Kooperativer Bibliotheksverbund

In: Modern Pathology, Elsevier BV, Vol. 31, No. 5 ( 2018-05), p. 732-743

Materialart: Online-Ressource

ISSN: 0893-3952

URL: Article

DOI: 10.1038/modpathol.2017.186

Sprache: Englisch

Verlag: Elsevier BV

Publikationsdatum: 2018

ZDB Id: 2041318-X

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 1640-1640

Kurzfassung: Background: The diagnosis of Burkitt lymphoma (BL) is usually based on histopathology (HP), immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) of lymph node or extranodal tissue excisional biopsy and occasionally, on flow cytometry (FCM) of cell suspensions. Accuracy of classical HP/IHC method is highly dependent on the quality sample fixation and takes substantial processing time. In addition, a range of antibodies used in IHC may be insufficient because CD20+/BCL6+/CD10+/BCL2- is not specific for BL. Furthermore, a need for surgery in cases of abdominal presentation may cause delay in initiating curative systemic treatment. Gene expression profiling studies demonstrated that HP/IHC criteria for distinguishing BL from diffuse large B-cell lymphoma (DLBCL) are often inadequate, and 20-30% of BL and DLBCL cases are misdiagnosed and thus inadequately treated. In addition, 5-10% of BL cases have no chromosomal translocation involving the MYC gene (MYC¯) detectable by FISH. We have recently described a BL MYC¯ with recurrent chromosome 11q aberrations. Methods: We evaluated 78 cases of BL, initially diagnosed with HP/IHC, by FCM, classical cytogenetics (CC), and FISH, using cell suspension obtained with fine needle aspiration biopsy (FNAB) of peripheral lymph nodes (n=39), abdominal mass (n=31), cerebrospinal fluid (n=1), pleural effusion (n=4), and bone marrow (n=3). The samples containing at least 70% BL cells were evaluated. 68 cases were MYC+(male/female 52/16, median age/range 34/3-64/, HIV+: 9) and 10 were MYC¯ (male/ female 9/1, median age/range 25/18-62/, all HIV-). Antigen expression on BL cells was compared with normal lymphocytes as well as isotype controls. Antigen expression level was categorized into: [–] - no expression ( 〈 20% cells positive), [+/–] - expression on ≥20%, 〈 100% cells, and [+] - expression on 100% of cells. Expression of CD (19, 20, 22, 23, 52, 79β), FMC7, HLADR, and CD (5, 25, 38, 43, 44, 45, 16 & 56, 56, 52, 62L, 71), BCL2 on BL cells was described as mean fluorescence intensity (MFI) value in comparison to MFI of these antigens on B - and T - lymphocytes, respectively. This procedure allows quantitative and comparative evaluation of pan-B antigens (i.e.: CD19 vs CD20 vs CD22 on BLs). Dim or bright expression was also defined on dot plots. All 78 cases showed cytological features of classical or non-classical BL on smears and all were confirmed by cytogenetic analysis (CC - 56/78pts, FISH - 78/78) with simple karyotype and set of FISH probes including MYC, BCL2 and BCL6. In addition, CCND1, ATM, MLL and telomeric 11q probe were used to evaluate BL MYC¯ cases. Results: We identified characteristic qualitative and quantitative immunophenotypic pattern in both MYC+ and MYC¯ BL subgroups. All MYC+ and MYC¯ BL cases were CD45/CD19/CD20/CD22 - positive (MFI CD20 〉 MFI CD19 〉 MFI CD22), majority were CD10/CD43/CD52/CD56/CD79/HLA-DR - positive, and often FMC7 and CD138 positive while they were usually negative for CD5/CD11c/CD23/CD25/CD62L/BCL-2. Expression of CD62L was mostly seen on the small subpopulation of cells. We found a heterogenic type of CD44 and surface light/heavy chains (IgH) of immunoglobulin expression in both types of BL. The moderate intensity expression of clonal sIg and no κ/λ expression was found in 82% and 18% of MYC+, and in 70% and 30% MYC¯ BL cases, respectively.The most frequent pattern of IgH expression was IgM+ (48% and 33,5% in MYC+ and MYC¯, respectively) as well both IgD+/IgM+ (40% and 33,5% in MYC+ and MYC¯, respectively). In addition, proliferative activity measured by CD71 expression was detected in all BL samples on 100% of cells. MYC+ cases demonstrated significantly higher CD38 expression level and absence of CD16 & CD56 expression compared to MYC¯ cases. Conclusions: Combined use of FNAB/FCM/CC/FISH is a reliable method for diagnosing BL. BL has a characteristic immunophenotype on FCM examination. MYC+ and MYC¯ cases differ in the level of CD38 and CD16 & CD56 expression. CD38 overexpression correlates with MYC rearrangement in MYC+ cases. FCM of a cellular suspension obtained by the FNAB is a safe, relatively non-traumatic, rapid (2 hours), and cost-effective procedure at our institution. Newly diagnosed BL is an oncologic emergency and a quick diagnostic decision is of critical importance in clinical practice. Therefore, we believe that FNAB/FCM/CC/FISH should be the optimal method for diagnosing BL in reference centers. Disclosures No relevant conflicts of interest to declare.

