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.
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.
Nishio
Mitsufumi
M
Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan. m-nishio@med.hokudai.ac.jp
Fujimoto
Katsuya
K
Yamamoto
Satoshi
S
Endo
Tomoyuki
T
Sakai
Toshiya
T
Obara
Masato
M
Kumano
Kohki
K
Minauchi
Koichiro
K
Yamaguchi
Keisuke
K
Takeda
Yukari
Y
Sato
Norihiro
N
Koizumi
Kazuki
K
Mukai
Masaya
M
Koike
Takao
T
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
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007132:Immunoglobulin Isotypes; D000069283:Rituximab