title: Hypogammaglobulinemia with a selective delayed recovery in memory B cells and an impaired isotype expression after rituximab administration as an adjuvant to autologous stem cell transplantation for non-Hodgkin lymphoma.
abstract: OBJECTIVE
  Some studies have indicated patients who received rituximab as adjuvant to stem cell transplantation had an increased risk of developing severe hypogammaglobulinemia. The mechanism of this hypogammaglobulinemia is unknown, although investigators have hypothesized a further delay in the B-cell recovery as one potential etiology. The aim of this study is to clarify the mechanism(s) of this hypogammaglobulinemia.
  
  
  METHODS
  A total of 14 patients with high-risk CD20+ lymphoma underwent an autologous peripheral blood stem cell transplantation (APBSCT). After a hematological recovery, rituximab was given weekly for up to four doses as an adjuvant therapy.
  
  
  RESULTS
  After a median follow up of 33.5 months, we found six patients (group A) who had hypogammaglobulinemia, while the eight other patients (group B) had normal serum immunoglobulin levels. A phenotypical analysis revealed that group A patients had already achieved B-cell recovery. However, we found a severe delay in the recovery of CD27+ memory B cells, especially in the IgD-/CD27+ switched populations in group A, but CD27 negative naive B-cells reverted to a normal range in both groups. Consistent with this, reverse transcriptase-polymerase chain reaction studies with peripheral blood mononuclear cells revealed that most patients in group A lacked more than two classes of isotype transcripts.
  
  
  CONCLUSIONS
  Abnormal repertoires and impaired isotype expression are seen in patients with common variable immunodeficiency, these data suggested that rituximab after APBSCT can affect not only the B-cell quantities, but also the recovery of the B-cell repertoires.
authors.affiliation: Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan. m-nishio@med.hokudai.ac.jp
authors.forename: Mitsufumi
authors.initials: M
authors.lastname: Nishio
authors.forename: Katsuya
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Endo
authors.forename: Toshiya
authors.initials: T
authors.lastname: Sakai
authors.forename: Masato
authors.initials: M
authors.lastname: Obara
authors.forename: Kohki
authors.initials: K
authors.lastname: Kumano
authors.forename: Koichiro
authors.initials: K
authors.lastname: Minauchi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Yukari
authors.initials: Y
authors.lastname: Takeda
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sato
authors.forename: Kazuki
authors.initials: K
authors.lastname: Koizumi
authors.forename: Masaya
authors.initials: M
authors.lastname: Mukai
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
mesh_terms: D000328:Adult; D000361:Agammaglobulinemia / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes / Q000276:immunology; D003131:Combined Modality Therapy; D005260:Female; D049671:History, 18th Century; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000235:genetics; D007156:Immunologic Memory; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D000069283:Rituximab; D014182:Transplantation, Autologous
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007132:Immunoglobulin Isotypes; D000069283:Rituximab