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  • 1
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5094-5094
    Abstract: The aetiology and pathogenesis of Myelodysplastic Syndrome (MDS) remain poorly characterized. One mechanism invoked to explain the apparent discrepancy between cellular marrow and peripheral blood cytopenias in patients with MDS is programmed cell death (apoptosis), which occurs with increased frequency in MDS marrow. Higher rates of apoptosis have been observed in Refractory Anaemia (RA) and Refractory Anaemia with Excess Blasts (RAEB) compared with transforming MDS or acute leukaemia while others have found increased rates in late stages of disease. Cell death may be triggered by activated T cells (in an attempt to eliminate the armful clone), secretion of death proteins/inhibitory cytokines (TNFα, Fas/Fas-L) and interleukin-6, expression of the pro-apoptotic proteins of Bcl-2 family, and/or through a relative deficiency in hematopoietic growth factors (stromal defects). Increased expression and release of TNF-related apoptosis inducing ligand (TRAIL), also known as Apo2 ligand (Apo2L) at the bone marrow level is likely to impair erythropoiesis and to contribute to the degree of anaemia, the major clinical feature of MDS. The exact mechanism by which TRAIL eliminates tumour cells preferentially or selectively is not known. One possibility is differential expression of agonistic receptors 1 and 2 (TRAIL-R1 and -R2), also known as death receptors, DR4 and DR5, and antagonistic or modulatory receptors, TRAIL-R3 and R4, also known as decoy receptors, DcR1 and DcR2. An alternative mechanism would be differential expression of, or functional defects in, cytoplasmatic inhibitors of apoptosis such as FADD-like converting enzyme (ICE)–inhibitory protein (FLIP) or other inhibitory IL -1 apoptotic proteins (IAP) likely survivin. Although increased programmed cell death in MDS may occur as an early rescue or compensatory response to deregulated clonal proliferation, it may also represent a pathophysiologic consequence of the epigenetic changes associated with the disease biology of MDS as we have already referred (EHA 2008). However the MDS remain an inadequately characterized disorder and novel strategies for studying disease pathogenesis and progression continue to shape our understanding and approach to diagnosing and treating. With this study we hope to contribute to the identification of molecular markers involved in apoptotic signalling pathways that could be related with MDS and that could interfere with the prognosis, namely the evolution to acute leukaemia, and with the therapeutic approach. For this purpose we have examined the expression of proteins involved in apoptotic pathways (membranar and mitochondrial) namely Bax, Bcl-2, p53, Fas/FasL, TRAIL/TRAIL-Rs and survivin, in CD34 bone marrow cells populations collected at diagnosis from 23 patients with de novo MDS and in 6 ITP (non-malignant controls). The expression of the proteins was evaluated by flow cytometry using monoclonal antibodies. The median age was 77 years (33–84), M/F=12/11, WHO subtypes: RCMD (n=12), RA (n=2), RCMD-RS (n=1), CMML (n=2), RAEB-2 (n=5), 5q- syndrome (n=1) and IPSS: low (n=6), intermediate-1 (n=6) and intermediate-2 (n=2), in patients with cytogenetic results. Two of the patients (both RAEB-2) evolve to acute leukemia, with a median follow-up of 24 months (12–65). Our results show that CD34 MDS patients cells have an higher Bax/Bcl-2 ratio, Bax, survivin, cit c, TRAIL-R3 and TRAIL-R4 levels and lower levels of Bcl-2, TRAIL, TRAIL-R1, Fas and Fas-L compared with non-malignant controls. However RA patients have the higher Bax, Fas, Fas-L, TRAIL-R3 and survivin levels while RAEB-2 patients have the lowest. This subtype of patients (RAEB-2) also show a decrease in Bax/Bcl-2 ratio, lower levels of TRAIL-R2 and higher levels of Bcl-2. This study suggest that apoptosis deregulation may be implicated in MDS. However, in RA an increase in apoptosis predominates while in RAEB the resistance to apoptosis may contribute to a less favourable prognosis and may influence the transition to acute myeloid leukaemia. Furthermore, we hope that the identification of all that molecular markers may contribute to identify new risk patients groups and molecular therapeutic targets.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 2
