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ACR 2015 | Daily Highlights
Lymphoma in Patients with Granulomatosis with PolyangiitisAbstract: 869
Presenter: Karin Hjorton
Co-Authors: Erik Hellbacher, Christer Sundstrom, Eva Baeckstrom and Ann Knight
The risk of malignancy in patients with Granulomatosis with Polyangiitis (GPA) is increased, as shown in several previous studies. The risk of lymphoma has been described as high as 4-5-fold increased. In addition, lymphoma in the sinonasal region, especially NK/T-cell lymphoma, has been reported to mimic GPA localized to the ear-throat-nose (ENT) region. Several previous publications report cases where a sinonasal lymphoma initially was misdiagnosed as GPA. We therefore had a particular interest in investigating the presence of lymphoma localized in the ENT-region. Our aim in this study was to assess the clinical characteristics and treatment of patients with GPA complicated by lymphoma and to describe the lymphoma types, sites and prognosis in a population-based setting.
From the Swedish population based patient register all individuals with a diagnosis of GPA between 1964 and 2012 were identified (n=3,224). Through linkage with the Swedish cancer register all lymphoproliferative malignancies (ICD7:200-202) registered after the first discharge listing GPA were identified. The medical records of all patients with GPA and lymphoma were collected and the GPA diagnosis was evaluated using the EMEA Consensus Algorithm for Classification of Vasculitis (1). To confirm the lymphoma diagnosis all lymphoma tissues were retrieved and classified according to the latest WHO classification. Clinical data of both GPA and lymphoma were collected from the medical files.
In all, 24 GPA-patients with malignant lymphoma were identified. 20 of these were B-cell lymphomas, and only two T-cell lymphomas (Table). Only one of the lymphomas was localized to the ENT-area, a diffuse large B-cell lymphoma in the hard palate. The majority of the patients had generalized GPA disease, most (75%) had been treated with cyclophosphamide for their GPA, many for long periods and with high doses; the median cumulative dose was 40g. The mean time from GPA to lymphoma diagnosis was 10 years (0-22). The majority of the lymphomas were aggressive and the median survival after lymphoma diagnosis was only 4 months.
PE was used for rapidly progressive glomerulonephritis (RPGN) in 126 (83%) [mean SCR 465±257 µmol/l; including <250, 250–500 and >500 µmol/l in one-third each], 64 (42%) alveolar hemorrhage most often RPGN-associated, 23 (15%) with extensive and severe multiple mononeuropathy, usually of acute onset (<4 weeks) and severe motor weakness, and 7 (5%) with extensive skin necrosis. M0 median BVAS was 18. Median (range) PE was 7 (1–12) sessions over a median of 11 (1–43) days.
After median follow-up of 22 (range 1–125) months post-PE onset, 18 (12%) had died, including 11 within M1–6. Renal function of 126 PE-treated RPGN patients improved significantly, as assessed by estimated glomerular filtration rate (eGFR) using MDRD, reaching a plateau between M3 and M6 post-PE onset, and maintaining eGFR through follow-up M24. According to M0-SCR (µmol/l) subgroup, M0-to-M6 eGFR (ml/min), respectively, rose from 33.3 to 47.3 (P<0.0001) for <250, from 13.5 to 34.7 (P<0.0001) for 250–500, and from 6.9 to 32.9 (P<0.0001) for >500. PE-session numbers were similar for the 3 M0-SCR subgroups, with eGFR improving as that number rose, suggesting a PE dose-dependent effect on eGFR recovery.
PE resolved alveolar hemorrhages in all 64 patients, enabling O2-therapy or MV discontinuation, after a median of 15 days.
Motor weakness regressed markedly in 23 PE-treated extensive mononeuritis patients. Severe motor-weakness (MRC <3/5) declined from M0 52% to 23%, 19% and 12.5% at M3, M6 and M12 post-PE onset.
End-stage renal disease and/or mortality rates were similar among M0-SCR groups but higher for MPO- than PR3-ANCA+ patients. PE-attributable adverse events occurred in 63%. No one died during PE.
The findings in this population-based setting indicate that the lymphomas developing in patients with GPA are aggressive with a poor prognosis. T-cell lymphoma or lymphoma localized to the ENT-area are not a prominent finding. The study emphasizes the need for awareness of lymphoma and long-term follow-up of patients with GPA.
1. Watts, R et al. Ann Rheum
Das Risiko für Lymphome ist bei GPA gemäss Studien etwa 4-5 fach erhöht. Selten und deshalb leider oft über Monate verpasst sind NK/T Zelllymphome im Nebenhöhlen/Nasenraum. Diese können eine GPA imitieren. Man muss an diese Differentialdiagnose denken wenn ein „loko-regionärer Wegener“ therapieresistent ist.
Die schwedische Autorengruppe analysierte 3224 Patienten mit einer GPA aus einem Zeitraum von 1964 bis 2012 und verglich die Angaben mit dem Schwedischen Krebsregister. Sie identifizierte 24 Patienten, 20 mit B Zell-Lymphomen. Die meisten Patienten litten unter einer „generalisierten GPA“ und bekamen Cyclophosphamid (Endoxan), oft für lange Perioden und in hohen Dosen (mittlere kumulative Dosis 40g). Der Zeitraum zwischen GPA-Diagnose und Lymphomdiagnose betrug im Mittel 10 Jahre, die Prognose war schlecht.
Obwohl es sich um die grösste Registerarbeit über dieses Thema handelt, bleibt letztlich die Frage offen, ob die Lymphome krankheits- oder therapie-bedingt waren. In Berücksichtigung der Risiken, die eine ANCA-assoziierte Vaskulitis quo ad vitam birgt, erscheint das Risiko eines Lymphoms vergleichsweise klein.
Prof. Dr. Peter M. Villiger
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