ALBERT

Description: Abstract 4785 Background The karyotype is an important predictor of outcome in adults with acute lymphoblastic leukemia (ALL). Some groups have reported the negative prognostic value of complex karyotype (CK, defined as ≥5 unrelated chromosomal abnormalities) in adult ALL (Moorman et al, Blood. 2007:109;3189-97). On the other hand, monosomal karyotype (MK, defined as ≥2 distinct autosomal chromosome monosomies or 1 single monosomy in the presence of structural abnormalities) has been associated with a worse outcome in patients with acute myeloid leukemia. We aimed to assess the prognostic value of cytogenetic abnormalities, especially CK and MK, in adults with ALL treated with protocols of the Spanish PETHEMA Group. Patients and Methods The karyotypes of 783 adult ALL patients from 63 Spanish centers treated according to the protocols of the PETHEMA Group between 1993 and 2011 were reviewed. The several PETHEMA protocols were risk-adapted (standard-risk –SR–, high-risk –HR–) or subtype-oriented (Philadelphia chromosome [Ph+] ALL -with or without imatinib-, and Burkitt's ALL [BL]). The impact of the main cytogenetic abnormalities as well as of the CK and MK on complete remission (CR) rate, CR duration, overall survival (OS) and event-free survival (EFS) was analyzed. Results The median age of the series was 33 years (range 15–82) and 448 patients (57.2%) were male. The karyotypes of 560 out of 783 patients were evaluable after review: normal karyotype 153 patients, t(9;22) 120, t(v;11q23) 30, t(8;14), t(8;22) or t(2;8) 47, high hyperdiploidy (〉50 chromosomes) 53, low hyperdiploidy (47–50 chromosomes) 52, hypodiploidy (45–39 chromosomes) 32 and extreme hypodiploidy (

Description: Myeloablative transplant has been investigated in poor prognosis indolent lymphoma; although recurrence rate is low it is associated with high mortality; the use of non-myeloablative conditioning regimens could reduce TRM maintaining the GVH effect. Up to May 2006, 35 patients with follicular NHL received a Non Myeloablative related allogeneic according to two prospective multicenter trials; conditioning regimen consisted of Fludarabine 150 mg and Melphalan 70–140 mg. GVHD prophylaxis consisted of CSA plus short-course MTX. All patients received filgrastim-stimulated peripheral blood stem cells from a HLA related identical donor. Median age at transplant was 50 years (34–62) and 16 (46%) had received a previous autologous transplant. At transplant, 5 patients (14%) were in CR1 (after several lines of chemotherapy), 9 (25%) in 〉CR1, 12 (34%) in PR, 1 (3%) had stable disease (after 3 chemotherapy lines) and 8 (23%) progressive disease. All patients engrafted. Acute GVHD developed in patients 19 (54%) (17patients (48%) grade II-IV). Chronic GVHD developed in 18 out of 27 patients at risk (67%), being extensive in 11 (41%). Disease was evaluated at day +100 and at that moment 23 patients were in CR, (85%) 1 (4%) in PR, two (7%) had stable disease and 9 patients ( 26%) have died. With a median follow up of 60 months (range: 32–80 months), 20 patients (57%) are alive disease free, and 14 (43%) have died, 12 of them (37%) due to transplant toxicity and 2 patients (6%) due to progression. Overall Survival (OS) and Event Free Survival (EFS) are 57 and 54 % respectively. Analysing variables which influence on OS and EFS, patients 55 years have a OS significantly shorter than those