    In: Clinical and Experimental Medicine, Springer Science and Business Media LLC, Vol. 16, No. 3 ( 2016-8), p. 333-343
    Type of Medium: Online Resource
    ISSN: 1591-8890 , 1591-9528
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2054398-0
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  • 3
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4620-4620
    Abstract: Abstract 4620 Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by dyshematopoiesis and high susceptibility to acute myeloid leukemia. Deregulated epigenetic mechanisms are likely involved in the pathogenesis of MDS. Gene silencing through aberrant CpG island methylation is the most extensively analyzed epigenetic event in human tumorigenesis and has huge diagnostic and prognostic potential. Aberrant methylation of gene promoter region is responsible for inappropriate gene silencing, and it has been associated to initiation and progression of cancer. However, in the MDS disease process, more and more gene dysfunction has been related with the pathogenesis. FLT3 and c-KIT are important members of the receptor tyrosine kinase family that are overexpress or dysexpress in many malignant hematologic diseases. However, little is known about the distribution and the role of these proteins in MDS. The study is to investigate the role of receptor tyrosine kinase FLT3 and c-KIT expression in patients with myelodysplastic syndromes (MDS) and their clinical implication. We have at moment examined c-kit protein (CD117) expression by flow cytometry, in CD34 bone marrow cells collected at diagnosis of 12 patients with de novo MDS and 5 non-neoplastic patients (controls). FLT3 mutations, in particular Internal Tandem Duplications (ITD) and the D835 mutation were analysed by PCR-RFLP. The median age was 72 years (22–89), gender M/F=5/7, WHO subtypes: RCMD (n=6), RA (n=3), RARS (n=1), AREB-2 (n=1), CMML (n=1) and IPSS: low (n=6), intermediate-1 (n=5) and intermediate-2 (n=1). None of the patients evolved to acute leukemia, with a median follow up of 24 months (7–74). Our preliminary results show an increase in c-KIT expression in CD34 positive cells in MDS patients as compared with controls. However, the percentage of c-KIT protein expressing cells was also higher than in the controls in particular in CD34 negative cells. There was a correlation of the c-kIT protein expression with the CD34 antigen of the cells. Expression is correlated with the WHO MDS classification and with IPSS, being highest in RAEB-2 and INT2 MDS prognostic group. These results suggest that the elevated c-KIT expression could maintain the affected clone in MDS. Besides that we didn't find any FLT3 mutations in our population However further data and refinement of data analysis are needed to confirm our results and to predict clinical outcomes. The preliminary results suggest that c-KIT expression could be helpful to the pathogenesis and prognosis prediction of MDS patients. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 4
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4577-4577
