05). Patients with positive MRD at both day 35 and day 55 were related to a significantly poor outcome (P<.0001), but not for patients with negitive MRD at day 35. The overall outcomes for ALL patients treated with protocol SCMC-ALL-2005 in SCMC are lower than in developed countries. Factors including age, gender, risk group and MRD results at day 55 were associated with treatment outcomes in childhood ALL.

Clinical significance of the TNF-α receptors, TNFRSF2 and TNFRSF9, on cell migration molecules Fascin-1 and Versican in acute leukemia

In human hematologic malignancies, some of the TNF receptor family members are up-regulated and have the ability to evoke reactions favoring tumor progression. Moreover, cell migration molecules, Fascin-1 and Versican are involved in proliferation, migration and invasion of cancer cells. They are linked to many human cancers. Therefore, we conducted this study to evaluate both the plasma and leukocytes concentrations of tumor necrosis factor receptor super family 2 (TNFRSF2), TNFRSF9, Fascin-1 and Versican in patients with acute leukemia, as well as to correlate these values with clinical features and treatment outcome. Therefore, forty-eight patients with acute myeloid leukemia (AML), thirty-two patients with acute lymphoblastic leukemia (ALL) and fifteen control subjects were included. TNFRSF2, TNFRSF9, Fascin-1 and Versican were measured in plasma and leukocytes of all subjects by enzyme-linked immunosorbent assay. We found that plasma TNFRSF9 was highly elevated in ALL and AML as compared with the control group. In addition, AML patients who failed to achieve complete remission showed a significant increase in leukocytes TNFRSF9 level. TNFRSF2 is significantly increased in plasma and leukocytes of ALL patients when compared with the control group and AML patients. Fascin-1 significantly increased in AML, but not in ALL cases. Plasma and leukocytes levels of Versican significantly increased in AML compared to both control and ALL subjects. Plasma Versican correlated with poor response to induction of chemotherapy in AML cases. In conclusion, TNFRSF2 and TNFRSF9 could act as a possible prognostic biomarkers for the outcomes of ALL patients and TNFRSF9 could be a potential target in AML. Versican may be used as a diagnostic biomarker and as a predictor of the response to chemotherapy in AML. In addition, plasma Fascin-1 is a potential biomarker for AML.

Allogeneic stem cell transplantation in acute lymphoblastic leukemia patients older than 60 years: a survey from the acute leukemia working party of EBMT.

Hematopoietic stem cell transplantation (HSCT) is being increasingly explored as a treatment modality for older patients with acute lymphoblastic leukemia (ALL). Yet, concerns regarding the long term outcome of transplantation in older patients limit the wide spread applicability of this approach. In this analysis we set out to determine the outcome of ALL patients over the age of 60 who underwent reduced intensity HSCT. Herein, we present the experience of the acute leukemia working party (ALWP) of the EBMT in this age group. We analyzed a cohort of 142 patients transplanted in first remission with a median age of 62 (range 60–76 years) and a median follow-up period of 36 months post-transplant. At 3 years, overall survival (OS) and leukemia-free survival were 42% and 35%, respectively. Multivariate analyses identified cytomegalovirus (CMV) donor-recipient matching (CMV D+/R+) to be significantly associated with inferior OS. Patients transplanted from unrelated donors experienced increased grade II-IV acute graft versus host disease compared to those receiving grafts from matched related donors [Hazard ratio (HR) of 3.7, 95% confidence interval (CI), 1.75–7.8; p = 0.0005). Outcome was not impacted by Philadelphia chromosome status. A select subset of older ALL patients will benefit from extended survival and a disease free state following HSCT.

Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia

Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (Bu) to decrease toxicity. This retrospective study analyzed TBI and Bu on outcomes of ALL patients 18–60 years old, in first or second complete remission (CR), undergoing HLA-compatible sibling, related, or unrelated donor HCT, who reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014. TBI plus etoposide (25%) or cyclophosphamide (75%) was used in 819 patients, and intravenous Bu plus fludarabine (41%), clofarabine (30%), cyclophosphamide (15%), or melphalan (13%) was used in 299 patients. Bu-containing regimens were analyzed together, since no significant differences for patient outcomes were noted between them. Bu patients were older, with better performance status; took longer to achieve first CR and receive HCT; were treated more recently; and were more likely to receive peripheral blood grafts, antithymocyte globulin, or tyrosine kinase inhibitors. With median follow-up of 3.6 years for Bu and 5.3 years for TBI, adjusted 3-year outcomes showed treatment-related mortality Bu 19% versus TBI 25% (P = .04); relapse Bu 37% versus TBI 28% (P = .007); disease-free survival (DFS) Bu 45% versus TBI 48% (P = .35); and overall survival (OS) Bu 57% versus TBI 53% (P = .35). In multivariate analysis, Bu patients had higher risk of relapse (relative risk, 1.46; 95% confidence interval, 1.15 to 1.85; P = .002) compared with TBI patients. Despite the higher relapse, Bu-containing conditioning led to similar OS and DFS following HCT for ALL.

