Long-term remission in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting (R-HDS regimen).
Mantle cell lymphoma (MCL) is rarely cured with standard-dose chemotherapy. From January 1997 to February 2000, 28 previously untreated advanced-stage MCL patients younger than 61 years of age were treated at 9 Italian hematologic departments with 3 cycles of standard-dose debulking chemotherapy followed by a high-dose rituximab-supplemented sequence (R-HDS) including intravenous administration of high-dose cyclophosphamide, high-dose cytarabine, high-dose melphalan, and high-dose mitoxantrone plus melphalan. Study end points included toxicity, clinical and molecular response rates, long-term event-free survival (EFS), and overall survival (OS) rates, as well as the ability to harvest tumor-free peripheral blood stem cells. Optimal amounts of polymerase chain reaction-negative (PCR-negative) CD34+ cells were collected from all 20 informative patients. One patient died of toxicity. All 27 patients assessable for response achieved a complete response (CR), of which 24 remain in continuous complete remission (CCR) after a median follow-up of 35 months. Three patients had transient evidence of PCR-detectable disease in the bone marrow. The OS and EFS rates at 54 months were 89% and 79%, respectively. These results compare with the 42% OS rate and the 18% EFS rate observed in 35 age-matched historic controls treated with standard-dose chemotherapy at the participating centers. The use of rituximab in combination with high-dose chemotherapy represents a very effective in vivo purging method. The R-HDS regimen can be safely applied in a multicenter hematology setting and leads to long-term EFS and OS in the majority of patients with an otherwise incurable disease.
Gianni
Alessandro M
AM
Division of Medical Oncology C--Donazione Cristina Gandini, Istituto Nazionale Tumori, Milan, Italy. alessandro.gianni@unimi.it
Magni
Michele
M
Martelli
Maurizio
M
Di Nicola
Massimo
M
Carlo-Stella
Carmelo
C
Pilotti
Silvana
S
Rambaldi
Alessandro
A
Cortelazzo
Sergio
S
Patti
Caterina
C
Parvis
Guido
G
Benedetti
Fabio
F
Capria
Saveria
S
Corradini
Paolo
P
Tarella
Corrado
C
Barbui
Tiziano
T
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D016465:Bone Marrow Purging / Q000379:methods*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007937:Leukapheresis; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D018365:Neoplasm, Residual; D036102:Peripheral Blood Stem Cell Transplantation; D016133:Polymerase Chain Reaction; D012074:Remission Induction; D012189:Retrospective Studies; D000069283:Rituximab; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D003561:Cytarabine; D000069283:Rituximab; D003520:Cyclophosphamide; D008942:Mitoxantrone; D008558:Melphalan