Skip to main content
Top
Published in: Pediatric Nephrology 6/2018

01-06-2018 | Original Article

Infusion reactions associated with rituximab treatment for childhood-onset complicated nephrotic syndrome

Authors: Koichi Kamei, Masao Ogura, Mai Sato, Shuichi Ito, Kenji Ishikura

Published in: Pediatric Nephrology | Issue 6/2018

Login to get access

Abstract

Background

Infusion reaction (IR) is defined as an adverse event within 24 h after monoclonal antibody infusion. In non-Hodgkin lymphoma, IR incidence following rituximab treatment is high (77–80%), but there are no data in complicated nephrotic syndrome.

Methods

Records of rituximab infusions in patients with complicated nephrotic syndrome between February 2006 and December 2014 at the National Center for Child Health and Development were reviewed. Rituximab was administered at doses of 375 mg/m2. The severity of IR was evaluated using the Common Terminology Criteria for Adverse Events ver. 4.0.

Results

For 309 rituximab infusions in 159 patients (male, 110; median age, 12 years), IR was observed in 165 infusions (53.4%). Respiratory symptoms were most common (66% of all events). Ninety-five percent of the IR was observed within 3 h after rituximab infusion initiation. Sixty-eight percent of the events were classified as grade 1 and others classified as grade 2. Only 18% required medical intervention. CD20 cell count in patients with IR was significantly higher than in patients without IR. Incidence of IR was similar in subsequent rituximab treatment after B-cell recovery. Patients who experienced IR at first rituximab treatment were more likely to experience recurrent IR with subsequent treatments compared to those not having IR at initial treatment (odds ratio 3.64; p < 0.001).

