Risk of secondary hypogammaglobulinaemia after Rituximab and Fludarabine in indolent non-Hodgkin lymphomas: A retrospective cohort study

Leuk Res. 2015 Dec;39(12):1382-8. doi: 10.1016/j.leukres.2015.10.013. Epub 2015 Nov 4.

Abstract

The occurrence of secondary hypogammaglobulinemia (SH) after chemo-immunotherapy represents a potential side effect in patients with indolent non-Hodgkin lymphomas (iNHL). Few data are available on SH occurring after chemotherapy and/or Rituximab (R). We retrospectively investigated the incidence and the risk factors for SH and infectious complications in patients with iNHL after chemo-immunotherapy. Two hundred and sixty six patients treated between 1993 and 2011 were studied. Patients with a basal hypogammaglobulinemia or a monoclonal component were excluded. The incidence of SH was 2.2×1000 person-years (95% CI 1.6-2.9). Exposure to Fludarabine-based schedules (Fbs)±R was associated with a hazard ratio (HR) of 18.1 (95% CI: 4.3-77.0). Conversely, exposure to CHOP±R or CVP±R was not a risk factor (HR 0.3, 95% CI: 0.1-0.8; HR 0.3, 95% CI: 0.08-1.4, respectively). The role of R was studied comparing cohorts differing only for R; no differences were found comparing R-CHOP/R-CVP versus CHOP/CVP (HR 1.07, 95% CI: 0.38-3.05) and R-Fbs versus Fbs (HR 2.07, 95% CI: 0.62-6.99). Autologous stem cell transplantation (ASCT) is also a risk factor (HR: 5.2, 95% CI 2.1-13.0). SH patients presented a high risk for pneumonia development (HR 7.07 95% CI: 2.68-18.44). We recommend monitoring of serum immunoglobulins in an attempt to reduce the probability of infection after Fbs or ASCT.

Keywords: Fludarabine; Hypogammaglobulinemia; Non-Hodgkin lymphoma; Rituximab.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Marrow / pathology
  • Cyclophosphamide / administration & dosage
  • Disease Susceptibility
  • Doxorubicin / administration & dosage
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • IgG Deficiency / chemically induced*
  • IgG Deficiency / epidemiology
  • Immunocompromised Host
  • Immunotherapy / adverse effects
  • Incidence
  • Kaplan-Meier Estimate
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / pathology
  • Lymphoma, Non-Hodgkin / therapy
  • Male
  • Middle Aged
  • Pneumonia / etiology
  • Prednisone / administration & dosage
  • Proportional Hazards Models
  • Retrospective Studies
  • Rituximab / administration & dosage
  • Rituximab / adverse effects*
  • Transplantation, Autologous
  • Vidarabine / administration & dosage
  • Vidarabine / adverse effects
  • Vidarabine / analogs & derivatives*
  • Vincristine / administration & dosage
  • Young Adult

Substances

  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Vidarabine
  • fludarabine
  • Prednisone

Supplementary concepts

  • CHOP protocol
  • COP protocol 2