High Dose Aracytine, Rituximab, and Dexamethasone Based Chemotherapy for Elderly Patients with Mantle Cell Lymphoma.
Authors: Kotb Rami , Boisjoly Josie-Anne , Lepine Mariette , Beauregard Patrice , Sawan Bassem , Turcotte Eric 
Published: October 2019

Abstract
Mantle cell lymphoma (MCL) mainly affects elderly and long term response to standard chemotherapy is deceiving. The addition of Rituximab or high dose chemotherapy regimens may improve these results, but have not been evaluated in elderly patients or those with significant comorbidities. We thought to evaluate the safety and efficacy of a High dose Aracytine (Cytosine arabinoside), Rituximab and Dexamethasone (HARD) chemotherapy regimen in elderly patient with aggressive mantle cell lymphoma.
Patients and methods: All patients with relapsing, refractory or de novo aggressive MCL were eligible despite comorbidities. All received Rituximab 375 mg/m2 and Dexamethasone 40 mg/d x3 days per cycle. The dose of Aracytine was modulated according to the general condition and accompanying comorbidities. Revised data included clinical and biological parameters, pathology specimens, CT and PET scans. Comorbidities were assessed according to medical records. Patients who received at least one cycle of HARD were analysed for tolerance; and those who completed scheduled treatment or with treatment interruption due to intolerance or insufficient response were analysed for efficacy.
Results: Between November 2005 and August 2007, eight consecutive MCL patients, 5 males, 3 females; median age 72.6 years (65–77) were treated by HARD based chemotherapy. All presented with aggressive histological pattern and stage III/IV disease. The majority had performance score >2 (6/8), high serum LDH (6/8), high β2microglobulin (5/5) and Hemoglobin level <12 g/dL (5/8). The FLIPI score was High/High-Intermediate in seven patients. The Charlson comorbidity score was >5 for seven patients and principal documented comorbidities were coronary heart disease (3/8), cardiac systolic dysfunction (3/8), cerebrovascular diseases (3/8), chronic renal insufficiency (4/8), and chronic respiratory disorders (3/8). A total number of 27 HARD cycles were given. All received planned doses of Rituximab and dexamethasone. The median initial dose of Aracytine was 2.55 g/m2 (1.12–4 g/m2), which was subsequently modified according to tolerance. Five patients also received at least one cycle of concomitant Cisplatinum (average dose 20–60 mg/m2). Primary prophylactic G-CSF was given to 5 patients. There were five episodes of thrombopenia and five episodes of anemia requiring transfusions. One patient developed acute transfusion reaction complicated by myocardial infarction, pulmonary edema and acute renal failure that responded to medical treatment. One cycle of HARD was complicated by febrile neutropenia. There was no treatment associated mortality. Two patients are still under treatment and are only evaluated for tolerance. Two other patients were refractory to one and two cycles of HARD and died rapidly from disease progression. Of note that both had >150 x109circulating lymphoma cells/L at treatment. Four patients (67%) responded favourably: 3 complete remissions maintained with 22, 14 and 10 months of follow-up; and one partial remission that persisted for 15 months before progression.
Conclusion: HARD is safe in elderly and fragile patients with MCL, provide that the dose is modulated according to comorbidities. Despite this dose modulation, the response rate seems very interesting and compares favourably with other regimens adapted for young and physically fit patients.