ALBERT

Description: Introduction The JAK2 V617F mutation is present in almost all Polycythemia Vera (PV) and in 60-70% of Essential Thrombocythemia (ET) cases. There are experimental evidences that this acquired clonal driving mutation is involved in disease phenotype in murine models and in humans. However, it is still unclear if the %V617F changes over time and if it is necessary to systematically quantify %V617F at diagnosis and during follow-up. Patients and Methods We are conducted a prospective multicentre (n=5) study cohort in newly diagnosed PV and ET patients, harvested before any cytotoxic therapy and at 3 years, with the aim to correlate the %V617F at diagnosis, the %V617F 3 years later, and the variation of the %V617F between y0 and y3 with clinical evolution. Primary or secondary myelofibrosis, and secondary leukemia were not included. The primary objective is to determine whether an increase of %V617F between diagnosis and after 3 years could be related to a poor evolution of the disease. A secondary objective is to determine whether the %V617F at diagnosis is associated with the evolution at 3y. The primary endpoint is the worsening (Y / N) at y3 defined by the presence of at least one of the following criteria: leukocytosis 〉12G / L or immature granulocytes 〉2% or erythroblasts 〉1%; anemia or thrombocytopenia not related to treatment toxicity; development or progressive splenomegaly; thrombocytosis on cytoreductive therapy; patients inadequately controlled with treatment (defined by at least one treatment change for reason other than an adverse event). Results To date, 201 patients have been included. Clinical datas are currently available for the 176 first included (91 PV and 85 ET; 90 females and 86 males) and %V617F measurement for 167 cases. At diagnosis, overall median age was 65, identical for PV and ET patients, but curiously women were a little older than men (72 vs 65, p

Description: At the present time, Essential Thrombocythaemia (ET) remains an exclusion diagnostic since no diagnostic finding can definitely distinguish between clonal and reactive thrombocytosis (RT). In addition, no biological marker predicts readily the thrombotic risk of ET. We investigated by flowcytometry the diagnosis and prognosis value of PMP, RP and CD36 expression, as platelets parameters easily available in routine laboratory in 34 ET patients and 49 controls. Membrane platelet CD36 expression were stained by indirect immunofluorescence with specific anti-CD36 antibody and anti mouse IgG FITC (Biocytex, France), analyzed on FACSCalibur cytometer (BD), quantified using the calibration beads (Platelet Calibrator, Biocytex) and expressed as antigen molecules/platelet. RP were determined after RNA thiazole orange labeling (10 ng/ml, 45 min, at room temperature, in the dark). Assays performed after TRAP (Thrombin receptor activating peptide) stimulation demonstrated the specificity of the labeling (data not shown). PMP were identified on forward and side scatter after CD41a-PE or isotype control (Immunotech) labeling. ET was diagnosed according to revised PVSG criteria in 11 men and 23 women. The median age was 63 y (24–85) and the median platelet count was 674 x109/l (249–1324). At the time of evaluation, 19 patients received antiplatelets therapy, 9 oral chemotherapy, 10 exhibit arterial thrombosis (AT), 1 venous thrombosis and one, included in the AT group, experimented venous thrombosis as well. RP, CD36 and PMP were significantly increased in ET as compared to controls (P =.01, 10−4,

