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Letters to the Editor
Dose-adjusted EPOCH-rituximab or intensified B-non-Hodgkin lymphoma therapy for pediatric pri- mary mediastinal large B-cell lymphoma. Results from the study B-NHL-BFM-04 and the NHL-BFM registry 2012
Treatment outcomes for children and adolescents with primary mediastinal large B-cell lymphoma (PMBCL) with chemotherapy designed for childhood mature B- non-Hodgkin lymphoma (B-NHL) are inferior to those of children with other B-NHL-subtypes.1-3 Consequently, B-NHL-type chemotherapy was first intensified and sub- sequently replaced by dose-adjusted chemo- immunotherapy with etoposide, prednisone, cyclophos- phamide, doxorubicin, and rituximab (DA-EPOCH-R) in the NHL-Berlin-Frankfurt-Münster (BFM)-study group. DA-EPOCH-R resulted in superior event-free (EFS) and
overall survival (OS) compared to the previous B-NHL chemotherapy, however, in four patients central nervous system (CNS)-relapses occurred.
Treatment of children with PMBCL by chemotherapy protocols without rituximab including high-dose methotrexate, etoposide, ifosfamide, cyclophosphamide, cytarabine, vincristine, and corticosteroids, combined with intrathecal chemotherapy resulted in EFS rates at 5 years of 53–70%.1-3 In order to improve outcome, treat- ment was intensified for patients with PMBCL in the trial B-NHL-BFM-04 (B04) by adding two courses of chemotherapy and prolonging the infusion time of high- dose methotrexate. In 2010, a modified DA-EPOCH-R regimen was recommended for PMBCL by the NHL-BFM study committee on the basis of a 5-year EFS of 93% in adults with PMBCL in a phase II study.4 The modifica- tions included the addition of a least one dose of intrathe- cal triple therapy (ITT), and a cumulative doxorubicin
Table 1. Clinical characteristics of the children and adolescents with primary mediastinal large B cell lymphoma.
All eligible
Patients N95 (N=116) (N=20)
Study
B04 45 - N95 19 19 REG12 52 1
Sex
f 62 7 m 54 13
Stage**
III 94 20 IV 1 - not evaluable* 19 - unknown 2 -
CNS involvement
not analyzed 16 - no 100 20
Bone marrow involvement
not analyzed 11 -
no 104 20
yes 1-1-
Treatment
B04 (N=29)
29
DA EPOCH R (N=67)
16
-- - 51
17 38 12 29
19 55 1 - 9 10 - 2
8 8 21 59
Age at diagnosis (years) mean
range
LDH at diagnosis (U/L)
mean
range
above normal range
<500 56 14 500 – <1,000 47 5 ≥1,000 13 1
Duration of follow-up (months)
mean 59 77 range 2–211.8 2–211.8
4 7 24 6
15.8 1.4–21.7
14.7 1.4–17.9
15.7 10.3–18.6
608 252–1,322 25/29 (86%) 13
12
16.2 8.4–21.7
578 188–1,698 64/67 (96%) 29
30
562 187–1,698 89/96
445 187–1,267 unknown***
*no initial assessment of central nervous system (CNS) or bone marrow involvement; **St. Jude staging system;15 ***upper limit of normal not reported in the study N95.NHL: N95: study NHL-BFM 95; B04: study B-NHL BFM 04; REG12: NHL-BFM Registry 2012; f: female; m: male; LDH: lactate dehydrogenase; DA-EPOCH-R: dose-adjusted etoposide, prednisone, cyclophosphamide, doxorubicin, and rituximab.
4 8
73 48 12.5–144.2 7.6–123.2
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haematologica | 2021; 106(12)