title: Pentostatin/cyclophosphamide with or without rituximab: an effective regimen for patients with Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma.
abstract: BACKGROUND
  Pentostatin has demonstrated significant activity as a single agent in patients with low-grade B-cell and T-cell lymphomas and is less myelosuppressive than other purine analogues.
  
  
  METHODS
  We conducted a phase II trial with the combination regimen of PC-R (pentostatin/cyclophosphamide with or without rituximab) in 14 patients with Waldenstrom's macroglobulinemia (WM) and 3 patients with lymphoplasmacytic lymphoma (LL) without monoclonal serum immunoglobulin M (IgM), followed by a maintenance regimen with rituximab (375 mg/m2 every 3 months) for patients exhibiting a complete response (CR) or a partial response (PR) after 4-6 cycles. Nine patients were untreated, and 8 had been previously treated with 1-3 regimens. The first 9 patients received PC therapy (pentostatin 4 mg/m2 plus cyclophosphamide 600 mg/m2), and 8 patients received the same combination with rituximab 375 mg/m2 on day 1. Cycles were repeated every 3 weeks.
  
  
  RESULTS
  An objective tumor response after PC and PC-R was confirmed in 11 of 17 evaluable patients (64.7%), with 2 CRs (11.7%) and 9 PRs (52.9%). In patients who received rituximab (n = 13) simultaneously or subsequently, the overall response rate was 76.9%. Grade 2/3 nausea and grade 2 vomiting was generally mild based on World Health Organization criteria. Grade 3 hematologic toxicity occurred after 9 of 49 cycles (18.3%), and grade 4 toxicity occurred after 2 cycles (4%). Ten patients were subsequently treated with rituximab every 3 months for 2-9 cycles to date (median, 4 cycles). No patients have had disease relapse to date, and all exhibited stable IgM serum levels. In 3 patients with a PR after completion of chemotherapy, remission has improved further, with normalization of the IgM level in 1 patient and another patient exhibiting a CR.
  
  
  CONCLUSIONS
  Our data indicate that PC-R is safe and highly effective in patients with WM. Maintenance therapy with rituximab for WM as a single infusion every 3 months can be administered safely and can improve remission status.
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany. manfred_hensel@med.uni-heidelberg.de
authors.forename: Manfred
authors.initials: M
authors.lastname: Hensel
authors.forename: Matthias
authors.initials: M
authors.lastname: Villalobos
authors.forename: Martin
authors.initials: M
authors.lastname: Kornacker
authors.forename: Fatime
authors.initials: F
authors.lastname: Krasniqi
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015649:Pentostatin / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D000069283:Rituximab; D008258:Waldenstrom Macroglobulinemia / Q000097:blood / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D007075:Immunoglobulin M; D015649:Pentostatin; D000069283:Rituximab; D003520:Cyclophosphamide