Description: Background: R-DHAP regimen (rituximab, cisplatin, dexamethasone, high dose cytarabine) based on the 1988 Velasquez's study is a standard scheme used to treat relapsed Non-Hodgkin lymphomas (NHL). Cisplatin is frequently substituted with oxaliplatin to avoid nephrotoxicity, resulting in R-DHAX that is currently prescribed in first or second line treatment for aggressive NHL. However data are scarce. We compared the nephrotoxicity of cisplatine to oxaliplatine in R-DHA-platinum in this setting. Methods: All consecutive patients with NHL treated by R-DHAP or R-DHAX in Angers hospital between the 1st January 2007 and the 31th December 2014 were included. Either cisplatin 100 mg/m2 during 24 hours (R-DHAP) or oxaliplatin 130 mg/m2 during 2 hours (R-DHAX) were associated at d1 with cytarabine (2000 mg/m2 during 3 hours, two doses, d 2), dexamethasone (40 mg, d 1-4) and rituximab (375mg/m2, d 1) (Details on table 1). Cisplatin dosage were reduced from 25% to 50% according to individual renal tolerance. Up to 6 courses were delivered. Serum creatinine was recorded before each course of chemotherapy and was checked between d3 and d15 after administration, allowing to trace individual profiles of trajectories for their levels. These trajectories were clusterized in order to detect the existence of homogeneous patterns of evolution. This is a classical, semiparametric group-based statistical approach (Ref 1). Concomitant nephrotoxic drugs and events (sepsis…) were recorded to identify potential bias. Results: 21 patients received R-DHAP and 32 received R-DHAX. 6 patients switched from R-DHAP to R-DHAX due to nephrotoxicity. 2 different homogeneous clusters appeared. Cluster A included a majority of R-DHAX: 31 R-DHAX (88.6%), 3 R-DHAP (8.6%), 1 R-DHAP who changed to R-DHAX (2.9%). Cluster B contained a majority of R-DHAP: 11 R-DHAP (64.7%), 1 R-DHAX (5.9%), 5 R-DHAP to R-DHAX (29.4%) (p = 7.5.10-9). Cluster A graphic profile appeared less toxic than cluster B according to average serum creatinine level (mean cluster A: 70.2 µmol/L; mean cluster B: 99.5 µmol/L (p = 2.2.10-16)). Patients treated with R-DHAP experienced more severe renal failure than patients treated with R-DHAX (Chi-square test: p = 2.9.10-8, table 2). Nephrotoxic concomitant treatments have no significant discriminant effect. No differences were observed between either R-DHAP versus R-DHAX or cluster A versus B patients, as regards to age, sex, malnutrition status, histology, stage of the lymphoma, performans status, comorbidities including renal comorbidities and the history of nephrotoxic therapy. No significant difference was shown in OS and EFS (respectively, p = 0.463 and p = 0.290). Conclusions: Although R-DHAX is now widely used in NHL treatment, our study is one of the first to evaluate efficacy and renal tolerance of this treatment. R-DHAX nephrotoxicity is not significant whereas most patients receiving R-DHAP had significant acute renal impairment. We found no difference as regards to survival. A prospective study should compare these schedules in NHL to adapt future practices and improve morbidity. Table 1. Patients characteristics Caractéristics DHAP DHAX Total Sex M 14 (66.7%) 23 (71.9%) 37 (69.8%) F 7 (33.3%) 9 (28.1%) 16 (30.2%) Age (years) Median (min-max) 61 (34-80) 61 (39-77) 61 (34-80) BMI 〈 18 0 0 0 18 to 25 9 (42.9%) 17 (53.1%) 26 (49.1%) 〉 25 12 (57.1%) 15 (46.9%) 27 (50.9%) Performans Status (N=49) PS 〉 = 2 3 (17.6%) 2 (6.3%) 5 (10.2%) PS 〈 2 14 (82.4%) 30 (93.8%) 44 (89.8%) Comorbidities Renal 1 (4.8%) 3 (9.4%) 4 (7.5%) Cardiovascular 8 (38.1%) 13 (40.6%) 21 (39.6%) Other 12 (57.1%) 16 (50%) 28 (52.8%) More than 2 comorbidities 6 (28.6%) 9 (28.1%) 15 (28.3%) Histologie NHL low grade 5 (23.8%) 5 (15.6%) 10 (18.9%) NHL High grade 15 (71.4%) 25 (78.1%) 40 (75.5%) CLL 1 (4.8%) 2 (6.3%) 3 (5.6%) Ann Arbor Stage I 0 0 0 II 2 (9.5%) 2 (6.3%) 4 (7.5%) III 2 (9.5%) 2 (6.3%) 4 (7.5%) IV 16 (76.2%) 26 (81.3%) 42 (79.2%) Previous chemotherapy Nephrotoxic 2 (9.5%) 3 (9.3%) 5 (9.4%) Non nephrotoxic 17 (80.9%) 21 (65.6%) 38 (71.7%) Albumine blood level 〈 = 30 5 (23.8%) 5 (15.6%) 10 (18.9%) LDH 〉 N 11 (52.4%) 12 (37.5%) 23 (43.4%) Total 21 32 53 Table 2. Renal Failures grade R-DHAP R-DHAX No renal failure 13 (27.7%) 100 (74.6%) Renal Failure 34 (72.3%) 34 (25.4%) (Reference 1: Group-based trajectory modeling in clinical research, Nagin et al. Annu Rev Clin Psychol. 2010) Disclosures No relevant conflicts of interest to declare.

