Gene expression profiling has revealed that over one third of genes more highly expressed in PMBL than other DLBCLs are characteristically expressed in classical Hodgkin Lymphoma (HL) suggesting a biological relationship (

J Exp Med
198
:
851
,
2003
). PMBL and HL also share mediastinal presentation, young age, female predominance, prominent sclerosis and CD30 expression. Although some cases lie in a pathological “grey zone” between HL and PMBL, the latter is distinguished by robust CD20 expression. Like HL, local mediastinal failure after doxorubicin-based regimens has led to routine mediastinal xRT, which is associated with secondary malignancies and coronary disease. We analyzed the outcome of DA-EPOCH in 36 untreated PMBLs. No pts received xRT except for CNS PMBL. DA-EPOCH was administered with G-CSF for 2 cycles beyond CR for 6 to 8 cycles as described (
Blood
99
:
2685
,
2002
). The first 14 pts were on a DA-EPOCH study and the last 22 on a DA-EPOCH-Rituximab study. Most pts had adverse prognostic features with bulky disease, elevated LDH and extranodal sites, which were balanced among the 2 series. IHC in 34 cases was consistent with gene expression profiling of PMBL with frequent CD20+ 33/33 (100%), infrequent CD10+ 1/26 (4%) and variable BCL-6+ 17/24 (71%) and MUM-1+ 8/22 (36%) expression. Tumor proliferation by MIB-1 was high with a median (range) of 82% (54–98). IHC markers were similar among the 2 series. EFS and OS are shown below with a median follow-up of 8.6 and 3.4 yrs, respectively, for pts receiving DA-EPOCH −/+ R. Rituximab was associated with a significantly improved EFS (p=0.036) and trend in improved OS (p=0.10) by 2-tailed exact log-rank test. In conclusion, pt characteristics were consistent with the clinical-pathological and molecular definition of PMBL and prognostic features were similar to other series (
Haematologica
87
:
1258
,
2002
). These results suggest for the first time that rituximab significantly improves the outcome of PMBL and that DA-EPOCH-R obviates routine mediastinal xRT. DA-EPOCH-R may be more effective than CHOP-based treatment because it overcomes high tumor proliferation and employs pharmacodynamic dosing. Although needing confirmation, our results suggest DA-EPOCH-R without xRT is highly effective for PMBL. Patient Characteristics

Patient Characteristics

CharacteristicsAll PatientsDA-EPOCHDA-EPOCH-R
Total Patients 36 14 22 
Gender (F/M) 23/13 (1.77) 9/5 (1.8) 14/8 (1.75) 
Median age, y (range) 33 (12–70) 34 (20–62) 33 (12–70) 
Median Mass cm (range) 8.9 (3–16) 8.4 (5.1–15.7) 10 (3–16) 
Bulky mass > 6 cm 29 (83%) 11 (85%) 18 (82%) 
ECOG PS > 1 4 (11%) 2 (14%) 2 (9%) 
Stage III or IV 15 (42%) 7 (50%) 8 (36%) 
LDH > Normal 26 (72%) 12 (86%) 14 (64%) 
Extranodal sites 20 (56%) 7 (50%) 13 (59%) 
Pleural effusion 9 (25%) 3 (21%) 6 (27%) 
CharacteristicsAll PatientsDA-EPOCHDA-EPOCH-R
Total Patients 36 14 22 
Gender (F/M) 23/13 (1.77) 9/5 (1.8) 14/8 (1.75) 
Median age, y (range) 33 (12–70) 34 (20–62) 33 (12–70) 
Median Mass cm (range) 8.9 (3–16) 8.4 (5.1–15.7) 10 (3–16) 
Bulky mass > 6 cm 29 (83%) 11 (85%) 18 (82%) 
ECOG PS > 1 4 (11%) 2 (14%) 2 (9%) 
Stage III or IV 15 (42%) 7 (50%) 8 (36%) 
LDH > Normal 26 (72%) 12 (86%) 14 (64%) 
Extranodal sites 20 (56%) 7 (50%) 13 (59%) 
Pleural effusion 9 (25%) 3 (21%) 6 (27%) 
View Large
Figure
View largeDownload slide
Figure
View largeDownload slide

Figure

Topics:
epoch protocol, primary mediastinal large b-cell lymphoma, rituximab, brachial plexus neuritis, radiation therapy, extranodal disease, gene expression profiling, neoplasms, antigens, cd30, cd20 antigens

Author notes

Corresponding author

2005, The American Society of Hematology
2005
Sign in via your Institution