Sperm aneuploidy frequencies analysed before and after chemotherapy in testicular cancer and Hodgkin's lymphoma patients

Abstract Early stage HL patients (pts) benefit from a short course of chemotherapy combined with IF radiotherapy. In our previous experience six courses of VBM chemotherapy (Stanford regimen) were administered with IF radiotherapy. However, despite good clinical results, the schedule was modified in terms of total chemotherapy cycles delivered, in order to reduce the risk of long term toxicities. PET and CT scan were performed at staging to identify a low risk patients (pts) group. From May 2001 to November 2006, 32 treatment naïve Hodgkin’s lymphoma pts (18 male, 14 female) were treated with four courses of VBM chemotherapy (D1, 8: Vinblastine 6 mg/sm, Bleomycin 10 mg/sm, Methotrexate 30 mg/sm, repeated every 28 days) followed by IF radiotherapy. Median age was 37 years (range 16–73). Main histology was classical HL in 26 pts, while lymphocyte predominant was observed in 6 pts. Pts were all stage I-IIA (no bulky disease), no more than three sites involved, performance status 0–1 and ESR < 50. CT scans were performed before and after chemotherapy and radiotherapy. PET scans were performed before and after chemotherapy in 26 pts, and after radiotherapy if not performed before or in case of positivity after chemotherapy. Chemotherapy was usually well tolerated: three pts experienced G3-4 neutropenia while the main non- haematological toxicities recorded were G3 transaminitis in 3 pts and G1-2 neuroconstipation/abdominal pain in 18 pts. IF radiotherapy was performed one month after the last chemotherapy cycle; median dose administered was 30Gy (range 26–30.4). At the end of chemotherapy 7 pts were PET positive. While one patient developed progressive disease, the other six pts became negative after radiotherapy and are still in complete remission (CR). 29 pts (90%) completed the whole program obtaining a CR. Two pts progressed before radiotherapy, while one patient shifted to an anthracycline containing schedule after two cycles due to stable disease. With a median follow-up of 42 months (range: 7–73), all pts are alive. 1 out of 29 CR pts progressed and is now receiving intensive chemotherapy program with autologous stem cell transplant. In our experience four cycles of VBM chemotherapy combined with IF radiotherapy is an effective program. Furthermore this regimen that doesn’t contain alkylating agents or anthracyclines avoids alopecia and decreases the risk of long term toxicity. PET scan effectively helps to identify low risk early stage HL pts that can take advantage of this therapeutic approach.

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Primary Non-Hodgkin's Lymphoma of the Cranial Vault; MRI Features Before and After Treatment

Clinical Radiology ◽

10.1053/crad.2002.1062 ◽

2002 ◽

Vol 57 (10) ◽

pp. 948-950 ◽

Cited By ~ 11

Author(s):

D.A.C Duyndam ◽

D.H Biesma ◽

J.P.M van Heesewijk

Keyword(s):

Hodgkin’S Lymphoma ◽

Hodgkin's Lymphoma ◽

Cranial Vault ◽

Non Hodgkin’S Lymphoma ◽

Mri Features ◽

Non Hodgkin's Lymphoma ◽

Before And After

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ASH2L drives proliferation and sensitivity to bleomycin and other genotoxins in Hodgkin’s lymphoma and testicular cancer cells

10.1101/2020.08.12.248559 ◽

2020 ◽

Author(s):

Daniel Constantin ◽

Christian Widmann

Keyword(s):

Testicular Cancer ◽

Hodgkin’S Lymphoma ◽

Gene Knockout ◽

Clinical Importance ◽

Hodgkin's Lymphoma ◽

Whole Genome ◽

Cell Models ◽

Core Component ◽

Methyl Transferase ◽

Low Levels

AbstractIt is of clinical importance to identify biomarkers predicting the efficacy of DNA damaging drugs (genotoxins) so that non-responders are not unduly exposed to the deleterious effects of otherwise inefficient drugs. Using a whole genome CRISPR/Cas9 gene knockout approach we have identified that low levels of ASH2L cause resistance to genotoxins. ASH2L is a core component of the H3K4 methyl transferase complex. We show that ASH2L absence decreases cell proliferation and favors DNA repair upon genotoxin exposure. The cell models we have used are derived from cancers currently treated either partially (Hodgkin’s lymphoma), or entirely (testicular cancer) with genotoxins. For such cancers, ASH2L levels could be used as a biomarker to predict the response to genotoxins. Our data also indicate that patients with low ASH2L expressing tumors do not develop resistance to ATR inhibitors. In these patients, such inhibitors may represent an alternative treatment to DNA damaging drugs.

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Phase II Trial of Infusional Cyclophosphamide, Doxorubicin, and Etoposide in Patients With HIV-Associated Non-Hodgkin’s Lymphoma: An Eastern Cooperative Oncology Group Trial (E1494)

Journal of Clinical Oncology ◽

10.1200/jco.2004.08.195 ◽

2004 ◽

Vol 22 (8) ◽

pp. 1491-1500 ◽

Cited By ~ 76

Author(s):

Joseph A. Sparano ◽

Sandra Lee ◽

Michael G. Chen ◽

Tipu Nazeer ◽

Avi Einzig ◽

...

