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  • 1
    Publication Date: 2010-11-19
    Description: Abstract 4832 Background Myeloproliferatives neoplasms (MPN) are clonal stem cell disorders characterized by proliferation of one or more of the myeloid lineages, associated with genetic abnormalities that include translocations or point mutations of genes that encode cytoplasmic or tyrosin quinase (TK) receptor proteins. This produces an abnormal constitutively activation of signal transduction pathways, leading to an unregulated proliferation. According to the WHO criteria, MPN are classified into BCR-ABL+/Philadelfia Ph+: chronic myeloid leukemia (CML) and MPN BCR-ABL fusion-/Ph-. A single acquired point mutation, JAK2V617F, has been described in 95% of Polycytemia vera (PV), in 50 % of essencial thrombocythemia (ET) and idiopathic myelofivrosis (IMF), and generally absent in MPN Ph+. In the last years, it has been described the co-ocurrence of both BCR-ABL and V617F mutation in few cases of CML patients. We report here the rare and concomitant ocurrence of JAK2V617F mutation with BCR-ABL translocation at presentation in atypical CML. Methods Blood samples from six patients with clinical suspicion of MPN diagnosis, were referred to our laboratory to cytogenetic studies and molecular analysis of BCR-ABL fusion gene expression by conventional RT-PCR and JAK2V617F status mutation by ASO-PCR in three of them. All patients showed a slightly elevated white blood cells level (7200-25900), trombocythosis (700 -1036 platelets) and small splenomegaly. Three patients, after CML diagnosis, recieved Imatinib therapy and were monitored by quantitative BCR-ABL real time PCR. Due to persistent thrombocytosis, slightly elevated white blood cells level and small splenomegaly; JAK2 status was analized in these blood specimens, and later retrospectively in the stored initial diagnosis samples. Results BCR-ABL rearrangement (b3a2 isoform) and JAK2V617F mutation were identified in all 6 patients at diagnosis. Three cases showed lack of Ph chromosome, 1 patient showed 15 % Ph+ metaphases and in the remained two patients no data was available. Quantitative PCR for BCR-ABL expression performed in 3 patients during follow-up (8-12 months) showed BCR-ABL/BCR ratio 〈 = 0.0018 % (scored according to the International Scale) and the presence of JAK2V617F mutation. Retrospective assessment of stored bood samples showed that JaK mutation was already present at the time of the diagnosis of CML. Conclusions The coexistence of both genetic defects, BCR-ABL fusion gene and JAK2V617F mutation in NMP patients is a rare and uncommon feature. We found 6 MPN patients hourboring both genetics features in blood dignosis samples. In three cases JAK2V617F mutation was detected in MPN patients BCR-ABL positive after the remission induction with Imatinib. The rapid remission of BCR-ABL transcript, after a short period of Imatinib treatment, led us to think that BCR-ABL fusion gene expression was present in a low burden at diagnosis. The complete reduction of BCR-ABL rearrangement, after the imatinib therapy, and the persistence of JAK 2 mutation suggests two possible mechanisms for this double genetic alteration: 1) a haematopoyetic cell subclone with a pre-existing JAK2V617F acquires the BCR-ABL fusion gene, which confers a selective advantage to double mutant progenitor; 2) two clons, one of them having BCR-ABL rearrangement, and the other one the JAK2V617F mutation (biclonal origin). These cases intend to contribute to the discussion about the onset of the molecular alterations, and their correlation with the differente phenotypes and clinical management. Disclosures: No relevant conflicts of interest to declare.
