Age: 71.0
Sex: M
Vaccine: COVID19
Symptoms: Body temperature, Computerised tomogram abdomen, Computerised tomogram pelvis, Computerised tomogram thorax, Culture urine
Clinical narrative: Rituximab-induced lympholysis and pancytopenia; This literature-non-study case was reported in a literature article and describes the occurrence of PANCYTOPENIA (Rituximab-induced lympholysis and pancytopenia) in a 71-year-old male patient who received mRNA-1273 (Moderna COVID-19 Vaccine) for COVID-19 prophylaxis.       Previously administered products included for Drug use for unknown indication: rituximab (Weekly 375 mg/m2 intravenous  (IV) rituximab for a total of four doses started on August 4, 2014, resulted in excellent responses. Maintenance rituximab weekly ×4 every 6 months was given for 2 years until June 29, 2016 and without any complications.) from 04-Aug-2014 to 29-Jun-2016. Past adverse reactions to the above products included No adverse event with rituximab. Concurrent medical conditions included Anemia (He had been asymptomatic and under observation until he had worsening anemia and thrombocytopenia.) since June 2014, Thrombocytopenia (He had been asymptomatic and under observation until he had worsening anemia and thrombocytopenia.) since June 2014 and Waldenstrom's macroglobulinemia.   On 29-Jan-2021, the patient received first dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) 1 dosage form. On 26-Feb-2021, received second dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) dosage was changed to 1 dosage form. In 2021, the patient experienced PANCYTOPENIA (Rituximab-induced lympholysis and pancytopenia) (seriousness criterion hospitalization). The patient was treated with RITUXIMAB (intravenous) on 08-Mar-2021 at a dose of 375 milligram/sq. meter; VANCOMYCIN for Penicillin allergy, at an unspecified dose and frequency; AZTREONAM for Penicillin allergy, at an unspecified dose and frequency and LEVOFLOXACIN for Pseudomonas infection NOS, at an unspecified dose and frequency. At the time of the report, PANCYTOPENIA (Rituximab-induced lympholysis and pancytopenia) was resolving. Related    DIAGNOSTIC RESULTS (normal ranges are provided in parenthesis if available): On 23-Mar-2011, Biopsy bone marrow: Waldenstrom's macroglob-ulinemia (WM). On 10-Feb-2021, Positron emission tomogram: showed diffuse lymphadenopathy. On 08-Mar-2021, SARS-CoV-2 test: (Negative) Negative. On 10-Mar-2021, SARS-CoV-2 test: (Negative) Negative. On 29-Mar-2021, Flow cytometry: Peripheral blood flow cytometry: % of absolute lymphocyte counts showed on Day 22 T cell was 90.1%, CD4:CD8 ratio was 2.3, NK cell was 8.4%, B cell and Plasma cell was 0%.  Day 22 since rituximab infusion, and 28-April-2021 (Day 53 since rituximab infusion, Showed that B cells were virtually absent and there was no diagnostic immunophenotypic abnormalities detected.. On 29-Mar-2021, Lymphocyte count (0.96-4.84): On day 22, 1.80x103 /µl. On 28-Apr-2021, Flow cytometry: Peripheral blood flow cytometry: % of absolute lymphocyte counts showed on Day 53 T cell was 85.0%, CD4:CD8 ratio was 1.9, NK cell was 12.2%, B cell and Plasma cell was 0%. On 28-Apr-2021, Lymphocyte count (0.96-4.84): On day 53, 1.97x103 /µl. On an unknown date, Biopsy bone marrow: Repeat BMB showed more than 80 % (>80) involvement the bone marrow by Waldenstrom's macroglob-ulinemia (WM). and BMB again confirmed recurrent Waldenstrom's macroglob-ulinemia (WM) with approximately 75% involvement of bone marrow.. On an unknown date, Blood culture: (Negative) Negative. On an unknown date, Blood pressure measurement: 97/55 mmHg Patient was immediately brought to our emergency  room where he was found mildly hypotensive. On an unknown date, Blood smear test: Peripheral blood smear showed pancytopenia with marked leukopenia secondary to moderate neutropenia and marked lymphocytopenia. On an unknown date, Blood test (82-185 mg/dl): 81 mg/dl On day 3 and 9 mg/dl On day 3. On an unknown date, Body temperature: 39.9 degree Celsius. On an unknown date, Computerised tomogram abdomen: Not revealed any possible source of infection. On an unknown date, Computerised tomogram pelvis: Not revealed any possible source of infection. On an unknown