Delayed redistribution of CD27, CD40 and CD80 positive B cells and the impaired in vitro immunoglobulin production in patients with non‐Hodgkin lymphoma after rituximab treatment as an adjuvant to autologous stem cell transplantation

Abstract

SummaryRecent studies have indicated that patients who received rituximab as an adjuvant to stem cell transplantation (SCT) demonstrated an increased risk of developing severe hypogammaglobulinaemia, which was found to be a result of delayed recovery of CD27 positive memory B cells and impaired isotype expression. It appears that rituximab influences both the quantity and quality of B-cell redistribution. Precisely how the B-cell repertoire regenerates after anti-CD20-mediated transient B-cell depletion in patients with nonHodgkin lymphoma (NHL) remains to be elucidated. This study performed a phenotypical analysis of B cells in 17 NHL patients who received rituximab as an adjuvant to autologous SCT. The median period after final administration of rituximab was 36 months (range, 12-43 months). Surface antigen expression of CD27, CD40 and CD80 in NHL patients was statistically significantly different from healthy controls (n ¼ 14). Moreover, B cells from NHL patients showed significantly impaired IgG and IgA production upon engagement of surface immunoglobulin receptors in the presence of interleukin (IL)-2, IL-10 and CD40 ligand in comparison with samples from healthy controls. The delayed recovery of memory B cells with an abnormal cell marker expression and function demonstrates that naive B cells may fail to differentiate into plasma cells, resulting in hypogammaglobulinaemia after autologous SCT and rituximab therapy.

Delayed acquisition of somatic hypermutations in repopulated IGD+CD27+ memory B cell receptors after rituximab treatment

“…It has been shown in various diseases, including SLE (31) and non-Hodgkin's lymphoma (40). The reduced mutational rate of IgDϩ memory B cells after rituximab treatment does not seem to be related to RA or ongoing methotrexate therapy, since we observed the same pattern of few or no mutations 1 year after rituximab treatment in a patient with SLE who had received no additional immunosuppressive treatment (data not shown).…”

Delay in B-lymphocyte recovery and function following rituximab for EBV-associated lymphoproliferative disease early post-allogeneic hematopoietic SCT

“…12 Lymphoma patients who receive rituximab as adjuvant or maintenance following autologous HSCT, however, have been reported to have an increased risk of developing severe and long-lasting hypogammaglobulinemia despite quantitative CD19 þ B-lymphocyte recovery. [20][21][22][23] Laboratory studies in patients with lymphoma or alloantibodies before kidney transplantation have shown a delayed recovery of CD19 þ /CD27 þ B-memory cells and impaired isotype expression following rituximab therapy as seen in patients with common variable immunodeficiency, suggesting that rituximab can affect not only B-cell quantities but also the recovery of functional B-cell repertoires and differentiation into plasma cells. 20,21,24,25 Little is known of the consequences of rituximab therapy on B-lymphocyte depletion and recovery in patients with PTLD following allogeneic HSCT, particular in pediatric patients.…”

“…[20][21][22][23] Laboratory studies in patients with lymphoma or alloantibodies before kidney transplantation have shown a delayed recovery of CD19 þ /CD27 þ B-memory cells and impaired isotype expression following rituximab therapy as seen in patients with common variable immunodeficiency, suggesting that rituximab can affect not only B-cell quantities but also the recovery of functional B-cell repertoires and differentiation into plasma cells. 20,21,24,25 Little is known of the consequences of rituximab therapy on B-lymphocyte depletion and recovery in patients with PTLD following allogeneic HSCT, particular in pediatric patients. Although incubation of B cells with anti-CD20 antibody depletes normal circulating B cells and has variable effects on cell cycle progression and signaling, the detailed biologic functions of CD20 remain uncertain.…”

“…), administered on days þ 1, þ 3, þ 6, þ 11. Primary engraftment was achieved in all patients and occurred after a median of 22.5 days (range, [16][17][18][19][20][21][22][23][24][25][26][27][28]; two patients had secondary graft failure at days 98 and 225 (patient nos. 2 and 4).…”

Septic polyarthritis with Ureaplasma urealyticum in a patient with prolonged agammaglobulinemia and B-cell aplasia after allogeneic HSCT and rituximab pretreatment

“…A recent study analyzed B-cell sub-populations in 17 lymphoma patients, 12-43 months after the last dose of rituximab. 10 They demonstrated a delayed recovery of memory B cells, a defect in expression of co-stimulatory molecules and impaired immunoglobulin production in vitro. With this report, we wish to increase physician awareness of impaired immune reconstitution of the B-cell compartment and associated possible infections in HSCT patients receiving lymphocytotoxic chemotherapies including rituximab.…”