Conclusions

In patients with complicated nephrotic syndrome, respiratory symptoms were the major type of IR, mostly observed within 3 h of infusion. Incidence of IR was lower and its severity milder in patients with complicated nephrotic syndrome than those with lymphoma.
Literature
1.
go back to reference Vogel WH (2010) Infusion reactions: diagnosis, assessment, and management. Clin J Oncol Nurs 14:E10–E21CrossRefPubMed Vogel WH (2010) Infusion reactions: diagnosis, assessment, and management. Clin J Oncol Nurs 14:E10–E21CrossRefPubMed
2.
go back to reference Winkler U, Jensen M, Manzke O, Schulz H, Diehl V, Engert A (1999) Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 94:2217–2224PubMed Winkler U, Jensen M, Manzke O, Schulz H, Diehl V, Engert A (1999) Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 94:2217–2224PubMed
3.
go back to reference Bienvenu J, Chvetzoff R, Salles G, Balter C, Tilly H, Herbrecht R, Morel P, Lederlin P, Solal-Celigny P, Audhuy B, Christian B, Gabarre J, Casasnovas O, Marit G, Sebban C, Coiffier B, Groupe d’Etude des Lymphomes de l’Adulte (2001) Tumor necrosis factor alpha release is a major biological event associated with rituximab treatment. Hematol J 2:378–384CrossRefPubMed Bienvenu J, Chvetzoff R, Salles G, Balter C, Tilly H, Herbrecht R, Morel P, Lederlin P, Solal-Celigny P, Audhuy B, Christian B, Gabarre J, Casasnovas O, Marit G, Sebban C, Coiffier B, Groupe d’Etude des Lymphomes de l’Adulte (2001) Tumor necrosis factor alpha release is a major biological event associated with rituximab treatment. Hematol J 2:378–384CrossRefPubMed
4.
go back to reference Byrd JC, Murphy T, Howard RS, Lucas MS, Goodrich A, Park K, Pearson M, Waselenko JK, Ling G, Grever MR, Grillo-Lopez AJ, Rosenberg J, Kunkel L, Flinn IW (2001) Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity. J Clin Oncol 19:2153–2164CrossRefPubMed Byrd JC, Murphy T, Howard RS, Lucas MS, Goodrich A, Park K, Pearson M, Waselenko JK, Ling G, Grever MR, Grillo-Lopez AJ, Rosenberg J, Kunkel L, Flinn IW (2001) Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity. J Clin Oncol 19:2153–2164CrossRefPubMed
5.
go back to reference Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, Levy R (1994) Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood 84:2457–2466PubMed Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, Levy R (1994) Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood 84:2457–2466PubMed
6.
go back to reference Maloney DG, Grillo-López AJ, Bodkin DJ, White CA, Liles TM, Royston I, Varns C, Rosenberg J, Levy R (1997) IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin’s lymphoma. J Clin Oncol 15:3266–3274CrossRefPubMed Maloney DG, Grillo-López AJ, Bodkin DJ, White CA, Liles TM, Royston I, Varns C, Rosenberg J, Levy R (1997) IDEC-C2B8: results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin’s lymphoma. J Clin Oncol 15:3266–3274CrossRefPubMed
7.
go back to reference Maloney DG, Grillo-López AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, Janakiraman N, Foon KA, Liles TM, Dallaire BK, Wey K, Royston I, Davis T, Levy R (1997) IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood 90:2188–2195PubMed Maloney DG, Grillo-López AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, Janakiraman N, Foon KA, Liles TM, Dallaire BK, Wey K, Royston I, Davis T, Levy R (1997) IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood 90:2188–2195PubMed
8.
go back to reference McLaughlin P, Grillo-López AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK (1998) Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 16:2825–2833CrossRefPubMed McLaughlin P, Grillo-López AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK (1998) Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 16:2825–2833CrossRefPubMed
9.
go back to reference Davis TA, White CA, Grillo-López AJ, Velásquez WS, Link B, Maloney DG, Dillman RO, Williams ME, Mohrbacher A, Weaver R, Dowden S, Levy R (1999) Single-agent monoclonal antibody efficacy in bulky non-Hodgkin’s lymphoma: results of a phase II trial of rituximab. J Clin Oncol 17:1851–1857CrossRefPubMed Davis TA, White CA, Grillo-López AJ, Velásquez WS, Link B, Maloney DG, Dillman RO, Williams ME, Mohrbacher A, Weaver R, Dowden S, Levy R (1999) Single-agent monoclonal antibody efficacy in bulky non-Hodgkin’s lymphoma: results of a phase II trial of rituximab. J Clin Oncol 17:1851–1857CrossRefPubMed
10.