Description: Abstract 4137 Introduction: There are no studies in the literature about the frequency of liver infiltration by splenic marginal zone lymphoma (SMZL). In the last review published by the International Group of SMZL (Matutes E et al, Leukemia 2008;22:487) clinical liver infiltration seems to be infrequent and it is considered, as other organ involvement, to appear during the course of the disease and confers a bad prognosis. Objective: To investigate in a selected sample of patients with SMZL the prevalence of liver infiltration, as well as its possible prognostic implication in survival or transformation. Material and methods: In the majority of our SMZL patients who underwent a splenectomy between 1995 and 2001, a liver biopsy was realised during the surgical procedure in order to investigate hepatic infiltration by lymphoma. Results: Forty-eight patients with SMZL were diagnosed in our center during this period; of them, 19 were splenectomized being liver biopsy performed in 16 (only in those cases that gave informed consent). Splenectomy was performed at diagnosis in 11 patients (time from diagnosis to splenectomy 〈 3 months). Liver biopsy was positive for SMZL infiltration in 81.3% (13/16) of the cases. Baseline demographic and clinical characteristics of both groups of patients are shown in the following table; there were no significant differences between the groups. We neither find statistical significant differences in overall survival between both groups: mean overall survival for positive and negative liver biopsy patients was 116 ± SD 13 months and 74 ± 29 months, respectively (p=0.69). Conclusion: Histological hepatic infiltration is present in almost all SMZL patients when splenectomized. In our experience, this finding has no prognostic implication. Due to the small number of patients of this study, its significance is limited but to the best of our knowledge, it is the first report that investigates the prevalence of liver infiltration in SMZL and its impact in survival. Larger series are necessary to confirm our findings. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction Recurrent Copy Number Alterations (CNA) in genes potentially involved in the pathogenesis of ALL have been identified in genes involved in B-cell development, cell cycle regulation, proliferation, apoptosis and drug resistance. Their independent prognostic significance in adult ALL patients is controversial. The aim of this study was to analyze the prognostic significance of CNA in a series of 96 high-risk, Ph-negative, B-precursor adult ALL patients treated according to risk-adapted protocols from the Spanish PETHEMA Group. Methods MLPA assays (MRC-Holland) were performed for the following genes: IKZF1, IKZF2, IKZF3, EBF1, CDKN2A/B, PAX5, ETV6, BTG1, RB1, hsa-miR-31, X/Y PAR1 region genes (CRLF2, CSF2RA, IL3RA) and 14q32.33 region genes (IGH D, MTA1, KIAA0284). Fragment analysis was made by Genescan in an ABI-3130 sequencer (Applied Biosystems). Data normalization provided a value indicative of the presence or absence of CNA: 0-0.20 homozygous deletion, 0.21-0.70 heterozygous deletion, 0.71-1.30 normal, 1.31-1.70 heterozygous duplication and 1.71-2.20 homozygous duplication. Univariable and multivariable analyses including the most relevant clinical parameters (age, WBC count, phenotype, cytogenetics, CNS involvement) were performed for CR attainment, CR duration and OS. Results The median age [range] of the 96 patients was 39 [15-72] years, 50 (52%) patients were males, with a median WBC count 14.3 x109/L [0.4-388]. Phenotype: early pre-B 19 (20%), common 51 (54%), pre-B 22 (24%), unknown 2 (2%). Cytogenetics: normal 18 (19%), hyperdiploid 5 (5%), hypodiploid 2 (2%), near haploid 6 (6%), t(1;19) 7 (8%), 11q23/MLL 11 (12%), complex 1 (1%), other 27 (29%), no growth 17 (18%). The most frequent CNA deletions involved CDKN2A/B (43/96, 45%), PAX5 (34/94, 36%), IKZF1 (32/95, 34%), hsa-miR-31 (25/96, 26%), 14q32.33 region (18/96, 19%), RB1 (17/96, 18%), EBF1(12/91, 13%) and X/Y PAR (10/96, 10%). The most frequent duplications involved X/Y PAR (11/96, 12%) and 14q32.33 region (7/96, 7%). The CR rate was 83% (80/96), the median (95%CI) of CR duration was 2.7 years (0-5.9) and the median (95%CI) of OS was 2.1 (1.0-3.2), being the median (range) follow-up of the series of 3.8 (0.6-8.0) years. Table 1 shows the results of univariable and multivariable analyses. By multivariable analyses advanced age and EBF1 deletions were significantly associated with less CR rate, WBC count and X/Y PAR duplication were associated with shorter CR duration, and advanced age and CDKN2A/Bdeletion were associated with shorter OS. Conclusions The CNA of EBF1, X/Y PAR1 genes and CDKN2A/Bhave independent prognostic significance in adult patients with high-risk, Ph-negative, B-precursor ALL. This study suggests that these genetic studies should be added to the initial work-up of these patients for more accurate prognostic assessment Supported by grants PI10/01417, RD12-0036-0029 from Instituto Carlos III, 2014 SGR225 (GRE) from Generalitat de Catalunya and a grant from the Spanish Society of Hematology and Hemotherapy (2012). Abstract 3798. Table 1. Results of the univariable and multivariable studies. Variable CR rate CR duration OS P (univ) OR (95%CI) P (univ) HR (95%CI) P (univ) HR (95%CI) Age 0.011 0.93 (0.89 - 0.98) NS - 0.005 1.03 (1.01 - 1.05) WBC NS -

Description: The efficacy of intrathecal (IT) depot formulation of liposomal cytarabine (DepoCyte®) in the treatment of CNS involvement in patients with ALL has been only demonstrated in individual cases or series with a small number of patients. A retrospective review was performed of all cases in which IT depot cytarabine was employed as compassionate therapy of CNS involvement of ALL and lymphoblastic lymphoma in Spain. From February 2004 to March 2006, 10 cases (6 females) were recorded (ALL, 6, lymphoid blast crisis [BC] of Ph’ CML, 2, and lymphoblastic lymphoma, 2). The median (range) age was 31 (5–50) yr. Three patients (2 with ALL and another with BC-CML) had leukemic meningeosis at the time of diagnosis: 2 received IT depot cytarabine as adjuvant therapy after triple IT therapy (TIT) (BC-CML) and TIT plus cranial irradiation (ALL), whereas the remaining case (ALL) only received IT depot cytarabine. The remaining 7 patients (ALL, 4, lymphoblastic lymphoma, 2, and BC-LMC, 1) presented CNS relapse. CNS prophylaxis in these patients consisted of TIT plus cranial irradiation (2 patients with ALL), TIT (2 patients with ALL and 2 with lymphoblastic lymphoma), whereas the patient with BC-LMC did not receive any prophylaxis. IT depot cytarabine was administered as the only treatment for CNS relapse in one patient with ALL, as treatment of a second CNS relapse in 2 ALL patients and as adjuvant to other therapies in 4 patients (to TIT in other patient with ALL, to TIT plus radiotherapy in the patient with BC-CML, and to radiotherapy in the 2 patients with lymphoblastic lymphoma). In the 4 evaluable cases (one patient with ALL and CNS involvement at diagnosis and 3 patients with ALL and CNS relapse, 2 with second CNS relapse) treated with IT depot cytarabine as the only drug, clearance of blasts in cerebrospinal fluid (CSF) was observed with sustained response in two (at 7 and 22 months). The remaining 2 patients presented neurologic and systemic progression at 3 and 2 months, respectively. The median number of IT depot cytarabine administrations was 4 (1–9). Concurrent systemic dexamethasone therapy (4 mg twice/day/5 days) was administered with each dose of IT depot cytarabine. Side effects included headache (5 patients), dizziness (2) vomiting (2) and nausea (1). Depot formulation of cytarabine was effective in achieving CNS remission in ALL patients with CNS involvement or relapse. The administration of depot formulation of cytarabine was well tolerated. This justifies the development of a clinical trial to evaluate the efficacy and safety of IT depot cytarabine in meningeal involvement of ALL.