LÉP MARGINÁLIS ZÓNA LYMPHOMÁS BETEGEINKEN ELVÉGZETT SPLENECTOMIA EREDMÉNYEI Egyed Miklós*, Kollár Balázs*, Rajnics Péter*, Hussain Alizadeh*,Karádi Éva*,

Az előadások a következő témára: "LÉP MARGINÁLIS ZÓNA LYMPHOMÁS BETEGEINKEN ELVÉGZETT SPLENECTOMIA EREDMÉNYEI Egyed Miklós*, Kollár Balázs*, Rajnics Péter*, Hussain Alizadeh*,Karádi Éva*,"— Előadás másolata:

1 LÉP MARGINÁLIS ZÓNA LYMPHOMÁS BETEGEINKEN ELVÉGZETT SPLENECTOMIA EREDMÉNYEI Egyed Miklós*, Kollár Balázs*, Rajnics Péter*, Hussain Alizadeh*,Karádi Éva*, Puskás Attila * /Pajor László **,Tüske László *** Tóth László*** Somogy Megyei Kaposi Mór Oktató Kórház Hematológiai és Sebészeti Osztály * Pécsi Tudományegyetem, Általános Orvostani Központ Pathológiai Osztály** Zala Megyei Kórház Sebészeti és Pathológiai Osztály ***

2 Splenikus marginalis zóna lymphoma Ritka B sejtes lymphoproliferativ betegség (LP..2%-a) a lép fehér pulpa centrum germinativumait involválja a köpenyzónát is elfoglalva a 2008-as WHO klasszifikációban önálló entitás…korábban SLVL Splenomegalia, csontvelő és perif vér gyakran érintett..CD 20+,CD79a+,..CD5-,CD10- CD23- felszini IgM,IgD általában + Hepatitis C infectioval való összefüggés…autoimmun jelenségek 7q31-32 deleció áll mögötte,de igazán kóros génműködést (target-) nem igazoltak miRNS expresszio megváltozása... T sejt független B-sejt aktiváció/proliferáció

3 Lép marginális zóna lymphoma Általában indolens lefolyás jellemzi, több mint 10 éves túléléssel..........20%-ban agresszivvé válhat(4 éves túlélés) Adatok összesitett esetekből, retrospektiv elemzésekből származnak. prospectiv, randomizált vizsgálat alig van. Prognosztikus score rendszerek megállapitása folyamatban Kezelés szükségessége—mint CLL-ben +splenomegalia tünetei Korábbi adatok a splenectomia mellett szóltak..azonnal megoldja a nagy lép okozta problémákat és megszünnek a cytopeniák, 5 éves PFS !! De a splenectomia veszélyes, főleg idős betegeken KT nem eredményes Rituximab nagyon effectiv Hepatitis C virus pozitiv esetekben antivirális kezelés!!

4 Splenectomia versus Rituximab az irodalomban

5 Treatment of splenic marginal zone lymphoma: splenectomy versus rituximab Semin Hematol. 2010 Apr;47(2):143-7. Bennett M1, Schechter Splenic marginal zone lymphoma (SMZL) is an uncommon indolent B-cell lymphoma causing marked splenic enlargement with CD20-rich lymphoma cells infiltrating blood and bone marrow. In the pre-rituximab era, the treatment of choice for patients with symptomatic splenomegaly or threatening cytopenia was splenectomy, since chemotherapy had limited efficacy. Responses to splenectomy occurred in approximately 90% of patients. However, SMZL patients are often elderly and poor surgical risks. Since approval of rituximab, treatment of such patients with the anti-CD20 antibody both alone or in combination with chemotherapy has shown remarkable responses. In retrospective series of rituximab monotherapy totaling 52 patients, including both chemotherapy-naive and -refractory patients, overall responses of 88% to 100% were noted with marked and prompt regression of splenomegaly and improvement of cytopenias. Sustained responses occurred both with and without rituximab maintenance in 60% to 88% of patients at 3 years Relapsed patients responded to second courses of rituximab monotherapy. Overall survival was comparable to that reported following splenectomy. These results suggest that splenectomy should no longer be considered as initial therapy for SMZL but rather as palliative therapy for patients not responsive to immunotherapy with or without chemotherapy.

6 Treatment of splenic marginal zone lymphoma with rituximab monotherapy: progress report and comparison with splenectomy Oncologist. 2013;18(2):190-7. Kalpadakis C1, Pangalis GA, Angelopoulou MK, Sachanas S..: Treatment of splenic marginal zone lymphoma (SMZL) patients is not standardized. Recent data suggest that rituximab is highly effective and could be considered as initial therapy. AIM:To assess the efficacy of rituximab monotherapy in a large series of patients with SMZL and compare these results with splenectomy results. METHODS:The studied population included 85 patients. 58 received rituximab at a dose of 375 mg/m2 per week for 6 weeks as induction followed by maintenance at the same dose every 2 months for 1-2 years, whereas 27 patients were treated using splenectomy only. RESULTS:The overall response rate to rituximab 2 months after the end of induction was 95% (complete response [CR], 45%; unconfirmed CR, 26%; partial response, 24%). The median times to hematologic and clinical response were 2 weeks and 3 weeks, respectively. Forty-three of 55 patients already completed the maintenance phase: 28 sustained their initial response, 14 improved their response, and one progressed. Eighty-five percent of splenectomized patients responded, and two were treated with rituximab as consolidation after splenectomy and achieved a CR. The 5-year overall and progression-free survival (PFS) rates for rituximab-treated and splenectomized patients were 92% and 77% (p =.09) and 73% and 58% (p =.06), respectively. Furthermore, maintenance therapy with rituximab resulted in a longer duration of response (at 5 years, PFS was 84% for patients receiving maintenance and 36% for patients without maintenance, p <.0001).CONCLUSIONS :Rituximab is a very effective and well-tolerated therapy and may be substituted for splenectomy as the first-line treatment of choice for patients with SMZL.

