title: Rituximab administration within 6 months of T cell-depleted allogeneic SCT is associated with prolonged life-threatening cytopenias.
abstract: The monoclonal anti-CD20 antibody Rituximab (RTX) is increasingly used in allogeneic stem cell transplantation (SCT) to treat lymphoproliferative disorders and chronic graft-versus-host disease (GVHD). RTX administration can be complicated by delayed and prolonged neutropenia, but the mechanism is unclear. We report the occurrence of profound cytopenias following RTX given in the conditioning regimen or early after T cell-deplete SCT to treat B cell lymphoproliferative disorders or chronic GVHD (cGVHD). Between 2006 and 2009, 102 patients (median age: 43 years, range: 13-68 years), received a myeloablative matched-sibling T cell-deplete SCT for lymphoid or myeloid hematologic disorders. Neutropenia occurring within 4 weeks of treatment developed in 16 of 17 patients given RTX within the first 190 days after SCT. Fourteen patients developed severe neutropenia (count <0.5 K/μL) lasting up to 10 months and 12 required hospitalization to treat severe neutropenic infections. Six of the 14 patients died of infection complicating GVHD treatment. Recovery of lymphocytes and immunoglobulins was also delayed, with a significantly lower absolute lymphocyte counts (ALC) at 9 months and 12 months post-SCT compared to patients with cGVHD not treated with early RTX (P < .02). In contrast, patients receiving RTX 1 year after SCT experienced only moderate neutropenia 3 to 5 months after treatment lasting 10 to 20 days while maintaining absolute neutrophil count (ANC) >1.0 × 10⁹/L. Although RTX rapidly controlled cGVHD, we conclude that its administration early after T cell-deplete SCT is associated with prolonged profound and life-threatening cytopenias, and should be avoided.
authors.affiliation: Stem Cell Allotransplantation Section, Hematology Branch, Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. mciverza@nhibi.nih.gov
authors.forename: Zachariah
authors.initials: Z
authors.lastname: McIver
authors.forename: Nicole
authors.initials: N
authors.lastname: Stephens
authors.forename: Andrew
authors.initials: A
authors.lastname: Grim
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001772:Blood Cell Count; D004906:Erythrocyte Count; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008212:Lymphocyte Depletion; D008214:Lymphocytes / Q000473:pathology; D008231:Lymphopenia / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D010976:Platelet Count; D016016:Proportional Hazards Models; D012307:Risk Factors; D000069283:Rituximab; D033581:Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D013601:T-Lymphocytes / Q000166:cytology*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069283:Rituximab