Description: Introduction: The prognosis of older patients treated for acute myeloid leukemia (AML) relies on cytogenetic/molecular classifications as well as their ability to tolerate intensive induction therapy for which comorbidities have an important impact. A prognostic model has been elaborated to incorporate these two variables, cytogenetic/molecular risk and comorbidities evaluated by the Hematopoietic Cell Transplantation - Comorbidity Index (HCT-CI) (Sorror et al. 2017). The AML-composite model (AML-CM), which also incorporates hypoalbuminemia and high LDH levels at diagnosis, has been recently updated to incorporate the new European LeukemiaNet (ELN) 2017 classification (Sorror et al. 2019). In this study, we aimed to confirm the predictive impact of the revised AML-CM in an independent cohort and to explore which parameters were the most relevant for predicting early mortality and relapse. Patients and Methods: All patients (pts) older than 60 years diagnosed with AML who received intensive induction therapy in our department between 2004 and 2017 were included. Patients with acute promyelocytic leukemia were excluded. They received induction therapy with idarubicin 8 mg/m2 for 5 days and cytarabine 100 mg/m2 for 7 days with or without lomustine 200 mg/m2 on day 1. Patients in first complete remission (CR1) were to receive six consolidation courses with idarubicin 8 mg/m2 for one day and cytarabine 100 mg/m2 for 5 days and maintenance therapy with oral methotrexate and mercaptopurine. The HCT-CI and the revised AML-CM were calculated as previously described (Sorror et al. 2005; Sorror et al. 2019) using individual patient medical records. Early mortality was defined as death within one month after the start of induction therapy. The ELN 2017 classification, the HCT-CI, and the revised AML-CM were considered to determine which parameters - comorbidities or cytogenetic/molecular risk - were associated with each outcome. Results: Ninety-nine pts were included in the study with a median age of 66 years-old (range: 60 - 82). Twenty-seven pts (27%) had secondary AML (prior solid tumor requiring chemotherapy and/or radiation therapy in 11 pts and prior hematological malignancy in 16 patients). According to the ELN 2017 classification, 24 (24%) were favorable, 53 (54%) were intermediate, and 22 (22%) were adverse. The most frequent comorbidities included liver disease (30 pts, low/moderate, 5 pts, severe), previous cancer (22 pts), and arrythmia (22 pts). Thus, 13 (13%), 25 (25%), 44 (45%), and 17 (17%) pts had a revised AML-CM score of 1-4, 5-6, 7-9, and 〉10, respectively. 78 pts (79%) achieved CR1, with 10 early deaths (10%) due to toxicity (early mortality) and 11 induction failures (11%). Fifteen pts received allogeneic SCT. 54 (55%) relapsed, and 72 (73%) died with a median follow-up of 18 months (range: 0 - 167). Both the HCT-CI and the AML-CM were associated with increased early mortality (OR: 1.4, 95% CI: 1 - 1.8, p=0.03 for HCT-CI and OR: 1.3, 95% CI: 1-1.7, p=0.03 for AML-CM) whereas the ELN 2017 classification had no impact. The predictive value of the AML-CM for early mortality was not superior to the HCT-CI (area under the curve - AUC: 0.76, p=0.01, and 0.76, p=0.01, respectively). The risk of relapse was only associated with an unfavorable ELN 2017 classification (OR: 8.8, 95% CI: 1.1 - 70, p=0.04). It was the most predictive parameter for relapse, in comparison to the HCT-CI and the revised AML-CM, but this did not reach statistical significance (AUC: 0.62, p=0.08). The AML-CM clearly distinguishes 4 groups with different prognosis (Figure, p 10, respectively (OR: 1.4, 95% CI: 1.2 - 1.8, p

Description: Tanasi et al present a prospective strategy for identifying patients with Philadelphia-like acute lymphoblastic leukemia, demonstrating the efficacy of early introduction of tyrosine kinase inhibitors in improving outcomes.

