Prolonged survival and low incidence of late toxic sequelae in advanced follicular lymphoma treated with a TBI-free autografting program: updated results of the multicenter consecutive GITMO trial

Abstract

This study provides an updated report of the consecutive multicenter Gruppo Italiano Trapianto Midollo Osseo trial employing an intensified, purging-free, total body irradiationfree, high-dose sequential chemotherapy schedule with peripheral blood stem cell autograft (i-HDS) in advanced-stage follicular lymphoma (FL). Special interest has been devoted to late toxicities and outcome in terms of molecular status. Ninetytwo untreated FL patients aged p60 were enrolled by 20 Italian centers and evaluated on an intention-to-treat basis. Main findings are as follows: (1) 5.5-years overall survival projection of 80% (median follow-up: 68 months), with no differences related to age-adjusted IPI score; (2) 46 (50%) of 92 patients presently in continuous complete remission; (3) projected longterm progression-free survival exceeding 80% for patients collecting PCR-negative stem cell harvests or achieving molecular remission within the first 2 years from the end of therapy; (4) actuarial 5-years risk of developing secondary myelodysplasia and acute myeloid leukemia of 3.7%, with most of these events occurring in patients re-treated for recurrent lymphoma. These results demonstrate that i-HDS is feasible, effective and safe even in terms of long-term outcome. As the HDS schedule can be easily supplemented with Rituximab, it is one of the best options for random comparison with Rituximabsupplemented conventional chemotherapy.

Persistence of minimal residual disease in bone marrow predicts outcome in follicular lymphomas treated with a rituximab-intensive program

“…Most studies showed that MRD negativity is associated with a superior outcome and acts as an independent predictor. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] However, a few studies failed to confirm this observation. [25][26][27][28] In particular, a recent report by van Oers et al 28 failed to demonstrate any benefit of achieving postinduction PCRnegative status.…”

“…[1][2][3] The risk for recurrence is more pronounced among patients older than 60 years, as they often receive less-intense treatments. 4 Considerable evidence indicates that the persistence of polymerase chain reaction (PCR)-detectable residual tumor cells in the bone marrow (BM) and, to a lesser extent, peripheral blood is an independent predictor of relapse in FL [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] ; nevertheless, a few studies have failed to confirm this observation. [25][26][27][28] Concerns about the value of minimal residual disease (MRD) detection as an effective prognostic tool have been raised, particularly when applied to The results of this study were the subject of an oral presentation at the 2012 American Society of Hematology annual meeting.…”

Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage

“…In addition, prerituximab data suggest that HDS regimens might be associated with fewer second tumors compared with alternative autografting programs potentially because there is no TBI and large stem cell grafts are infused. 16,17 The present multicenter, open-label, randomized phase 3 trial took advantage of these observations. We compared a rituximab-supplemented version of HDS (R-HDS) with 6 courses of CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) supplemented by an identical number of rituximab courses (CHOP-R) in high-risk patients with FL.…”

Clinical implications and prognostic role of minimal residual disease detection in follicular lymphoma

“…large series of studies [Gribben et al 1991a[Gribben et al , 1991b[Gribben et al , 1992Hardingham et al 1995;Corradini et al 1997;Moos et al 1998;Freedman et al 1999;López-Guillermo et al 1998;Apostolidis et al 2000;Rambaldi et al 2002Rambaldi et al , 2005Ladetto et al 2002Ladetto et al , 2006Ladetto et al , 2008Corradini et al 2004;Ghielmini et al 2004;Brown et al 2007;Hirt et al 2008;Goff et al 2009;Morschhauser et al 2012]. MRD can be detected using different methods, including cytogenetics, flow cytometry, PCR-based tools and potentially also with hightrough output sequencing methods [Faham et al 2012;Ladetto et al 2012a].…”