GEORG(HESS((MAINZ)(
(
DO(WE(STILL(NEED(ASCT(IN(MCL?(–(CON(
(
Department(of(Haematology,(Oncology(and(Pneumology,(University(Medical(School(of(the(Johannes(
Gutenberg>University,(Mainz,(Germany(
Mantle!Cell!Lymphoma,!like!other!lymphomas,!has!been!defined!as!an!incurable!disease!with!
conventional! chemotherapy.! Consequently,! attempts! to! overcome! this! therapeutic!
limitation!are!highly!attractive.!Early!experiences!with!autologous!stem!cell!transplantation!
following! high! dose! chemotherapy! (HDT)! showed! long! term! remissions! for! patients! with!
relapsed! MCL(1,! 2),! which! in! turn! raised! the! question,! if! early! use! of! this! modality! could!
result! in! real! or! functional! cure! in! this! disease.! With! this! idea! HDT! widely! has! been!
introduced!in!the!therapeutic!algorithm!for!MCL!in!the!first!line!treatment!for!younger,!fit!
patients.! However,! until! now,! in! all! trials! and! retrospective! analysis! applying! HDT! a!
continuous! relapse! pattern! can! be! noted! (3>7),! thereby! failing! to! demonstrate! obvious!
curative!potential,!although!some!long!term!remissions!have!been!observed.!!
!
In!turn,!this!limitation!raises!the!question,!if!at!least!a!substantial!benefit!in!progression!free!
survival!and!finally!overall!survival!analyzed!by!Kaplan>Meyer>estimates!can!be!observed!to!
justify!the!use!of!HDT!upfront.!Unfortunately,!only!a!single!randomized!comparison!exists,!
addressing!the!value!of!additive!HDT!until!today.!In!this!trial!consolidative!HDT!was!tested!
against! IFN! maintenance! in! MCL! patients! after! chemotherapy! induction! treatment(8).!
Indeed,! a! difference! in! the! median! PFS! was! noted! (17! vs.! 39! months! in! favor! of! HDT),!
however,! the! trial! failed! to! demonstrate! OS! benefit.! Long! term! follow>up! for! 14! years! did!
show!an!overall!survival!benefit!for!the!first!time!(Zoellner!et!al,!manuscript!in!preparation),!
however,! after! adjusting! for! the! use! of! Rituximab! this! difference! disappeared.! Several!
retrospective! analyses! confirmed! a! potential! benefit! on! PFS! of! HDT,! but! again,! in! none! a!
robust!OS!benefit!could!be!found.!Most!interesting!results!come!from!a!large!series!in!which!
more! than! 1000! patients! were! analyzed(6).! Whereas! a! PFS! and! OS! benefit! of! HDT! was!
demonstrated!in!the!primary!analysis,!after!risk!adjustment!this!difference!disappeared.!In!
the!long!term!follow!up!of!the!Nordic!trial!2!(9)!there!was!continuous!drop!in!overall!survival,!
although! the! authors! reported! on! plateauing! after! 15! years,! which! however! is! only! a! very!
limited!number!of!patients.!In!summary,!until!now!there!is!no!clear!evidence!for!an!overall!
survival!benefit!for!HDT!in!MCL.!
!
In!the!meantime,!other!developments!have!influenced!the!current!treatment!algorithm!for!
MCL! substantially.! First,! Rituximab! has! been! shown! to! improve! efficacy! of! chemotherapy!
and! combinations! like! BR! have! shown! excellent! long! term! results,! even! without! R>
maintenance.!The!latter!has!been!shown!to!be!associated!with!an!OS!benefit!for!patients!of!
all! age! groups,! with! or! without! a! HDT! containing! consolidation(5,! 10).! Rituximab! has! been!
shown!to!be!an!equalizer!to!dose!intensification!in!other!lymphoma!entities!and!following!
the!results!of!the!recent!follow!up!report!on!the!GLSG!data!(Zoellner!et!al,)!this!effect!seems!
to!be!observable!in!MCL!as!well.!Second,!cytarabinoside!(Ara>C)!has!clearly!proven!to!be!of!
great!merit!in!MCL.!Hyper>CVAD!has!been!one!of!the!first!regimen!which!has!been!used!for!
MCT!with!a!at!this!time!impressive!response!rate!and!remission!duration(2,!11)!and!these!
results! subsequently! have! stimulated! the! design! of! the! Nordic>regimen,! which! can! be!
SCIENTIFIC PROGRAMME
SESSION I
HODGKIN’S DISEASE
DEBATE I
IS THERE STILL A ROLE
FOR COMBINED MODALITY
THERAPY FOR EARLY
STAGE CHL?
SESSION II
T-CELL LYMPHOMA
ROUNDTABLE I
FUTURE DIRECTIONS IN
T-CELL LYMPHOMA
SESSION III
FOLLICULAR LYMPHOMA
DEBATE II
CAN WE AVOID
CHEMOTHERAPY IN
THE MANAGEMENT OF
FOLLICULAR LYMPHOMA?
SESSION IV
RARE LYMPHOMAS –
MARGINAL ZONE
LYMPHOMA AND
WALDENSTRÖM M
ACROGLOBULINEMIA
ROUNDTABLE II – WHERE
TO GO IN RARE B-CELL
LYMPHOMAS
SESSION V
MANTLE CELL LYMPHOMA
SESSION VI
DIFFUSE LARGE B-CELL
LYMPHOMA
DEBATE III
DO WE STILL NEED ASCT
IN MCL?
SESSION VII
NOVEL THER APEUTIC
CONCEPTS IN B-CELL
LYMPHOMAS
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
DISCLOSURES