Humoral immune depression following autologous stem cell transplantation is a marker of prolonged response duration in patients with mantle cell lymphoma

Abstract

Rituximab maintenance (RM) after autologous stem cell transplantation (ASCT) is standard-of-care for young patients with mantle cell lymphoma (MCL). RM may enhance post-transplantation immune depression and risk of infections. We compared infection incidence and immune consequences of RM versus observation in transplanted MCL patients. All randomized patients included in the LyMa trial were eligible. The following parameters were collected prospectively: occurrence of fever, infection, hospitalization, neutropenia, hypogammaglobulinemia, CD4 lymphopenia and γ globulin (Ig) substitution. The post-ASCT period was divided into four periods in order to assess the possible effects of RM or ASCT on immune status. Each arm included 120 patients. Concerning infection incidence and all biological parameters, there was no difference between the two arms during the first year post ASCT. After this period, RM patients were more exposed to fever (P=0.03), infections (P=0.001), hypogammaglobulinemia (P=0.0001) and Ig substitution (P<0.0001). Incidences of hospitalization, neutropenia and CD4 lymphopenia were not different between the two arms. The number of rituximab injections was correlated with infections and hypogammaglobulinemia, P<0.0001 and P=0.001; but was not correlated with neutropenia and CD4 lymphopenia. Ig substitution did not modify infection incidence. Patients who presented hypogammaglobulinemia <6 g/L or <4 g/L had longer 3-years progression-free survival (PFS), this applies to RM patients (P=0.012 and P=0.03) and to the global cohort (P=0.008 and P=0.003). Hypogammaglobulinemia did not influence overall survival. Occurrence of infectious event, neutropenia and CD4 lymphopenia did neither influence PFS nor overall survival. Post-ASCT RM in MCL patients causes sustained hypogammaglobulinemia, which is independently correlated with improved PFS.

Figure 1.

Infection sites. (A) Graphical repartition of infections sites. (B) Number of infections per infection sites presented with median time of occurrence.

Figure 2.

Rates of polynuclear neutrophils, γ globulins and CD4 lymphocytes according to treatment arms. (A) Polynuclear neutrophils (PNN), (B) γ globulins and (C) CD4 lymphocytes.

Figure 3.

Progression-free survival from randomization according to occurrence of hypogammaglobulinemia <6 g/L and hypogammaglobulinemia <4 g/L. Representation of progression-free survival (PFS) in (A) the whole cohort and in (B) the rituximab maintenance (RM) arm according to γ globulin status <6 g/L and PFS in (C ) the whole cohort and in (D) the RM arm according to occurrence of hypogammaglobulinemia <4 g/L. GAMMAG: γ globulin rate.