date, Computerised tomogram thorax: Not revealed any possible source of infection. On an unknown date, Culture urine: (Negative) Negative. On an unknown date, Flow cytometry: Peripheral blood flow cytometry: % of absolute lymphocyte counts showed on Day 3 T cell was 98.7 %, CD4:CD8 ratio was 6.1, NK cell was0.9%, B cell and Plasma cell was 0%. On an unknown date, Haemoglobin (14.0-17.0 gram per decilitre): 11.5 gram per decilitre Compared to the laboratory results Before the rituximab infusion, his hemoglobin decreased from 11.5 to 9.3 g/dl., 9.3 gram per decilitre On day 1, 8.2 gram per decilitre On day 2, 8.3 gram per decilitre On day 3, 8 gram per decilitre On day 4, 9.9 gram per decilitre On day 8, 10.4 gram per decilitre On day 22 and 12.7 gram per decilitre On day 53. On an unknown date, Heart rate: Maximum heart rate 95 beats/min and not febrile anymore.. On an unknown date, Hepatitis B: (Negative) Negative. On an unknown date, Influenza A virus test: (Negative) Negative. On an unknown date, Influenza B virus test: (Negative) Negative. On an unknown date, Interleukin level: 18.93 pg/ml On day 3 Reference range =5.00. On an unknown date, Interleukin-2 receptor assay (532-1891 pg/ml): 21,822 pg/ml On day 3. On an unknown date, Lymphocyte count (0.96-4.84): 1.93 Compared to the laboratory results Before the rituximab infusion,  absolute lymphocyte counts decreased from 1.93 × 103 /µl to 0.15 × 103 / µl, On day 1, 0.15x103 /µl, On day 2, 0.58x103 /µl, On day 3, 0.57x103 /µl, On day 4, 0.52x103 /µl and On day 8, 1.86x103 /µl. On an unknown date, Natural killer cell count: 0.9 % On day 3, 8.4 % On day 22 and 12.2 % On day 53. On an unknown date, Neutrophil count (1.44-7.26): Compared to the laboratory results Before the rituximab infusion,  absolute neutrophil counts decreased from 2.36×103 /µl to 0.85×103 /µl, On day 1, 0.85x103 /µl, On day 2, 1.21x103 /µl, On day 3, 1.09x103 /µl, On day 4, 1.52x103 /µl, On day 8, 1.46x103 /µl, On day 22, 1.53x103 /µl and On day 53, 2.55x103 /µl. On an unknown date, Platelet count (150-400): Compared to the laboratory results Before the rituximab infusion, platelet counts decreased from 84×103 /µl to 26×103 /µl, On day 1, 26x103 /µl, On day 2, 28x103 /µl, On day 3, 30x103 /µl, On day 4, 33x103 /µl, On day 8, 59x103 /µl, On day 22, 76x103 /µl and On day 53, 178x103 /µl. On an unknown date, Respiratory pathogen panel: (Negative) Mycoplasma pneumoniae, Legionella pneumophila, and Streptococcus pneumoniae all were negative.. On an unknown date, Respiratory syncytial virus test: (Negative) Negative. On an unknown date, Vital signs measurement: Stable. On an unknown date, White blood cell count (4.0-11.0): Compared to the laboratory results Before the rituximab infusion,  white blood cells decreased from 4.7×103/µl to 1.0×103/µl, On day one, 1x103 /µl, On day 2, 1.8x103 /µl, On day 3, 1.7x103 /µl, On day 4, 2x103 /µl, On day 8, 3.5 x103 /µl, On day 22, 3.8 x103 /µl and On day 53, 5.2x103 /µl.     For mRNA-1273 (Moderna COVID-19 Vaccine) (Unknown), the reporter considered PANCYTOPENIA (Rituximab-induced lympholysis and pancytopenia) to be related.    No concomitant medication was reported.  Patient was found to have worsening anemia and thrombocytopenia on 29-Jan-2021.The treatment plan was reinitiated rituximab weekly 4 doses followed by maintenance rituximab every 6 months or every year. Scheduled prior to the confirmation of the WM relapse, he received his first dose and second dose of moderna vaccine. He was presented to infusion center for the first dose of rituximab on 08-Mar-2021. Approximately 70 min into infusion, he reported feeling cold and was shivering. Rituximab infusion was paused, and normal saline was started. He stopped shivering and reported symptomatic improvement within 5 min. Approximately 10 min later, rituximab was restarted at previously tolerated rate of 200 mg/h and then increased by 50 mg/h every 30 min. He had no other symptoms for the remainder of infusion and tolerated well up to the maximal rate of 400 mg/h. Patient's family reported that after returning home, he developed a fever, chills, disorientation, confusion, and nausea without emesis. He did not have headache, vision