    Abstract: Background: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) has become the international standard for diffuse large B-cell lymphoma (DLBCL) staging and is widely used for response assessment. In the past few years, the prognostic value of a variety of imaging-derived quantitative parameters has been investigated. One of these parameters is the distance between the 2 lesions that are farthest apart (Dmax). Dmax is a simple feature that captures lymphoma dissemination and has been reported to be a strong prognosticator of shorter progression-free survival (PFS) and overall survival (OS) in DLBCL patients (pts). Methods: Retrospective analysis of 146 pts with newly diagnosed Ann Arbor stage III-IV DLBCL, NOS, treated with R-CHOP(-like) regimens, between January 2010 and December 2019 in a tertiary center. Dmax was normalized with the body surface area [standardized Dmax (SDmax)]. The receiver operating characteristic curve (ROC) method was applied in resetting the optimal cut-off point for predicting prognosis and treatment outcome. The Kaplan-Meier method was used to describe time-to-event end points. A p-value of 0,05 was used as cut-off for significance. Results: Dmax was available for 40 pts. The median age at diagnosis was 63 years (24-78); 58% of pts were male. Most pts (69%) presented lactate dehydrogenase (LDH) above the upper limit of normal (ULN); 40% presented lymphopenia (lymphocyte count below 1000/μL), and 26% had albumin levels below 3.2 g/dL. Bone marrow (BM) infiltration occurred in 41% of pts, and 5% had central nervous system (CNS) involvement at diagnosis. According to the international prognostic index (IPI), 74% of pts were high-intermediate (HI) and high (H) risk; according to National Comprehensive Cancer Network (NCCN)-IPI, 68% of pts were HI and H risk. According to the cell of origin (COO) 63% of pts presented non-germinal center DLBCL. A complete metabolic response (CMR) on interim PET/CT was observed in 65% of pts, and 71% presented a CMR on end-of-treatment (EOT) PET/CT. At EOT the overall response rate was 80%. Seven percent of pts presented CNS relapse. The 5-year PFS was 58.5% and the 5-year overall survival (OS) was 69.4%. Higher SDmax was significantly associated with BM and CNS involvement at diagnosis (p=0.034 and p=0.049, respectively), as well as with CNS relapse (p=0.048). No statistically significant association was found between SDmax and the following features: lymphocyte count of & lt; 1000/μL (p=0.505), albumin levels & lt; 3.2 g/dL (p=0.140), LDH & gt; ULN (p=0.501), IPI risk ≥ HI risk (p=0.719), NCCN-IPI ≥ HI risk (p=0.239) and COO (p=0.493). There was a tendency, although not significant, towards a lower rate of CMR on interim and EOT PET/CT in pts with higher SDmax (p=0.072 and p=0.077, respectively). A higher SDmax had no statistically significant impact on either PFS (HR 0.456; p=0.500) or OS (HR 0.339; p=0.561). The combination of NCCN-IPI and SDmax allowed to identify a subgroup of pts with low (L) risk and low-intermediate (LI) risk NCCN-IPI and higher (≥ 4.1cm) SDmax with inferior 5-year OS (87.5% vs 50%; HR 4.64; p=0.031) and with a trend towards an inferior 5-year PFS (75% vs 50%; HR 1.92; p=0.166). Conclusions: In our cohort, a higher SDmax was associated with some high-risk features, as well as with a trend towards an inferior response to treatment. Additionally, the combination of SDmax and NCCN-IPI allowed to identify a subgroup of L risk and LI risk pts with inferior OS and a trend towards an inferior PFS. Interpretation of these results may be limited by the small sample size. The role of Dmax in DLBCL prognostication may therefore require further validation before widespread clinical use. Disclosures Gomes: Takeda: Consultancy; Gilead: Consultancy; Janssen: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
    detail.hit.zdb_id: 1468538-3
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  • 5
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5606-5606