Materialart: Online-Ressource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.1640.1640

Sprache: Englisch

Verlag: American Society of Hematology

Publikationsdatum: 2014

ZDB Id: 1468538-3

ZDB Id: 80069-7

In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3928-3928

Kurzfassung: Abstract 3928 Poster Board III-864 Background and aim In contrast to T lymphoblastic leukemia (T-ALL), there is a little data on the incidence and prognostic value of immunologic subtypes of adult T lymphoblastic lymphoma (T-LBL) as the use of flow cytometry in the absence of leukemia may be problematic. Our aim was to define immunophenotype of T-LBL and T-ALL in 51 consecutive patients by use of the flow cytometry (FCM) of tissue aspirates if peripheral blood (PB) and bone marrow (BM) were uninvolved. We also evaluated prognostic value of immunophenotype and clinical features of adult patients treated on uniform ALL protocol. Methods Between 1997 and 2006, 51 adult patients with T-LBL/ALL were treated according to the GMALL (German Multicenter Study Group for Adult ALL) 05/93 and T-LBL/2004 protocols (D.Hoelzer et al., Blood 2002; 99:4379). Immunophenotype was determined by specimen immunohistochemical staining and by FCM of cellular suspension obtained from lymph nodes (n=22), skin tumors (n=2) or mediastinal mass (n=9) by fine needle aspiration biopsy (FNAB), as well as of BM (n=6), PB (n=7) and pleural fluid (n=5). Disease subtype was defined according to WHO 2008 classification. Pro-T: cCD3+, CD7+, CD2-, CD1a-, CD34+/-; pre-T: cCD3+, CD7+, CD2+, CD1a-, CD34+/-; cortical T: cCD3+, CD7+, CD2+, CD1a+, CD34-, CD4+, CD8+; medullary T: cCD3+, sCD3+, CD7+, CD2+, CD1a-, CD34-, CD4+ or CD8+. Recognition of pan-T-cell CD antigens (pTAg) expression included: CD1a, CD2, cCD3, sCD3, CD4, CD5, CD7, CD8 and CD10, CD16 & CD56, CD56, CD13, CD15, CD33. Results Patients (pts) characteristics: ALL (BM+ 〉 20%): 37%, LBL: 63%, age 〈 35: 80%, males: 75%, median WBC: 22 G/L, Hb: 13.6 g/dl, plt: 267 G/L, mediastinal mass (MM): 92%, primary CNS+: 10%, PS 0-1: 60%, LDH 〉 normal: 69% of pts. Immunophenotype: pro-T: 20%, pre-T: 12%, cortical: 51%, medullary: 12%, blastic plasmacytoid dendritic cell neoplasm with skin manifestation: 6% of pts. Number of pTAg present: 0-3: 39%, and 4-7: 61% of pts. Most frequently expressed pTAg were: CD7: 86%, CD5: 78%, CD2: 69%, CD1a: 47%, and CD56: 59%. Myeloid markers: CD13/33/15 were expressed in 14%/23%/10% of pts. Complete and partial remission (mostly residual MM) rate was 75% and 21%. With a median follow up for surviving patients of 62 months, 5 yr overall (OS) and disease-free (DFS) survival (95%C.I.) was 45% (31%; 59%) and 46% (32%, 60%), respectively. 5 yr OS for pts with CD2 and more than 3 pTAg present was 61% and 63% compared to 7% and 19% for pts without CD2 and 3 or less pTAg, (p=0.004 and 0.025) respectively. CD1a expression was favorable but of unconfirmed significance (p=0.09). On Cox's analysis of clinical features, only PS and LDH were predictive for OS and DFS and only expression of CD2 among immunophenotypic variants was significant for OS (p=0.004) and DFS (p=0.004). Conclusion Combined use of fine needle aspiration biopsy and flow cytometry is a reliable method for defining immunologic subtype of lymphoblastic lymphoma. In a prospective evaluation of 51 consecutive T-LBL/ALL patients treated on GMALL protocols, expression of CD2 antigen – mostly consistent with cortical and pre-T subtypes, and presence of more than 3 pTAg along with PS less than 2 and normal LDH were predictive for favorable outcome. Disclosures: No relevant conflicts of interest to declare.

