Kooperativer Bibliotheksverbund

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

Abstract: (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.

Type of Medium: Online Resource

ISSN: 2072-6694

URL: Article

DOI: 10.3390/cancers13081911

Language: English

Publisher: MDPI AG

Publication Date: 2021

detail.hit.zdb_id: 2527080-1

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

Abstract: 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.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.2679.2679

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.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

Abstract: 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.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2017.35.15_suppl.7560

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2017

detail.hit.zdb_id: 2005181-5

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

Type of Medium: Online Resource

ISSN: 0893-3952

URL: Article

DOI: 10.1038/modpathol.2017.186

Language: English

Publisher: Elsevier BV

Publication Date: 2018

detail.hit.zdb_id: 2041318-X

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

Abstract: 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.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.1640.1640

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

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

Abstract: 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.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V114.22.3928.3928

Language: English

Publisher: American Society of Hematology

Publication Date: 2009

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

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

Abstract: 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.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.1754.1754

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e18512-e18512

Abstract: e18512 Background: Anaplastic large cell lymphoma ALK positive (ALCL ALK+) is frequently referred to as easily curable disease, however, patients with more than 1 IPI risk factors have a poor outcome. ALCL ALK negative (ALCL ALK-) have usually higher IPI score and there is no general consensus on what treatment is the optimal. We evaluated data on 26 consecutive patients with ALCL ALK+ and ALCL ALK- treated uniformly at our institution between July 2004 and April 2011. Methods: 26 patients with ALCL ALK+ or ALCL ALK- were treated according to GMALL B-ALL/NHL 2002 protocol (Hoelzer D et al. Blood 2007; 110: Abstr. 518) without rituximab. Kaplan-Meier method and Cox’s model were used to analyze overall survival time and progression free survival time. Results: ALK protein expression was tested in 26 patients, 19(73%) were positive, 5(27%) were negative. Median age was 33 years (range 16-53). 14 pts (54%) were male, 20 (77%) were in clinical stage (CS) III or IV, 16 (61,5%) had B symptoms, 10(38,5%) had bulky disease, 10 (38,5%) had LDH 〉 N, and 20 (77%) had IPI score 〉 1. The overall response rate (ORR) was evaluated in 23 of 26 patients. The ORR was 87% (20/23 patients). After median follow up of 26 months (range; 6-90) overall (OS) and progression free survival (PFS) at 2 years was 67%: 95% C.I.=[48%, 86%] and 65%: 95% C.I.=[48%, 82%] , respectively. On multivariate analysis none of factors: CS III and IV, B symptoms, bulky disease, IPI score 〉 2, LDH 〉 N, ALK expression influenced OS and PFS. The major toxicity was reversible myelosuppression: grade 4 neutropenia occurred after every cycle. Other complications included mucositis and infection. Two toxic deaths (7,6%) from sepsis occurred during neutropenia after first cycle of treatment. Conclusions: These results suggest that GMALL- B-ALL/NHL 2002 protocol is an effective treatment for both ALCL ALK + and ALCL ALK-, however, toxicity is remarkable, with neutropenia and infection being most frequent complications.

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/jco.2012.30.15_suppl.e18512

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2012

detail.hit.zdb_id: 2005181-5

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. e19525-e19525

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/jco.2015.33.15_suppl.e19525

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2015

detail.hit.zdb_id: 2005181-5

In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-06-22)

Abstract: Primary mediastinal B-cell lymphoma (PMBL) is currently curable in 85–95% of patients. Treatment regimens frequently used include RCHOP ± radiotherapy, DAEPOCH-R, or occasionally more intensive protocols. Here we present results of treatment of 124 patients with PMBL over a period between 2004 and 2017 with the use of a protocol designed for aggressive B-cell lymphoma GMALL/B-ALL/NHL2002 including 6 cycles of alternating immunochemotherapy with intermediate-dose methotrexate in each cycle, and reduced total doxorubicin dose (100 mg/m 2 for whole treatment). Majority of patients (77%) received consolidative radiotherapy. A median (range) age of patients was 30 (18–59) years, and 60% were female. With a median (range) follow up of 9 (1–17) years, 5-year overall survival (OS) and 5-year progression free survival (PFS) were 94% and 92%, respectively. Positron emission tomography—computed tomography (PET-CT) results at the end of chemotherapy were predictive for outcome: OS and PFS at 5 year were 96% and 94% in PET-CT negative patients, respectively, and 70% and 70% in PET-CT-positive patients (p = 0.004 for OS, p = 0.01 for PFS). Eight (6%) patients had recurrent/refractory disease, however, no central nervous system (CNS) relapse was observed. Acute toxicity included pancytopenia grade 3/4, neutropenic fever, and treatment related mortality rate of 0.8%. Second malignancies and late cardiotoxicity occurred in 2.4% and 2.4% of patients, respectively. Intensive alternating immunochemotherapy protocol GMALL/B-ALL/NHL2002 is curative for more than 90% of PMBL patients and late toxicity in young patients is moderated. The attenuated dose of doxorubicin and intermediate dose of methotrexate may contribute to low incidence of late cardiotoxicity and effective CNS prophylaxis.

Type of Medium: Online Resource

ISSN: 2045-2322

URL: Article

DOI: 10.1038/s41598-022-14067-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2022

detail.hit.zdb_id: 2615211-3