    Abstract: BACKGROUND: Plasma cell leukemia (PCL) is a rare disorder representing 2-4% of malignant plasma cell diseases and constitutes their most aggressive form. It presents either as primary disease (pPCL) or as secondary leukemic transformation (sPCL) of multiple myeloma (MM). It has a poor prognosis compared to MM, and the results of conventional therapy are disappointing though autologous stem cell transplantation (aSCT) may improve survival. AIMS: We aim to evaluate clinical characteristics, prognostic factors and treatment outcome of patients (pts) with pPCL and sPCL. METHODS: We conducted a single center retrospective study of pts diagnosed since January/2006 to June/2018. The diagnosis was based on the presence of ≥20% or ≥2x109/L peripheral blood (PB) plasma cells (PCs) (WHO, 2016). Response to treatment was evaluated according to IMWG consensus criteria (2016). Statistical analysis was performed with a significant level set at p 〈 0.05. All risk factors with p 〈 0.15 in univariate model were further entered into multivariate analysis. RESULTS: A total of 24 pts were included, 46% male, with a median age at diagnosis of 67y (44-78). At baseline, most of the pts had a poor performance status (PS), with ECOG≥2 (63%). From those, 66.7% (n=16) had pPCL and 33.3% (n=8) sPCL. In elderly pts ( 〉 65y), sPCL was less common (21.4 vs 50%; p=NS). In sPCL, median time from MM diagnosis to sPCL diagnosis was 27.3 months. IgG was the most frequent subtype (42%), followed by light-chain κ (17%) and λ (17%). Median PB-PCs was 4x109/L (0.4-65) with a median relative proportion of 34% (17-85) by PB smear and 26% (10-71) by flow cytometry. At diagnosis, 75% of pts presented anemia, 38% renal impairment, 31% hypercalcemia, 69% bone disease and 33% extramedullary disease. According to the International Staging System (ISS), 79.0% had ISS III, 10.5% ISS II and 10.5% ISS I. Abnormal lactate dehydrogenase (LDH) level was present in 71% of pts (median 497 U/L). FISH analysis was performed in 11 pts, 50% presenting high-risk cytogenetic abnormalities [del(17p) and/or t(4;14) and/or t(14;16)]. The expression of CD56 in PB and bone marrow PCs was positive in 82% and 86% of pts, respectively. Median number of therapeutic lines after PCL diagnosis was 1 (1-4), with 58% of pts receiving a novel agent, and all sPCL pts had been treated with a novel agent previously to the PCL diagnosis. In our cohort, 1st line therapy included novel agents in 42% pts (bortezomib in 7, IMIDs in 1 and both in 2 pts), 38% received a protocol including anthracycline and 29% pts only received palliative treatment. Overall response rate (ORR) to 1st line therapy in PCL was 42%, being significantly higher in pPCL (56 vs 13%; p=0.04). One third of the pts have received aSCT. Median overall survival (OS) was 4.1 months, with a significant decreased OS in sPCL (0.4 vs 4.5 months; p=0.002); 71% died directly from disease progression and 29% from other causes. Three-month, 1-year and 2-years OS was 54%, 29% and 17%, respectively. In our cohort, sPCL (HR 3.41; 95% CI 1.29-8.97; p=0.013) and non-response to 1st line therapy (HR 4.82; 95% CI 1.85-12.57; p=0.001) were associated with increased risk of death. Treatment with bortezomib (any time) was related with a reduced risk of mortality (HR 0.21; 95% CI 0.07-0.62; p=0.005) as well as an anthracycline-based regimen (HR 0.34; 95% CI 0.13-0.85; p=0.022) and aSCT (1.5 vs 18.5 months, p=0.045), but not an IMIDs-based protocol (HR 0.66; 95% CI 0.26-1.73; p=0.40). On the other side, ISS stage, renal impairment, bone disease, high-risk cytogenetic abnormalities and high LDH levels did not present a predictive value for OS. In a multivariate analysis only a higher age at diagnosis (HR 0.92; 95% CI 0.86-0.99; p=0.020), and aSCT (HR 0.07; 95% CI 0.01-0.55; p=0.012) predicted higher OS. CONCLUSIONS: PCL has a poor prognosis and low ORR to conventional treatment. Inversely to MM, no major prognostic improvements have been observed. Although limited by sample size, our study shows that response to 1st line therapy, bortezomib-based and anthracyclines-based regimens as well as consolidation with aSCT improve outcome by lengthening OS, which was not observed with IMIDs-based treatments. A higher age, probably due to a less incidence of sPCL, was also associated with a decreased risk of death. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 6