Materialart: Online-Ressource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V114.22.3928.3928

Sprache: Englisch

Verlag: American Society of Hematology

Publikationsdatum: 2009

ZDB Id: 1468538-3

ZDB Id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 1754-1754

Kurzfassung: Background: MYC, BCL2 and BCL6 are known to be altered in high grade B-cell lymphoma (HGBL). Double/triple-hit lymphomas (D/THLs) are characterized by chromosomal rearrangementsof MYC, BCL2 and/or BCL6. D/THLs have been included in the updated 2016 WHO classification, as a new category of "High grade B-cell lymphoma with rearrangements" (HGBL-R) or Diffuse Large B-cell lymphoma (DLBCL) entity, depending on morphology/cytogenetic features. BCL2 protein is expressed in a much higher proportion of DLBCL and HGBL, not otherwise specified (HGBL,NOS), and is often associated with a concomitant expression of MYC and BCL6. Most of HGBLs do not carry BCL2/MYC/BCL6 rearrangements and are referred to as "double/triple-expressor lymphomas" (D/TELs). D/THLs patients usually progress rapidly, are resistant to R-CHOP immunochemotherapy, and have very poor prognosis. D/TELs also have a worse outcome than other DLBCL,NOS. BCL2 overexpression is observed in both germinal centre B-cell-like (GCB) and non-GCB HGBL. We have previously described a diagnostic algorithm for subtypes of HGBL based on flow-cytometry immunphenotyping (FCM) with CD38 overexpression, which correlates with MYC rearrangement assessed in fine needle aspiration biopsy (FNAB) samples. Here, we propose that patients with HGBL/DLBCL,NOS, with BCL2 overexpression, especially those with D/THLs and D/TELs, may benefit from DA-EPOCH-R (dose-adjusted cyclophosphamide, doxorubicin, etoposide, vincristine, prednisone with rituximab) treatment. Methods: 30 patients (male/female 18/12, median age/range 51/35-76/) diagnosed with DLBCL,NOS (13 pts), HGBL-R (11 pts), HGBL,NOS (2 pts), primary mediastinal B-cell lymphoma - PMBL (3 pts) and DLBCL,leg type (1 pt), based on 2016 WHO classification, were treated with DA-EPOCH-R as first-line therapybetween January 2015 - July 2016. Clinical stage III or IV and IPI 3 or more were found in 27 pts (90%) and 22 pts (73%), respectively. All cases were evaluated by histopathological/immunohistochemical/flow-cytometry examination (HP/IHC/FCM), with panels of antibodies, including also CD5/CD10/CD20/CD38/BCL2/BCL6/MYC. In most cases, MYC, BCL2, BCL6 and, in case of relapse, also TP53 status was evaluated by karyotyping (CC) and FISH. Results: Considering the cell-of-origin, there were 20 pts with GCB, 3 non-GCB, 4 CD5+ and 3 PMBL. In addition, 15 pts were DEL, 12 - TEL, 3 - one-expressor lymphoma, 8 - D/THL, 12 - one-hit lymphoma and 10 - non-hit lymphoma, mostly with BCL2 overexpression. Karyotype was successfully assessed in 70%, while BCL2 overexpression was found in 83% of HGBL pts. MYC, BCL2, and BCL6 rearrangement was found in 48%, 35% and 21%, respectively. In 50%, 46% and 54% of cases there was an increase in copy number/amplification of MYC, BCL2 and BCL6, respectively. In 15 evaluable pts., overall and complete response was 80% and 53%, respectively. Median follow-up of HGBL pts treated with DA-EPOCH-R was 5 months (range 1-17), and the probability of one year overall survival was 91%, 95% C.I. (80%,100%). Progression free survival at 1 year was 62%, 95C.I. (36%,90%). 3 of 4 patients with progressive disease had TP53 deletion. The main toxicity was pancytopenia with neutropenia grade 3 or more in 24 pts (80%). Treatment-related mortality due to septic shock occurred in 2 patients (7%). Conclusions: DA-EPOCH-R regimen shows a promising activity considering D/THL and D/TEL-associated drug resistance. DA-EPOCH-R regimen seems to overcome drug resistance associated with BCL2/MYC/BCL6 overexpression, but not with TP53 deletion. Combining HP/IHC with FNAB/FCM/CC/FISH is a reliable method for D/THL and D/TEL diagnosis but the most sensitive method for fast MYC/BCL2 rearrangement assessment in DHL is FNAB/FCM CD38 and BCL2 overexpression. Disclosures Rymkiewicz: Takeda: Other: travel, accommodation; Roche: Other: travel, accommodation. Romejko-Jarosinska:Celgene: Other: travel, accommodation; Servier: Other: travel, accommodation; Sanofi- Aventis: Other: travel, accommodation. Paszkiewicz-Kozik:Sandos: Other: fee; Hospira: Other: fee; Sanofi: Other: accommodation; Roche: Other: travel, accommodation. Domanska-Czyz:Roche: Other: travel, accommodation; Amgen: Other: travel, accommodation. Ostrowska:Roche: Other: travel, accommodation; Amgen: Other: travel, accommodation. Dabrowska-Iwanicka:Genzyme: Other: travel, accommodation; Roche: Other: travel, accommodation. Osowiecki:Sandoz: Other: travel, accommodation; Roche: Other: travel, accommodation. Sikorska-Mali:Roche: Other: travel, accommodation. Szymanski:Stada: Other: travel, accommodation. Swierkowska-Czeneszew:Stada: Other: travel, accommodation; Roche: Other: travel, accommodation; Amgen: Other: travel, accommodation. Prochorec-Sobieszek:Roche: Other: travel, accommodation. Walewski:Mundipharma: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Other: travel, accommodation, Research Funding; Takeda: Consultancy, Honoraria, Other: travel, accommodation; Roche: Consultancy, Honoraria, Other: travel, accommodation, Research Funding; Teva: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Other: travel, accommodation; Sanofi: Honoraria, Other: travel, accommodation; Janssen-Cilag: Consultancy; Boehringer Ingelheim: Consultancy; Karyopharm: Consultancy; Ariad: Consultancy; Servier: Consultancy; GSK/Novartis: Research Funding; Genetics: Other: travel, accommodation; Sanofi: Other: travel, accommodation.