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  • 2
    Publication Date: 2015-12-03
    Description: Introduction. Multiple Myeloma (MM) is a heterogeneous, incurable disease. Several prognostic scores have been developed to estimate response to treatment, progression free survival (PFS) and overall survival (OS). The International Staging System defines 3 stages with distinct prognostic significance, using serum beta 2 microglobulin (b2M) and serum albumin. However, due to a higher power of risk discrimination, current guidelines recommend to stratify patients according to cytogenetics (CG) and treat high-risk patients with Bortezomib (BZ)-based therapies. In Uruguay, BZ is financed and regulated by a National Funding Board and is approved for high-risk MM or renal impairment at diagnosis or at relapse. As a consequence, the patients included in this study are a selected high risk MM subgroup. Even though proteasome inhibitors have improved outcomes for many high-risk MM patients, some still present short response duration and poor survival. Identifying simple factors that can predict response to BZ would be useful in order to better select the most appropriate therapeutic choice. Patients and Methods. We conducted a retrospective study to evaluate MM response to BZ-based therapy according to b2M, serum creatinin (Cr) and CG. Forty-seven MM patients [median age 59 years (38-77), females 25 (53%)] from two public centers treated with BZ-based combinations were included. According to local regulatory policies, only patients with renal failure and/or high risk CG features received BZ as first line therapy (n=31). Other 16 individuals received BZ combinations for relapsed/refractory disease. Patients received a median of 5 cycles of BZ (3-6). Nineteen individuals (40%) received high dose melphalan and autologous stem cell transplantation after BZ-based induction. At diagnosis, 28 (59%) had an ISS 3, 24 (51%) patients had serum Cr higher than 2 mg/dL and 14 (30%) exhibited high risk CG. Responses to BZ therapy were evaluated according with International Myeloma Working Group criteria as complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD) and progressive disease (PD). Responses were analyzed depending on b2M level, serum Cr and CG. Comparison between groups was made by chi-square test. PFS and OS were calculated by the Kaplan-Meier method. Survival was compared between groups by log-rank test. Results. No differences in responses to BZ-based therapies were found when comparing patients with low (lower than 5,5 mg/L) versus high b2M levels (CR/VGPR 44,4 vs 44% respectively, p=0.97), low versus high serum Cr (CR/VGPR 34 vs 55% respectively, p=0.18) and standard versus high risk CG (CR/VGPR 46,7 vs 38,5% respectively, p=0.62). Patients with renal failure (serum Cr 2 mg/dL or higher at diagnosis, n=23) had a median of 53% (0 - 88%) reduction in Cr levels after receiving at least three cycles of BZ therapy. Eleven of them (47,8%) had normal renal function after completing BZ treatment. From 9 patients requiring dyalisis at diagnosis, 4 were out of dyalisis after BZ treatment. No significant differences in PFS and OS were observed when patients with low versus high b2M levels and standard versus high risk CG were compared. Patients with low Cr levels at diagnosis show a significantly better OS compared with those with Cr higher than 2 mg/dL (median OS not reached versus 42 months respectively, p=0.004), with no differences in PFS. Conclusion. In a selected high risk MM patients group treated with BZ-based therapies, similar response rates were obtained in individuals with high or low b2M levels, Cr levels, and standard or high risk CG. Although individuals with renal failure at diagnosis exhibit similar quality of responses than standard patients, long term OS of this group is still impaired and further improvements in therapy are needed. Note: GB and ER have contributed in equal parts to this work. Disclosures No relevant conflicts of interest to declare.