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4574-4574
    Abstract: Background: Diffuse large B cell Lymphoma (DLBCL), the most common non-Hodgkin lymphoma, is a clinical and biological heterogeneous entity. R-CHOP is the standard treatment, however 30%-40% of DLBCL patients will have primary refractory or relapsed disease. Several prognostic scoring systems, that include simple clinical parameters, have been developed to assist risk stratification and treatment decisions, namely the International Prognostic Index (IPI), the National Comprehensive Cancer Network IPI (NCCN-IPI) and the GELTAMO-IPI. However, the accurate identification of very high-risk patients is not accomplished by these scores. Recently, the Kyoto Prognostic Index (KPI) was able to identify an extremely poor prognostic group in a Japanese cohort and was proposed as a new robust prognostic model for DLBCL. Our aim was to assess the discriminative performance of IPI, NCCN-IPI and GETALMO-IPI in overall survival (OS) and progression-free survival (PFS) and compare them with the new score KPI, in a cohort of DLBCL patients treated with immunochemotherapy. Methods: Retrospective analysis of HIV-negative DLBCL patients, newly diagnosed between 2010 and 2019 in a single tertiary center, treated with R-CHOP/R-CHOP-like protocol. The Kaplan-Meier method was used to estimate the probabilities of OS and PFS. Stratified models for each of the risk scores (IPI, NCCN-IPI, GELTAMO-IPI and KPI) were compared using Akaike's information criterion (AIC) and the Harrell's concordance index (C-index). The inter-score classification concordance was evaluated by Cohen's kappa test. P-value & lt;0.05 was considered statistically significant. Results: We included 232 patients, 52.6% (n=122) male, with a median age of 64 years (22-87). According to IPI, patients classified as Low (L), Low-Intermediate (LI), High-Intermediate (HI) and High (H) were 73 (31.47%), 59 (25.43%), 63 (27.16%) and 37 (15.95%), respectively. According to NCCCN-IPI, patients classified as L, LI, HI and H were 23 (9.91%), 94 (40.52%), 89 (38.46%) and 26 (11.21%), respectively. GETALMO-IPI was calculated in 170 of 232 patients, classified as L, LI, HI and H in 14 (8.24%), 119 (70.0%), 22 (12.94%) and 15 (8.82%), respectively. According to KPI, patients classified as L, LI, HI and H were 67 (28.88%), 122 (52.59%), 31 (13.36%) and 12 (5.17%), respectively. Between KPI and IPI, a fair concordance was observed (kappa 0.363; with only 10 [27%] IPI-H patients classified as KPI-H, and 10 [83.3%] patients KPI-H as IPI-H). Slight concordance was observed between KPI and NCCN-IPI (kappa 0.115; 9 [34.6%] patients NCNN-IPI-H classified as KPI-H, and 9 [75%] patients KPI-H as NCCN-IPI-H), as well as between KPI and GELTALMO-IPI-H (kappa 0.175; 6 [40%] patients GELTALMO-IPI-H classified as KPI-H, and 6 [60%] patients KPI-H as GELTALMO-IPI-H). With a median follow-up of 55.2 months, 5-year median OS and PFS for the global cohort were not reached (NR) and 128.2 months, respectively. All the scores identify different prognosis groups for OS and PFS, although with modest ability to distinguish between intermediate and high-risk groups (Table 1; Figure 1). GELTAMO-IPI provided the best fit for the data in both OS and PFS (AIC 479.4 and 631.0, respectively) followed by NCCN-IPI (AIC 727.3 and 933.8) and IPI (AIC 738.3 and 937.9), while KPI had the worst performance (AIC 745.6 and 943.7). NCCN-IPI discriminated better between patients with poor and favorable OS (C-index 0.667), compared with the remaining scores (C-index for IPI, GELTAMO-IPI and KPI 0.653, 0.647 and 0.612, respectively). Concerning PFS, IPI had the best discrimination capacity (C-index 0.6313), followed by NCCN-IPI (C-index 0.6232), GELTAMO-IPI (C-index 0.6086) and KPI (C-index 0.5940). Conclusions: In our cohort, GELTAMO-IPI had the best fit to the observed data regarding OS and PFS. NCCN-IPI and IPI discriminated better between patients with poor