Materialart: Online-Ressource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.1754.1754

Sprache: Englisch

Verlag: American Society of Hematology

Publikationsdatum: 2016

ZDB Id: 1468538-3

ZDB Id: 80069-7

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 7560-7560

Kurzfassung: 7560 Background: 2016 update of the WHO 2008 classification of lymphoid neoplasms introduced new categories of highly aggressive B lymphomas (BCL): high grade B lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements (HGBLR) and HGBL not otherwise specified (NOS). The prognosis for HGBL is generally considered poor, the optimal therapy is unknown. Here we evaluated outcome after first line treatment in patients with a diagnosis of HGBLR, HGBL, NOS, and DLBCL at our institution. Methods: Medical records of 591 consecutive patients with aggressive BCL were evaluated, archived pathology reports and samples were reviewed, diagnosis revised if necessary according to 2016 update of WHO classification. We identified 16 cases of HGBLR (3%), 26 cases of HGBL, NOS (4%), and 565 cases of DLBCL (93%). Response to first line therapy, progression free survival (PFS), and overall survival (OS) were calculated and compared between these three entities. Results: DLBCL patients were treated with RCHOP between 2005-2012, HGBL patients were treated between 2005-2016 with RDAEPOCH (n = 31, 5%), RCHOP or other regimens. For the first line treatment in patients with DLBCL, HGBLR and HGBL NOS, the overall response/complete response rate was 92%/75%, 81%/56%, 93%/65%, respectively (p = NS). After a median (range) follow up of 42(1-155) months, median PFS and OS for DLBCL was not reached. For both HGBLR and HGLB, NOS patients median PFS was 10 months, median OS was 16 months. The HR for risk of progression in patients with HGBLR vs DLBCL and HGBL NOS vs DLBCL was 2.4 (1.1-4.7), p = 0.01 and 2.0 (1.1-3.5), p = 0.01. The HR for risk of death, for HGBLR vs DLBCL and HGLB NOS vs DLBCL was 2.59(1.32-5.07), p 〈 0.01 and 1.8(0.9-3.3), p = 0.08. The risk of progression and the risk of death in HGBLR vs HGBL, NOS was similar, for PFS: 1.08 (0.46- 2.5), p = NS for OS: 1.2 (0.5 -3,1) p = NS. Conclusions: Our data confirms reports by others on poor prognosis for patients with a diagnosis of HGBL with MYC and BCL2 and/or BCL6 rearrangements as well as HGBL, NOS with an increased risk of death and risk of progression compared to DLBCL patients. There was no difference in outcome between HGBL-R and HGBL, NOS patients in our series.

Materialart: Online-Ressource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2017.35.15_suppl.7560

Sprache: Englisch

Verlag: American Society of Clinical Oncology (ASCO)

