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In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 29-30

Abstract: Richter syndrome (RS) occurs during the disease course of 2 to 10% of Chronic Lymphocytic Leukemia (CLL). Diffuse Large B-Cell Lymphoma (DLBCL) subtype accounts for 90-95% of RS cases. While presenting with the same morphology as de novo DLBCLs, DLBCL subtype of RS is associated with a very poor outcome. Proteins are the primary cellular biological effectors. Proteome composition is highly dependent on regulatory mechanisms located both upstream and downstream translation (transcriptional regulation, post-translational modifications, protein metabolism). Thus, the analysis of the genome and the transcriptome only allows a putative extrapolation of the expressed proteome. Proteomic studies have been performed in the context of de novo DLBCLs (Fornecker et al. Sci Rep. 2019), unravelling a set of proteins associated with refractoriness. In CLL, it showed different profiles according to IGHV mutational status after B-Cell Receptor activation (Perrot et al. Blood 2011). No proteomic study of RS has been carried out to date. RS sample selection was performed across 7 French institutions affiliated to the FILO (French Innovative Leukemia Organization). A total of 49 fresh frozen biopsies were collected, including 28 de novo DLBCLs and 21 RS, mostly treated with first line R-CHOP. All biopsies were centrally reviewed. RS samples were characterized, with data on CLL-RS clonal relationship and mutational status for a 13-gene panel representing the most frequently mutated genes in CLL. Only DLBCL subtype RS samples with at least 50% tumor purity (range 50-95%) and a minimum 10 mg weight were selected. Peptide measurements were performed using liquid chromatography coupled with tandem mass spectrometry, according to published methods (Muller et al. Sci Rep. 2018). Stringent quality controls were applied to ensure sample integrity, abundance accuracy and overall reproducibility. Proteome reconstruction at peptide and at protein level was achieved with a specifically devised pipeline involving conditional filtering, full normalization, categorization and imputation of missing values. These tools made use of the R/Bioconductor DEP package (Zhang et al. Nat Protoc. 2018). Supervised (Bayesian linear models) and unsupervised (hierarchical clustering, K-means, PCA) analyses were further applied to identify differential protein signatures. These were functionally annotated with ReactomePA (Yu et al. Mol Biosyst. 2016) for pathways and STRING (Szklarczyk et al. Nucleic Acids Res. 2019) for association networks. Extended proteomics analysis identified 1,772 proteins, among which 191 were differentially expressed (False Discovery Rate/FDR & lt; 0.05) in RS samples compared to de novo DLBCLs, with 82 increased and 109 decreased proteins. Hierarchical clustering revealed a highly correlated expression profile of these top candidates and clearly separated the 21 RS and the 28 de novo DLBCL samples (Figure 1). Sample distribution was independent from chemosensitivity/resistance, for DLBCL samples, and also unrelated to GCB/Non-GCB phenotype according to Hans algorithm, Epstein-Barr virus positivity or tumor purity. Functional interactome is an in silico protein-protein interaction network built on published data from the literature and available in public databases. The functional interactome computed from the 82 proteins overexpressed in RS showed a strongly enriched association network (protein-protein interactions; p-value & lt; 1e-16), with an over-representation in BCR pathway, VEGF signaling, JAK-STAT pathway and Interleukin-12, Rho GTPase, and actin coiling (FDR & lt; 0.05; Figure 1). Proteins underexpressed in RS (109) also displayed highly associated interactions (p-value & lt; 1e-16) with a main node including proteins involved in cell death regulation, extracellular matrix organization, regulation of Insulin Growth Factor, and signaling by receptor tyrosine kinase (FDR & lt; 0.05; Figure 1). Here we performed proteomics on a 49-sample cohort of 28 de novo DLBCLs and 21 RS, which revealed a specific and differential signature in RS. This includes increased expression of targets within the druggable signaling pathways BCR and JAK-STAT. Furthermore the decrease in proteins involved in cell death regulation and extracellular matrix organization suggests resistance mechanisms to apoptosis and immune system in RS. Disclosures Dartigeas: Janssen: Honoraria; Roche: Honoraria; Gilead: Other: non-financial support. Tausch:AbbVie: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding. Leblond:AstraZeneca: Consultancy, Honoraria; Lilly: Consultancy; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria; Gilead: Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Travel/accommodations/expenses, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel/accommodations/expenses, Research Funding, Speakers Bureau. Thieblemont:Hospira: Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Bristol-Myers Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Incyte: Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Bayer: Honoraria. Stilgenbauer:Mundipharma: Consultancy, Honoraria, Other, Research Funding; Novartis: Consultancy, Honoraria, Other, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; Genentech: Consultancy, Honoraria, Other: travel support, Research Funding; Genzyme: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Other: travel support, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: travel support, Research Funding; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding. Guieze:abbvie: Honoraria, Other: advisory board, travel funds; janssen cilag: Honoraria, Other: advisory board, travel funds; roche: Other: travle funds; gilead: Honoraria, Other: travel funds; astrazanecka: Honoraria, Other: advisory board. Perrot:Amgen, BMS/Celgene, Janssen, Sanofi, Takeda: Consultancy, Honoraria, Research Funding. Feugier:astrazeneca: Consultancy, Honoraria, Research Funding; abbvie: Consultancy, Honoraria, Research Funding; roche: Consultancy, Honoraria, Research Funding; gilead: Consultancy, Honoraria, Research Funding; janssen: Consultancy, Honoraria, Research Funding. Broséus:AstraZeneca: Consultancy, Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Gilead: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-137061