and favorable OS and PFS, respectively, although the differences in the C-index were small, and all scores exhibited an acceptable difference between short and long survival times. KPI did not seem to improve the capacity for predicting OS and PFS in our population, which could be explained by differences in pathophysiology and genetics of DLBC of Asian and Western patients. Novel risk scores that integrate molecular tumor features might help improve risk stratification, especially in high-risk group. Figure 1 Figure 1. Disclosures Gomes: Takeda: Consultancy; Gilead: Consultancy; Janssen: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 7
    In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2500-2500
    Abstract: Introduction Interim response evaluation by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) (iPET) in diffuse large B cell lymphoma (DLBCL) is encouraged to rule out disease progression and has been suggested to be predictive of survival. However, treatment guidance by iPET is not yet recommended for DLBCL in clinical practice. The aim of our study was to assess the predictive value of iPET in progression free survival (PFS) and overall survival (OS) in DLBCL patients (pts), interpreted according to visual and semiquantitative methods. Methods Single centre retrospective analysis of pts diagnosed with DLBCL from 2010 to 2019, uniformly treated with R-CHOP/R-CHOP-like protocols (6-8 cycles) and submitted to iPET assessment after 3-4 cycles of treatment, with no therapy change based on the latter. The iPET findings were interpreted using the visual Deauville 5-point scale (DS) and quantitative comparison of maximum standardized uptake value (SUVmax) before and during treatment. The percentage decrease in SUVmax between baseline PET (PET0) and iPET (ΔSUVmax) was calculated as follows: ΔSUVmax = (PET0 SUVmax-iPET SUVmax)/PET0 SUVmax × 100%. iPET with DS of 1-3 and ΔSUVmax ≥66% was defined as negative. Agreement between the 2 methods, DS and ΔSUVmax, was assessed by Cohen´s k computation. Cox regression model was used to estimate PFS and OS. Risk factors with p & lt;0.1 in the univariate analysis were included in the multivariate model. Results A total of 335 pts were diagnosed with DLBCL. Forty-one percent (n=138) underwent iPET and SUVmax was available for 86 pts. Of these, 55.8% were male, with median age of 60 years old (24-84). At diagnosis, 72.1% presented with advanced stage disease, 55.8% with abnormal lactate dehydrogenase (LDH) and 49.4% with B symptoms. Bone marrow involvement and extranodal disease was present in 12% and 76.7%, respectively. According to International Prognostic Index (IPI) score, 44.7% of pts were intermediate-high/ high-risk. At interim evaluation, 26.7% (n=23) had an iPET positive by DS, while 17.4% (n=15) had a ΔSUVmax & lt;66%. Nine patients (10.5%) had an iPET positive by DS and ΔSUVmax & lt;66%. A fair agreement between DS and ΔSUVmax was observed (k=0.333). Primary refractoriness (PrR) and/or disease progression, defined according to Lugano criteria, was seen in 22.1% of the pts. iPET positivity, measured either by DS (OR 6.45 [95%CI: 1.68-24.82], p=0.007) or ΔSUVmax (OR 5.42, [95%CI: 1.39-21.12] , p=0.015), showed predictive value of PrR, improved by combining the DS and the ΔSUVmax in iPET interpretation (OR 2.36 [95%CI: 1.35-4.13], p=0.003) (Figure 1). For a median follow-up of 50.1 months, median PFS was not reached (NR) and was higher in iPET negative pts, regardless of the interpretation by DS (84.3% versus 49.0% at 5 years; HR 4.27, p & lt;0.001) or ΔSUVmax ≥66% (91.5% versus 60.4% at 5 years; HR 3.63, p=0.003). The impact of iPET negativity when assessed by DS became not significant after multivariate analysis (HR 2.86, p=0.07), however remained predictive of PFS when interpreted by ΔSUVmax ≥66% (HR 3.53, p=0.02). Median OS was NR and was higher in the iPET negative group, when assessed by DS (89.3% versus 62.2% at 5 years, HR 3.49, p=0.01). By