scholarly journals Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project

Blood ◽  
2009 ◽  
Vol 113 (20) ◽  
pp. 4834-4840 ◽  
Author(s):  
Kenneth R. Carson ◽  
Andrew M. Evens ◽  
Elizabeth A. Richey ◽  
Thomas M. Habermann ◽  
Daniele Focosi ◽  
...  

Rituximab improves outcomes for persons with lymphoproliferative disorders and is increasingly used to treat immune-mediated illnesses. Recent reports describe 2 patients with systemic lupus erythematosus and 1 with rheumatoid arthritis who developed progressive multifocal leukoencephalopathy (PML) after rituximab treatment. We reviewed PML case descriptions among patients treated with rituximab from the Food and Drug Administration, the manufacturer, physicians, and a literature review from 1997 to 2008. Overall, 52 patients with lymphoproliferative disorders, 2 patients with systemic lupus erythematosus, 1 patient with rheumatoid arthritis, 1 patient with an idiopathic autoimmune pancytopenia, and 1 patient with immune thrombocytopenia developed PML after treatment with rituximab and other agents. Other treatments included hematopoietic stem cell transplantation (7 patients), purine analogs (26 patients), or alkylating agents (39 patients). One patient with an autoimmune hemolytic anemia developed PML after treatment with corticosteroids and rituximab, and 1 patient with an autoimmune pancytopenia developed PML after treatment with corticosteroids, azathioprine, and rituximab. Median time from last rituximab dose to PML diagnosis was 5.5 months. Median time to death after PML diagnosis was 2.0 months. The case-fatality rate was 90%. Awareness is needed of the potential for PML among rituximab-treated persons.

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3505-3514 ◽  
Author(s):  
Richard K. Burt ◽  
Ann E. Traynor ◽  
Richard Pope ◽  
James Schroeder ◽  
Bruce Cohen ◽  
...  

Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis are immune-mediated diseases that are responsive to suppression or modulation of the immune system. For patients with severe disease, immunosuppression may be intensified to the point of myelosuppression or hematopoietic ablation. Hematopoiesis and immunity may then be rapidly reconstituted by reinfusion of CD34+progenitor cells. In 10 patients with these autoimmune diseases, autologous hematopoietic stem cells were collected from bone marrow or mobilized from peripheral blood with either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and G-CSF. Stem cells were enriched ex vivo using CD34+ selection and reinfused after either myelosuppressive conditioning with cyclophosphamide (200 mg/kg), methylprednisolone (4 g) and antithymocyte globulin (ATG; 90 mg/kg) or myeloablative conditioning with total body irradiation (1,200 cGy), methylprednisolone (4 g), and cyclophosphamide (120 mg/kg). Six patients with multiple sclerosis, 2 with systemic lupus erythematosus, and 2 with rheumatoid arthritis have undergone hematopoietic stem cell transplantation. Mean time to engraftment of an absolute neutrophil count greater than 500/μL (0.5 × 109/L) and a nontransfused platelet count greater than 20,000/μL (20 × 109/L) occurred on day 10 and 14, respectively. Regimen-related nonhematopoietic toxicity was minimal. All patients improved and/or had stabilization of disease with a follow-up of 5 to 17 months (median, 11 months). We conclude that intense immunosuppressive conditioning and autologous T-cell–depleted hematopoietic transplantation was safely used to treat these 10 patients with severe autoimmune disease. Although durability of response is as yet unknown, all patients have demonstrated stabilization or improvement.


Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3505-3514 ◽  
Author(s):  
Richard K. Burt ◽  
Ann E. Traynor ◽  
Richard Pope ◽  
James Schroeder ◽  
Bruce Cohen ◽  
...  

