Rituximab during Pregnancy: Serum Levels, B Cell Counts and Immunoglobulin Levels in Mother and Child.
Authors: Friedrichs Birte , Tiemann Markus , Wenger Michael K. , Verpoort Karl , Schmitz Norbert 
Published: April 2020

Abstract
Recently the first cases of lymphoma patients treated with rituximab and combination chemotherapy during pregnancy were reported. We report on a patient with Burkitt’s lymphoma who was treated with rituximab and CHOP therapy early during pregnancy. We were able to monitor rituximab concentrations, B-/T- cell counts and immunoglobulin levels. After delivery these parameters were also measured in the newborn child.
A 35-year-old female was diagnosed with CD20+ Burkitt’s lymphoma of the left breast in week 15 of pregnancy. The minimum stage was IIEA; however, the patient also had hepatosplenomegaly. We started treatment with four weekly infusions of rituximab (375mg/m2)(week 16,17,18,19). Treatment was well tolerated with minimal side effects; a minor response was documented by MRI of the breast and ultrasound of previously enlarged axillary lymph nodes. At that time, a decision was made to continue treatment with 6 courses of Cyclophosphamid, Doxorubicin, Vincristin and Prednison (CHOP) at 3 week intervals (week 21, 24, 27, 30, 33, 36). The first 4 courses were preceded by rituximab (375mg/m2). Immunotherapy was tolerated without significant problems. At the end of therapy (week 37) a complete remission was achieved, again documented by MRI and ultrasound. During therapy the child’s growth and intrauterine development were closely monitored by the attending gynecologist. No deviation from normal development were registered.
In week 41 of pregnancy the patient delivered a healthy girl (3780g, 55cm, APGAR score 9/10/10) via caesarean section. The girl is now 19 month old, has repeatedly been seen by her pediatrician who reported completely normal growth and developmental status. The mother received high-dose therapy (BEAM) followed by autologous peripheral blood stem cell transplantion 2 months after delivery and has remained in CR with a normal performance status. As the mother has been extremely compliant we were able to repeatedly measure B cell counts, immunoglobulin levels and rituximab concentrations not only in the patient but also in the baby (table 1).
Interestingly, at the time of birth very high serum levels of rituximab were measured in the child. Nonetheless a normal B cell recovery was seen during the following weeks, immunological status reached normal values 4 month after delivery and no overt infectious complications have been reported. As to our knowledge, for the first time data of rituximab serum concentrations are available from mother and child. To conclude, in this case combination of immuno- and chemotherapy could be safely administered, achieving a CR in the patient without causing any mental or developmental retardation in the newborn child. In accordance with other reports, this case supports the safety and efficacy of Rituximab administration during pregnancy.
Table 1: B/T cell counts and Rituximab concentrations in mother and child during and after treatment with R-CHOP Time Mother Child *values within normal range week of pregnancy/ B-cells T-cells Rituximab B-cells T-cells Rituximab week after delivery CD 19+ CD 3+ CD 19+ CD 3+ cells/μl cells/μl ng/mL cells/μl cells/μl ng/mL 20 0 946 27 0 640 34 4 337 at birth 0 779 9750 0 93 32095 +4 0 759 70 6616* 5399 +18 37 504 &lt;500 1460* 5475* 700