Dreyling, M.

Hiddemann, W.

Stahel, R. A.

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Minimum Clinical Recommendations for diagnosis, treatmentand follow-up of newly diagnosed follicular lymphomaIncidence. Follicular lymphomas present worldwide the second mostfrequent subtype of nodal lymphoid malignancies.. The incidence of this disease has rapidly increased duringrecent decades and has risen from 2–3/100 000/year duringthe 1950 s to more than 5–7/100 000/year recently.Diagnosis. Diagnosis should always be based on a surgical specimen/excisional lymph node biopsy providing enough materialfor fresh frozen and formalin-fixed samples [II, A].To ensure adequate quality, immediate processing by anexperienced pathology institute has to be guaranteed. Fineneedle aspirations or core biopsies are inappropriate fora proper diagnosis and should only be used in the rarepatients requiring emergency treatment.. The histological report should give the diagnosis accordingto the World Health Organisation classification.Staging and risk assessment. Since treatment substantially depends on the stage of thedisease, initial staging should be thorough particularly in thesmall proportion of patients with early stages I and II (15–20%). Initial work-up should include a CT-scan of thethorax, abdomen and pelvis, and a bone marrow aspirateand biopsy [IV, C]. A complete blood count, routine bloodchemistry including LDH and uric acid as well as screeningtests for HIV and hepatitis B and C are required.. The staging is given according to the Ann Arbor systemwith mentioning of bulky disease.. For prognostic purposes, a Follicular Lymphoma-specificInternational Prognostic Index (FLIPI) has been recentlyrecommended [III, B].Treatment planStage I. In the small proportion of patients with limited stages I,radiotherapy is the treatment of choice with a curativepotential. Radiotherapy should be performed as extendedfield irradiation [II, B].. In selected patients with large tumor burden systemictherapy as developed for advanced stages may also be used[IV, B].Stage II–IV. In the large proportion of patients with advanced stage IIIand IV disease no curative therapy is yet established. Sincethe natural course of the disease is characterized by spon-taneous regressions in 15–20% of cases and varies fromcase to case, chemotherapy should be initiated only uponthe occurrence of symptoms including B-symptoms, hema-topoietic impairments, bulky disease or lymphoma pro-gression [II, B].. If complete remission and long progression-free survival isto be achieved, rituximab in combination with chemother-apy (COP, CHOP and fludarabine-containing schemes suchas FCM) should be considered [I, B]. Single agent fludara-bine or chlorambucil remain an alternative [III, B]. Inselected cases with contraindications for chemotherapy,antibody monotherapy alone may be discussed [II, B].Consolidation. Meta-analysis suggests a survival benefit with interferon-aas maintenance therapy that has to be balanced against tox-icity. Rituximab prolonged progression-free survival in arandomized trial. Myeloablative radiochemotherapy fol-lowed by autologous stem cell transplantation remainsinvestigational [I, B].. Radio-immunotherapy and potentially curative allogeneicstem cell transplantation may be discussed especially insecond and higher relapses.Response evaluation. Adequate radiological tests should be done after ever 2–3cycles of therapy and after completion of chemotherapy.Patients with incomplete or lacking response should be eval-uated for early salvage regimens.Follow-up. History and physical examination every 3 months for 2years, every 6 months for 3 additional years, and sub-sequently once a year with special attention to transform-ation and secondary malignancies including secondaryleukemia [V, D].. Blood count at 3, 6, 12 and 24 months, then only as neededfor evaluation of suspicious symptoms.. Evaluation of thyroid function in patients with irradiation tothe neck at 1, 2 and 5 years.Annals of Oncology 16 (Supplement 1): i56–i57, 2005doi:10.1093/annonc/mdi819q 2005 European Society for Medical Oncology. Minimal adequate radiological or ultrasound examinationsat 6, 12 and 24 months after end of treatment.NoteLevels of Evidence [I–V] and Grades of Recommendation[A–D] as used by the American Society of Clinical Oncologyare given in square brackets. Statements without grading wereconsidered justified standard clinical practice by the expertauthors and the ESMO faculty.Literature1. Solal-Celigny P, Roy P, Colombat P et al. Follicular lymphomainternational prognostic index. Blood 2004; 104: 1258–1265.2. MacManus PM, Hoppe RT. Is radiotherapy curative for stage I andII low grade follicular lymphoma? Results of a long term follow-upstudy of patients treated at Stanford University. J Clin Oncol 1996;14: 1282–1290.3. Stuschke M, Hoederath A, Sack H. Extended field and total centrallymphatic radiotherapy for early stages nodal centroblastic-centrocy-tic lymphoma: Results of a prospective multicenter study. Cancer1997; 80: 2273–2284.4. Horning SJ, Rosenberg SA. The natural history of initially untreatedlow-grade non-Hodgkin’s lymphomas. N Engl J Med 1984; 311:1471–1475.5. Marcus R, Imrie K, Belch A et al. CVP chemotherapy plus Rituxi-mab compared with CVP as first-line treatment for advanced follicu-lar lymphoma. Blood 2005; 105: 1417–1423.6. Ghielmini M, Schmitz SF, Cogliatti SB et al. Prolonged treatmentwith rituximab in patients with follicular lymphoma significantlyincreases event-free survival and response duration compared withthe standard weekly 4 schedule. Blood 2004; 103: 4416–4423.Coordinating authors for the ESMO Guidelines Task Force:W. Hiddemann1, M. Dreyling1 & R. A. Stahel21Invited authors, Klinikum Grosshadern, Med. Klinik III,Ha¨matologie/Onkologie, Marchioninstrasse 5, D-81377 Mu¨nchen,Germany; 2Assigned task force member, Div. of Oncology, UniversityHospital, Ra¨mistr. 100, CH-8091 Zu¨rich, SwitzerlandApproved by the ESMO Guidelines Task Force: August 2002, last updateDecember 2004.Correspondence to:ESMO Guidelines Task ForceESMO Head OfficeVia La Santa 7CH-6962 Viganello-LuganoSwitzerlandi57

Minimum Clinical Recommendations for diagnosis, treatment and follow-up of newly diagnosed follicular lymphoma

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