contrast, ΔSUVmax ≥66% did not prove to be predictive of OS (85.8% versus 65.7% at 5 years, HR 2.63, p=0.06). The impact of iPET negativity on OS was not significant upon multivariate analysis, regardless scan measurement by DS or ΔSUVmax ≥66% (HR 4.01, p=0.07 for DS, and HR 1.06, p=0.94, for ΔSUVmax ≥66%). Interestingly, combined visual and semiquantitative analysis allowed to identify a very high-risk subgroup of patients in our cohort, with significantly inferior PFS and OS (PFS: HR 9.60, p & lt;0.001, 81.3% vs 22.2% at 5 years; OS: HR 5.20, p & lt;0.001, 86.7% vs 44.4% at 5 years) (Figure 2). Conclusion Our results showed that, in our cohort, ΔSUVmax semiquantitative method in iPET interpretation has an independent predictive value of PFS, but not of OS. iPET sub-analysis with combined DS and ΔSUVmax allowed to identify a very high-risk group of DLBCL pts with markedly inferior PFS and OS. In addition, both DS and ΔSUVmax are good predictors of primary refractoriness, particularly when both visual and semiquantitative methods are combined. Figure 1 Figure 1. Disclosures Gomes: Takeda: Consultancy; Gilead: Consultancy; Janssen: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2021
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  • 8
    In: Blood Advances, American Society of Hematology, Vol. 6, No. 4 ( 2022-02-22), p. 1278-1295
    Abstract: Secondary acute myeloid leukemia (sAML) comprises a heterogeneous group of patients and is associated with poor overall survival (OS). We analyze the characteristics, treatment patterns, and outcomes of adult patients with sAML in the Programa Español de Tratamientos en Hematología (PETHEMA) registry. Overall, 6211 (72.9%) were de novo and 2310 (27.1%) had sAML, divided into myelodysplastic syndrome AML (MDS-AML, 44%), MDS/myeloproliferative AML (MDS/MPN-AML, 10%), MPN-AML (11%), therapy-related AML (t-AML, 25%), and antecedent neoplasia without prior chemotherapy/radiotherapy (neo-AML, 9%). Compared with de novo, patients with sAML were older (median age, 69 years), had more Eastern Cooperative Oncology Group ≥2 (35%) or high-risk cytogenetics (40%), less FMS-like tyrosine kinase 3 internal tandem duplication (11%), and nucleophosmin 1 (NPM1) mutations (21%) and received less intensive chemotherapy regimens (38%) (all P & lt; .001). Median OS was higher for de novo than sAML (10.9 vs 5.6 months; P & lt; .001) and shorter in sAML after hematologic disorder (MDS, MDS/MPN, or MPN) compared with t-AML and neo-AML (5.3 vs 6.1 vs 5.7 months, respectively; P = .04). After intensive chemotherapy, median OS was better among patients with de novo and neo-AML (17.2 and 14.6 months, respectively). No OS differences were observed after hypomethylating agents according to type of AML. sAML was an independent adverse prognostic factor for OS. We confirmed high prevalence and adverse features of sAML and established its independent adverse prognostic value. This trial was registered at www.clinicaltrials.gov as #NCT02607059.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2022
    detail.hit.zdb_id: 2876449-3
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  • 9
    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 17, No. 1 ( 2017-02), p. e64-e65
    Type of Medium: Online Resource
    ISSN: 2152-2650
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
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    detail.hit.zdb_id: 2193618-3
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  • 10
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 5756-5756