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  • 3
    Publication Date: 2014-12-06
    Description: Introduction: patients with hematologic malignancies (HM) admitted in intensive care units (ICU) have been traditionally seen as patients with very poor prognostic. Recently reports have informed that mortality has dropped and nowadays is in the order of 40-60 %, this is still high but closer to mortality in non-malignant patients admitted in an ICU. In an attempt to change this view we perform a study in order to evaluate the results and prognostic factors that contribute to mortality in HM patients who need critical care assistance. Methods: a retrospective study in 62 patients with HM who were admitted in ICU in the University Hospital, Hospital de Clinicas from Uruguay from 2003 to 2012. These 62 patients had 82 admissions, which are the population of our trial. Statistical analysis: Values are expressed as mean +/- standard deviation (SD), median and percentages. Comparison variable most used: discharge of ICU: dead or alive. Both groups were compared using Student's t test and Chi square. Multivariate logistic regression analysis was performed. Overall survival with Kaplan Meier. Significance p
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  • 4
    Publication Date: 2011-11-18
    Description: Abstract 4520 Between June 1995 and June 2011, we performed 133 Autologous Stem Cell Transplantation (ASCT) in patients with NHL. Long term results of treatment and outcome were analyzed. The data presented were obtained from the Statistical Center of the Center for International Blood and Marrow Transplant Research. Median age was 48 years (range 18–65), 9% ≥ 60 years, 77 males and 55 females. The histology was: 98 (74%) B NHL, Follicular Lymphoma (FL) 26 (20%), Diffuse large B Cell Lymphoma (DLBCL) 47 (35%), Primary Mediastinal Large B Cell Lymphoma 12 (9%), Mantle cell Lymphoma (MCL) 6(4.5%), Marginal Zone Lymphoma 4 (3%), Small Lymphoplasmocytic 2 (1.5%), precursor B Lymphoplasmoblastic 1 (1%), and 35 (26%) T NHL, Peripheral T Cell Lymphomas NOS 12 (9 %), Anaplastic LC, T/N Cell systemic 9 (6.5%), Anaplastic LC, T/N Cell cutaneous 1(1%) and T/NK Cell Lymphoma 7 (5%), Angioinmunoblastic T Cell Lymphoma 2 (1.5%), Mycosis Fungoides 2 (1.5%), other T Lymphoma 2 (1.5%). We emphasize that 59 % of the patients had advanced disease at the moment of the transplant: 41% CR1, 11% CR2, 5% REL1, 8% primary induction failure, other 33% (CR3+, PR, and REL2+), and 2% missing/unknown. Condition regimens were BEAC 88%, BEAM 10% and CBV 2%. Stem cells source: 74% peripheral blood stem cells (PBSC) and 26% received bone marrow (BM) and PBSC. Overall survival was 86% (95 CI, 80–92) at 1 year, 78% (95 CI, 70–85) at 3 years and 71% (95 CI, 62–79) at 5 years. Median follow up of survivors was 96 months (3–181). Primary cause of death was relapsed or progression. We concluded that high dose therapy and Autologous Stem Cell Transplantation is an effective and feasible therapy for patients with high risk NHL. However relapse continues to be the most common cause of treatment failure. Newer strategies such monoclonal antibodody, require further investigation but early reports appear promising in reducing relapses in ASCT. Disclosures: No relevant conflicts of interest to declare.
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  • 5
    Publication Date: 2015-12-03
    Description: Background: Febrile neutropenia (FN) is among the leading causes of mortality and morbidity in hemato-oncologic patients undergoing cytotoxic chemotherapy. The management of FN is typically algorithm-driven. The effectiveness in reducing FN related mortality of the antibacterial protocol proposed by the international guidelines is already reported. In this regard, most of the popular guidelines are based on clinical trials conducted in developed countries. Little is known about results in developing countries where patients delay consultation and have socio-cultural vulnerabilities. The aim of our study was to assess the results of the implementation of a local FN protocol in patients undergoing intensive chemotherapy regimens at Hospital de Clinicas in Uruguay. Methods: We assessed a retrospective study with patients that have undergone intensive chemotherapy in our hemato-oncology service between 2011 and 2014. We included 127 neutropenia episodes (37 patients), with a median age