Publikationsdatum: 2017

ZDB Id: 2005181-5

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 2679-2679

Kurzfassung: Background: Burkitt lymphoma (BL) is characterized by a non-specific morphology and immunophenotype, a high proliferation rate, MYC rearrangements (MYC +), and by a simple karyotype. However, 5% of BL cases have no MYC rearrangements (MYC -) detectable by FISH. It is a matter of debate whether a true MYC (-) BL does exist.The WHO 2008 classification does not clearly define MYC (-) BL cases, and such cases are often misdiagnosed and treated as diffuse large B-cell lymphoma (DLBCL). We have previously described a provisional category of aggressive B-cell lymphoma unclassifiable (BCLU) with recurrent chromosome 11q aberrations, referred to as B-NHL(11q), with clinical, pathomorphological, and gene expression profile features typicalof BL,but MYC (-). B-NHLs(11q) carry proximal gains and telomeric losses of 11q. Karyotyping (CC) and FISH defined the gain region as dup(11)(q23q13) involving CCND1, ATM and KMT2A. As we have recently shown, BL and B-NHL(11q) express different levels of CD38 and CD16 & CD56, and both have lower levels of miRNA-155, -21 and -26a than DLBCL. Here we describe a series of BL patients with a set of critical 11q aberrations and propose a diagnostic algorithm for a rapid work-up. Methods: Within a group of 82 BL cases diagnosed and treated with the BL protocol at our institution, we identified 15 cases of B-NHL(11q) with BL features and 11q aberrations: MYC (-) in 11(male/female 10/1, median age [range] 24 [18-62] ) and MYC (+) in 4 cases (male/female 3/1, median age [range] 36.5 [20-82] ). In MYC (-) pts, the disease was confined to a single site in 82%, was bulky ( 〉 7 cm) in 64% with diameter 〉 20 cm in 45% of cases. BL, BCLU and DLBCL diagnosis according to WHO 2008 classification was based on histopathological/immunohistochemical examination (HP/IHC), CC, FISH, and clinical characteristics in all pts. For the final evaluation, the flow cytometry (FCM) immunophenotype, array comparative genomic hybridization (aCGH) data, and miRNA expression was assessed on samples obtained by the fine needle aspiration biopsy (FNAB). In the B-NHL(11q) cases we identified 11q duplication, dup(11q), with an inversion (inv) of the duplicated region and a deletion of its telomeric region, referred to as critical set of 11q aberrations, as opposed to non-critical aberration set that did not involve all three changes. B-NHL(11q) cells were evaluated with the panel of antibodies by IHC (CD20/CD10/BCL6/ BCL2/MUM1/MYC/Ki-67/CD43/CD44), and by FCM with CD (19, 20, 22, 23, 52, 79β, 81, 5, 25, 38, 43, 44, 45, 16 & 56, 56, 52, 62L, 71, 200), FMC7, HLADR, and BCL2. All B-NHL(11q) cases were evaluated by CC, FISH (MYC, BCL2, BCL6, CCND1, ATM, KMT2A and telomeric 11q) and aCGH. The relative positions of CCND1, ATM, and KMT2A within a duplicated region on the aberrant chromosome 11 were used to identify inversions. Results: A median follow-up of MYC (-) B-NHL(11q) pts treated with the BL regimen was 30 months, and 2-yr OS was 72% (95% CI: 45%, 99%). In 53% of B-NHL(11q) pts tingible body macrophages were less pronounced than in classic BL. All MYC (-) and MYC (+) B-NHLs(11q) cases presented the same phenotype and Ki-67 index of 100% and met the IHC criteria for BL. In MYC (-) and MYC (+) B-NHLs(11q) pts, all with a simple or less simple karyotype, we confirmed a critical or non-critical 11q aberrations in 10 and 5 