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4112-4112

Abstract: Introduction: About 2 to 10% of patients (pts) diagnosed with Chronic Lymphocytic Leukemia (CLL) develop diffuse large B-cell lymphoma (DLBCL, so-called Richter transformation (RT)) over long-term follow-up. The outcomes of pts with RT are variable and poorly understood and there is no consensus on the best therapeutic approach. The aim of this study was to analyze the clinical characteristics, outcomes and factors predictive of survival in a large series of RT from the French Innovative Leukemia Organization (FILO). Methods: Biopsy-confirmed RT (limited to DLBCL and excluding Hodgkin lymphoma) diagnosed from 2001 to 2018 were identified from eight FILO centers. Clinical and biological characteristics of CLL and RT at diagnosis, including cytogenetics, clonal relation with the pre-existing CLL, Epstein-Barr virus (EBV) status, cell of origin (COO) analyzed by immunohistochemistry and RT score (Tsimberidou AM et al, J Clin Oncol, 2006) were analyzed as well as treatment and outcomes. Overall survivals (OS) were defined as time from CLL and RT diagnosis to death from any cause and analyzed using the Kaplan-Meier method. Statistical analyses were performed with SAS version 9.4. Results: A total of 70 CLL pts who developed RT were identified. The median age at CLL diagnosis was 62 years old (range 35-82), and 50 (71.4 %) were male. The median time to transformation was 5.5 years (range 0 to 22 years), with 12 simultaneous diagnosis of CLL and RT. Prior to RT, 20 (29%) pts had not been treated for CLL, 50 received one (n=21) or more (n= 29) line of treatment ; 6 pts had received a novel agent (ibrutinib, idelalisib or venetoclax). The median age at RT diagnosis was 68 years old (range 42-88). All biopsies were centrally reviewed; 38/58 pts (66%) had elevated LDH ( 〉 1.5N) ; 35/65 pts (54 %) had bulky disease (≥ 5 cm); 10/54 (18.5%) pts had del(17p) or TP53 mutation ; 9/42 pts (21%) had a complex karyotype (at least 3 abnormalities). The CLL and RT were clonally related in 27/27 (100%) tested pts. COO by Hans algorithm was non germinal center B cell-like (GCB) in 26/28 pts (93%). EBV was positive or detected in 5/40 (12.5%) pts. The median of Ki67 positivity was 70% (range 30% to 100%). The RT score (based at RT diagnosis on ECOG performance status 2-4, LDH 〉 1.5 x normal, platelets 〈 100 x 109/L, tumor size 〉 5 cm and 〉 1 prior therapy for CLL) was : low risk in 17 pts (31%), low-intermediate risk in 10 pts (19%), high-intermediate risk in 14 pts (25%) and high risk in 14 pts (25%). The most common first-line treatment of RT was immunochemotherapy (n=57, 87%) including R-CHOP-like regimen (n=48, 73%). Autologous or allogeneic transplantation was performed for 7 pts (11%). Response to first-line treatment was complete or partial response in 26 pts (40%), and stable disease or progression in 39 pts (60%). After a median follow-up of 8 years, 51/64 pts (80%) have died. The main causes of death were progressive DLBCL (n=36, 71%), infection (n=8, 16%) or progressive CLL (n=2, 4%). The median OS of the cohort from CLL and RT diagnosis (Figure 1) were 7.8 years and 9.5 months, respectively. In univariate analysis, patients with TP53 disruption at CLL stage, low platelets count, elevated LDH, elevated beta2-microglobulin, high ECOG score, high RT score, EBV positivity and absence of response to first-line RT treatment had worse OS. The ECOG score, platelets count and TP53 disruption remain significant in multivariate Cox-regression. Last, we compared the clinical and biological parameters of two Richter groups defined as: (i) short-term survivors ( 〈 12 months, n = 34) and (ii) long-term survivors ( 〉 48 months, n = 18). Long survival was significantly associated with elevated platelets count, low LDH, low ECOG, low RT score and response to RT first-line treatment. Discussion: The clinical outcomes of RT patients is poor and novel treatment options are needed. However, a group of long-term survivors was identified, characterized by elevated platelets count, low LDH, low ECOG, low RT score and response to immunochemotherapy. Disclosures Leblond: Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Cymbalista:Janssen: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; Sunesis: Research Funding; Roche: Research Funding; Abbvie: Honoraria. Guièze:Abbvie: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Roche: Honoraria. Broseus:Janssen: Honoraria; Gilead: Honoraria; Novartis: Research Funding. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-128053

