Severe Pancytopenia after Obinutuzumab-Chlorambucil Therapy for CLL with Fatal Outcome

Case Report

Ann Hematol Oncol. 2020; 7(7): 1313.

Severe Pancytopenia after Obinutuzumab-Chlorambucil Therapy for CLL with Fatal Outcome

Stang A1,3*, Weilert H1,3, Harrington B2,3 and Becker HF2,3

¹Department of Hematology, Oncology & Palliative Care, Asklepios Hospital Barmbek, Germany

²Department of Pneumology & Intensive Care Medicine, Asklepios Hospital Barmbek, Germany

³Faculty of Medicine, Semmelweis University, Asklepios Campus Hamburg, Germany

*Corresponding author: Axel Stang, Department of Hematology, Oncology & Palliative Care and Faculty of Medicine, Asklepios Hospital Barmbek, Rübenkamp 220, 22307 Hamburg, Germany

Received: August 11, 2020; Accepted: October 03, 2020; Published: October 10, 2020


Standard first-line treatment of Chronic Lymphatic Leukemia (CLL) usually consists of immune-chemotherapy and results in long-lasting remissions in most cases. Overall survival with the second-generation anti-CD20 antibody obinutuzumab was shown to be better than with rituximab when given together with chlorambucil. Although the treatment is generally well tolerated, there seems to be a trend towards more Severe Adverse Events (SAEs) with obinutuzumab than with rituximab and more fatal obinutuzumab-related SAEs being observed in clinical practice than reported in clinical trial treatments. Here, we report the case of a 72-year-old female patient with CLL that developed severe pancytopenia shortly after starting of obinutuzumab-chlorambucil treatment. She presented with neutropenia-related bilateral lung infiltrates, required invasive ventilation for acute hypoxic respiratory failure, and finally died from fatal bilateral stroke under prolonged thrombocytopenia. This case highlights that vigilance is required for rare but potentially fatal prolonged myelotoxicity related to treatment protocols containing anti-CD20 antibodies, specifically obinutuzumab, and for potentially fatal adverse thrombotic arterial events despite the presence of thrombocytopenia, specifically ischemic strokes.

Keywords: Obinutuzumab; Pancytopenia; Hematotoxicity; Chronic lymphatic leukemia; Fatal adverse event; Bilateral stroke


Obinutuzumab is a novel type II anti-CD20 monoclonal Antibody (mAb) recently approved for first-line treatment in patients with Chronic Lymphatic Leukemia (CLL) in combination with chlorambucil [1]. Therapeutic efficacy of obinutuzumab is superior to rituximab in the approved CLL setting, but there seems to be a trend towards higher hematotoxicity and more Severe Adverse Events (SAEs) with obinutuzumab than with rituximab [2,3]. Moreover, fatal obinutuzumab-related SAE rates appear to be higher in clinical practice (7.3%) [4] than those reported in clinical trial treatments (≤4%) [1-3]. We report a case of severe prolonged pancytopenia after obinutuzumab-chlorambucil therapy for CLL resulting in death from fatal bilateral strokes under invasive ventilation required for respiratory failure caused by pulmonary infiltrates.

Case Presentation

A 72-year-old female patient presented to the emergency department due to fever and Acute Respiratory Failure (ARF) in June 2019. Since March 2019, she had dual antiplatelet therapy (aspirin, ticagrelor) after implantation of drug-eluting stents for acute coronary syndrome. Between April and May 2019, she had been treated with two 14-day cycles chlorambucil (administered orally at 0.5 mg/kg on days 1,2 and 3) and one cycle chlorambucil plus obinutuzumab (administered intravenously at 1.000 mg on days 1, 8 and 15) for B-CLL (total doses: 108 mg of chlorambucil, and 3.000 mg of obinutuzumab). Prior to B-CLL therapy, blood cell counts showed atypical lymphocytosis (counts 95.000 x109/L) with mild pancytopenia (hemoglobin 9.4 g/dL, neutrophils 1.5 x109/L, platelets 120 x109/L). At presentation, the patient had severe pancytopenia (hemoglobin 5.7 g/dL, leucocytes 0.1 x109/L, neutrophils 0 x109/L, platelets 4 x109/L). Physical examinations (including blood pressure, pulse rate, neurologic and cardiologic status), ultrasound examinations (including echocardiography and carotid Doppler), and laboratory tests were normal except increased inflammatory parameters (CRP 318 mg/L). Arterial blood gas analysis showed hypoxic ARF (PaO2 61 mmHg, PaCO2 28.5 mm Hg, PaO2/FiO2 135), and CT-scans revealed bilateral pulmonic infiltrates (Figure 1). The initial working diagnosis was hypoxic ARF due to pneumonia under severe post-therapeutic pancytopenia, and the patient received antibiotic treatment (piperacillin/tazobactam, clarithromycin), Granulocyte Colony Stimulating Factor (G-CSF), Red Blood Cell (RBC) and platelet transfusions, and oxygen. Dual antiplatelet therapy was interrupted.

Citation: Stang A, Weilert H, Harrington B and Becker HF. Severe Pancytopenia after Obinutuzumab- Chlorambucil Therapy for CLL with Fatal Outcome. Ann Hematol Oncol. 2020; 7(7): 1313.