Description: Abstract 3921 Introduction: Hairy cell leukemia (HCL) is a rare hematologic disorder, and the place of emerging treatments, such as BRAF inhibitors, remains to be defined. We conducted a large, multi-center, retrospective survey in France to determine the frequency of malignancy in HCL patients (pts) and their families, and to analyze the long-term effects of the established purine nucleotide analogs (PNA) cladribine (C) and pentostatin (P). Methods: Physician members of the Société Française d'Hématologie were surveyed on their management of HCL pts over the past 30 years. Clinicians completed a form that collected data concerning personal and familial medical history of pts, with particular focus on hematologic malignancies, solid tumors, clinical and biological presentation at HCL diagnosis, therapeutic options, response to treatment, time to relapse, secondary malignancies and cause of death. Results: The survey included 36 French clinical centers and 487 HCL cases (mean patient age 59y; range 29–90y). In the centers surveyed, HCL diagnosis was established after examination of peripheral blood and/or bone marrow and by immunophenotyping. Solid tumors and hematologic malignancies were present before HCL diagnosis in 45 cases (9.2%). A further 38 pts (7.8%) with pre-existing cancers were diagnosed with HCL after a median time of 89mo (range 1–529mo). At diagnosis, three HCL pts presented with follicular lymphoma, monoclonal gammopathy of undetermined significance, or large cell B cell lymphoma. Four pts developed HCL within a median time of 33mo (range 30–38mo) after diagnosis of B-cell lymphoproliferative disorders. In 93 pts (19.1%), at least one family member developed neoplasia: solid tumors=75 pts (15.4%); acute or chronic hematologic malignancies=18 pts (3.7%) with one familial HCL case. Twenty-three pts (4.7%) received no treatment for a median follow-up of 32mo (1–293). Three hundred and forty-five pts (70.8%) received just one first-line treatment (C=68.1%, P=23.8%, interferon [IFN]=3.8%, other=4.3%), and 119 pts (16.6%) received two-to-seven lines of therapy. After first-line treatment, complete responses were observed in 365 pts (74.9%; P=85.1%, C=85.0%, IFN=61.1%). Median duration of response was 41 months (1–270; C=40.5mo [1–188; 234 pts], P=43.0mo [1–209; 80 pts], IFN=74mo [24–270; 13 pts], other=21mo [2–186; 15 pts]). After second line treatment, the median duration of response decreased to 33mo (1–261; 80 pts) (C=27mo [1–159; 39 pts], P=38.5mo [0–206; 24 pts]) and also tended to differ according to first-line regimen (Table). After third-line treatment, the median duration of response decreased again to 24mo (2–224; 24 pts) (C=46mo [2–92], P=20mo [2–166], other=22mo [2–224]). After 60 months follow-up (range 1–384mo), overall survival at 5 years was 95%. Twenty-nine pts (6%) had died (11 deaths were HCL-related), and a further 53 pts (10.9%) developed second malignancies (39 solid tumors and 14 hematologic malignancies). Second malignancies occurred 6 months after HCL diagnosis in 50 pts. Conclusions: This study highlights the high frequency of cancers in HCL pts and their family members, suggesting a role for genetic factors in the development of the disease. The survey also confirms the high efficacy of PNA, and we therefore need to be cautious in adopting innovative new therapies treatment such as BRAF inhibitors or immunotoxins into first-line care. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 881 T-cell acute lymphoblastic leukemia (T-ALL) represents a heterogeneous group of acute leukemias, which account for 25% of adult ALL. The GRAALL group recently reported a significant improvement in the outcome of BCR-ABL negative adult ALL using an intensified treatment protocol and a significantly better outcome in T-ALL harbouring NOTCH1 and/or FBXW7 (N/F) mutations compared to unmutated cases. Despite this, a third of N/F mutated T-ALL patients relapse and the identification of a T-ALL subgroup with very favorable outcome remains desirable. In a series of 212 adult T-ALLs included in the multicenter randomized GRAALL-2003 and 2005 trials, we searched