pts, respectively. In 87% of pts we identified dup(11q), of two types: the larger part between 11q12.1 and 11q24.3 bands, and the smaller part between 11q22.3 and 11q24.1, with an additional multiplication of KMT2A inside the duplication region. In 13% of cases an inv without dup(11q) was detected. We found an inv of dup(11q) region in 73% of all cases, and no inv in dup(11q) in 2 MYC (+) cases only. Bulky tumors of 〉 20 cm correlated with increased KMT2A copy number in B-NHLs(11q)cases. Conclusions: B-NHL(11q) cases are clinically homogenous while 11q aberrations are heterogeneous. We believe that BLs MYC (-) do exist. Combination of HP/IHC with FNAB/FCM/CC/FISH is a reliable method for credible diagnosis of BLMYC (-). BLMYC (-) should only be diagnosed in cases where critical 11q aberrations and a simple karyotype are identified. BCLU(11q) or DLBCL(11q) cases should be diagnosed if there are more complex karyotypes accompanied by 11q aberrations of any type. We hypothesize that in BLMYC (-) and other aggressive B-NHL(11q), 11q aberrations may determine clinical and pathomorphological features equivalent to those resulting from MYC rearrangements. Disclosures Walewski: Gilead: Consultancy, Honoraria, Other: travel, accommodation; Seattle: Other: travel, accommodation; GSK/Novartis: Research Funding; Genetics: Other: travel, accommodation; Celgene: Honoraria, Other: travel, accommodation, Research Funding; Teva: Consultancy, Honoraria; Servier: Consultancy; Karyopharm: Consultancy; Boehringer Ingelheim: Consultancy; Ariad: Consultancy; Takeda: Consultancy, Honoraria, Other; Roche: Consultancy, Honoraria, Other: travel, accommodation, Research Funding; Sanofi: Honoraria, Other: travel, accommodation; Mundipharma: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy.

Materialart: Online-Ressource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.2679.2679

Sprache: Englisch

Verlag: American Society of Hematology

Publikationsdatum: 2015

ZDB Id: 1468538-3

ZDB Id: 80069-7

In: Cancers, MDPI AG, Vol. 13, No. 8 ( 2021-04-15), p. 1911-

Kurzfassung: (1) Background: T-cell lymphoblastic lymphoma (T-LBL) is extremely rare and highly aggressive, with no practical risk model defined yet. The prognostic value of T-LBL immunological subtypes is still a matter of controversy. (2) Methods: We re-evaluated 49 subsequent adult T-LBL patients treated according to the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) protocols, 05/93 (n = 20) and T-LBL 1/2004 (n = 29), 85.7% of which achieved complete remission (CR). (3) Results: The 5/10-year overall survival (OS) and event-free survival (EFS) were 62%/59% and 48%/43%, respectively. In 96% of patients, flow cytometry analyses defining the WHO 2008 immunophenotypes were available. Cortical, early/pro-T/CD2(−), early/pre-T/CD2(+), and mature subtypes were identified in 59.5%, 19%, 15%, and 6.5% of patients, respectively. Overall, 20% of patients had the early T-cell precursor (ETP)-LBL immunophenotype, as proposed by the WHO 2017 classification. For the early/pro-T/CD2(−) subtype, the five-year OS and EFS were 13% and 13%, while for all the other, non-pro-T subtypes, they were 69% and 67%. By multivariate analysis, only CD2(−) status and age 〉 35 years emerged as strong, independent factors influencing OS and EFS, while the risk of CR failure was influenced by age only ( 〉 35 years). (4) Conclusions: ETP was non-significant for OS, unless an ultra-high-risk pro-T/CD2(−) subtype was concerned.