Abstract Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis are immune-mediated diseases that are responsive to suppression or modulation of the immune system. For patients with severe disease, immunosuppression may be intensified to the point of myelosuppression or hematopoietic ablation. Hematopoiesis and immunity may then be rapidly reconstituted by reinfusion of CD34+progenitor cells. In 10 patients with these autoimmune diseases, autologous hematopoietic stem cells were collected from bone marrow or mobilized from peripheral blood with either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and G-CSF. Stem cells were enriched ex vivo using CD34+ selection and reinfused after either myelosuppressive conditioning with cyclophosphamide (200 mg/kg), methylprednisolone (4 g) and antithymocyte globulin (ATG; 90 mg/kg) or myeloablative conditioning with total body irradiation (1,200 cGy), methylprednisolone (4 g), and cyclophosphamide (120 mg/kg). Six patients with multiple sclerosis, 2 with systemic lupus erythematosus, and 2 with rheumatoid arthritis have undergone hematopoietic stem cell transplantation. Mean time to engraftment of an absolute neutrophil count greater than 500/μL (0.5 × 109/L) and a nontransfused platelet count greater than 20,000/μL (20 × 109/L) occurred on day 10 and 14, respectively. Regimen-related nonhematopoietic toxicity was minimal. All patients improved and/or had stabilization of disease with a follow-up of 5 to 17 months (median, 11 months). We conclude that intense immunosuppressive conditioning and autologous T-cell–depleted hematopoietic transplantation was safely used to treat these 10 patients with severe autoimmune disease. Although durability of response is as yet unknown, all patients have demonstrated stabilization or improvement.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 609.1-609
Author(s):  
J. Sabo ◽  
N. Singh ◽  
D. A. Crane ◽  
D. R. Doody ◽  
M. A. Schiff ◽  
...  

Background:Women with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) have greater risk of adverse obstetric and birth outcomes than women without these conditions. Infant outcomes are less well-studied. It is unknown whether re-hospitalization after delivery occurs more often for affected mothers and their infants.Objectives:We compared obstetric outcomes among women with and without RA or SLE, and birth outcomes among their infants. Maternal and infant rehospitalizations <2 years of delivery were also compared.Methods:This population-based cohort study used linked birth-hospital discharge data from Washington State for 1987-2014. International Classification of Disease 9th revision (ICD9) codes identified all women with RA (ICD9 714.X, 725.X) and SLE (ICD9 710, 710.0, 710.1) in the hospital discharge record at delivery, and a 10:1 comparison group of women without these codes. Analyses were restricted to singleton live births (1,223 RA; 1,354 SLE). Poisson regression with robust standard errors estimated relative risks (RR) and 95% confidence intervals (CI) for selected outcomes, accounting for delivery year, maternal age, and parity.Results:Many adverse outcomes were more common among RA and SLE cases than among comparison women. Preeclampsia occurred more often during pregnancies of women with RA (RR 1.42, 95% CI 1.17-1.71) or SLE (RR 2.33, 95% CI 2.01-2.70), as did preterm rupture of membranes (PROM, RR 2.85, 95% CI 2.20-3.72 for RA; RR 3.28, 95% CI 2.54-4.23 for SLE). Cesarean deliveries were more common among nulliparous women in both groups (RR 1.32, 95% CI 1.18-1.48 for both conditions). Infants of women with RA or SLE were more likely to weigh <2500 g (RR 2.08, 95% CI 1.72-2.52 for RA; RR 4.88, 95% CI 4.27-5.58 for SLE), be small for gestational age (RR 1.25, 95% CI 1.07-2.50; RR 2.30; 2.04-2.59, respectively), delivered at <32 weeks gestation (RR 1.83, 95% CI 1.13-2.97; RR 5.13, 95% CI 3.75-7.01, respectively), and require neonatal intensive care unit admission (NICU, RR 1.89, 95% CI 1.56-2.30; RR 2.71, 95% CI 2.25-3.28, respectively). Infants of women with SLE were more likely to have a malformation (RR 1.46, 95% CI 1.21-1.75) or die within 2 years (RR 2.11, 95% CI 1.21-3.67). Rehospitalization levels among both women with RA (RR 2.22; 1.62-3.04) and SLE (RR 2.78, 95% CI 2.15-3.59) were greatest <6 months of delivery and declined over time. Infants of women with SLE had increased rehospitalization <6 months (RR 1.64, 95% CI 1.36-1.98).Conclusion:Consistent with prior literature, we found women with RA or SLE experienced many adverse outcomes. In our data, these included preeclampsia, PROM, and cesarean deliveries, with increased risks more notable among women with SLE. Infants of women with either condition were more likely to weigh <2500g, be <32 weeks gestation, small for gestational age, and require NICU admission than infants of comparison women. Only infants of women with SLE had increased malformations. Maternal rehospitalization after delivery was more common in both groups; most marked at <6 months. Infant rehospitalizations were increased in both cohorts to a lesser extent. Close follow-up during this time period is crucial to minimize adverse outcomes.Disclosure of Interests:Julianna Sabo: None declared, Namrata Singh: None declared, Deborah A. Crane: None declared, David R. Doody: None declared, Melissa A. Schiff: None declared, Beth A. Mueller Shareholder of: Household owns shares in AstraZeneca


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