for N/K-RAS (exon 1) mutations and PTEN (exon 7 mutations and gene deletion by CGH-array SNP-6 Affymetrix®) defects, which are considered as “type B3” mutations involved in pre-TCR signalling. Overall survival (OS) and event-free survival (EFS) were estimated by the Kaplan-Meier method, and then compared by the log-rank test. NOTCH1 and/or FBXW7 mutations were identified in 143 (67%) of the 212 patients and lack of N/F mutation was associated with a poor prognostic. N-RAS, K-RAS and PTEN mutations were identified in 3/191 (1.6%), 17/191 (8.9%) and 17/175 (9.7%) patients, respectively. PTEN genomic deletions/mutations and N/K-RAS activating mutations were virtually mutually exclusive. N/K-RAS mutations were more frequent in TCR negative phenotype and CNS positive T-ALLs, but did not correlate with other classical parameters, EGIL phenotype, N/F status, or cortico- or chemo-sensitivity. PTEN alterations were more frequent in mature TCR expressing, SIL-TAL+, N/F unmutated cases with high leukemic bulk tumors, but did not significantly differed with respect to age, gender, CNS involvement, cortico- or chemo-sensitivity. When analyzed separately, N/K-RAS mutations or PTEN genomic abnormalities demonstrated trends to a worse outcome. We then analyzed the effect of N/K-RAS mutations and/or PTEN genomic abnormalities on the good prognosis associated with N/F mutations by a multivariate Cox model for EFS and OS, entering the two N/F and RAS/PTEN covariates, as well as an interaction term. The prognostic significance of N/F mutations was still observed (HR, 0.26 [95% CI, 0.15–0.46] and 0.26 [95% CI, 0.14–0.49] with P

Description: In elderly pts, the prognosis of AML associated with poor risk cytogenetics or secondary to either MDS or previous cancer is so bad that only supportive care or investigational studies are usually recommended. Fit patients may achieve CR after conventional induction, but early relapse appears to be nearly inescapable whatever classical consolidation or maintenance therapy is used. Therefore, the GOELAMS investigated the impact of a maintenance using two agents mainly used in MDS, ie AZA and Len. Between March 2011 and February 2013, 117 pts from 27 centers (median age 69 yrs; 60-80) with previously untreated poor prognosis AML were included. Poor Risk factors were either preceding MDS (n=52), previous cancer (n=37) or centrally reviewed (IL) poor risk cytogenetics (n=83) defined as complex karyotype (≥3 abnormalities, n=65), monosomal karyotypes (n=54), del or - 5 (n=61) or 7 (n=44), 3q abnormality (n=9) or MLL rearrangement except for t(9;11) (n=5). Median WBC was 2.9 G/L (0.5-160), 7 pts had WBC ≥ 30 G/L. Induction chemotherapy included Lomustine 200 mg/m² po d1, Idarubicine 8 mg/m²/d (d1-5), Cytarabine 100mg/m²/d CI (d1-7). Patients in CR received 12 maintenance cycles alternating every 28 days AZA (sc 75 mg/m²/d1-7) and Len (10mg/d1-21), which started if PMN and platelets were 〉1 G/L and 100 G/L respectively. After d42, subsequent cycles were reduced to 50 mg/m²/d and 5 mg/d. GCSF was allowed in case of PMN 〈 0.5 G/L after 7 days or febrile neutropenia. At the end of induction, CR was achieved in 56% (65 pts) without any predictive factor, 9% died from infection (n=6), cerebral hemorrhage (n=1) or MOF (n=4) and 35% (41pts including 5 CRp) failed to achieve CR. The 12 planned maintenance courses could be given to 21 pts (32%) (median: 6). Few toxicities were observed. AZA courses were slightly more toxic than Len courses (table 1). Table 1.AZA courses %Len courses %Gr 3/4 neutropenia46.8/ 27.339.7 /17.6Antibiotics for fever at home6.97Hospitalization for febrile neutropenia0.52.7RBC transfusions55.4Gr 3 Thrombopenia2016Platelets transfusion8.67.9Interval between courses 〉 35 days26.118.4Median time interval between courses31 d28 dCourses with doses reductions9.621.6 Maintenance courses were interrupted because of relapse (n= 34, 77%), alloSCT (n=4 %), count error (n=1 %) or toxicities (n =5, 11%) occurring after Len (depression, vascular purpura and pseudomembranous diarrhea, sudden death, all during cycle 1) or after Aza (atrial fibrillation and cardiac dysfunction). Twenty