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BACKGROUNDSome copy number alterations (CNAs) have independent prognostic significance for adults with acute lymphoblastic leukemia (ALL). METHODSThis study analyzed via multiplex ligation-dependent probe amplification the frequency and prognostic impact of CNAs of 12 genetic regions in 142 adolescents and adults with de novo precursor B-cell ALL. RESULTSThe cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion (59 of 142 or 42%) was the most frequent CNA, and it was followed by Ikaros family zinc finger 1 (IKZF1) losses (49 of 142 or 35%). IKZF1 deletions were more prevalent in Philadelphia chromosome (Ph)-positive ALL and were associated with advanced age and high white blood cell (WBC) counts. The multivariate analysis showed that advanced age and early B-cell factor 1 (EBF1) deletions were associated with chemotherapy resistance in both the whole series (hazard ratios, 0.949 and 0.135, respectively) and the Ph-negative subgroup (hazard ratios, 0.946 and 0.118, respectively). High WBC counts and focal IKZF1 deletions correlated with disease recurrence (hazard ratios, 1.005 and 1.869, respectively), whereas advanced age and CDKN2A/B losses influenced overall survival in both the whole series (hazard ratios, 1.038 and 2.545, respectively) and the Ph-negative subgroup (hazard ratios, 1.044 and 2.105, respectively). CONCLUSIONSDeletions of EBF1, IKZF1, and CDKN2A/B have an independent adverse prognosis for adolescents and adults with B-precursor ALL, and this suggests that these CNAs should be included in the initial risk assessment of ALL. Cancer 2015;121:3809-3817. (c) 2015 American Cancer Society. Deletions of early B-cell factor 1, cyclin-dependent kinase inhibitor 2A/B, and Ikaros family zinc finger 1 are independent markers of a poor prognosis for uniformly treated adolescent and adult patients with B precursor acute lymphoblastic leukemia.

Background and objectives: Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare entity, presenting especially in adult smoker women. It is characterized by an increase of serum IgM, DR7-HLA haplotype, cytogenetic abnormalities and multiple IgH/BCL-2 rearrangements. To date, it has not been elucidated whether this is a benign or premalignant disorder. We analyzed the PPBL characteristics with especial attention to its evolution. Patients and methods: Thirty-five PPBL patients from 5 hospitals in Catalonia were retrospectively analyzed. A simultaneous morphologic review of the blood smears was performed by members of the GCCH in a 16 multiple-observer optic microscope. Clinical and biological data were also analyzed. Results: PPBL presents in the majority of cases with persistent polyclonal B-cell lymphocytosis and affects primarily smoker women. The morphologic hallmark, in absence of viral infections, is the presence of activated lymphocytes with bilobulated and/or cleaved nuclei, and nuclear pockets in the ultrastructural study. Increased serum IgM. HLA-DR7 haplotype, chromosomal abnormalities such as i(3)(q10) and multiple IgH/BCL-2 rearrangements were detected. Thirty-four out of 35 patients are alive after a median follow up of 70.7 months. One patient died because of lung adenocarcinoma and another developed a follicular lymphoma without relation to PPBL Conclusions: PPBL has an asymptomatic and stable evolution, although it frequently presents genetic abnormalities. It remains unknown whether it is a premalignant entity, similar to monoclonal gammopathies of unknown significance. Hence, accurate cytologic diagnosis and follow-up are essential. (C) 2010 Elsevier Espana, S.L. All rights reserved.

