WENZHOU, CHINA — Since 1993, nearly 30,000 veterans have received care for chronic lymphocytic leukemia at the VA. CLL patients tend to be older and male, as are many veterans, and CLL also is considered a presumptive condition for veterans exposed to Agent Orange or certain other herbicides during the Vietnam War.
Because of that, federal health clinicians, in the midst of a COVID-19 pandemic, might have special interest how the novel coronavirus affects CLL patients.
An article in The Lancet Hematology addressed that issue. Researchers in China, where the first significant outbreak of COVID-19 occurred, determined that clinical and biochemical data of COVID-19 might be partly masked by coexisting chronic lymphocytic leukemia, suggesting the use of better diagnostic strategies, such as the use of superior CT differential techniques like radiomics.1
The authors also posited that patients with compromised immune status might have a longer incubation period after infection but said the underlying mechanisms weren’t yet known. The researchers said, “It remains uncertain whether the combination of chemotherapy, corticosteroids, α-interferon, and immunoglobulins could work synergistically in patients with chronic lymphocytic leukemia and COVID-19.”
Most of those suppositions are based on the case of a 39-year-old man with a medical history of non-Hodgkin lymphoma and chronic lymphocytic leukemia attended in Wenzhou, China. He presented at the hospital on Feb. 16, 2020, after four days of fever, sore throat, productive cough, and dyspnea.
The authors noted that previous history of treatment for non-Hodgkin lymphoma consisted of six courses of 21 days of R-CHOP chemotherapy in 2007. His previous treatment for chronic lymphocytic leukemia started in November 2018, with oral chlorambucil (10 mg/m2) per day. He became non-compliant in December 2019, stating that improvements derived from treatment did not outweigh the cost and follow-up time required.
The study pointed out that, at admission, the most relevant clinical findings included body temperature of 38·5°C, white blood cell counts of 91·85 × 109 cells per L, lymphocyte percentage of 96%, hemoglobin of 85 g/L, platelet count of 79 × 109 cells per L, high-sensitive C-reactive protein 21·5 mg/L, β2-microglobulin of 4·76 μg/mL, and lactic acid dehydrogenase of 429 U/L. They emphasized that plasma concentrations of IgG, IgM, and IgA were markedly reduced (3·18 g/L for IgG, 0·45 g/L for IgM, and <0·17 g/L for IgA).
On the other hand, the concentration of plasma brain natriuretic peptide, estimated glomerular filtration rate, concentration of liver enzymes, and echocardiogram results were determined to be unremarkable. Bone marrow aspiration was not done at the time of assessment.
Other hematological investigations included a Binet stage C, Rai stage IV, and European Cooperative Oncology Group performance score of 1. A CT scan of the chest showed bilateral ground-glass opacities and a small amount of fluid in the left pleural cavity. Suspecting COVID-19, the attending physician and ordered testing, and a real-time RT-PCR assay result was positive.
Once in the isolation ward, the patient started treatment with a reduced dose of oral chlorambucil (2 mg) twice per day to treat his frail condition due to his CLL. He also received nebulized α-interferon (5 000 000 international units) twice per day, intravenous human immunoglobulin (20 g) once per day, and intravenous methylprednisolone (40 mg) every 12 hours for the treatment of COVID-19, as recommended by the Chinese COVID-19 Interim Management Guidance (sixth edition).
During the first nine days, the patient had relapsing fever with temperature ranging from 36·6°C to 39·6°C, PaO2/FiO2 less than 300 mm Hg, and with a Sequential Organ Failure Assessment score of 4. The patient was given non-invasive ventilation therapy until dyspnea eased by the eighth day.
At that point, the treatment plan changed to low-dose intravenous methylprednisolone (40 mg) every 12 hours with oral chlorambucil (2 mg) twice per day for the next four days. A follow-up chest CT on March 1, 2020, indicated substantial improvement with a significant reduction of pulmonary exudative lesions.
With improvement in symptoms, the patient’s temperature returned to normal, according to the report.
Yet, the researchers pointed out, repeated real-time RT-PCR test remained positive for COVID-19 infection. He was scheduled for an additional seven days of observation until all clinical criteria for hospital discharge were met. Those were: more than three days of normal body temperature, resolved respiratory symptoms, substantially improved acute exudative lesions on chest CT, and two consecutive negative COVID-19 infection tests.
When that threshold was reached, he transferred to the inpatient hematology department for further management.
- Jin XH, Zheng KI, Pan KH, Xie YP, Zheng MH. COVID-19 in a patient with chronic lymphocytic leukaemia. Lancet Haematol. 2020;7(4): e351–e352. doi:10.1016/S2352-3026(20)30074-0