Methods: In the Nordic Lymphoma Group MCL Project newly diagnosed stage II-IV MCL patients < 66 years receive induction treatment and peripheral-blood stem-cell (PBSC) harvest, followed by BEAM/BEAC with PBSC support. In the MCL1 Protocol, the induction was maxi-CHOP x 3 (CTX 1200 mg/m2, doxorubicin 75 mg/m2, VCR 2mg D1, prednisolone 100 mg D1-5). Stem-cells were mobilised by maxi-CHOP + G-CSF. Because of the high failure rate in MCL1 (Figure 1) the MCL2 protocol was activated adding 2 series of high-dose Ara-C (3g/m2 BID D1-2) and 2 standard doses of rituximab (R) (375 mg/m2) to the induction program. Stem cells were mobilised by Ara-C + G-CSF + rituximab D1 + D9 for in-vivo purging. In both protocols patient-specific molecular markers were sought established before treatment start, and stem-cells and follow-up blood and bone-marrow samples assessed for MCL by PCR or flow cytometry.

Results: Table 1

Compared Results of the Nordic Lymphoma Group MCL1 and MCL2 Protocols

NORDIC MCL PROTOCOL #MCL1 (1997–2000)MCL2 (2000-)P value
Supported by the Nordic Cancer Union 
No. of Pts included/eval. for response 42/42 120/88  
Response pretransplant 31/42 86/88 0.002 
CR/resp pretransplant 11/31 51/86 0.04 
No. transplanted 27 86  
Eval. for response posttransplant 27 82  
CR/Response posttransplant 25/27 76/82 NS 
Molecular response posttransplant 5/13 38/42 0.0003 
PCR-neg. stem-cell products (of tested) 2/16 22/25 0.00005 
3-year failure-free survival (104 pts eval.) 24% 68% 0.0001 
3-year relapse-free survival (RFS) 45% 76% 0.04 
3-year molecular RFS survival ND 67%  
3-year overall survival 60% 85% 0.02 
NORDIC MCL PROTOCOL #MCL1 (1997–2000)MCL2 (2000-)P value
Supported by the Nordic Cancer Union 
No. of Pts included/eval. for response 42/42 120/88  
Response pretransplant 31/42 86/88 0.002 
CR/resp pretransplant 11/31 51/86 0.04 
No. transplanted 27 86  
Eval. for response posttransplant 27 82  
CR/Response posttransplant 25/27 76/82 NS 
Molecular response posttransplant 5/13 38/42 0.0003 
PCR-neg. stem-cell products (of tested) 2/16 22/25 0.00005 
3-year failure-free survival (104 pts eval.) 24% 68% 0.0001 
3-year relapse-free survival (RFS) 45% 76% 0.04 
3-year molecular RFS survival ND 67%  
3-year overall survival 60% 85% 0.02 
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Posttransplant maintenance treatment: In MCL2, patients in clinical stable response but molecular relapse are offered R 4 std. doses. So far, isolated molecular relapse occurred in 11 pts. of whom 10 received R: Four became PCR neg., one did not respond and later relapsed, five are not yet evaluable. Conclusion: By comparing MCL1 results with preliminary results of the still ongoing MCL2 study we conclude that the addition of HD Ara-C and R to the induction treatment significantly increases the

• clinical response rate pretransplant

• molecular response rate

• No. of tumor-cell free grafts

• failure-free, relapse-free and overall survival

Rituximab maintenance treatment can induce 2nd molecular remission, the clinical significance hereof still unknown.

Figure
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Figure

Topics:
cyclophosphamide, doxorubicin, prednisone, and vincristine, cytarabine, follow-up, frequency of responses, mantle-cell lymphoma, polymerase chain reaction, purging, rituximab, tissue transplants, brachial plexus neuritis

Author notes

Corresponding author

2005, The American Society of Hematology
2004
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