Prolonged hypogammaglobulinemia following rituximab treatment for post transplant Epstein–Barr virus-associated lymphoproliferative disease

Viral-load and B-lymphocyte monitoring of EBV reactivation after allogeneic hemopoietic SCT in children

“…In fact, in our cohort, a combination of careful clinical monitoring, high-level cutoff of EBV-DNA viral load and monitoring of CD20 þ lymphocyte in the presence of mid-level EBV reactivation allowed for a significant reduction in the number of patients who received preemptive rituximab (9 of 87, 10%), compared with what would append using other approaches with a standard cutoff 41000 geq/ml (43 of 87, 49%). Considering the risk of severe adverse events associated with rituximab administration in post transplant patients, [10][11][12][13][14] such as allergic reactions and long-lasting hypogammaglobulinemia, the adoption of our strategy could be helpful for a more precise and refined treatment of EBV-PTLD. …”

“…9 However, this technology is not widely available, and therefore rituximab may represent a life-saving treatment for this complication, even if its use has been associated with severe adverse events (for example, immediate reactions or severe pneumopathy) 10,11 and delay in B-lymphocyte recovery that may last even for years. [12][13][14] The aim of this study was to evaluate whether measurements of both EBV-DNA viral load and percentage of CD20 þ lymphocytes could be used in the preemptive management of EBV-PTLD in children undergoing allogeneic HSCT.…”

Subcutaneous immunoglobulin in lymphoproliferative disorders and rituximab-related secondary hypogammaglobulinemia: a single-center experience in 61 patients

“…In particular, anti-CD20 monoclonal antibody (rituximab) is known to be associated with the development of prolonged secondary hypogammaglobulinemia. 1 Long-lasting antibody defects have been reported following rituximab treatment (both in monotherapy or in combination with chemotherapy) in patients with indolent and aggressive B-non-Hodgkin lymphomas (including CLL), [2][3][4] post-transplant Epstein-Barr virus-associated LPDs, [5][6][7][8] postautologous bone marrow transplantation, [9][10][11] and HIV-associated lymphomas. 12 It is worthy of note that the use of rituximab in the setting of non-hematologic conditions (autoimmune cytopenias 13 and rheumatoid arthritis 14 ) has extended the spectrum of secondary hypogammaglobulinemias following anti-CD20 therapy.…”

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

“…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. 26 B-cell lymphopenia of approximately 6 months duration has been observed in 12/15 adult patients who received rituximab in preemptive indication, 8 and a few cases of prolonged hypogammaglobulinemia have been published, [27][28][29][30] of whom one provided laboratory evidence for similar mechanisms as described in the lymphoma setting. However, the situation may be more complex as additional factors may contribute following allogeneic HSCT, including engraftment, expansion and differentiation of lymphopoiesis, immunological processes between host and graft, the action of immunosuppressive agents and active EBV infection, which upon itself may be associated with immunodeficiency 31 and secondary graft failure as in two of the six patients described in this report.…”

“…), 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).…”