Pre-emptive treatment with rituximab of molecular relapse after autologous stem cell transplantation in mantle cell lymphoma.
OBJECTIVE
Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT).


METHODS
MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m(2) weekly for 4 weeks.


RESULTS
Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR.


CONCLUSIONS
Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.
Andersen
Niels S
NS
Department of Hematology L-4041, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. ns_andersen@msn.com
Pedersen
Lone B
LB
Laurell
Anna
A
Elonen
Erkki
E
Kolstad
Arne
A
Boesen
Anne Marie
AM
Pedersen
Lars M
LM
Lauritzsen
Grete F
GF
Ekanger
Roald
R
Nilsson-Ehle
Herman
H
Nordström
Marie
M
Fredén
Susanne
S
Jerkeman
Mats
M
Eriksson
Mikael
M
Väärt
Jaan
J
Malmer
Beatrice
B
Geisler
Christian H
CH
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D015321:Gene Rearrangement; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy; D018365:Neoplasm, Residual / Q000188:drug therapy* / Q000235:genetics; D016133:Polymerase Chain Reaction; D012008:Recurrence; D000069283:Rituximab; D033581:Stem Cell Transplantation / Q000379:methods*; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D007143:Immunoglobulin Heavy Chains; D000069283:Rituximab