go back to reference Piro LD, White CA, Grillo-López AJ, Janakiraman N, Saven A, Beck TM, Varns C, Shuey S, Czuczman M, Lynch JW, Kolitz JE, Jain V (1999) Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. Ann Oncol 10:655–661CrossRefPubMed Piro LD, White CA, Grillo-López AJ, Janakiraman N, Saven A, Beck TM, Varns C, Shuey S, Czuczman M, Lynch JW, Kolitz JE, Jain V (1999) Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. Ann Oncol 10:655–661CrossRefPubMed
11.
go back to reference Davis TA, Grillo-López AJ, White CA, McLaughlin P, Czuczman MS, Link BK, Maloney DG, Weaver RL, Rosenberg J, Levy R (2000) Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin’s lymphoma: safety and efficacy of re-treatment. J Clin Oncol 18:3135–3143CrossRefPubMed Davis TA, Grillo-López AJ, White CA, McLaughlin P, Czuczman MS, Link BK, Maloney DG, Weaver RL, Rosenberg J, Levy R (2000) Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin’s lymphoma: safety and efficacy of re-treatment. J Clin Oncol 18:3135–3143CrossRefPubMed
12.
go back to reference Lenz HJ (2007) Management and preparedness for infusion and hypersensitivity reactions. Oncologist 12:601–609CrossRefPubMed Lenz HJ (2007) Management and preparedness for infusion and hypersensitivity reactions. Oncologist 12:601–609CrossRefPubMed
13.
go back to reference Schwartzberg LS, Stepanski EJ, Fortner BV, Houts AC (2008) Retrospective chart review of severe infusion reactions with rituximab, cetuximab, and bevacizumab in community oncology practices: assessment of clinical consequences. Support Care Cancer 16:393–398CrossRefPubMed Schwartzberg LS, Stepanski EJ, Fortner BV, Houts AC (2008) Retrospective chart review of severe infusion reactions with rituximab, cetuximab, and bevacizumab in community oncology practices: assessment of clinical consequences. Support Care Cancer 16:393–398CrossRefPubMed
14.
go back to reference Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242CrossRefPubMed Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242CrossRefPubMed
15.
go back to reference Kunkel L, Wong A, Maneatis T, Nickas J, Brown T, Grillo-López A, Benyunes M, Grobman B, Dillman RO (2000) Optimizing the use of rituximab for treatment of B-cell non-Hodgkin's lymphoma: a benefit-risk update. Semin Oncol 27(6 Suppl 12):53–61PubMed Kunkel L, Wong A, Maneatis T, Nickas J, Brown T, Grillo-López A, Benyunes M, Grobman B, Dillman RO (2000) Optimizing the use of rituximab for treatment of B-cell non-Hodgkin's lymphoma: a benefit-risk update. Semin Oncol 27(6 Suppl 12):53–61PubMed
16.
go back to reference Chung CH (2008) Managing premedications and the risk for reactions to infusional monoclonal antibody therapy. Oncologist 13:725–732CrossRefPubMed Chung CH (2008) Managing premedications and the risk for reactions to infusional monoclonal antibody therapy. Oncologist 13:725–732CrossRefPubMed
17.
go back to reference Ishikura K, Matsumoto S, Sako M, Tsuruga K, Nakanishi K, Kamei K, Saito H, Fujinaga S, Hamasaki Y, Chikamoto H, Ohtsuka Y, Komatsu Y, Ohta T, Nagai T, Kaito H, Kondo S, Ikezumi Y, Tanaka S, Kaku Y, Iijima K, Japanese Society for Pediatric Nephrology (2015) Clinical practice guideline for pediatric idiopathic nephrotic syndrome 2013: medical therapy. Clin Exp Nephrol 19:6–33CrossRefPubMed Ishikura K, Matsumoto S, Sako M, Tsuruga K, Nakanishi K, Kamei K, Saito H, Fujinaga S, Hamasaki Y, Chikamoto H, Ohtsuka Y, Komatsu Y, Ohta T, Nagai T, Kaito H, Kondo S, Ikezumi Y, Tanaka S, Kaku Y, Iijima K, Japanese Society for Pediatric Nephrology (2015) Clinical practice guideline for pediatric idiopathic nephrotic syndrome 2013: medical therapy. Clin Exp Nephrol 19:6–33CrossRefPubMed
18.
go back to reference Iijima K, Sako M, Nozu K, Mori R, Tuchida N, Kamei K, Miura K, Aya K, Nakanishi K, Ohtomo Y, Takahashi S, Tanaka R, Kaito H, Nakamura H, Ishikura K, Ito S, Ohashi Y, Rituximab for Childhood-onset Refractory Nephrotic Syndrome (RCRNS) Study Group (2014) Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 384:1273–1281CrossRefPubMed Iijima K, Sako M, Nozu K, Mori R, Tuchida N, Kamei K, Miura K, Aya K, Nakanishi K, Ohtomo Y, Takahashi S, Tanaka R, Kaito H, Nakamura H, Ishikura K, Ito S, Ohashi Y, Rituximab for Childhood-onset Refractory Nephrotic Syndrome (RCRNS) Study Group (2014) Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 384:1273–1281CrossRefPubMed
19.
