Study Investigating the Cardiotoxicity of Anthracyclines in Patients With Diffuse Large B-Cell

All patients enrolled in the study will have to be treated with a chemo immunotherapy scheme R-CHOP with doxorubicin, with doxorubicin analogue or non pegylated liposomal anthracycline (R-COMP; Sec. 648 DM) administered every 21 days for 6 cycles. In unfavourable patients (stage II-IV) are allowed 2 additional cycles of rituximab at the end of the 6 cycles of R-CHOP.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Histologically confirmed Diffuse Large B-Cell Lymphoma diagnosis
* Patient eligible to receive 6 cycles of R-CHOP or R-CHOP like chemotherapy at full doses
* Age ≥ 18
* Stage I-IV
* Written informed consent
* ECOG Performance Status 0-3
* Ventricular Ejection Fraction (VEF) ≥40%
* No previous treatment for lymphoma (except for RT-IF)
* Negative β-HCG pregnancy test result at diagnosis for female of childbearing potential
* Use of acceptable method of contraception during the study and for 3 months after receiving the last dose of study drug for patients with childbearing potential
* Availability of the patient to be followed for all the phases of the chemotherapy treatment and for the subsequent follow-up

Exclusion Criteria:

* Inability to schedule a treatment at full doses of chemoimmunotherapy R-CHOP or R-CHOP-like for different reasons
* Central nervous system involvement due to lymphoma
* HIV
* Active cardiac pathology including heart failure, left ventricular dysfunction documented by a LVEF \<40%, arrhythmias (rapid atrial fibrillation, frequent ventricular arrhythmias), valvular aortic or mitral disfunction \> moderate, ischemic heart disease (myocardial infarction or acute coronary syndrome for over 6 months, angina at rest or with mild efforts)
* Previous treatment for lymphoma
* Other malignancy in the 3 years prior to the diagnosis of lymphoma with exception of non-melanoma skin cancer or in situ carcinoma
* Any other co-existing medical condition that would preclude participation in the study (uncontrolled bacterial or viral or fungal infection)
* Pregnant, or lactating and breastfeeding female

• BACKGROUNDHarris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994 Sep 1;84(5):1361-92. No abstract available. PMID 8068936
• BACKGROUNDFisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. doi: 10.1056/NEJM199304083281404. PMID 7680764
• BACKGROUNDInternational Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med. 1993 Sep 30;329(14):987-94. doi: 10.1056/NEJM199309303291402. PMID 8141877
• BACKGROUNDTilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood. 2003 Dec 15;102(13):4284-9. doi: 10.1182/blood-2003-02-0542. Epub 2003 Aug 14. PMID 12920037
• BACKGROUNDPfreundschuh M, Trumper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rube C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. doi: 10.1182/blood-2003-06-2094. Epub 2004 Feb 24. PMID 14982884
• BACKGROUNDPfreundschuh M, Trumper L, Kloess M, Schmits R, Feller AC, Rube C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. doi: 10.1182/blood-2003-06-2095. Epub 2004 Mar 11.