Gr3/4 AE were reported among 441 cycles (0.56%/courses). Median follow-up for survivors was 38 mo (26-47). Median OS was 10 mo, with 21% 2y OS. Median CR duration was 7 mo (1-30). Impact of prognostic factors on DFS is shown table 2. Within poor risk factors, Cytogenetic abnormalities appeared as even poorer than previous MDS or cancer. Table 2.CR %CR NDFS median moP VALUE1y DFS %2y DFS %All patients56657.941.512.3Age ≥ 7058.3288.6 vs 7.746.417.9WBC ≥ 3.3 G/L48.1267.0 vs12.423.111.5Previous MDS51.92713.8 vs 6.4.0551.922.2MDS only68.41316.8 vs 6.4.00869.230.8Previous cancer54207.5 vs 7.9355Cancer only80812.4 vs 7.755012.5Poor cytogenetic53445.1 vs 15.3.0429.56.8Complex caryotype49.2324.8 vs 12.9.012259.4Monosomal caryotype50274.6 vs 12.9.00218.57.4Chromosome 5 abnormality52.5325 vs 13.8.00218.86.3Chromosome 7 abnormality54.5243.6 vs 12.00120.84.23q55.6510.4 vs 7.740017p deletion48.5165.0 vs 10.52512.5MLL8043.4 vs 8.4250poor cytogenetic + MDS42.997.7 vs 7.944.422poor cytogenetic + cancer46.774.8 vs 7.928.90poor cytogenetic + cancer + MDS71.453.4 vs 8.4200cancer + MDS00---Poor cytogenetic only rev aza57.5236.3 vs 12.9.05521.74.3Poor cytogenetic only SA255436.430.220.9 In the previous GOELAMS SA2 trial, 78 pts with poor risk cytogenetics without secondary leukemia received the same LIA induction followed in CR by maintenance therapy with 6 mini-reinductions (Ida 10mg/m² d1, cytarabine 50 mg/m²x2/d d1-5) and 6MP-MTX for 2years. In the present study, the DFS of the group of pts with poor risk cytogenetics without previous cancer or MDS is very similar. This alternating azacitidine/lenalidomide maintenance improved DFS and OS of pts without poor risk cytogenetics (median 15.7 and 24 mo). In this setting, it could be randomly compared to conventional chemotherapy maintenance. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Background: Although the prognosis of patients with hematological malignancies admitted to the intensive care unit (ICU) has improved over the past years, it remains poor in allogeneic stem cell transplantation (SCT) recipients and thus admission of these patients to the ICU remains controversial. Our center has flexible admission criteria, especially regarding graft-versus-host disease (GVHD). We thus performed a retrospective study to assess prognostic factors of survival in allogeneic SCT recipients who are admitted according to this policy. Methods: All allogeneic SCT recipients between 2002 and 2013 who were admitted to the medical ICU in our center were included. Details on patients, graft procedures, GVHD, ICU admission, and outcome were collected from individual medical records. Potential prognostic factors were explored by logistic regression analysis for ICU and hospital discharge. Cox regression analysis was performed for overall survival. Results: Of 344 patients who underwent allogeneic SCT during the study period, 92 patients (27%) were admitted to the ICU. Median time from transplantation to ICU admission was 53 days (range: -4 to 2273 days). Median age was 52 (range: 20-69). They received myeloablative (27%), sequential treatment with chemotherapy and reduced-intensity conditioning (RIC) (27%) or RIC (46%). Donors were mostly unrelated donors (59%) while graft source was mostly peripheral blood stem cells (78%) (bone marrow: 13%, cord blood: 9%). 66% patients could be discharged from the ICU and 46% from hospital whereas one year survival was 24%. No demographic or SCT parameter was associated with ICU or hospital discharge, or with overall survival. Grade 2-4 acute GVHD (34 patients, 37%) and refractory acute GVHD (12 patients, 13%) had a significant impact on hospital discharge (11/34 patients alive, OR: 2.4, 95% CI: 1-5.8, p=0.05; 2/12 patients alive, OR: 5, 95% CI: 1-24, p=0.05, respectively) but not with ICU discharge (20/34 patients alive, p=0.25; 7/12 patients alive, p=0.53, respectively). Chronic GVHD was present in 11 patients (12%) without impact on survival. At admission to the ICU, patients had a median SOFA (Sequential Organ Failure Assessment) of 7 (range 1-16), a median LODS (Logistic Organ Dysfunction System) of 4 (range 0-17), and a median APACHE II (Acute Physiology And Chronic Health Evaluation II) of 19 (range 8-42). The SOFA and LODS are efficient for determining ICU discharge (OR: 1.3, 95% CI: 1.1-1.5, p=0.003; OR: 1.3, 95% CI: 1.1-1.5, p=0.002, respectively). 