title: A phase II clinical trial of intensive chemotherapy followed by consolidative stem cell transplant: long-term follow-up in newly diagnosed mantle cell lymphoma.
abstract: Mantle cell lymphoma (MCL) is associated with high relapse rates and poor survival when treated with conventional chemotherapy, with or without rituximab. We report the long-term follow-up of a phase II clinical trial using a new intensive multiagent chemotherapeutic regimen [cyclophosphamide, teniposide, doxorubicin and prednisone (CTAP) alternating with vincristine and high-dose methotrexate and cytarabine (VMAC)] in newly diagnosed MCL. Following 4-6 cycles of CTAP/VMAC induction, patients aged < or =65 years proceeded to consolidative autologous haematopoietic stem cell transplantation (auto-HSCT), while patients < or =55 years who had a HLA-identical sibling received allogeneic-HSCT (busulfan/cyclophosphamide conditioning for both). Twenty-five untreated MCL patients enrolled on the protocol between 1997 and 2002. Among evaluable patients, overall response rate (ORR) was 74% following induction chemotherapy. Seventeen patients received HSCT (autologous-13/allogeneic-4). On intent-to-treat analysis, ORR for patients who received consolidative HSCT was 100% (complete remission 76%). Therapy was well-tolerated with 4% treatment-related mortality (including HSCT). The 5-year event-free-survival (EFS) and overall survival (OS) for all patients was 35% and 50% respectively. Furthermore, at 66-months median follow-up, the 5-year EFS and OS for patients who received consolidative auto-HSCT was 54% and 75% respectively. Patients who received auto-HSCT had improved outcomes compared to no auto-HSCT (EFS P = 0.001; OS P = 0.0002). CTAP/VMAC induction followed by consolidative auto-HSCT for newly diagnosed MCL is associated with high ORR and durable survival.
authors.affiliation: Robert H. Lurie Comprehensive Center of Northwestern University, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. a-evens@northwestern.edu
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Evens
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
authors.forename: Nanjiang
authors.initials: N
authors.lastname: Hou
authors.forename: Beverly P
authors.initials: BP
authors.lastname: Nelson
authors.forename: Alfred
authors.initials: A
authors.lastname: Rademaker
authors.forename: David
authors.initials: D
authors.lastname: Patton
authors.forename: Seema
authors.initials: S
authors.lastname: Singhal
authors.forename: Olga
authors.initials: O
authors.lastname: Frankfurt
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Steven T
authors.initials: ST
authors.lastname: Rosen
authors.forename: Jayesh
authors.initials: J
authors.lastname: Mehta
authors.forename: Leo I
authors.initials: LI
authors.lastname: Gordon
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004812:Epidemiologic Methods; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D016898:Interferon-alpha; D007376:Interleukin-2