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Excellent outcome of young adults with aggressive non-Hodgkin lymphomas treated with CHOP-like regimens

Leukemia volume 28, pages 2260–2263 (2014)Cite this article

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Progress in the treatment of hematologic malignancies in adolescents and young adults (AYA) has been reported to be less impressive when compared with the advances achieved in children and older adults during the last two decades.1 Whether this is related to disease biology in this age group, treatment regimens or factors related to care delivery in this age group is a current topic of discussion. In non-Hodgkin lymphoma (NHL), significant differences between children and adults have been reported with respect to incidence and outcome.2 Diffuse large B-cell lymphoma (DLBCL), anaplastic lymphoma (ALCL) and Burkitt lymphoma (BL) are the most common NHL subtypes in children, whereas DLBCL and follicular lymphoma are the most frequent subtypes in adults. Clinicopathological studies have recently shown that the more favorable NHL subtypes are more frequently found in children when compared with adults. Also, molecular analysis of pediatric mature B-cell lymphomas has recently demonstrated a significantly higher proportion of molecular Burkitt lymphoma than diagnosed by morphologic assessment alone in children in comparison with adults.3 In addition, additional molecular markers (for example, ABC subtype, BCL-2 expression) associated with a poor prognosis in DLBCL seem to increase with age.4 These data support the hypothesis that lymphoma biology rather than treatment approaches may explain at least some of the observed outcome differences. DLBCL and BL in children are frequently treated using identical regimens, which usually include cyclophosphamide, high-dose methotrexate and cytarabine with initial high-dose intensity, as well as anthracyclines, such as in the BFM (Berlin-Frankfurt-Münster trial group) trials.5 In adults, only BL is treated with comparable short-course protocols, whereas DLBCL routinely receive R-CHOP-like regimens, consisting of cyclophosphamide, doxorubicin, vincristine and prednisolone. In addition, risk groups used for treatment stratification (five risk groups R1–R4+central nervous system (CNS), which include disease stage, initial LDH serum level, resection status and CNS involvement), differ between pediatric patients and young adults. Therefore, the treatment of adolescents (15–18 years) and young adults (18–39 years) with DLBCL differs significantly, and experts disagree on the optimal treatment in the adolescent–young adults age group.1 In a small study of treating adult patients with a pediatric regimen, outcome for adults was marginally inferior to the outcome achieved in children.5 To determine whether age is a risk factor for the outcome in AYA aged 18–35 years treated with CHOP-like regimens, we analyzed the treatment outcome of 598 patients treated within six prospective phase II and III trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL) from 1992 to 2008.

Data were collected from six consecutive trials. The NHL-B16 (n=154) and high-CHOEP-phase I/II+III7,8 (n=30+103) trials were conducted without rituximab, whereas the MINT trial9 (n=206) and Mega-CHOEP phase II+III10, 11, 12 (n=53+52) included rituximab in the experimental arms. Five hundred and eighty-nine out of 598 lymphoma biopsies were assessed by a reference panel; 71% patients were diagnosed with a DLBCL and only 2% with Burkitt oder Burkitt- like lymphoma. The remaining 27% had rarer aggressive lymphoma entities' subtypes of B- and T-cell origin. Of the 598 patients, 167 (28%) patients were treated with and 431 (72%) without rituximab. The NHL-B1, high-CHOEP and MINT trials included good-prognosis patients, whereas the Mega-CHOEP trial included poor-prognosis patients. For this analysis, we divided patients into three different age groups (18–25, 26–30 and 31–35 years). In addition, we analyzed the population with and without rituximab separately due to the fact that the groups with and without rituximab differed in size and that randomization between rituximab-containing regimens had not been performed for the whole study population. Radiation was part of the study protocol in all trials, except the Mega-CHOEP phase II study (n=545). Two hundred and forty-seven (45%) patients received consolidation radiation at bulky disease sites and extranodal sites according to study protocol, 75 patients (49%; age 18–25: 26 patients; 26–30: 25 patients; 31–35: 24 patients) in the group treated with rituximab, 172 patients (44%; age 18–25: 58 patients; 26–30: 58 patients; 31–35: 58 patients) in the group without. Event-free survival (EFS) and overall survival (OS) were estimated according to Kaplan–Meier method, differences between groups were compared using the log-rank test. Multivariate analyses were performed using Cox proportional hazard model. Patient characteristics were analyzed using χ2 test and, if necessary, using Fisher’s exact test. Significance level was at 0.05, two sided. Analysis was performed using SPSS 19.0 (IBM-SPSS, Ehningen, Germany).

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Acknowledgements

KH, LT and SZ collected clinical data, analyzed the data and wrote the manuscript. SZ, MZ and ML performed data analyses and gave final approval of the manuscript. GH, GW, NS and MP collected clinical data and gave final approval of the manuscript.

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  1. K Hohloch and S Zeynalova: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology and Medical Oncology, Georg August University, Goettingen, Germany

    K Hohloch, G Wulf & L Trümper

  2. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany

    S Zeynalova, M Ziepert & M Loeffler

  3. Department of Internal Medicine I, University of Saarland, Saar, Germany

    G Held & M Pfreundschuh

  4. Department of Hematology and Stem Cell Transplantation, St Georg Asklepios Hospital, Hamburg, Germany

    N Schmitz

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on behalf of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL)

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Correspondence to L Trümper.

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Hohloch, K., Zeynalova, S., Held, G. et al. Excellent outcome of young adults with aggressive non-Hodgkin lymphomas treated with CHOP-like regimens. Leukemia 28, 2260–2263 (2014). https://doi.org/10.1038/leu.2014.213

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