An Alternative Donor Is a Valid Option Compared to a Matched-Unrelated in Allogeneic Stem Cell Transplantation for Acute Lymphoblastic Leukemia in CR2: A Report of 841 Patients from the EBMT Acute Leukemia Working Party

▪Background: In acute lymphoblastic leukemia (ALL) in CR1, the indications of allogeneic stem cell transplantation (allo-SCT) remain under debate, given the recent availability of new therapeutic tools including novel chemotherapy agents, monoclonal antibodies and T cell cellular therapies as well as sensitive molecular techniques to assess minimal residual disease (MRD). In contrast, allo-SCT for ALL in CR2 is a well-established procedure. At the same time, unmanipulated grafts are increasingly used in the haplo-setting, and innovative regimens for GvHD prophylaxis have been adopted with encouraging results.Aims :The current study aimed to compare the outcomes of ALL patients (pts) who do not have a matched sibling and received allo-SCT in CR2 from a matched-unrelated donor 10/10 (MUD) versus alternative donors: unrelated donor 9/10 (UD), cord blood unit (CBU) and haplo-identical T replete donor (HD).Methods:Patients with ALL in CR2 who underwent a first allo-SCT with a MUD or an UD, a CBU or HD, reported between 2005 and 2015 to the registry of the EBMT ALWP, were included.The major endpoints were to assess overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), non-relapse mortality (NRM), and graft-versus-host disease-free, relapse-free survival (GRFS)Results:Four hundred twenty eight pts received a MUD 10/10, 171 pts an UD 9/10, 148 pts a CBU and 94 a T replete HD. Median age was lower in the CBU group compared to the other groups (26.1 yrs (18-76) vs 31.6 (18-74) , p<10-4). There was a higher proportion of patients who underwent allo-SCT within 18 months following diagnosis in the HD group :42.5% vs 32.5%, p=0.05 (36.9% in MUD 10/10, 28% in UD 9/10, and 24% in CBU groups, respectively). The median time to relapse to transplant was similar in the 4 groups (p=0.68). The number of Philadelphia chromosome positive ALL pts and of positive MRD at transplant were comparable in the 4 groups (p=0.60 and p=0.74, respectively).At 2 years, for the overall population, LFS was 36.9% (95% CI: 33.2-40.6), OS 42.6% (95% CI: 38.8-46.5), RI 32.4% (95% CI: 28.9-35.9), NRM 30.7% (95%CI: 27.4 -34.1), and GRFS 30% (95%CI: 26-33). As to the outcomes, in univariate analysis, no differences were found between the 4 groups. In multivariate analysis, 3 predictive factors were associated with an improved LFS: the time from diagnosis to transplant >18months (DxTx>18 m)(HR=0.66, 95%CI, 0.54-0.81, p<10-4), a Karnofsky score at transplant ≥90% (KS) (HR=0.77, 95%CI, 0.62-0.97, p=0.02),and the year of transplant (HR=0.95, 95%CI: 0.91-0.99, p=0.02), whereas age was associated with a lower LFS (HR=1.103 per 10 years, 95%CI:1.023-1.19, p=0.01).For OS, HD compared to MUD 10/10, patient age, and CMV positivity were associated with lower OS (HR=1.42, 95%CI 1.02-1.99, p=0.04; HR=1.10, 95%CI 1.02-1.19, p=0.018; and HR=1.27, 95%CI 1.02-1.58, p=0.03; respectively), whereas 3 predictive factors were associated with better OS: DxTx>18m, KS ≥90% and the year of transplant. In multivariate analysis for RI, only DxTx>18m was a protective factor (HR=0.49, 95%CI, 0.38-0.65, p<10-4). In multivariate analysis for GVHD II-IV, a HD was associated with a higher risk compared to MUD 10/10 (HR=0.028, 95%CI: 1.05-2.30, p=0.03). At 2 years, in univariate analysis, the cumulative incidence of chronic GVHD was not statistically different between the 4 groups and no risk factors were identified in multivariate analysis. In multivariate analysis for NRM, patient age and CMV positivity were factors associated with a higher NRM (HR=1.14, 95%CI, 1.03-1.27, p=0.015; HR=1.50, 95%CI, 1.09-2.05, p=0.011), while year of transplant was the only factor associated with lower NRM (HR=0.94, 95%CI, 0.88-0.99, p=0.027). Finally, considering GRFS at 2 years, DxTx>18m and the year of transplant were associated with better GRFS (HR=0.69, 95%CI, 0.57-0.84, p<10-3 and HR=0.96, 95%CI, 0.92-0.99, p=0.04).ConclusionAllo-SCT may rescue more than one third of pts with ALL in CR2. Importantly, once a matched sibling donor is not available the donor type being unrelated or alternative did not have any impact on patients’ LFS, RI, NRM and GRFS. When compared to a MUD 10/10, an T replete HD was associated with lower OS and higher aGVHD II-IV. Interestingly, DxTx>18m was a major prognostic factor for both LFS and RI. Therefore, as compared to a MUD 10/10, a UD 9/10, a CBU, but also a T replete HD could be considered as valid options in adult pts with ALL in CR2. DisclosuresApperley:Bristol Myers Squibb: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Incyte: Speakers Bureau; Ariad: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau.