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BACKGROUND According to Europe’s Beating Cancer Plan, the number of cancer survivors is growing every year and is now estimated at over 12 million in Europe. A main objective of the European Commission is to ensure that cancer survivors can enjoy a high quality of life, underlining the role of digital technology and eHealth apps and tools to achieve this. OBJECTIVE The main objective of this study is the development of a user-centered artificial intelligence system to facilitate the input and integration of patient-related biopsychosocial data to improve posttreatment quality of life, well-being, and health outcomes and examine the feasibility of this digitally assisted workflow in a real-life setting in patients with colorectal cancer and acute myeloid leukemia. METHODS A total of 60 patients with colorectal cancer and 30 patients with acute myeloid leukemia will be recruited from 2 clinical centers: Universitätsmedizin der Johannes Gutenberg-Universität Mainz (Mainz, Germany) and IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” (IRST, Italy). Psychosocial data (eg, emotional distress, fatigue, quality of life, subjective well-being, sleep problems, and appetite loss) will be collected by questionnaires via a smartphone app, and physiological data (eg, heart rate, skin temperature, and movement through step count) will be collected by a customizable smart wrist-worn sensor device. Each patient will be assessed every 2 weeks over their 3-month participation in the ONCORELIEF study. Inclusion criteria include patients with the diagnosis of acute myeloid leukemia or colorectal cancer, adult patients aged 18 years and older, life expectancy greater than 12 months, Eastern Cooperative Oncology Group performance status ≤2, and patients who have a smartphone and agree to use it for the purpose of the study. Exclusion criteria include patients with a reduced cognitive function (such as dementia) or technological illiteracy and other known active malignant neoplastic diseases (patients with a medical history of treated neoplastic disease are included). RESULTS The pilot study started on September 1, 2022. As of January 2023, we enrolled 33 patients with colorectal cancer and 7 patients with acute myeloid leukemia. As of January 2023, we have not yet started the data analysis. We expect to get all data in June 2023 and expect the results to be published in the second semester of 2023. CONCLUSIONS Web-based and mobile apps use methods from mathematical decision support and artificial intelligence through a closed-loop workflow that connects health professionals and patients. The ONCORELIEF system has the potential of continuously identifying, collecting, and processing data from diverse patient dimensions to offer health care recommendations, support patients with cancer to address their unmet needs, and optimize survivorship care. CLINICALTRIAL German Clinical Trials Register (DRKS) 00027808; https://drks.de/search/en/trial/DRKS00027808 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/45475

Allogeneic stem cell transplantation (alloHSCT) in first complete remission (CR1) remains the consolidation therapy of choice in Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). The prognostic value of measurable levels of minimal residual disease (MRD) at time of conditioning is a matter of debate. We analyzed the predictive relevance of MRD levels before transplantation on the clinical outcome of Ph+ ALL patients treated with chemotherapy and imatinib in 2 consecutive prospective clinical trials. MRD evaluation before transplantation was available for 65 of the 73 patients who underwent an alloHSCT in CR1. A complete or major molecular response at time of conditioning was achieved in 24 patients (37%), whereas 41 (63%) remained carriers of any other positive MRD level in the bone marrow. MRD negativity at time of conditioning was associated with a significant benefit in terms of risk of relapse at 5 years, with a relapse incidence of 8% compared with 39% for patients with MRD positivity (P = .007). However, thanks to the post-transplantation use of tyrosine kinase inhibitors (TKIs), disease-free survival was 58% versus 41% (P = .17) and overall survival was 58% versus 49% (P = .55) in MRD-negative compared with MRD-positive patients, respectively. The cumulative incidence of nonrelapse mortality was similar in the 2 groups. Achieving a complete molecular remission before transplantation reduces the risk of leukemia relapse even though TKIs may still rescue some patients relapsing after transplantation.

Developing optimal radiation-free central nervous system prophylaxis is a desirable goal in acute lymphoblastic leukemia, to avoid the long-term toxicity associated with cranial irradiation. In a randomized, phase II trial enrolling 145 adult patients, we compared intrathecal liposomal cytarabine (50 mg: 6/8 injections in B-/T-cell subsets, respectively) with intrathecal triple therapy (methotrexate/cytarabine/prednisone: 12 injections). Systemic therapy included methotrexate plus cytarabine or L-asparaginase courses, with methotrexate augmented to 2.5 and 5 g/m(2) in Philadelphia-negative B- and T-cell disease, respectively. The primary study objective was the comparative assessment of the risk/benefit ratio, combining the analysis of feasibility, toxicity and efficacy. In the liposomal cytarabine arm 17/71 patients (24%) developed grade 3-4 neurotoxicity compared to 2/74 (3%) in the triple therapy arm (P=0.0002), the median number of episodes of neurotoxicity of any grade was one per patient compared to zero, respectively (P=0.0001), and even though no permanent disabilities or deaths were registered, four patients (6%) discontinued intrathecal prophylaxis on account of these toxic side effects (P=0.06). Neurotoxicity worsened with liposomal cytarabine every 14 days (T-cell disease), and was improved by the adjunct of intrathecal dexamethasone. Two patients in the liposomal cytarabine arm suffered from a meningeal relapse (none with T-cell disease, only one after high-dose chemotherapy) compared to four in the triple therapy arm (1 with T-cell disease). While intrathecal liposomal cytarabine could contribute to improved, radiation-free central nervous system prophylaxis, the toxicity reported in this trial does not support its use at 50 mg and prompts the investigation of a lower dosage. (clinicaltrials.gov identifier: NCT-00795756).

SUMMARY While adult acute lymphoblastic leukemia (ALL) is curable in 40–50% of the patients, the individual prognosis is rather unpredictable due to associated biological and clinical risk factors. In both B- and T-precursor ALL, minimal residual disease (MRD) represents the most sensitive prognostic marker, useful to support critical treatment decisions, ranging from allogeneic stem cell transplantation in patients with inadequate MRD response to chemotherapy only in MRD responsive ones. This optimized risk-adapted strategy allows to spare transplant-associated morbidity and mortality in patients curable by chemotherapy. Further progress is expected from the integration of the MRD-based strategy with improved pediatric-type regimens and novel targeting agents for discrete ALL subsets. These changes are increasing the cure rate to above 50%.

We evaluate the long-term results of a prospective clinical study enrolling more than 100 adult patients with Burkitt lymphoma/leukemia. Depending on extent of disease, treatment consisted of six to eight rituximab infusions and four to six courses of intensive chemotherapy (attenuated in patients aged >55 years) with high-dose methotrexate, fractionated ifosfamide/cyclophosphamide, other drugs in rotation, and intrathecal chemoprophylaxis. One-hundred five patients were treated (median age 47 years, range 17-78 years); 48% had Burkitt leukemia, 25% were older than 60 years, 37% had an Eastern Cooperative Oncology Group performance score >1, and 14% were positive for human immunodeficiency virus. The complete response rate and 3-year overall and disease-free survival rates were 79%, 67% and 75%, respectively, ranging from 100% to 45% for survival (P=0.000) and from 100% to 60% for disease-free survival (P=0.01) in patients with low, intermediate and high adapted International Prognostic Index scores. In multivariate analysis, only age (≤ versus >60 years) and performance status (0-1 versus >1) retained prognostic significance, identifying three risk groups with overall and disease-free survival probabilities of 88% and 87.5%, 57% and 70.5%, 20% and 28.5% (P=0.0000 and P=0.0001), respectively. The relapse rate was only 7% in patients treated with an intercycle interval ≤ 25 days. This regimen achieved 100% curability in patients with low adapted International Prognostic Index scores (21% of total), and very close to 90% in patients aged ≤ 60 years with performance score 0-1 (48% of total). Rapid diagnosis of Burkitt lymphoma/leukemia with prompt referral of patients to prevent clinical deterioration, and careful supervision of treatment without chemotherapy delay can achieve outstanding therapeutic results. ClinicalTrials.gov ID, NCT01290120.

Acute lymphoblastic leukemia (ALL) is curable in about 40-50% of adult patients, however this is subject to ample variations owing to several host- and disease-related prognostic characteristics. Currently, the study of minimal residual disease (MRD) following induction and early consolidation therapy stands out as the most sensitive individual prognostic marker to define the risk of relapse following the achievement of remission, and ultimately that of treatment failure or success. Because substantial therapeutic advancement is now being achieved using intensified pediatric-type regimens, MRD analysis is especially useful to orientate stem cell transplantation choices. These strategic innovations are progressively leading to greater than 50% cure rates.

Carbon monoxide (CO) exposure of an islet donor frequently leads to islet allograft long-term survival and tolerance in recipients. We show here that CO confers its protective effects at least in part by suppressing Toll-like receptor 4 (TLR4) up-regulation in pancreatic beta cells. TLR4 is normally up-regulated in islets during the isolation procedure; donor treatment with CO suppresses TLR4 expression in isolated islets as well as in transplanted grafts. TLR4 up-regulation allows initiation of inflammation, which leads to islet allograft rejection; islet grafts from TLR4-deficient mice survive indefinitely in BALB/c recipients and show significantly less inflammation at various days after transplantation compared with grafts from a control donor. Isolated islets preinfected with a TLR4 dominant negative virus before transplantation demonstrated prolonged survival in recipients. Despite the salutary effects of TLR4 suppression, HO-1 expression is still needed in the recipient for islet survival: TLR4-deficient islets were rejected promptly after being transplanted into recipients in which HO-1 activity was blocked. In addition, incubation of an insulinoma cell line, betaTC3, with an anti-TLR4 antibody protects those cells from cytokine-induced apoptosis. Our data suggest that TLR4 induction in beta cells is involved in beta cell death and graft rejection after transplantation. CO exposure protects islets from rejection by blocking TLR4 up-regulation.

Background With the advent of imatinib and the other tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1, the outcomes of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) improved substantially. Nonetheless, allogeneic stem cell transplantation (alloSCT) in first complete remission (CR1) remains the consolidation therapy of choice in Ph+ ALL. Evidence is emerging that post-transplant relapse is influenced by the persistence of minimal residual disease (MRD), with an inferior outcome of patients undergoing transplantation with measurable level of MRD (Sramkova L et al, Pediatr Blood Cancer 2007; Bar M et al. Leuk Res Treatment 2014). Considering that a deeper molecular response can probably be achieved with innovative targeted therapies, such as second and third-generation TKIs or immunotherapy, an accurate evaluation of MRD values before alloSCT may be very relevant. Aim of the study. To evaluate the predictive relevance of MRD levels before transplant in Ph+ALL patients in CR1 on the probabilities of (i) overall survival (OS), (ii) relapse incidence (CIR) and (iii) leukemia free survival (LFS) Patients and methods. One hundred and six adult patients (median age 41.2, range 19-62) with newly diagnosed Ph+ ALL (as determined by cytogenetic or molecular analysis) were enrolled into 2 prospective NILG protocols (09/00 ClinicalTrial.gov Identifier: NCT00358072 and 10/07 ClinicalTrial.gov Identifier: NCT00358072) and were treated with chemotherapy and imatinib. One hundred (94%) achieved CR1, of whom 72 patients underwent an alloSCT in CR1 and are the subject of this report. MRD was determined by quantitative polymerase chain reaction (RQ-PCR) according to validated methods. Results. Among the 72 patients undergoing alloSCT, MRD status before transplant was available for 65 patients (90%). Twenty-four patients (37%) achieved a complete molecular response (BCR-ABL/ABL For the whole patient cohort (n=106), the median follow-up was 2.8 years (range 0.06-11.8), with a 5 years OS of 41%. The OS of patients receiving alloSCT was 50%. The MRD negativity at time of conditioning was associated with a significant benefit in terms of risk of relapse with a CIR of 8% compared to 39% of patients with MRD positivity (p=0.007) (Figure 1A). Nonetheless, the LFS and OS probability were not significant different in MRD- compared to MRD+ patients (58% vs 41%, p=0.17 and 58% vs 49%, p=0.55, respectively) (Figure1B), likely due to the effective post-relapse treatment with TKIs and/or DLI. The cumulative incidence of non relapse mortality was similar in MRD- compared to that of MRD+ group (33% vs 20%, p=0.22). Conclusions. Our results confirm that patients undergoing alloSCT with measurable levels of MRD show a significant increase risk of relapse after transplant. These results highlight the importance of achieving a complete molecular remission before transplant that should be considered an essential prerequisite for successful alloSCT. Table 1. Patients' characteristics according to MRD group Characteristics MRD negative (N=24) MRD positive (N=41) P Age years , median (range) 45.0 (21.4-58.2) 42.7 (18.5-62.4) 0.95 Male sex (%) 16 (67) 15 (37) 0.01 WBC, X 109/L, median (range) 27.7 (0.9-350.0) 12.0 (1.1-680.0) 0.12 Hemoglobin, g/dL, median (range) 11.4 (5.4-14.6) 9.0 (3.7-16.5) 0.02 Platelets, X 109/L, median (range) 41.0 (4.0-336.0) 34.0 (3.0-325.0) 0.44 LDH, U/L median (range) 1231 (353-8104) 715 (65-6194) 0.12 Conditioning regimen (%)Reduced intensity Myeloablative 4 (17)20 (83) 7 (17)34 (83) 1.00 Donor type (%)SiblingUnrelated 13 (54)11 (46) 18 (44)23 (56) 0.73 Graft type (%)Bone marrow Peripheral blood Cord blood 3 (12)20 (83)1 (4) 9 (22)31 (76)1 (2) 0.91 Figure 1. CIR and LFS according to MRD group Figure 1. CIR and LFS according to MRD group Disclosures No relevant conflicts of interest to declare.

Highly aggressive T-cell acute lymphoblastic leukemia with t(8;14)(q24;q11): extensive genetic characterization and achievement of early molecular remission and long-term survival in an adult patient

Introduction Since the landmark study of Omura et al. (Blood 1980;55:199), validating cranial irradiation as an adjunct to intrathecal (IT) methotrexate, no other randomized trial of CNS prophylaxis was performed in adult ALL. Although the risk of CNS relapse is now only 1-4%, irradiation contributes to cumulative CNS toxicity together with high-dose methotrexate/cytarabine (HD-M/A), or is logistically difficult, so that developing an effective radiation-free CNS prophylaxis remains an important clinical task. IT DepoCyte® (ITD) might be advantageous, the slow release of liposome-associated cytarabine allowing therapeutic concentrations in the cerebrospinal fluid for 14+ days. An open trial reported prohibitive CNS toxicity from ITD in 6/31 patients (Jabbour et al. Blood 2007;109:3214), but ITD to ITD and HD-M/A to ITD intervals were short (14 and 10 days, respectively) and no patient suffered from CNS relapse. Methods In a phase II randomized trial (ClinicalTrials.gov NCT-00795756) we evaluated toxicity and feasibility (as primary study endpoint) of ITD 50 mg in comparison with IT triple therapy (ITT: methotrexate 12,5 mg, cytarabine 50 mg, prednisone 40 mg). Stratification was by cell lineage and risk class. ITT was given on d1 of courses 1,2,4,6,8; d15 of courses 1,2,8; and d1 of maintenance cycles 2-5 (12x). ITD was given on d1 of courses 1,2,4,6,8; d15 of courses 1,8 (T-ALL only); and d1 of maintenance cycle 2 (6-8x). The shortest ITD to ITD interval was 14 days in T-ALL (courses 1-2 [3x] and 8 [2x]), otherwise it was 21 days between ITD and any prior/subsequent ITD and HD course. ALL therapy consisted of eight induction-consolidation courses followed by risk/minimal residual disease-oriented maintenance or stem cell transplantation (SCT). In HD courses 3,7 (M/A) and 5 (M/Asparaginase) M dosage was 2.5 g/m2 (Ph- B-ALL) and 5 g/m2 (T-ALL) up to 55 years, and A 2 g/m2. Imatinib was used with de-intensified chemotherapy in Ph+ ALL; selected high-risk subsets received early SCT. Results Between 2007-12 201 total patients were enrolled and 141 randomized to ITT (n=73) or ITD (n=68). Median age was 42 years (range 18-68) and risk subsets (ITT/ITD) were SR-B 27.4%/29.4%; HR-B Ph- 26%/25%, Ph+ 23.3%/22.1%, SR-T 5.5%/5.9%, HR-T 17.8%/17.7%. Complete remission was 89% (n=65)/89.7% (n=61). Rates of actual v planned IT injections during induction-consolidation cycles 1-8, after removal of study losses (resistance, early death, SCT, toxicity and relapse), were ITT 374/415 (90.1%) v ITD 219/245 (89.3%) (P=0.76). Although toxicity/medical reasons caused 5 ITD patients to discontinue permanently the study v none in ITT arm (P=0.02), toxicity-driven omissions of IT therapy were marginally increased in ITD arm (29/415 [6.9%] v 24/245 [9.8%]; P=0.20). Neurologic toxicity occurred in 20 (27.4%) ITT v 36 (53%) ITD patients, respectively (P=0.002). According to NCI CTC grading (G), neurotoxicity episodes were GI 7 v 10 (P=0.36), GII 13 v 32 (P=0.003), GIII 4 v 12 (P=0.04), GIV 1 v 5 (P=0.12). GIII-IV neurotoxicity developed in 5/73 (6.8%) ITT patients v 10/52 (19.2%) and 5/16 (31.2%) B- and T-ALL ITD patients, respectively (P= 0.01), correlating in T-ALL with the second/third q14d ITD at courses 1,2,8 (4/5 patients, 5/6 episodes). Apart from reversible headache/radicular pain, the most serious toxicity occurred in 3 (4.1%) ITT patients (seizures 1; leukoencephalopathy 1; loss of consciousness 1) v 5 (7.3%) ITD patients (loss of consciousness 4, 1 with seizures; cerebral oedema/pseudotumor cerebri 1) (P=0.48). Four-year overall and disease-free survival were 54% and 52.2% v 58.9% and 47.7% in ITT and ITD arms, respectively, and relapse rate was 32.3% v 24.6% (all P=NS). In ITT arm there were 2 (3%) CNS and 2 (3%) combined CNS/marrow relapses. In ITD arm only one poorly compliant subject not given any HD course had an isolated CNS relapse (1.6%); no other patient had a CNS recurrence. Conclusion A radiation-free CNS prophylaxis with six spaced ITD in conjunction with HD-M/A may be feasible and at least as effective as other regimens. Excluding reversible headache/radiculitis, serious CNS toxicity was not significantly increased compared with ITT regimen, although some patients were forced to discontinue IT prophylaxis. The occasionally severe CNS toxicity prompts the investigation of a lower ITD dosage (25 mg), also to limit GI-II side effects, and the tighter schedule used in T-ALL should be abandoned because too toxic. Disclosures: Bassan: Mundipharma Oncology; Sigma-Tau; Amgen: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Off Label Use: Liposome-encapsulated cytarabine (DepoCyte®) used in a prospective phase II randomized trial of CNS prophylaxis in ALL. Masciulli:Novartis: Research Funding; Ospedali Riuniti di Bergamo: Research Funding; AIFA (Italian Regulatory Agency): Research Funding; AMGEN S.p.A.: Research Funding; Genzyme Olanda: Research Funding; Gruppo Italiano Trapianti di Midollo Osseo (GITMO): Research Funding; Pierre Fabre Italia S.p.A.: Research Funding; Università Cattolica del Sacro Cuore, Roma: Research Funding; Università degli Studi di Firenze: Research Funding; Sigma-Tau: Research Funding; Myeloproliferative disorder Research Consortium: Research Funding; Celgene: Research Funding; Associazione Italiana Linfomi (AIL): Research Funding; Fondazione Italiana Linfomi (FIL): Research Funding; LaRoche: Research Funding. Gallamini:Millenium: Consultancy. Marfisi:Novartis: Research Funding; Ospedali Riuniti di Bergamo: Research Funding; AIFA (Italian Regulatory Agency: Research Funding; AMGEN S.p.A.: Research Funding; Genzyme Olanda: Research Funding; Gruppo Italiano Trapianti di Midollo (GITMO): Research Funding; Pierre Fabre Italia S.p.A.: Research Funding; Università Cattolica del Sacro Cuore-Roma: Research Funding; Università degli Studi di Firenze: Research Funding; Sigma-Tau: Research Funding; Myeloproliferative disorder Research Consortium: Research Funding; Celgene: Research Funding; Associazione Italiana Linfomi (AIL): Research Funding; Fondazione Italiana Linfomi (FIL): Research Funding; LaRoche: Research Funding. Marchioli:Associazione Italiana Linfomi (AIL): Research Funding; Celgene: Research Funding; Myeloproliferative disorder Research Consortium: Research Funding; Sigma-Tau: Research Funding; Università Cattolica del Sacro Cuore, Roma: Research Funding; Pierre Fabre Italia S.p.A.: Research Funding; Gruppo Italiano Trapianti di Midollo (GITMO): Research Funding; Genzyme Olanda: Research Funding; AMGEN S.p.A.: Research Funding; AIFA (Italian Regulatory Agency): Research Funding; Ospedali Riuniti di Bergamo: Research Funding; Novartis: Research Funding; Fondazione Italiana Linfomi (FIL): Research Funding; LaRoche: Research Funding; Università degli Studi di Firenze: Research Funding. Rambaldi:Italfarmaco: Honoraria; Sanofi: Honoraria; Novartis: Honoraria.

Abstract 1494 Introduction: Burkitt lymphoma (BL) and B-cell acute lymphoblastic leukemia (B-ALL) are very aggressive malignancies with poor prognosis unless treated with highly specific intensive programs. The German Multicenter Study Group for Adult ALL piloted a short intensive rituximab (R)-chemotherapy program that improved outcome compared to the prior regimen (Hoelzer et al, Blood 110:abstr 518, 2007). The Northern Italy Leukemia Group adopted the same protocol to treat 105 consecutive, unselected adult patients with BL and B-ALL. Aim: To assess long-term outcome and toxicity according to pre-therapy risk factors predominantly identified by higher age and/or performance status (PS) according to the Eastern Cooperative Oncology Group score. Patients and Methods: Between December 2002 and June 2010, 55 BL (stage III-IV 53%, bulky 45%, extranodal involvement 64%) and 50 B-ALL patients were treated. Median age was 47 years (range 17–78), 31% were >55 years, 15% had a PS >2, and 15% were HIV+. Treatment consisted of 6 R-chemotherapy courses (4 in stage I-II disease without mediastinal/extranodal involvement), two additional R doses at completion of chemotherapy and local radiotherapy in case of mediastinal/CNS disease or residual tumor. R-chemotherapy blocks were as follows: A) prednisone-cyclophosphamide prephase (course 1 only), R plus dexamethasone, vincristine, ifosphamide, HD-methotrexate, teniposide [or etoposide], Ara-C, intrathecal therapy [IT]; B) R plus dexamethasone, vincristine, cyclophosphamide, HD-methotrexate, adriamycin, IT; C) R plus dexamethasone, vindesine, HD-methotrexate, etoposide, HD-Ara-C. The A-C sequence was repeated once. Patients aged >55 years received only courses A and B with methotrexate 0.5 g/m2. Results: Eighty-three total patients (79%) achieved CR, 8 were refractory and 14 died of complications. All early deaths occurred in patients older than 40 years, correlated with stage III-IV BL or B-ALL (n=13), PS ≥1 (n=10), and were mainly caused by infections. Among CR patients, 67 (81%) received all planned therapy and 16 did not (toxicity/CR death 11, early relapse 3, other 2). The mean intercycle time (MIT) between chemotherapy courses was 29 days (range 22–52). After a median follow-up of 23.8 months (range 0.7–99), 65 patients (61%) were alive in 1st CR, 19 (18%) died of complications (7 in CR, including 2 late deaths due to secondary AML and cardiovascular accident), and 19 had refractory or recurrent disease. Ten of 67 patients treated with MIT >25 days relapsed within 6 months (15%), compared to one of 15 treated with MIT ≤25 days (7%, P=.34). Projected 3-year overall and disease-free survival and were 67% (OS) and 75% (DFS), respectively. In univariate analysis age, normal LDH, ECOG PS 55 years with PS ≥1 had the worst outcome (n=24; OS 28% and DFS 36%), those with PS=0 fared as well as patients aged ≤55 years with PS=0–1 (n=55; OS 89% and DFS 89%) and the younger patients with PS >1 represented an intermediate-good risk category (n=26; OS 61% and DFS 77%) (P=.0000). The incidence of TRM and relapse varied significantly among the 3 groups, each contributing almost equally to the final outcome. Conclusion: The excellent therapeutic potential of this treatment (89% cure rate) was confirmed in patients with PS=0, regardless of age, and in younger patients with PS=0–1, whereas the results were still good, though significantly inferior, with PS >1 (61% cure rate). Prompt diagnosis and referral of BL and B-ALL patients is essential for exploiting the prognostic advantage associated with a better PS, together with maximized anti-infectious measures and rapid re-cycling of chemo-immunotherapy blocks. Disclosures: No relevant conflicts of interest to declare.

Abstract 2131 Background. Some studies have shown how the use of pediatric-type therapy (PDT) and minimal residual disease (MRD)-oriented programs could improve outcome of adult ALL. Study Design. We included PDT elements in a pilot trial started January, 2008. Protocol 10/07 consisted of standard induction and late reinduction courses plus 3 PDT blocks (modified after BFM therapy) alternating with 3 lineage-targeted Methotrexate (LTM) blocks (B-precursor: 2.5 g/m2; T-precursor: 5 g/m2; Ph+ or age >55 years: 1.5 g/m2). LTM targeted a Methotrexate plasma concentration of ∼35 and ∼65 micromol/L in B- and T-ALL, respectively, in line with a therapeutic concept developed at St. Jude's Hospital (Memphis, TN, USA) in childhood ALL. The program was integrated by (a) a randomised, radiation-free central nervous system (CNS) prophylaxis study comparing intrathecal Methotrexate, Ara-C, and Prednisone (×12) vs. liposomal Ara-C (DepoCyte 50 mg, ×6 [B-ALL]-8 [T-ALL]); (b) the molecular evaluation of MRD at pre-fixed treatment weeks (w), to optimise risk stratification and indications for allogeneic stem cell transplantation (allo-SCT); and (c) by concurrent imatinib in patients with Ph+ ALL. The whole chemotherapy plus MRD study sequence was as follows: prephase (Prednisone, Cyclophosphamide) → induction (Idarubicin, Vincristine, Asparaginase, Dexamethasone) + w4 MRD → PDT1 (Cyclophosphamide, Vincristine, Idarubicin, Dexamethasone, Ara-C, 6-mercaptopurine) → LTM1 (plus high-dose Ara-C) + w10 MRD → PDT2 → LTM2 (plus Asparaginase) + w16 MRD → PDT3 → LTM3 (plus HD Ara-C) + w22 MRD → reinduction (Idarubicin, Vincristine, Cyclophosphamide, Dexamethasone). CNS prophylaxis was administered only during PDT blocks, with a minimum interval >15 days from/to LTM cycles. Risk classes were standard (SR: pre-B and WBC100, or CD1a-negative early or mature T phenotype; and to SR/HR patients with MRD >10-4 after LTM1 (w10) or detectable at any level after LTM3 (w22). Autologous SCT followed by maintenance was a suitable alternative when allo-SCT was not feasible. All patients not eligible to frontline allo-SCT and with low positive ( Results. Seventy-five of 81 evaluable patients (median age 40 years [range 18–65], 54% male, 23% T-ALL, 60% HR, 20% Ph+) achieved CR (92.5%); 55 of them (73.5%) were alive in CR1 at time of interim analysis (April, 2010). Sixteen patients relapsed (21.5%) and four died in CR of therapy-related complications (one after allo-SCT and 3 aged >55 years after a PDT cycle). With a maximum follow-up slightly >2 years (27.5 mos.), projected overall survival (OS) at 1.5 years is 73% (95% CI 57%-83%), and disease-free survival (DFS) 66% (95% CI 52%-77%). The best results were observed in patients aged 55 years and less (n=65, OS 79%) and those with T-ALL (n=20, OS 86%). These findings correlated well with a favourable early MRD response in Ph-negative subsets: 49% of evaluable cases achieved a major MRD response (10-4 (P=0.039). The flexible risk- and MRD-adapted SCT policy resulted in high early transplantability rate in patients with this indication (70% in T-ALL). Finally, the randomised CNS prophylaxis trial preliminarily confirmed the feasibility of intrathecal DepoCyte as planned (total randomised patients = 57). Conclusions. This regimen was highly active, yielding a >90% CR rate in unselected adults aged up to 65 years, with a major early MRD response of 63% in Ph-negative B-ALL and 87% in T-ALL. The toxicity observed after PDT blocks in a first group of patients aged >55 years required a reduction of PDT dose intensity in this age group. LTM therapy proved feasible, up to 5 g/m2 in T-ALL, and remarkable early OS/DFS rates were obtained in T-ALL and in unselected patients aged Disclosures: Bassan: Mundipharma: Consultancy, Research Funding. Off Label Use: Study is devoted to assess feasibility/toxicity/value of intrathecal liposome-encapsulated cytarabine (DepoCyte) vs standard intrathecal therapy as prophylaxis of CNS recurrence in adult ALL.