of 37 years (18-79 years). Acute myeloid leukemia 26 (24.4%), acute lymphoblastic leukemia 12 (9.4%), non-Hodgkin lymphoma 74 (58.4%) and Hodgkin Lymphoma 15 (11.8%). Low risk patients were excluded. Additionally, episodes linked with high risk regimens as acute myeloid leukemia induction chemotherapy and alemtuzumab therapy were excluded from the analysis. The initial antibiotic protocol consisted in piperacillin-tazobactam (4.5 gr every 6 hours). For patients with warning signs, more than one week of hospital stay, or having received in the last 30 days ciprofloxacin or 3er generation cephalosporin as prophylaxis meropenem (1gr every 8 hours) was indicated. Prophylactic antiviral (acyclovir) and antifungal (fluconazole) were given in every case. Modification of initial empirical treatment with piperacillin-tazobactam, changing to meropenem, was done if there was: a) deterioration in the clinical state, b) warning signs, hemodynamic instability or other organ dysfunction, c) persistent fever after 4 days of treatment, d) culture with antibiotic-resistant. In patients with hemodynamic instability, skin or soft tissue infection, suspected catheter-related infection or methicillin-resistant Staphylococcus aureus culture positive, vancomycin was added. Empirical antifungal coverage was considered in patients who had persistent fever after 6-7 days of antibiotic treatment without identified fever source. Results: FN incidence was 33.1% (42 episodes). The presence of FN was associated with both the duration and severity of neutropenia. Median days of neutropenia (below 500/μL) in patients with FN was 10.0 ± 7.9 (standard deviation) vs 6.0 ± 3.7 (standard deviation) in patients without FN (p=0,001). Microbiological isolation from any source was achieved in 28.6% of the episodes and bacteremia was the most prevalent (77%). Multiple-antibiotic-resistant (MR) Gram-negative bacillus (GNB) were isolated in 58,3% of all microbiological documented infections, followed by GNB 25%. In 25 episodes the initial treatment was piperacilin/tazobactam (59%), while in 17 episodes Meropenem was. 15 episodes (35.7%) required vacomycin treatment. 32% of the episodes in which the initial treatment was piperacilin/tazobactam, needed to escalate to Meropenem. The mortality rate of febrile neutropenia episodes was 3.9% (40% related to sepsis). Conclusions: In this work we observed high rate of microbiological documentation in FN episodes being bacteriemia the most frequent form and there was a predominance of MR-GNB. The high rate of GNB resistant to piperacilin/tazobactam, front line antibiotics in our protocol, and the early need to escalate to carbapenems raises the question whether it is necessary to change our antibiotic treatment protocol. Disclosures No relevant conflicts of interest to declare.
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  • 6
    Publication Date: 2006-11-16
    Description: Between 1995 and 2005, we performed 329 hematopoietic stem cell transplantation (HSCT), 286 autoulogous and 43 allogeneic. Long term results of treatment and outcome of ASCT in 100 Non Hodgkin Lymphoma (NHL) were analyzed. Median age was 47 years (range18 – 64) and the histology was: Follicular Lymphoma 15%, diffuse large B cell lymphoma (DLBCL) 47%, T lymphoma 27% and 11% others. At diagnosis 66% had advanced stage (III/IV), 40% had B symptoms, and 34% had extranodal involvement. Disease status at HSCT was: 5 % primary induction failure, 41% CR1, 20% CR2 +, 7% CRU, 12% relapsed. Number of prior chemotherapy regimens was 47% 2 lines, 20% 3 lines and 3% 4 lines; 27% had received prior induction or consolidation radiotherapy. Condition regimens consisted of BEAC (81%), BEAM (15%), others (4%). Stem cell source: 39% received BM + PBSC and 61% PBSC. Sixty nine are alive with a median survival of 3448 days (9.5 years). Median overall survival was similar in DLBCL (59%) and peripheral T lymphoma (60%). The best overall survival was observed in CR1 (77%) versus 52% in CR2 and 66% in PR1. Primary cause of death was relapsed or progression (24/31). We concluded that high dose therapy and autologous HSCT is an effective therapy for patients with poor risk NHL however relapse continues to be the most common cause of treatment failure. Newer strategies such as monoclonal antibody, require further investigation but early reports appear promising in reducing relapses in autologous HSCT.