7 h t t p : / / t h e o n c o l o g i s t. a l p h a m e d p r e s s. o r g / c o n t e n t / 1 8 / 2 / 1 9 0 / F 1. e x p a n s i o n. h t m l Kalpadakis C1, Pangalis GA, Angelopoulou MK, Sachanas SKalpadakis C1, Pangalis GA, Angelopoulou MK, Sachanas S..:: Oncologist. 2013;18(2):190-7.

8 Treatment of splenic marginal zone lymphoma: should splenectomy be abandoned? Leuk Lymphoma. 2013 Nov 6 Kalpadakis C1, Pangalis GA, Vassilakopoulos TP, Sachanas S, Angelopoulou Splenic marginal zone lymphoma (SMZL) is a rare chronic B-cell lymphoproliferative disorder… …. Furthermore, splenectomy is a major surgical procedure with significant morbidity or even mortality, especially in older patients Recent data suggest that rituximab is a very effective therapy with minimal toxicity and could replace splenectomy as first-line treatment. The overall response rate is > 90%, with almost half of responses being complete, while the 5-year progression-free survival is approximately 70%. Based on the current data, splenectomy could be abandoned as first-line treatment for patients with SMZL.

9 Long-term follow-up analysis of 100 patients with splenic marginal zone lymphoma treated with splenectomy as first-line treatment. Leuk Lymphoma. 2014 May 6 Lenglet J1, Traullé C, Mounier N, Benet C, Splenectomy is considered as one of the first-line treatments for symptomatic patients with splenic marginal zone lymphoma (SMZL). Between 1997 and 2012, 100 hepatitis C virus-negative patients with SMZL were treated by splenectomy as first-line treatment. Between 1997 and 2012, 100 hepatitis C virus-negative patients with SMZL were treated by splenectomy as first-line treatment. At 6 months, all patients but three recovered from all cytopenias. The median lymphocyte count at 6 months and 1 year was 11.51 × 10 9/L and 6.9 × 10 9/L, respectively. The median lymphocyte count at 6 months and 1 year was 11.51 × 10 9/L and 6.9 × 10 9/L, respectively. Median progression-free survival (PFS) was 8.25 years. The 5-year and 10-year overall survival (OS) rates were 84% and 67%, respectively. Histological transformation occurred in 11% of patients, and was the only parameter significantly associated with a shorter time to progression (p = 0.0001). Histological transformation occurred in 11% of patients, and was the only parameter significantly associated with a shorter time to progression (p = 0.0001). Significant prognostic factors for OS were age (p = 0.0356) and histological transformation (p = 0.0312). In this large retrospective cohort, we confirmed that splenectomy as first-line treatment in patients with SMZL corrected cytopenias and lymphocytosis within the first year and was associated with a good PFS. splenectomy as first-line treatment in patients with SMZL corrected cytopenias and lymphocytosis within the first year and was associated with a good PFS.

10 Splenikus marginalis zóna lymphomás betegeink összefoglaló táblázata

11 Splenikus marginalis zóna lymphoma-SLVL CD 20+,CD79a+,..CD5-,CD10-,CD23- felszini IgM,IgD általában + SZ.J 56 é ffi perifériás vérképe

12 Splenikus marginalis zóna lymphoma SZJ 56 éves ffi csontvelő

13 Splenikus marginalis zóna lymphoma SZ.J 56 béves ffi -lép MZL szövettani képe.. A tüsző két rétegű, kívül a világos lymphomás zóna, belül a kolonizált sötétebb csíracentrum, ez is beteg,a köpeny eltűnt. A vörös pulpában kis világos infiltrátumok. HE festés. Splenikus marginalis zóna lymphoma

14 Splenikus marginalis zóna lymphomás betegeink 5 nő-4 ffi Hepatitis C negativak 37-75 éves korban- jó állt állapot(ECOG 0-1) Indikáció: a nagy lép okozta panaszok és cytopeniák Műtéti szövődmény nem volt Jó válaszok a cytopeniák gyorsan megszüntek ---a parciális remissziókban enyhe lymphocytozis Előtte vaccinatio-azóta súlyos infectio-sepsis(OPSI) nem volt Progresszió egy betegben sem lépett fel a több mint 4 éves átlag követési időszak alatt

15 Splenikus marginalis zóna lymphomás betegeink Rituximab nem indikált Magyarországon SMZL-ben Splenectomia ma is jónak látszik

16 Köszönöm a megtisztelő figyelmet !