go back to reference Legeay C, Bittencourt H, Haddad E, Spiesser-Robelet L, Thépot-Seegers V, Therrien R (2017) A retrospective study on infusion-related reactions to rituximab in a heterogeneous pediatric population. J Pediatr Pharmacol Ther 22:369–374PubMedPubMedCentral Legeay C, Bittencourt H, Haddad E, Spiesser-Robelet L, Thépot-Seegers V, Therrien R (2017) A retrospective study on infusion-related reactions to rituximab in a heterogeneous pediatric population. J Pediatr Pharmacol Ther 22:369–374PubMedPubMedCentral
20.
go back to reference Henriquez KM, Hayney MS, Xie Y, Zhang Z, Barrett B (2015) Association of interleukin-8 and neutrophils with nasal symptom severity during acute respiratory infection. J Med Virol 87:330–337CrossRefPubMed Henriquez KM, Hayney MS, Xie Y, Zhang Z, Barrett B (2015) Association of interleukin-8 and neutrophils with nasal symptom severity during acute respiratory infection. J Med Virol 87:330–337CrossRefPubMed
21.
go back to reference Pitrez PM, Brennan S, Sly PD (2005) Inflammatory profile in nasal secretions of infants hospitalized with acute lower airway tract infections. Respirology 10:365–370CrossRefPubMed Pitrez PM, Brennan S, Sly PD (2005) Inflammatory profile in nasal secretions of infants hospitalized with acute lower airway tract infections. Respirology 10:365–370CrossRefPubMed
22.
go back to reference Kamei K, Takahashi M, Fuyama M, Saida K, Machida H, Sato M, Ogura M, Ito S (2015) Rituximab-associated agranulocytosis in children with refractory idiopathic nephrotic syndrome: case series and review of literature. Nephrol Dial Transplant 30:91–96CrossRefPubMed Kamei K, Takahashi M, Fuyama M, Saida K, Machida H, Sato M, Ogura M, Ito S (2015) Rituximab-associated agranulocytosis in children with refractory idiopathic nephrotic syndrome: case series and review of literature. Nephrol Dial Transplant 30:91–96CrossRefPubMed
23.
go back to reference Sato M, Ito S, Ogura M, Kamei K, Miyairi I, Miyata I, Higuchi M, Matsuoka K (2013) Atypical Pneumocystis jiroveci pneumonia with multiple nodular granulomas after rituximab for refractory nephrotic syndrome. Pediatr Nephrol 28:145–149CrossRefPubMed Sato M, Ito S, Ogura M, Kamei K, Miyairi I, Miyata I, Higuchi M, Matsuoka K (2013) Atypical Pneumocystis jiroveci pneumonia with multiple nodular granulomas after rituximab for refractory nephrotic syndrome. Pediatr Nephrol 28:145–149CrossRefPubMed
24.
go back to reference Chaumais MC, Garnier A, Chalard F, Peuchmaur M, Dauger S, Jacqz-Agrain E, Deschênes G (2009) Fatal pulmonary fibrosis after rituximab administration. Pediatr Nephrol 24:1753–1755CrossRefPubMed Chaumais MC, Garnier A, Chalard F, Peuchmaur M, Dauger S, Jacqz-Agrain E, Deschênes G (2009) Fatal pulmonary fibrosis after rituximab administration. Pediatr Nephrol 24:1753–1755CrossRefPubMed
25.
go back to reference Keir GJ, Maher TM, Ming D, Abdullah R, de Lauretis A, Wickremasinghe M, Nicholson AG, Hansell DM, Wells AU, Renzoni EA (2014) Rituximab in severe, treatment-refractory interstitial lung disease. Respirology 19:353–359CrossRefPubMed Keir GJ, Maher TM, Ming D, Abdullah R, de Lauretis A, Wickremasinghe M, Nicholson AG, Hansell DM, Wells AU, Renzoni EA (2014) Rituximab in severe, treatment-refractory interstitial lung disease. Respirology 19:353–359CrossRefPubMed
26.
go back to reference Sano Y, Nakano Y, Omoto M, Takao M, Ikeda E, Oga A, Nakamichi K, Saijo M, Maoka T, Sano H, Kawai M, Kanda T (2015) Rituximab-associated progressive multifocal leukoencephalopathy derived from non-Hodgkin lymphoma: neuropathological findings and results of mefloquine treatment. Intern Med 54:965–970CrossRefPubMed Sano Y, Nakano Y, Omoto M, Takao M, Ikeda E, Oga A, Nakamichi K, Saijo M, Maoka T, Sano H, Kawai M, Kanda T (2015) Rituximab-associated progressive multifocal leukoencephalopathy derived from non-Hodgkin lymphoma: neuropathological findings and results of mefloquine treatment. Intern Med 54:965–970CrossRefPubMed
27.
go back to reference Sokol J, Lisá L, Zeleňáková J, Balhárek T, Plameňová I, Staško J, Kubisz P (2017) Rituximab-associated progressive multifocal leukoencephalopathy. Vnitr Lek 63:60–64PubMed Sokol J, Lisá L, Zeleňáková J, Balhárek T, Plameňová I, Staško J, Kubisz P (2017) Rituximab-associated progressive multifocal leukoencephalopathy. Vnitr Lek 63:60–64PubMed
Metadata
Title
Infusion reactions associated with rituximab treatment for childhood-onset complicated nephrotic syndrome
Authors
Koichi Kamei
Masao Ogura
Mai Sato
Shuichi Ito
Kenji Ishikura
Publication date
01-06-2018
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 6/2018
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-018-3900-z

Other articles of this Issue 6/2018

Pediatric Nephrology 6/2018 Go to the issue