46 patients (50%) required invasive mechanical ventilation, 28 patients (30%) required vasopressors, 16 patients (17%) required renal replacement therapy, and 26 patients (28%) had liver failure (bilirubin 〉34µmol/l). Mortality was greatly associated with the number of organ failures: each new organ failure worsens the prognosis (Figure). One year OS rates were 31%, 27%, 23%, and 0% among patients with 0 (26 patients, 28%), 1 (26 patients, 28%), 2 (26 patients, 28%), and 3 to 4 (14 patients, 15%) organ failures, respectively (HR: 1.7, 95% CI: 1.4-2.1, p

Description: Abstract 3080 Poster Board III-17 Introduction The combination of imatinib with high-dose chemotherapy has been shown as very promising in patients with newly-diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) by several groups. Reported studies all demonstrated a higher response rate and an improved outcome as compared to the pre-imatinib era, but generally with a short follow-up. This was also observed in our GRAAPH-2003 study with complete remission (CR) rate, 18-month disease-free survival (DFS), and 18-month overall survival (OS) of 96%, 51%, and 65%, respectively (de Labarthe et al. Blood 2007). We report here the long-term results of this study with a longer median follow-up of 46 months. Patients & Methods From 2004 to 2005, 45 patients with newly-diagnosed Ph+ ALL (median age, 45 years; range, 16-59 years; 25 males and 20 female) were included in the GRAAPH-2003 study. Briefly, imatinib was started with HAM consolidation in good early responders (corticosensitive and chemosensitive ALL) or earlier during the induction course in combination with dexamethasone and vincristine in poor early responders. Imatinib was administered until allogeneic (if a matched familial donor or an unrelated donor matched at 9 or 10 of 10 HLA antigens) or autologous (if no donor and a good molecular response) stem cell transplantation (SCT). Results were compared with the results of the previous pre-imatinib LALA-94 trial (Dombret et al. Blood 2002). Results When compared to the former LALA-94 study, 4-year OS and DFS were estimated at 52% (36-66) versus 20% (14-26) (p=0.0001) and 43% (27-58) versus 20% (14-28) (p=0.002) in the GRAAPH versus LALA cohorts, respectively. In the GRAAPH-2003, all the 22 CR patients with a donor may receive allogeneic SCT in first CR. In addition, 10 CR patients without a donor but low post-HAM BCR-ABL level received autologous SCT. No significant differences were observed between the donor and the no-donor groups in terms of OS (55% versus 54% at 4 years; p=0.80) and DFS (47% versus 39% at 4 years; p=0.40). This result was partly explained by the good outcome observed in patients who received autologous SCT. The 4-year OS in the allogeneic SCT, autologous SCT, and no SCT groups were 55%, 80%, and 25%, respectively (auto versus allo, p=0.16; auto versus no SCT, p=0.008; allo versus no SCT, p=0.05). The 4-year DFS in the allogeneic SCT, autologous SCT, and no SCT groups were 47%, 50%, and 25%, respectively (auto versus allo, p=0.91; auto versus no SCT, p=0.27; allo versus no SCT, p=0.17). Overall, 4-year cumulative incidences of relapse and death in CR were estimated at 24% (14-40) and 32% (20-49), respectively, underlying the toxicity of the whole GRAAPH-2003 strategy. Notably, 7 of the 22 allografted patients died in CR, as compared to only 1 of the 10 autografted patients. Conclusion We show here that the beneficial impact of the combination of imatinib with chemotherapy is not transient and is preserved in the long term. Taking into account the good outcome of patients receiving autologous SCT and the toxicity of allogeneic SCT, the place and timing of SCT, as well as the optimal chemotherapy to be delivered with imatinib prior to SCT, must be carefully re-evaluated in further prospective trials. Disclosures Dombret: cejgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.