changes, rash, tinnitus, dyspnea, cough, chest pain, abdominal pain, or diarrhea. He denied previous reactions of this nature when receiving rituximab infusions in the past. Neutropenic fever protocol was initiated in the emergency room and the patient was started on antibiotics. Later, antibiotics were discontinued, and patient was discharged 3 days later. Flow cytometry of peripheral blood during the hospitalization confirmed that among the lymphocytes (23.1% of total cell counts), 98.7% were CD3+/CD5+ T cells with CD4:CD8 ratio of 6.1, 0.9% were natural killer (NK) cells while there were no CD19+/CD20+ B cells or CD38 plasma cells (0%) on day 3. Despite the history of WM, there was no evidence of clonality since the B cells were virtually absent. His blood cell counts were gradually recovered. He was currently under surveillance with monthly peripheral blood flow cytometry.  This is a literature non-study case concerning a 71-year-old male patient with medical history of Waldenstrom's macroglobulinemia, who was hospitalized due to the unexpected, serious event of Pancytopenia, after receiving the second dose of mRNA-1273 vaccine. 10 days after receiving the second dose of mRNA-1273, the patient had rituximab infusion for Waldenstrom's macroglobulinemia which later developed fever, chills, disorientation, confusion and nausea. The patient was brought to a hospital where he was mildly hypotensive. Blood counts were decreased and peripheral blood smear showed pancytopenia with marked leukopenia secondary to moderate neutropenia and marked lymphocytopenia. Neutropenic fever protocol was initiated and the patient was started on vancomycin, aztreonam and levofloxacin. Extensive infectious workups and imaging studies were unremarkable, therefore antibiotics were discontinued. Flow cytometry of peripheral blood showed no CD19+/CD20+ B cells or CD38 plasma cells. The patient was discharged 3 days later. Patient's blood cell counts gradually recovered however repeat flow cytometry (approximately 1 and 2 months after the second dose) continued showing that B cells were virtually absent and there was no diagnostic immunophenotypic abnormalities detected. Medical history of Waldenstrom's macroglobulinemia and concomitant use of rituximab remain as confounders for the event. The benefit-risk relationship of mRNA-1273 is not affected by this report.  Most recent FOLLOW-UP information incorporated above includes: On 13-Oct-2022: Live follow up received by safety on 14-OCT-2022 has Email with FTA received from team  and contains significant information: Reporter information, literature details, medical history, lab data, treatment drugs and event added and event seriousness were updated.; Sender's Comments: This is a literature non-study case concerning a 71-year-old male patient with medical history of Waldenstrom's macroglobulinemia, who was hospitalized due to the unexpected, serious event of Pancytopenia, after receiving the second dose of mRNA-1273 vaccine. 10 days after receiving the second dose of mRNA-1273, the patient had rituximab infusion for Waldenstrom's macroglobulinemia which later developed fever, chills, disorientation, confusion and nausea. The patient was brought to a hospital where he was mildly hypotensive. Blood counts were decreased and peripheral blood smear showed pancytopenia with marked leukopenia secondary to moderate neutropenia and marked lymphocytopenia. Neutropenic fever protocol was initiated and the patient was started on vancomycin, aztreonam and levofloxacin. Extensive infectious workups and imaging studies were unremarkable, therefore antibiotics were discontinued. Flow cytometry of peripheral blood showed no CD19+/CD20+ B cells or CD38 plasma cells. The patient was discharged 3 days later. Patient's blood cell counts gradually recovered however repeat flow cytometry (approximately 1 and 2 months after the second dose) continued showing that B cells were virtually absent and there was no diagnostic immunophenotypic abnormalities detected. Medical history of Waldenstrom's macroglobulinemia and concomitant use of rituximab remain as confounders for the event. The benefit-risk relationship of mRNA-1273 is not affected by this report.