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  • 7
    Publication Date: 2011-11-18
    Description: Abstract 4976 Between January 2002 and December 2010, we treated 207 NHL at the Hospital de Clínicas, Uruguayan University Hospital. These are 10 % of the NHL diagnosed in our country. There were 72 Diffuse Large B Cell Lymphoma (DLBCL), 34 Follicular Lymphoma (FL), 33 Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, 11 Mantle Cell, 10 T Cell, 7 MALT, 7 Anaplasic T, 6 Burkitt, 6 Lymphoblastic Lymphoma, 5 Lymphoplasmocytic, 4 Mycosis Fungoides, 3 Burkitt like, 2 Hairy cell Leukemia, 2 Esplenic Marginal zone, 2 LLGG, 2 angioinmunoblastic, 1 Prolymphocytic Leukemia. The mean of this retrospective study is to analyze the improvement in Overall Survival (OS) with the use of R in DLBCL and FL in HIV negative Uruguayan patients. The DLBCL were 72 patients, we analyze 61 because 5 were HIV positive and 6 were Primary CNS. There were 34 males and 27 females. The median age was 60 years (25-82). At diagnostics, the Ann Arbor Stratification was: 26 I-II, 10 with B symptoms, 35 III – IV, 20 with B symptoms. Nineteen (31 %) had Bulky disease and 18 (30 %) were primary extranodal disease. The International Prognostic Index was: 30%: 0–1; 28,5 %: 2; 28,5 %: 3; 13 %: 4. The delay between the first consult and treatment was 31 days (1-456). The Chemotherapy regimens used were in 35 CHOP-like (CHOP, CAPVE, CEOP, CMVP, CVP, m-BACOD) with a median of cycles of 6 (1-8), and in 22 R-CHOP with a median of cycles of 6 (1-8). Results DLBCL: In DLBCL treated with CHOP-like regimens the Overall Response (OR) (Complete Remission (CR) and Partial Remission (PR)) was 60 % with 37 % of CR and 23 % of PR. With R-CHOP the OR was 100 %, CR: 91 % and PR: 9 %. With a median of follow up of 23 month (0,8-106), the OS in patients treated with CHOP-like is 34,3 months and in R-CHOP it has not been reached yet, but it is not statistically significant: log rank (p=0,121). The OS at 24 months is 52 % in CHOP-like vs 80 % in R-CHOP. These results are very promising for the R- CHOP group. The Disease Free Survival (DFS) was 39,6 month (IC: 0–114,4) in CHOP-like and it has not been reached yet in patients with R-CHOP, but this is not statistically significant, log rank (p= 0,645). At 24 month the DFS was 60 % in CHOP-like and 67 % in R-CHOP. There were 34 patients with FL, we analyze 33 because we exclude HIV +. There were 19 females and 14 males. The median age was 62,5 years (33-79). At diagnostics, the Ann Arbor stratification was: 8 patients I -II, 3 with B symptoms, 25 III – IV, 12 with B symptoms. Twelve percent were bulky and 15 % begun with extranodal disease. Forty four percent had FLIPI 0–1, 36 % FLIPI 2 and 20 % 3 or more. The histological grade was in 3 % G1, 79 % G2 and 18 % G3 (15 % G3a and 3 % G3b). The median delay between the first consult and diagnostic was 24 days (5-765). The Chemotherapy regimens used were: in 18 patients CHOP like (CHOP, CAVPE, m-BACOD), median number of cycles 5 (1-6), in 9 patients R-CHOP with median of cycles of 6 (3-8) and in 3 patients R-CHOP-like (R-CAPVE, FCR, R-CVP), median of cycles 5 (3-6). Results FL: In FL treated with R-CHOP or R-CHOP-like regimens the OR was 92 % with 59 % CR and 33 % PR. With CHOP-like regimens the OR was 55 % with 17 % CR and 38 % PR. With a median follow up of 36 month (3-111), the median OS hasn't been reached. The OS at 24 and 36 month in patients treated with R-CHOP or R-CHOP-like was 82 % and 58 %, and in patients treated with CHOP-like 82 % and 67 % respectively. These are not statistically significant, log rank p=0,923. The median Progression Free Survival (PFS) in patients treated with CHOP-like regimens was 17 month (0-44) and it hasn't been reached in treated with R-Chemotherapy (R-CT). The PFS at 24 and 36 month was 36 % and 18 % in CHOP-like patients and 68 % and 55 % in R-CT patients. These difference also is not statistically significant, log rank p=0,66, but there is a great trend in benefit of R-CT. Discussion and conclusion: the use of the monoclonal antibodies in NHL's treatment has been an important issue and it is now use in first line treatment because it's benefits in OR, CR and OS. R was introduced in Uruguay in 2005 and it is government funded through Fondo Nacional de Recursos. In our series, there is an improvement in CR and a trend towards better results in OS and DFS when R-CHOP is used. In spite of the fact that it was not possible to demonstrate a statistically significant difference in view of the low number of patients, we think that this sample is highly representative of the reality of our country. Disclosures: No relevant conflicts of interest to declare.