Materialart: Online-Ressource

ISSN: 2072-6694

URL: Article

DOI: 10.3390/cancers13081911

Sprache: Englisch

Verlag: MDPI AG

Publikationsdatum: 2021

ZDB Id: 2527080-1

In: Medical Oncology, Springer Science and Business Media LLC, Vol. 28, No. 4 ( 2011-12), p. 1589-1595

Materialart: Online-Ressource

ISSN: 1357-0560 , 1559-131X

URL: Article

DOI: 10.1007/s12032-010-9614-0

Sprache: Englisch

Verlag: Springer Science and Business Media LLC

Publikationsdatum: 2011

ZDB Id: 1201189-7

ZDB Id: 605563-1

ZDB Id: 2008172-8

In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 3051-3051

Kurzfassung: Currently recommended treatment for the primary CNS lymphoma (PCNSL) involves high-dose methotrexate (HM) preferably in combination with high-dose cytarabine (HA). However, nearly half of the patients present with locally advanced disease and poor performance status (PS) prohibiting the use of this biologically challenging therapy. On the other hand, CHOP±Rituximab with or without HM is considered suboptimal due to generaly negative, if any, published results, and a strong belief in the existence of blood-brain barrier preventing bioavailability of doxorubicin to CNS tissue. In effect, patients with DLBCL of the CNS which is the most common type of PCNSL miss the benefits of the optimal treatment for DLBCL. We evaluated the outcome of patients treated at our institution with variety of regimens evolving over time including CHOP/CHOP-like + HM, HM ± HA, and CHOP-R (rituximab) + HM. Varying proportion of patients received whole brain radiotherapy (WBRT) as well. Patients and Methods Between 2000 and 2011, 92 patients diagnosed with PCNSL were treated. Median age (range) was 59 (19 – 79) years, female: 55%, ECOG performance score (PS) 0-1: 30%, 2: 21%, 3-4: 49%. Most common symptoms at diagnosis were: memory loss (56%), focal symptoms (54%), confusion (36%), depression (20%), seizures (20%), agitation (13%). Diagnosis was established by stereotactic biopsy (50%), craniotomy (48%), and cerebro-spinal fluid flow cytometry in two cases. Total resection of tumor was done in 22%, tumor gross resection (debulking) in 27%, and biopsy only in 51% of patients. Cerebral / spinal parenchyma was involved in 52%, deep brain sites - in 48%. Mass effect and brain edema were present in 70% and 81%, respectively. Multiple brain lesions were present in 39% of patients. Patients were treated on 3 consecutive protocols: 2000-2006 (n=27): CHOP/CHOP-like+HM [median (range) HM total dose: 6.3 g (1.9-21)] with WBRT in 67%, 2006-2010 (n=13): HM±HA including „Bonn“ protocol [median (range) HM total dose 16.8 g (3-25.3) and median (range) HA total dose: 12 g(8-41)] with WBRT in 23%, 2009-2011 (n=19): CHOP-R + HM [median (range) HM total dose: 20 g (3-42)] with WBRT in 26% of patients. 33 patients (36%) received variety of treatments with a palliative intent. Results In all 92 patients, 1-, 2-, and 4-year overall survival (OS) was 50%, 41%, and 24% respectively. In patients treated with a radical approach including intended HM dose of 3 g/m2 per cycle (n=59): 1-, 2-, and 4-year OS was 63%, 59%, and 35%, respectively. In this group, event-free survival (EFS) was 58%, 49%, and 32%, respectively. In patients with PS 0-1, 2, and 3-4, 3-year OS was 67%, 26%, and 8%, respectively. 3-year EFS in these patients was 56%, 27%, and 8%, respectivly (p=0.00). Two-year OS in patients with total tumor resection, debulking, or biopsy only, was 78%, 62%, and 14%, respectively (p=0.00). Deep structure involvement vs cerebral parenchyma was not predictive of OS or EFS (p=0.33). In patients treated with CHOP/CHOP-like+HM with a median follow-up (FU) of 122 months, 1-, 2-, and 4-year OS was 59%, 55%, and 37%, and corresponding EFS was 52%, 48%, and 29%, respectively. 4 patients (15%) died of treatment-related toxicity (TRT). In patients treated with HM±HA, with a median FU of 39 months, 1-, 2-, and 4-year OS was 61%, 54%, and 18%, and corresponding EFS was 53%, 38%, and 20%, respectively. 2 patients (15%) died of TRT. In patients treated with CHOP-R+HM, with a median FU of 30 months, 1-, 2-, and 4-year OS was 68%, 68%, and 49%, and corresponding EFS was 68%, 57%, and 57%, respectively. 12 of 19 patients in this group are alive with no evidence of disease.7 patients died, 3 from disease progression, and 3 (16%) from TRT. Conclusion Outcome of PCNSL patients was highly dependent on the baseline performance score with only few patients with PS 3-4 surviving 3 years. Extent of primary surgery was also predictive of survival. In our series of 92 patients treated on consecutive clincal protocols over a period of 10 years, no benefit to methotreaxte dose escalation or addition of high-dose cytarabine could be demonstrated. The most favorable outcome was achieved with CHOP-R combined with HM at a dose of 3 g/m² per cycle. Disclosures: No relevant conflicts of interest to declare.

