Treatment with rituximab of chronic lymphocytic leukemia in pregnancy

Lluch García, Rafael; Hernández-Lorente, Eva; Cárcel Corella, Paula

doi:10.1016/j.medcle.2020.01.037

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The clinical course of the disease is extremely heterogeneous. Most patients are asymptomatic, and the disease may be indolent for a long time. Its clinical manifestations are caused by the progressive infiltration of lymphocytes within the bone marrow, lymph nodes, and other tissues, as well as the immunological alterations that may appear.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>Chronic lymphocytic leukemia is the most common hematological malignancy in Western countries. It is rare before the age of 50 (incidence of 5/100,000 inhabitants/year), but its incidence increases with age and is considerable in people over 70 years old, reaching an incidence of 30/100,000 inhabitants/year. The mean age of the patients at diagnosis is 68–70 years, and it is more frequent among men than women (2:1).<a class="elsevierStyleCrossRef" href="#bib0010">2</a>The therapeutic strategies must be personalized whenever the disease requires treatment. Chemoimmunotherapy with fludarabine in combination with cyclophosphamide and rituximab (FCR) is the standard treatment in eligible patients under the age of 65. However, FCR is not as well tolerated by patients over the age of 65, who could benefit from treatment with bendamustine in combination with rituximab (BR), a combination that has yielded response rates similar to those of FCR but with fewer toxicities.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> Ibrutinib is another therapeutic option that is currently used in both age groups and the treatment of choice in cases of a p53 mutation.The diagnosis of a neoplastic disease during the first trimester of pregnancy makes it difficult to make decisions regarding the treatment of this condition. Little information is available on the safety of chemotherapy during pregnancy, although it is advised that such agents not be used during the first trimester because of their possible teratogenic effects.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>We hereby present the case of a 41-year-old pregnant woman, with no remarkable pathological history, who was diagnosed with CLL at 6 weeks of gestation. The blood tests performed revealed hemoglobin (Hb) levels of 10.6g/dl (11.5–16.5g/l), a white blood cell count of 372.9×109L–1 (4.2–11.5×109L–1), a lymphocyte count of 365.4×109L–1 (1–5×109L–1), a platelet count of 117×109L–1 (120–450×109L–1), lactate dehydrogenase (LDH) levels of 499U/L (208–378U/L), a normal blood biochemistry, and a negative direct antiglobulin test. Peripheral blood flow cytometry testing revealed CD5+, CD23+, and FMC− monoclonal B lymphocytes compatible with CLL. The fluorescence in situ hybridization (FISH) test was negative. Splenomegaly of 22cm was detected, without associated hepatomegaly nor lymph nodes. Binet stage B and Rai stage III. Two leukaphereses were performed at 10 and 11 weeks of gestation; however, given that no response was achieved, treatment with rituximab 375mg/m2 was started at week 14. The dose of this treatment was subsequently increased to 500mg/m2 administered every 3 weeks for a total of 6 cycles. The blood test performed after she received the second dose of rituximab revealed normal findings. After the fifth dose, the tests revealed a 15-cm splenomegaly. No treatment-related toxicities were reported.The ultrasounds performed at weeks 8, 11, 13, 16, 20, 22, 26, and 36 of gestation showed an adequately developed fetus. At 38 weeks of gestation, the patient underwent an elective cesarean section without complications. The newborn was a healthy 4.180-kg baby boy with an Apgar score of 9/10. Three months after the delivery, her follow-up blood tests revealed normal findings and the follow-up CT scan showed no signs of hepatosplenomegaly. She has not received any treatment ever since.Rituximab is an anti-CD20 monoclonal antibody indicated for certain hematological disorders and cataloged as a Food and Drug Administration (FDA) category C drug. However, its mechanism of cytotoxic action differs from that of other chemotherapy agents.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>In the case of our patient, rituximab reduced her lymphocyte count and allowed for a prolonged pregnancy. Our data show that the administration of standard doses of rituximab in early pregnancy caused no complications and had no serious effects on the fetus. Although little experience is available regarding its use in pregnant patients, rituximab is a potentially safer alternative to chemotherapy in patients requiring treatment during the first trimester." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Lluch García R., Hernández-Lorente E., Cárcel Corella P. Tratamiento con rituximab de la leucemia linfocítica crónica en el embarazo. Med Clin (Barc). 2021;156:525." ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:4 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Leucemia Linfática Crónica" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F. Bosch" 1 => "P. Abrisqueta" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:5 [ "editores" => "M.A.Sanz, E.Carreras" "titulo" => "Manual Práctico de Hematología Clínica" "paginaInicial" => "297" "paginaFinal" => "304" "serieFecha" => "2015" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guía de consenso nacionales para el estudio y tratamiento de los pacientes con leucemia linfocítica crónica" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.A. García" 1 => "P. Giraldo" 2 => "J. López" 3 => "E. Ríos" 4 => "J.L. Sastre" 5 => "M.J. Terol" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Clin (Barc)" "fecha" => "2013" "volumen" => "141" "paginaInicial" => "175.e1" "paginaFinal" => "175.e8" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "First line therapy in chronic lymphocytic leukemia: a Swedish nation-wide real-world study on 1053 consecutive patients treated between 2007 and 2013" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Eketorp" 1 => "A. Asklid" 2 => "H. Johansson" 3 => "J. Klintman" 4 => "J. Bjellvi" 5 => "S. Tolvgård" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3324/haematol.2018.200204" "Revista" => array:6 [ "tituloSerie" => "Haematologica" "fecha" => "2019" "volumen" => "104" "paginaInicial" => "797" "paginaFinal" => "804" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30467205" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety of rituximab therapy during the first trimester of pregnancy: a case history" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E. Kimby" 1 => "A. Sverrisdottir" 2 => "G. Elinder" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1600-0609.2004.00214.x" "Revista" => array:6 [ "tituloSerie" => "Eur J Haematol" "fecha" => "2004" "volumen" => "72" "paginaInicial" => "292" "paginaFinal" => "295" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15089769" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015600000010/v1_202105151030/S2387020621001960/v1_202105151030/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015600000010/v1_202105151030/S2387020621001960/v1_202105151030/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621001960?idApp=UINPBA00004N"]

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Vol. 156. Issue 10.

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