title: Risk of secondary hypogammaglobulinaemia after Rituximab and Fludarabine in indolent non-Hodgkin lymphomas: A retrospective cohort study.
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.
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Italy. Electronic address: federico-de-angelis@teletu.it.
authors.forename: Federico
authors.initials: F
authors.lastname: De Angelis
authors.affiliation: National Center for Epidemiology, Surveillance and Health Promotion, Italian National Institute of Health (ISS), Rome, Italy.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Tosti
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Italy.
authors.forename: Saveria
authors.initials: S
authors.lastname: Capria
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Russo
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Italy.
authors.forename: Gianna Maria
authors.initials: GM
authors.lastname: D'Elia
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Annechini
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Stefanizzi
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Italy.
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.affiliation: Hematology, Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pulsoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004198:Disease Susceptibility; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D017099:IgG Deficiency / Q000139:chemically induced* / Q000453:epidemiology; D016867:Immunocompromised Host; D007167:Immunotherapy / Q000009:adverse effects; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000209:etiology; D011241:Prednisone / Q000008:administration & dosage; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000069283:Rituximab / Q000008:administration & dosage / Q000009:adverse effects*; D014182:Transplantation, Autologous; D014740:Vidarabine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine; D011241:Prednisone
keywords: Fludarabine; Hypogammaglobulinemia; Non-Hodgkin lymphoma; Rituximab