Use of Cytarabine for Mantle Cell Lymphoma Treatment: 10 Years of Experience of a French Haematology Department

Mantle cell lymphoma (MCL) has been identified since 1994 in the Revised-European-American classification of Lymphoid neoplasm's. It's a rare and aggressive subtype representing 5% of all non-Hodgkin lymphomas (NHL) with a poor prognosis and a median overall survival (OS) of 30 to 43 months (m) due to refractory disease or frequently relapse. Chemotherapies including anthracyclines as CHOP regimen with or without rituximab are often used in first line treatment. Promising results have been obtained since 1998 with regimens including cytarabine and followed by intensive therapy with autologous stem-cell transplantation (ASCT) for younger patients. Since 1999 we adopted a policy of treating MCL with regimens including this molecule: younger and grafting patients received DHAP and rituximab (R-DHAP) regimen followed by intensive therapy with ASCT. Patients fit and aged over 65 years received 6 cycles of R-DHAP. Unfit patients over 65 years received R-COP-cytarabine regimen and older unfit and frail patients received cytarabine by subcutaneous (SC) weekly injections. We report a retrospective observational study of 10 years experience in our department.

From 09/1999 to 09/2009, we collect all cases of patients with a MCL diagnosis and treated by cytarabine regimen in our haematology department. All diagnosis was reviewed by pathologist and cytologist. We collected clinical, biological, histological, cytological, prognosis, therapeutic monitoring and survey data from the database of the regional structure of reference of lymphoma in Limousin in France. A descriptive and survival analysis was performed using Statview software.

During this period, we followed 54 patients with MCL, median age 70,5 [45-87], sex ratio 2,6. Diagnosis was performed on associations of the following samples: biopsie in 72,2% (n=39), bone marrow cytological aspect and immunophenotyping in 48,1% (n=26), blood cytological aspect and immunophenotyping in 70,4% (n=38). Cyclin D1 overexpression in molecular analysis was detected in 79,6% (n=43). Ann Arbor stage I/II 7,4% (n=4), III/IV 92,6% (n=50). ECOG 0/1 83,3% (n=45), ECOG 2 16,7% (n=9). MIPI score was Lower Risk (LR) for 25,9% (n=14), Intermediate Risk (IR) for 27,8% (n=15) and Higher Risk (HR) for 46,3% (n=25). Median OS is significantly different among the MIPI score (p<0,0021) with 37,7 months for HR versus 72,6 months for IR and not reached for LR. First line treatment were distributed among SC weekly injections of cytarabine 13% (n=7), COP+/−R-cytarabine for 25,9% (n=14) and DHAP+/−R for 61,1% (n=33). ASCT was performed for 29,6% (n=16) followed induction treatment by DHAP+/−R. Median OS and PFS are respectively 59,4 and 46,3 months for the total population. Patients received SC cytarabine have a median OS of 37,7 months and median PFS 27,3 months. Patients received COP+/−R-cytarabine have a median OS of 29,4 months and PFS 17,7 months. And patients received DHAP+/−R have not reached median OS and PFS. For patients received ASCT, median OS and PFS are not reached versus respectively 46,3 and 33,5 months for ungrafted patients. Median follow-up is 35,4 months [1-124,7] for all patients, 37,7 months [1,1-59,3] for patients treated by SC cytarabine, 18,1 months [2,6-81,9] for patients treated by COP+/−R-cytarabine and 39,8 months [1-124,7] for patients treated by DHAP+/−R.

The MIPI score was calculated a posteriori and validated in our series of patients distinguishing three different populations with significantly different survival (p<0,0021). Since 10 years, we usually used cytarabine in first-line treatment of MCL. Cytarabine regimen is associated with other molecule and adapted by age, comorbidities and renal function. In real life, the use of this molecule seems provide interesting results in term of survival and PFS particularly for younger receiving dose intensified regimens by R-DHAP followed by intensive therapy with ASCT. Several clinical trials include now cytarabine in their therapeutic schemes.

No relevant conflicts of interest to declare.