Combination immunochemotherapy with cyclophosphamide, doxorubicine, vincristine, prednisone and the anti-CD20 monoclonal antibody rituximab (R-CHOP) is the standard of care for patients (pts) with previously untreated high-grade (aggressive) non-Hodgkin’s lymphoma (aNHL). Dose intensification of CHOP has shown ambiguous results (Pfreundschuh, 2004; Ohmachi, 2011), but the dose-dense two-weekly schedule (R-CHOP-14) was not found to be superior to the three-weekly schedule (R-CHOP-21) (Cunningham, 2013). Since clinical trials are restricted to highly selected pts, we investigated effectiveness of R-CHOP-14 and R-CHOP-21 in unselected pts with aNHL treated in routine practice by German office-based haematologists.


The open, longitudinal, multicentre, clinical registry on lymphoid neoplasms (TLN Registry, registry NCT00889798) prospectively collects data on the treatment of pts with lymphoid B-cell neoplasms as administered by a network of over 260 German office-based haematologists. The choice of therapy is upon the discretion of the treating physician. All pts give their informed consent before onset of therapy. Pts are followed for 5 years. A broad set of data regarding patient and tumour characteristics, co-morbidities, all systemic treatments and response rates, date(s) of progression(s) and date of death are recorded. Automated plausibility and completeness checks with subsequently generated queries by the electronic data capture system ensure data reliability. In addition, data managers regularly check for plausibility and issue queries. Between May 2009 and August 2013 (date of present analysis), a total of 3,383 pts have been recruited.


Of 477 pts with aNHL (95% DLBCL), recruited at the start of 1st-line therapy and treated with R-CHOP, 43% were treated with the two-weekly schedule (R-CHOP-14) and 57% received the three-weekly schedule (R-CHOP-21). Both schedules were applied for median 6 cycles (range 2-8); less than 6 cycles were applied in 23% and 30% of pts, respectively.

Pts were median 67 years (yrs) old (33% ≤ 60 yrs), 47% female, 28% presented with tumour stage I (Ann Arbor), 27% with stage IV and 64% with at least one co-morbidity. 37% pts were of low risk (International Prognostic Index, IPI).

Pts treated with the R-CHOP-14 or R-CHOP-21 differed in gender (female: 42% vs. 50%), performance status (ECOG 0: 44% vs. 40%) and pre-existing co-morbidities (60% vs. 67%), with no difference in age. Pts treated with R-CHOP-14 were diagnosed less often with tumour stage I (22% vs. 33%).

Data on the application of Granulocyte colony-stimulating factor (G-CSF) were available for 381 pts. G-CSF was applied in 98% of pts treated with R-CHOP-14 and 61% of pts treated with R-CHOP-21. Pts treated with R-CHOP-21 and G-CSF were older (median 68 vs. 61yrs) than pts treated with R-CHOP-21 and no application of G-CSF.

Objective response rate (ORR) as assessed by the local site was: 98% for R-CHOP-14 and 94% for R-CHOP-21; the clinical (unconfirmed) complete remission rate (CRu) was 65% for R- CHOP-14 and 70% for R-CHOP-21 (p=0.32).

After a median follow-up of 22 months (maximum 51 months), 2-year progression-free survival rate (PFS) is 74% (1-year: 84%) for R-CHOP-14 and 82% (1-year: 85%) for R-CHOP-21. 2-year overall survival rate (OS) is 86% (1-year: 91%) for R-CHOP-14 and 85% (1-year: 89%) for R-CHOP-21. At time of analysis, 9% of pts (R-CHOP-14) and 8% (R-CHOP-21) have received a 2nd-line therapy. Overall, 7% of pts have been lost to follow-up.

At this point, the high rate of pts alive without progression (>80%) precluded multivariate regression analyses regarding factors affecting PFS or OS.


Our data show that in routine practice, independent of age, pts with good performance status and low burden of co-morbities are more likely to receive the dose-dense two-weekly R-CHOP-14 schedule than the three-weekly R-CHOP-21 schedule as 1st-line treatment. First outcome data show that the effectiveness (ORR, PFS and OS) of both schedules is similar despite the differences in pts selection.

DLBCL: Diffuse Large B-cell Lymphoma


Cunningham et al., The Lancet. Mai 2013;381(9880):1817–26 │ Ohmachi K et al., Ann Oncol. 2011;22(6):1382–91 │ Pfreundschuh M et al., Blood. 2004;104(3):634–41


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.

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