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  • 8
    Publication Date: 2015-12-03
    Description: Introduction Uruguayan population is 3,4 million, mostly caucasian (88%). Life expectancy is 77 years. Cancer is the second cause of death and the estimated incidence of Multiple Myeloma (MM) is 120 cases/year. Its diagnosis and monitoring are standardized and feasible, available nationwide. Treatment with Bortezomib, Thalidomide and stem cell transplant are available for all patients, regardless of their health care provider. However, there is no accurate data on MM incidence, care, treatment-results or mortality. The Uruguayan National Myeloma Registry is designed to document current clinical characteristics of newly diagnosed MM, management and outcome in a real-world setting. This information will be useful to plan strategies to improve our local approach and follow-up of this disease, reducing problems derived from extrapolating data from other realities. Methods This prospective national registry will include all MM diagnosed between January 2012 and January 2015 in all institutions, public and private, nationwide. Smoldering MM are not included. Data collection started in October 2014 and is being obtained from medical and day hospital reports at each institution. Our database includes detailed data of clinical characteristics, laboratory, citogenetics and FISH, treatment indicated, disease-related and treatment-related adverse events, response to treatment at onset and relapses, and cause of death. Results Up to now, 163 patients have been included in the registry (45% coverage). Median age at diagnosis was 67 years (range 33-94 years), 43% younger than 66 years. Distribution according Ig subtype was: IgG 52%, IgA 27,5%, Light chains 17%, non-secretor 2,6% and IgM 65 years (56% vs 33%). Suspension or dose reductions due to treatment-related toxicity were required more frequently in patients 〉 65 years (50% vs 20%). Neuropathy was the most common adverse effect reported (14%). Overall, 26% of patients received autologous stem cell transplantation (ASCT) after first line therapy; 46% in ≤ 65 years and 9% in 〉 65 years. After a median follow-up of 19 months, progression free survival (PFS) was 88,6% and overall survival (OS) 78,8% (82,9% in ≤ 65 years and 78,8% 〉 65 years). Discussion This first MM National Registry provides a thorough insight into the characteristics of MM patients in our country, which may become a useful instrument to improve MM care. With a 45% coverage, we show that MM is detected in advanced stage, with a high percentage of patients with impaired renal funcion. ASCT is indicated in a low percentage, particularly in those younger than 65 years; reasons for this should be addressed in future research. Longer follow-up is needed to address the impact of new drugs in survival. To the best of our knowledge there is no other MM registry of this kind ongoing in our region. This could become a suitable platform to share with other countries in order to perform high-quality population-based research on the field. Table 1. MM clinical characteristics at diagnosis ≤ 65 years (N=70) 〉65 years (N=93) Sex: F/M (%) 44/56 45/55 Age (median) 56 73 Creatinin 〉2 mg/dl (%) 44,9 33 Hemoglobin
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  • 9
    Publication Date: 2014-12-06
    Description: Lymphomas are the most frequent blood cancer. Current Lymphoma's guidelines recommend initial staging and interim surveillance computed tomography (CT) scan, repeated every 6-12 mo for the first 2 years (ys) after end of treatment. Recent studies show that patients receiving 8 or more CTs have a 2-fold increase in secondary malignancies. This risk is dose-dependent. Cumulative exposure in excess of 75mSv has been estimated to increase cancer mortality by 7.3%. At present, more than 80% Hodgkin's Lymphoma (HL) patients and more than 60% of NHL patients will be alive 5 ys after diagnosis. This percentage is higher in early stage disease (HL: 96 % overall survival (OS) at 5 ys; NHL: depends on the subtype, for DLBCL: 68-90 % at 5 