Keyword(s):

Highly Active Antiretroviral Therapy ◽

Hodgkin’S Lymphoma ◽

Eastern Cooperative Oncology Group ◽

Complete Response ◽

Hodgkin's Lymphoma ◽

Highly Active ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma ◽

Before And After ◽

Varying Length

Purpose To determine the effectiveness of an infusional chemotherapy regimen in patients with HIV-associated lymphoma treated before and after the use of highly active antiretroviral therapy (HAART) in routine clinical practice. Patients and Methods Ninety-eight assessable patients with HIV-associated intermediate- or high-grade non-Hodgkin’s lymphoma received cyclophosphamide 200 mg/m2/d, doxorubicin 12.5 mg/m2/d, and etoposide 60 mg/m2/d (CDE) given by continuous intravenous infusion for 4 days (96 hours) every 4 weeks plus filgrastim. Concurrent antiretroviral treatment consisted of the nucleoside analog didanosine in the first 43 patients enrolled before December 1996 (pre-HAART group), or HAART in the remaining 55 patients enrolled after that time (HAART group). Results Complete response occurred in 44 patients (45%; 95% CI, 35% to 55%). Failure-free survival and overall survival (OS) at 2 years was 36% (95% CI, 26% to 46%) and 43% (95% CI, 33% to 53%), respectively. At the time of the analysis, 30% in the pre-HAART group were alive compared with 47% in the HAART group; when adjusted for varying length of follow-up, patients in the HAART group had improved OS (P = .039). Patients in the HAART group experienced less grade 4 nonhematologic toxicity (22% v 42%; P = .037), thrombocytopenia (31% v 52%; P = .033), and anemia (9% v 27%; P = .021), and had fewer treatment-associated deaths (0% v 10%; P = .013). Conclusion Infusional CDE is an effective and potentially curative regimen for patients with HIV-associated lymphoma. Patients treated in the HAART era have less chemotherapy-associated toxicity and improved survival.

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Correction to: ASH2L drives proliferation and sensitivity to bleomycin and other genotoxins in Hodgkin’s lymphoma and testicular cancer cells

Cell Death and Disease ◽

10.1038/s41419-021-03386-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Daniel Constantin ◽

Christian Widmann

Keyword(s):

Testicular Cancer ◽

Cancer Cells ◽

Hodgkin’S Lymphoma ◽

Hodgkin's Lymphoma

A Correction to this paper has been published: https://doi.org/10.1038/s41419-021-03386-4

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Evaluation of Pulmonary Function and Bronchoalveolar Lavage Fluid in Elderly Non-Hodgkin's Lymphoma before and after COP-BLAM III Therapy.

Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics ◽

10.3143/geriatrics.31.705 ◽

1994 ◽

Vol 31 (9) ◽

pp. 705-710

Author(s):

Nozumi Niitsu

Keyword(s):

Pulmonary Function ◽

Bronchoalveolar Lavage ◽

Hodgkin’S Lymphoma ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Hodgkin's Lymphoma ◽

Non Hodgkin’S Lymphoma ◽

Non Hodgkin's Lymphoma ◽

Before And After

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ASH2L drives proliferation and sensitivity to bleomycin and other genotoxins in Hodgkin’s lymphoma and testicular cancer cells

Cell Death and Disease ◽

10.1038/s41419-020-03231-0 ◽

2020 ◽

Vol 11 (11) ◽

Cited By ~ 1

Author(s):

Daniel Constantin ◽

Christian Widmann

Keyword(s):

Testicular Cancer ◽

Hodgkin’S Lymphoma ◽

Gene Knockout ◽

Clinical Importance ◽

Cancer Cell Line ◽

Hodgkin's Lymphoma ◽

Limited Information ◽

End Joining ◽

Methyl Transferase ◽

Cancer Genome Atlas

AbstractIt is of clinical importance to identify biomarkers predicting the efficacy of DNA damaging drugs (genotoxins) so that nonresponders are not unduly exposed to the deleterious effects of otherwise inefficient drugs. Here, we initially focused on the bleomycin genotoxin because of the limited information about the genes implicated in the sensitivity or resistance to this compound. Using a whole-genome CRISPR/Cas9 gene knockout approach, we identified ASH2L, a core component of the H3K4 methyl transferase complex, as a protein required for bleomycin sensitivity in L1236 Hodgkin lymphoma. Knocking down ASH2L in these cells and in the NT2D1 testicular cancer cell line rendered them resistant to bleomycin, etoposide, and cisplatin but did not affect their sensitivity toward ATM or ATR inhibitors. ASH2L knockdown decreased cell proliferation and facilitated DNA repair via homologous recombination and nonhomologous end-joining mechanisms. Data from the Tumor Cancer Genome Atlas indicate that patients with testicular cancer carrying alterations in the ASH2L gene are more likely to relapse than patients with unaltered ASH2L genes. The cell models we have used are derived from cancers currently treated either partially (Hodgkin’s lymphoma), or entirely (testicular cancer) with genotoxins. For such cancers, ASH2L levels could be used as a biomarker to predict the response to genotoxins. In situations where tumors are expressing low levels of ASH2L, which may allow them to resist genotoxic treatment, the use of ATR or ATM inhibitors may be more efficacious as our data indicate that ASH2L knockdown does not affect sensitivity to these inhibitors.

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