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 3-5

Abstract: Richter Syndrome (RS) corresponds to the transformation of Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) into an aggressive lymphoma, in most cases a Diffuse Large B-Cell Lymphoma (DLBCL). RS outcome is variable and still poorly understood. The aim of our study was to analyze the clinical, biological and molecular features liable to predict survival in a retrospective series of newly diagnosed RS from the French Innovative Leukemia Organization (FILO). From 10 French centers, 103 biopsy-confirmed DLBCL subtype RS, diagnosed from 2001 to 2019, were identified. Fresh-frozen biopsies (FB) were available in 58 cases. All biopsies were centrally reviewed. Clinical and biological characteristics at CLL and RS diagnoses including cytogenetics, clonal relationship with the pre-existing CLL, Epstein-Barr virus (EBV) status, cell of origin (COO) according to the Hans algorithm, RS prognostic scores (Tsimberidou et al. J Clin Oncol. 2006, Rossi et al. Blood 2011) as well as treatment and outcomes were collected. Targeted next generation sequencing was used on RS FB for the following gene set: TP53, ATM, SF3B1, NOTCH1, BIRC3, FBXW7, RPS15, EGR2, MYD88, XPO1, POT1, BRAF, and NFKBIE. Overall Survival (OS) was defined as time from RS diagnosis until the date of death or end of follow-up and analyzed using Kaplan-Meier method. Multivariable analysis was performed using Cox regression model for variables with a p-value & lt;0.2 by bivariate analysis. Statistical analysis was performed with SASv9.4 (SAS Institute Inc., Cary, NC, USA). Clinical and biological characteristics and outcomes were broadly similar between the full 103-patient cohort and the subset of 58 patients with available gene mutation data. The latter only was considered for the subsequent analyses. The median age at CLL/SLL diagnosis was 60 (range 34-81) and 39 patients (67.2%) were male. Prior to RS, 24 (41.38%) received more than 1 line of treatment for CLL. The median time to transformation was 5 years (range 0-22). The median OS from RS diagnosis was 8 months (Figure 1a). The median age at RS diagnosis was 65.5 years (range 42-87). ECOG Performance Status (PS) was & gt;1 in 29/53 patients (54.8%) and 32/56 (57.1%) had a Bulky disease. Elevated Lactate DeHydrogenase (LDH) levels (≥ 1.5N) were found in 38/49 patients (77.6%). Unmutated IGHV was observed in 45/58 (77.6%) RS samples. CLL and RS were clonally related for 29/33 (87.9%) RS with available IGHV sequence at CLL diagnosis. TP53 disruption was detected in 34/56 (60.7%) RS cases including TP53 mutations in 23/58 (39.7%). According to Tsimberidou et al., 10/46 (21.7%) RS were in the low-risk group, 10 in the low-intermediate risk group, 11 (23.9%) in the high-intermediate risk group and the other 15 in the high-risk group. According to the Rossi score, only 4/51 RS (7.8%) were low risk, and 19 (37.3%) and 28 (54.9%) intermediate and high-risk, respectively. The most frequent treatment for RS was R-CHOP-like regimen [38/56 (67.9%)], 5 and 2 patients received autologous or allogeneic stem cell transplantation respectively. Most patients, 40/56 (71.4%) failed to reach complete remission