To analyze the main clinical and biological data and the response to therapy in 15 patients with primary gastrointestinal lymphoma (PGIL) from a series of 76 patients with HIV related non-Hodgkin's lymphoma (NHL) diagnosed in a single institution in a 13 years period.The main clinical, biological and evolutive data were recorded. Pathologic diagnosis of PGIL was made according to the REAL classification. Clinical stage was determined by the Ann Arbor system modified by Rohatiner et al. Response to therapy as well as overall survival (OS) were studied. Results were compared with non-PGIL HIV-related NHL patients.Mean age of the series was 38 years. Thirteen patients were male, and 8 intravenous drug abusers. Then had bad performance status (ECOG 2-4) and 11 B symptoms. All patients had a high grade malignant PGIL and the localization was gastric in 10 cases. The most frequent symptoms were abdominal pain (11 cases), gastrointestinal bleeding (4) and dysphagia (3). Ten patients had advanced stages (IIE2-IV). The median CD4 cell count was lower in PGIL patients (92 x 10(6)/l vs 148 x 10(6)/l; p0.05). Thirteen patients received intensive chemotherapy with CHOP regimen (in 5 surgical procedures were previously made). Complete response (CR) was obtained in 4 patients (31%) and 1 of them relapsed. Median OS was 10 months vs 16 months non-PGIL HIV-related lymphoma patients (p0.05).PGIL in HIV patients often presented advanced stages and high grade of malignancy. The most common localization is the stomach, and these patients usually have bad performance status and a low CD4 lymphocyte count. Response to therapy is poor. In our series OS was worse in PGIL patients than in the rest of HIV-related NHL, possibly due to the high degree of immunosuppression in the formers.

The aim of this study was to analyze the influence of age on the clinical and biological features as well as the results of treatment in 41 adult patients with acute lymphoblastic leukemia (ALL).The patients diagnosed with ALL from January 1989 to October 1995 in a single center were studied. Two groups of patients were analyzed based on age. The main clinical, hematologic and biochemical parameters, morphologic subtype and immunologic phenotype and the results of the cytogenetic study were analyzed. Likewise, the attainment of complete remission (CR), its duration and overall survival (OS) were also studied. Comparison of the cited variables and the results of treatment among the two groups of patients was performed.Group I was made of 19 (11 males, 8 females) patientsor = 50 years of age (mean age 65 +/- 9 years). Group II included 22 patients (11 males and 11 females) with a mean age of 28 +/- 11 years. Significant differences were only observed between the two groups in regard to the proportion of peripheral blood blasts (p0.02), serum LDH values (p = 0.05) and the performance status at the time of diagnosis ( p0.00007). In the patients in group 1 cytogenetic alterations were more frequent (10/16 vs 4/20, p0.02), being mainly pseudodiploid. Complete remission was achieved in 7/16 patients in group I and in 17/22 in group II (p0.02). The median duration of CR was 34 and 18 months, respectively. The median OS was 7 months in group 1 and 15 months in group II with an estimated survival at 5 years of 0% in group I and 38% in group II (p0.05).Patients with acute lymphoblastic leukemia over the age of 50 years have a worse general status and more cytogenetic alterations (particularly structural) than younger adult patients, presenting a lower probability of achieving complete remission and a shorter survival.

Granulocytic sarcoma (GS) is a solid tumor of extramedullary localization constituted by immature precursors from the granulocytic series. GS may be diagnosed in different malignant blood diseases involving the granulocytic series, acute non lymphoblastic leukemia (ANLL) being the most frequent, followed by myelodysplastic syndromes (MDS) and chronic myeloproliferative syndromes, specially chronic myeloid leukemia (CML) in blastic crisis. Although the diagnosis of GS is suspected with conventional cytologic and anatomopathologic studies, histochemical staining and immunohistochemical techniques are often required for definitive diagnosis. Five cases (4 males, 1 female; age range 22-77 years) diagnosed with GS in one center over a period of nine years (1984-1993) are described. The GS were located in the lymph nodes, the jaw, paravertebral region, gallbladder and retroperitoneum, respectively. Two patients had refractory anemia with excess of blasts (RAEB). Three patients had ANLL; in one GS constituted the form of relapse, in another GS presented at the time of diagnosis and in the remaining patient GS preceded the diagnosis of ANLL. All the patients died from 2 to 8 months after diagnosis of GS with no response to treatment being observed. Immunohistochemical study of the tumor was performed in 4 patients, being positive for lysozyme and the monocytic MAC-387 monoclonal antibody. Immunocytochemical study of the tumor blasts was carried out with positivity for CD15 being observed. Although uncommon, GS should be suspected in patients with ANLL or MDS with tumors of any localization and at any time during its evolution. Immunocytochemical and immunohistochemical studies are of great value to differentiate GS from other tumors, particularly anaplastic non Hodgkin's lymphomas.