    Abstract: BACKGROUND: In the last decades, multiple myeloma (MM) prognosis has been changing dramatically. Induction with novel agents, followed by high-dose melphalan and autologous hematopoietic stem cell transplantation (aHSCT) is the standard of care for newly diagnosed (ND) and transplant-eligible MM patients (pts). In 2015, a new score was validated [Revised International Staging System (R-ISS)], including data related to high-risk cytogenetic abnormalities (CA) [del(17p) and/or t(4;14) and/or t(14;16)] and serum lactate dehydrogenase (LDH) levels. Few recent studies have supported R-ISS as a reliable prognostic tool for estimating survival in MM pts submitted to aHSCT. AIMS: To determine whether R-ISS is a valid risk model for predicting progression free survival (PFS) and overall survival (OS) among a cohort of real-life aHSCT pts. METHODS: We conducted a single center retrospective study of ND symptomatic MM pts treated with novel agents (bortezomib, thalidomide or lenalidomide) undergoing aHSCT between Jan/2007 and Dec/2017. We excluded all pts with no available information about ISS, LDH and CA [detected by fluorescence in situ hybridization (FISH)]. Response to treatment was evaluated according to the International Myeloma Working Group consensus criteria (2016). Statistical analysis was performed using STATA v.14.2 and significant levels were set at p 〈 0.05. RESULTS: From the total number of 186 pts submitted to aHSCT, only 81 (45%) pts presented criteria to be included in our analysis; 62% were male, with a median age at aHSCT of 60y (28-70). IgG was the most frequent subtype (59%), followed by IgA (20%). At diagnosis, 38% of pts presented anemia, 14% renal impairment (RI), 20% hypercalcemia, 63% bone disease (BD) and 32% extramedullary disease (EMD). According to ISS, 30 (37%) pts presented stage I, 30 (37%) stage II, and 21 (26%) stage III at diagnosis. There were 38% pts with high-risk CA: 24% with del17p; 19% with t(4;14), and 20% with t(14;16). High LDH levels was seen in 48% of pts. Pts were re-staged at diagnosis according to R-ISS, resulting 17% in stage I, 61% in stage II, and 22% in stage III. Thus, 16 (20%) pts previously categorized as ISS I and 3 (4%) pts as ISS III were re-classified as R-ISS II. Median time from diagnosis to aHSCT was 9.7 months. All pts received induction therapy with novel agents (a bortezomib-based therapy in 89% of pts and an IMID-based in 12%), with 81% of pts responding to first line induction; 19% were refractory. At the time of aHSCT, all pts presented at least on partial response (PR) [62% at least very good partial response (VGPR)], with an increase in the proportion of pts in complete response (CR) from 15% to 20% before and after aHSCT, respectively. Maintenance therapy was performed in 31% of pts (79% thalidomide; 21% lenalidomide). At a median follow-up of 33.4 months, median OS had not been reached. Two-years OS was 62%. Median PFS from aHSCT was 67.4%.Neither high-risk CA nor high LDH levels individually predicted lower OS and PFS (p=NS). The 2-year OS for R-ISS I, II and III was 86 %, 61% and 44%, and the 2-year PFS was 79 %, 63% and 39%, respectively. In our cohort we observed statistical significance differences between R-ISS I and III at 2 years in what concerns PFS (p=0.025) and OS (p=0.017) . No differences were seen in between other R-ISS categories. When we stratified R-ISS stage II in two subgroups based on the presence or absence of high-risk CA no differences were found. Pts classified as R-ISS III presented anemia (p 〈 0.001) and RI (p=0.001) more frequently, but no differences concerning hypercalcemia, BD or EMD. CONCLUSIONS: In our real-life cohort, R-ISS at diagnosis was a reliable tool only to predict both OS and PFS between R-ISS I and III and not between other R-ISS subgroups. The main reasons that explain the absence of significance between all R-ISS subgroups were probably the very low number of pts with available cytogenetics compared with the total number of pts submitted to aHSCT in our center and the short follow up of our study. Larger real-life studies with a longer follow up are necessary to determine if R-ISS is a good risk stratification model to applicate to NDMM pts submitted to aHSCT in the era of novel agents. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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