after the first line. By bivariate analysis (Figure 1b-e), ECOG PS, platelet count and TP53 disruption worsened OS (p & lt;0.05) while the effect of the IGHV status was less important (p-value=0.07). By multivariable Cox regression model (Table 1), ECOG PS & gt;1, platelet count & lt;100x109/L, TP53 disruption or unmutated IGHV status significantly reduced OS (hazard ratios 2.99, 2.22, 2.96 and 1.77, p & lt;0.05 for all). NOTCH1 status had no significant impact. Similar results were obtained when a Cox regression model was realized with a backward and/or forward selection of variables respectively with stay p-value=0.05 and/or an entry p-value=0.2. RS outcome is poor. Here, we focused specifically on Richter cells on diagnostic biopsies for genetic analyses. Unmutated IGHV status was identified as prognostic factor for RS, in addition to the previously described: ECOG PS, platelet count and TP53 disruption. More molecular studies are necessary to increase knowledge about RS and improve the survival of patients with DLBCL-type RS. Disclosures Dartigeas: Janssen: Honoraria; Roche: Honoraria; Gilead: Other: non-financial support. Tausch:Roche: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding. Leblond:Roche: Consultancy, Honoraria, Other: Travel/accommodations/expenses, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Travel/accommodations/expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Amgen: Honoraria; AstraZeneca: Consultancy, Honoraria; Lilly: Consultancy. Thieblemont:Incyte: Honoraria; Bristol-Myers Squibb: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Hospira: Research Funding; Bayer: Honoraria. Laribi:abbvie: Honoraria, Research Funding; amgen: Research Funding; novartis: Honoraria, Research Funding; takeda: Research Funding. Stilgenbauer:F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Genentech: Consultancy, Honoraria, Other: travel support, Research Funding; Genzyme: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; Mundipharma: Consultancy, Honoraria, Other, Research Funding; Novartis: Consultancy, Honoraria, Other, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding. Guieze:abbvie: Honoraria, Other: advisory board, travel funds; janssen cilag: Honoraria, Other: advisory board, travel funds; roche: Other: travle funds; gilead: Honoraria, Other: travel funds; astrazanecka: Honoraria, Other: advisory board. Feugier:gilead: Consultancy, Honoraria, Research Funding; janssen: Consultancy, Honoraria, Research Funding; roche: Consultancy, Honoraria, Research Funding; abbvie: Consultancy, Honoraria, Research Funding; astrazeneca: Consultancy, Honoraria, Research Funding. Broséus:Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Gilead: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-137101

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Annals of Hematology, Springer Science and Business Media LLC, Vol. 85, No. 10 ( 2006-10), p. 711-716

Type of Medium: Online Resource

ISSN: 0939-5555 , 1432-0584

URL: Article

DOI: 10.1007/s00277-006-0152-y

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2006

detail.hit.zdb_id: 1458429-3

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 32 ( 2018-11-10), p. 3203-3210

