Does more intensive therapy have effects on mantle cell lymphoma? A clinical experience from the Lymphoma Treatment Study Group in Japan

Mantle cell lymphoma (MCL) is a rare subtype of B-celllymphoma characterized by amplification of cyclin D1.The effect of chemotherapies, such as CHOP (cyclophos-phamide, doxorubicin, vincristine, and prednisone), is oftentransient, and most patients die at median 3–5 years fromdiagnosis [1]. Before the rituximab era, a number of smallstudies evaluated the efficacy of high-dose chemotherapy(HDC) supported with autologous stem cell transplantation(ASCT), but did not find an evident contribution to survivalbenefit [2, 3]. Consequently, no single standard treatmentfor MCL has been established to date [4]. We thereforeconducted a nation-wide multicenter retrospective analysisof newly diagnosed patients with MCL in order to inves-tigate the efficacy and clinical outcome of each initialtreatments and HDC/ASCT in the rituximab era.Clinical data of 64 newly diagnosed MCL cases treated in12 institutions participating in the Lymphoma TreatmentStudyGroupinJapanbetween2001and2008werecollectedand analyzed by the end of April 2009. The data includedpatient characteristics [age, sex, performance status definedby European Cooperative Oncology Group (ECOG PS),clinical stage according to the Ann Arbor staging system,complete blood count, and serum lactate dehydrogenaselevel], as well as details of treatment and clinical outcome.Positivity of cyclin D1 and/or chromosomal abnormalityt(11;14)(q13;q32) in the biopsy specimen were required forthe diagnosis of MCL following the World Health Organi-zation classification system. This study was approved by theinstitutional review board in Nihon University ItabashiHospital, where the analysis was performed.Table 1 shows the clinical characteristics of all patientsand risk factors that might influence overall survival,including MCL international prognostic index (MIPI) [5].The median age of patients and median observation periodwere 64 years (range 47–80 years) and 34 months (range2–91 months), respectively. Most of patients were treatedwith rituximab-combined CHOP (R-CHOP)-based che-motherapy for a median 6 (range 2–8) cycles or R-Hyper-CVAD/MA regimen (rituximab, hyperfractionatedcyclophosphamide, vincristine, doxorubicin, and dexameth-asone alternating with high-dose methotrexate and cytara-bine), as initial treatment. As a result, 5-year overallsurvival (OS) and progression-free survival (PFS) for allpatients were 62 and 34%, respectively (Fig. 1a). Thecomplete response rate of the R-CHOP group was lowerthan that of the R-Hyper-CVAD/MA group (49 vs. 80%,P = 0.031), but there was no significant difference in OSor PFS (Fig. 1b, c). Sixteen patients (25%) received vari-ous combinations of HDC followed by ASCT. Amongthese patients, nine underwent HDC/ASCT in their firstcomplete remission, six were in a refractory phase of thedisease, and one was in a second remission. The clinicaloutcome of this group was quite encouraging, withouttreatment-related mortality or secondary malignancy dur-ing the observation period (93% of 5 year OS) (Fig. 1d).In this study, the majority of patients were treated withR-CHOP-based chemotherapy. After rituximab becameclinically available for treating B-cell lymphomas, theclinical outcome of MCL appeared to be improved.