ys). Considering this high survival rates and the demonstrated toxicity of radiation, avoiding CT scans overuse seems reasonable, especially in those with great chances of being cured. Methods A retrospective review of all biopsy-proven stage I-II HL and NHL diagnosed and treated at Hospital de Clínicas, Montevideo, Uruguay, from 1/1/2001 to 1/1/2013 was conducted. Data were obtained from our prospectively-intended database at Lymphoma Unit, and we expressed results with mean +/- SD and median using SPSS program. The cumulative effective radiation dose (CED) was calculated through standardized procedure-specific radiation dose levels. The primary objective was to analyze utility of interim / end of treatment body CT scan in detecting new areas of involvement and progression. Secondary objectives included number of CT performed, total radiation (mSv) received, utility of regular CT scanning in detecting preclinical relapse during follow-up. Results During this period, 73 patients were diagnosed stage I or II Lymphoma, 82% NHL and 18% HL. Most prevalent histologic subtypes were Nodular Sclerosis (9/13) and DLBCL (39/60). Median age at diagnosis was 55 years (15-82), with 34% aged
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  • 10
    Publication Date: 2019-11-13
    Description: INTRODUCTION Secondary Acute Myeloid Leukemia (s-AML) evolves from a previous hematopoietic clonal disease such as Myelodysplastic Syndromes (MDS/AML), myeloproliferative neoplasia (NPM/AML), medullary insufficiencies - aplastic anemia - (AA/AML) or exposure to chemo or radiotherapy (t-AML). The objective of this work is to describe and highlight the demographic, pathophysiologic and clinical-therapeutic characteristics of s-AML patients compared with p-AML. METHODS This is a retrospective cohort study based on the casuistry from 34 reference centers in Latin America during a period of 10 years (JAN10'-MAY19'). Patients ≥18 years old with primary AML, excluding the promyelocytic subtype (p-AML), and s-AML were admitted. Age, gender, performance status, comorbidity, cytogenetics, mutations, AML subtypes, extramedullary compromise, treatments and overall survival (OS) were analyzed. Statistically, Graph Pad Prism version 5.00 and, SPSS version 17 were used. RESULTS One thousand eleven patients with newly diagnosed AML were recruited, 693 (68.5%) corresponded to p-AML and 318 (31.5%) to s-AML. The demographic differences between p-AML and s-AML are shown on Table 1. Subtypes of s-AML: t-AML (18.5%), MDS/AML (58.2%), NMP/AML (13.5%), AA/AML (5.7%) and others s-AML (4.1%). Global median age was 58 years (R 18-93) and male 52%. Extramedullary compromise in CNS (3.2%) and other organs (5.5%). Seven hundred ninety-three cytogenetic studies were evaluable (based on MRC classification): High (22.3%), Intermediate (68.3%) and Low Risk (9.3%). FLT3 mutation was more frequently found in p-AML. In s-AML, the multivariate study showed short overall survival associated with ECOG ≥2 (HR:2.0), white blood count ≥ 50x109/L at diagnosis (HR:1.9), poor risk karyotype (HR:1.6) and age over 60 years (HR:1.5). At least, 883 patients received treatment (Table 2). During this study period, 211 patients (21%) were transplanted; 49 (23%) were s-AML; histoidentical related donor (46%), haploidentical (39%), non-related (8%) and autologous (7%). The median survival for all AML was 11.0 months with a statistically significant difference in favor of the p-AML (Figure 1). CONCLUSION Performance status (by ECOG ≥2), age ≥60, level of leukocytes a ≥50x109/L, poor risk karyotype and s-AML subtype at diagnosis had a significant worse impact on overall survival. Most patients with s-AML came from MDS, they were older and their incidence increased as the population aged. They presented more comorbidities and worse performance status. Undoubtedly, our findings showed that s-AML is a distinct high risk subset of myeloid disorder with adverse prognosis and represents a therapeutic challenge. Disclosures No relevant conflicts of interest to declare.
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