Abstract: Acute myeloid leukemia (AML) in elderly patients has a poor prognosis. In an attempt to improve outcome for these patients, the prospective open-label phase III LAM-SA 2007 (Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old) trial randomly assigned patients to a standard induction regimen with lomustine added or to a consolidation regimen with cytarabine and idarubicin. Patients and Methods Adults age 60 years or older with previously untreated AML who were fit to receive intensive chemotherapy and who were without unfavorable cytogenetics received standard chemotherapy with lomustine (idarubicin, cytarabine, and lomustine [ICL]) or without (idarubicin and cytarabine [IC] ). The primary objective of the study was overall survival (OS); secondary objectives were response rate, cumulative incidence of relapse (CIR), event-free survival (EFS), and safety. Results From February 2008 to December 2011, 459 patients were enrolled. Comparing patients in the IC and ICL arms, complete response or complete response with incomplete recovery was achieved in 74.9% versus 84.7% ( P = .01). The proportional hazards assumption was rejected for OS ( P = .02), which led us to consider two separate time intervals: during and after induction. There was no significant difference between the two arms during induction, although induction deaths were 3.7% versus 7.7%, respectively ( P = .11). However, significantly better results were observed after induction with an improved 2-year OS of 56% in the ICL arm versus 48% in the IC arm ( P = .02). At 2 years, EFS was improved at 41% in the ICL arm versus 26% in the IC arm ( P = .01). The CIR at 2 years was 41.2% in the ICL arm versus 60.9% in the IC arm ( P = .003). Grade 3 and 4 toxicities, mostly hematologic, were significantly higher in the ICL arm ( P = .04), and fewer patients required a second treatment after ICL. Conclusion Adding lomustine to standard chemotherapy significantly improved the outcome of elderly patients with AML.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2018.78.7366

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2018

detail.hit.zdb_id: 2005181-5

In: Cancer Cell, Elsevier BV, Vol. 32, No. 5 ( 2017-11), p. 716-716.e1

Type of Medium: Online Resource

ISSN: 1535-6108

URL: Article

DOI: 10.1016/j.ccell.2017.10.015

Language: English

Publisher: Elsevier BV

Publication Date: 2017

detail.hit.zdb_id: 2074034-7

detail.hit.zdb_id: 2078448-X

SSG: 12

In: Journal of Clinical Investigation, American Society for Clinical Investigation, ( 2023-9-26)

Type of Medium: Online Resource

ISSN: 1558-8238

URL: Article

URL: Article

DOI: 10.1172/JCI170169

DOI: 10.1172/JCI170169DS1

Language: English

Publisher: American Society for Clinical Investigation

Publication Date: 2023

detail.hit.zdb_id: 2018375-6

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 6 ( 2013-02-20), p. e90-e97

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2012.41.9549

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2013

detail.hit.zdb_id: 2005181-5

In: Cancer Medicine, Wiley, Vol. 8, No. 6 ( 2019-06), p. 3131-3141

Abstract: The different types of drug resistance encountered in chronic lymphocytic leukemia ( CLL ) cannot be fully accounted for by the 17p deletion (and/or TP 53 mutation), a complex karyotype (CK), immunoglobulin heavy‐chain variable region genes ( IGHV ) status and gene mutations. Hence, we sought to assess the associations between recurrent genomic abnormalities in CLL and the disease's development and outcome. To this end, we analyzed 64 samples from patients with CLL and gain of the short arm of chromosome 2 (2p+), which is frequent in late‐stage and relapsed/refractory CLL . We found that fludarabine/cyclophosphamide/rituximab (a common first‐line treatment in CLL ) is not effective in removing the 2p+ clone ‐ even in samples lacking a CK, the 17p deletion or unmutated IGHV . Our results suggest strongly that patients with CLL should be screened for 2p+ (using karyotyping and fluorescence in situ hybridization) before a treatment option is chosen. Longer follow‐up is now required to evaluate bendamustine‐rituximab, ibrutinib, and idelalisib‐rituximab treatments.

Type of Medium: Online Resource

ISSN: 2045-7634 , 2045-7634

URL: Issue

URL: Article

DOI: 10.1002/cam4.2019.8.issue-6

DOI: 10.1002/cam4.2123

Language: English

Publisher: Wiley

Publication Date: 2019

detail.hit.zdb_id: 2659751-2

In: Leukemia, Springer Science and Business Media LLC, Vol. 35, No. 6 ( 2021-06), p. 1597-1609

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-020-01009-z

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2008023-2