Materialart: Online-Ressource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V122.21.3051.3051

Sprache: Englisch

Verlag: American Society of Hematology

Publikationsdatum: 2013

ZDB Id: 1468538-3

ZDB Id: 80069-7

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 5040-5040

Kurzfassung: Background: Secondary central nervous system (CNS) involvement is an unfavorable risk factor with an impact on overall survival (OS) in malignant lymphoma. Methods: We conducted a retrospective analysis of secondary CNS involvement in patients diagnosed with Diffuse Large B-Cell lymphoma (DLBCL) on the first line treatment and after the end of treatment. We collected data on 361 patients diagnosed with DLBCL. Results: The median age (range) was 66 (17-91) years. All patients received first-line R-CHOP21 (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone) between 2006-2011. Patients with primary involvement of testis, nasopharynx, orbit and CNS received CNS prophylaxis with 15 mg methotrexate intrathecally (IT). Secondary CNS involvement was confirmed in 18 (4.9%) patients which stands for 24.6% (18/73) patients with relapsed lymphoma. Median time from first R-CHOP to lymphoma relapse was 10 months (range 3-33). CNS involvement in first 12 months of treatment was 3.9% (95% CI: 1.8%, 5.8%). Median (range) OS from diagnosis of CNS involvement was 3 (3-79) months. Clinical stage III/IV, IPI 4, breast, 2 or more extranodal sites and NCCN-IPI unfavorable site involvement increased the risk of CNS involvement. Three patients who had received methotrexate IT prophylaxis had CNS involvement at relapse. No patient with primary testis involvement had CNS relapse. Conclusion: Less than 5% of patients had secondary CNS involvement on first line treatment and after end of treatment. Advanced stage, high-risk IPI, 2 or more extranodal sites of involvement increased the risk of CNS involvement after first-line treatment for DLBCL. CNS prophylaxis appears effective in patients with primary testicular lymphoma Disclosures Walewski: Karyopharm: Consultancy; Roche: Consultancy, Honoraria, Other: travel, accommodation, Research Funding; Celgene: Honoraria, Other: travel, accommodation, Research Funding; Gilead: Consultancy, Honoraria, Other: travel, accommodation; Takeda: Consultancy, Honoraria, Other; Ariad: Consultancy; Janssen-Cilag: Consultancy; Mundipharma: Consultancy, Honoraria, Research Funding; Genetics: Other: travel, accommodation; Teva: Consultancy, Honoraria; Seattle: Other: travel, accommodation; GSK/Novartis: Research Funding; Boehringer Ingelheim: Consultancy; Sanofi: Honoraria, Other: travel, accommodation; Servier: Consultancy.

Materialart: Online-Ressource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.5040.5040

Sprache: Englisch

Verlag: American Society of Hematology

Publikationsdatum: 2015

ZDB Id: 1468538-3

ZDB Id: 80069-7