The management of non-Hodgkin's lymphomas (NHL) in AIDS is difficult because of the poor bone marrow reserve and immunosuppression of these patients. Combination chemotherapy is the treatment of choice in the subset of patients with good performance status and mild immunosuppression. Several combination chemotherapy regimens have been used in these patients but the results have been poor. We have studied the clinical and biological features, response to treatment, outcome and prognostic factors of 46 patients with NHL and HIV infection, diagnosed in a single institution between January 1988 and June 1997.Forty-six patients with NHL and HIV infection were treated with CHOP. Patients with previously treated systemic NHL, primary CNS NHL, performance status2 and active AIDS-defining opportunistic or neoplastic diseases were excluded. The parameters evaluated were: age, sex, risk activity, basic hematologic and biochemical parameters, CD4 lymphocyte count, B symptoms, stage (Ann Arbor), histologic subtype (REAL classification), International Prognostic Index (IPI), response to treatment, relative dose intensity (RDI), relapse free survival (RFS) and overall survival (OS). Uni- and multivariate analyses of prognostic factors were performed.Median age was 35 years and 40 patients were male. CD4 lymphocyte count was lower than 0.1 x 10(9)/L in 18 out of 38 cases, hypoalbuminemia was registered in 24 (52%), serum LDH was higher than 400 U/L in 20 (43%) and beta 2-microglobulin was higher than the normal range in 9 out of 20 patients (45%). Complete response was achieved in 18 patients (40%). Twenty-six patients received G-CSF after chemotherapy. Grade 4 neutropenia and fever were significantly more frequent in patients who did not receive G-CSF. Serum LDH400 U/L and hypoalbuminemia were the only parameters associated with a lower probability to achieve complete response (p = 0.015 and p = 0.025, respectively). The median RFS was 26 (6-47) months and no variable was found to have statistically significant influence on it. The median OS was 9.2 (4.5-14) months, and IPI score 1 and ESR60 mm/h were the only parameters identified as good prognostic factors in the multivariate analysis (p = 0.03 and 0.049, respectively).In spite of patient selection, the response to CHOP treatment in patients with NHL and HIV infection remains poor. Episodes of neutropenic fever are less frequent when G-CSF is administered after CHOP. The IPI score 1 is the most important favorable prognostic factor for survival.

To analyze the response to eradicative therapy and prognostic factors in 52 patients with primary gastrointestinal lymphoma (PGIL) diagnosed at a single institution in a 13 year period.The main clinical, biological and evolutive data were recorded. Pathologic diagnosis of PGIL was made according to the Working Formulation. Clinical stage was determined by the Ann Arbor system modified by Mushoff. The results of therapy as well as the influence of such characteristics on complete remission (CR), disease-free survival (DFS) and overall survival (OS) were studied.Mean age of the series was 53 years (SD 15). Thirty patients were males. HIV infection preceded PGIL diagnosis in 10 cases. Seventeen had bad performance status (ECOG 2-4) and 30 B symptoms. The PGIL localization was gastric in 31 cases and 29 had a low grade malignant lymphoma. B phenotype was demonstrated in 98% and 22 patients presented advanced stages (IIE2-IV). Treatment was radical surgery followed by intensive chemotherapy in 32 cases, intensive chemotherapy alone in 17, and surgical resection in 3. CR was obtained in 34 patients and 6 of them relapsed. The projected DFS from CR at 9 years was 72% and OS was 26%. CR and survival were not influenced by PGIL localization and treatment type. The main unfavourable prognostic factors were advanced stage (CR and OS), B symptoms (DFS and OS) and advanced ECOG score (CR, DFS and OS). Previous HIV infection had an independent prognostic influence on both CR and OS.In patients with PGIL, the achievement of CR, DFS and survival have been independent of the type of eradicative treatment used. Performance status, B symptoms and clinical stage have been the main prognostic factors. HIV infection carried an independent prognostic significance.