Patients and doctors get very worried about high white counts. Need they be?
I remember one holiday weekend spending days at the hospital with a young 13-year old boy with priapism - a prolonged and painful penile erection - caused by a high white count. What happens in these cases is that the blood vessels get blocked by aggregated white blood cells, so that normal circulation is prevented. We connected the lad up to a cell separator and performed leucocytapheresis on him to rapidly lower the white count. He also had to have a surgical procedure to decompress the organ, but I'm glad to say this combination of treatments was successful and sexual function was restored, although since his disease was chronic myeloid leukaemia (CML)in the days before imatanib and matched unrelated bone marrow transplantation, he eventually succumbed to blast transformation of his disease.
Priapism is a well known complication of CML but is seldom seen in other types of leukemia. It is one version of the leukostasis syndrome. Other features include rapidly progressive breathing difficulties and mental problems. It is thought to be caused very sticky bits of white cells and platelets forming aggregates and thrombi, and blocking the circulation. Some authors distinguish this from the hyperviscosity syndrome which produces similar effects because the blood becomes very viscous or treacly (thick and sticky, not actually sweet). This can be due to high cell content (either red or white) or high protein content (especially IgM or immune complexes). Nowadays, patients are seldom allowed to get high white cell counts except in CLL. The question everybody asks is whether hyperviscosity can occur in CLL. I think that the answer is probably in exceptional cases both hyperviscosity and leukostasis can occur.
Looking back over the old literature, my old mate Eric Preston reported three cases from Sheffield in 1978. The white counts were 500, 647 and 1000 respectively. The symptoms of hyperviscosity were relatively minor, but they did resolve after leucocytapheresis. These three patients did have raised blood viscosity measurements, but the authors noted that CLL does not raise the viscosity by as much as other leukemias for a given white count. There is another report from Kurlander and colleagues of a patient with a white count of 901 who had retinal hemorrhages, which can be a feature of hyperviscosity, though this patient also had hyperkalemia (a high potassium level) and kidney failure, which could also have caused them. Then in 1985 Maria Baer from Nashville reported a study of 16 CLL patients with white counts over 500. In one of them, with a white count of 968 there was a full blown hyperviscosity syndrome with headache, double vision, loss of balance, slurred speech, deafness and other neurological signs, which all recovered after leucocytapheresis (in America people talk about leukapheresis which implies that the machine takes the whiteness out of the blood, like a reverse washing machine). A second patient had what were in retrospect features of hyperviscosity, but she was treated as if she had leukemic meningitis and died. A third patient had retinal hemorrhages, but these can be caused by a lot of different things including high blood pressure. The 16 high white counts were drawn from a series of 210 patients in Nashville.
One of the problems about the early CLL papers is that before good immunophenotyping we could not be sure that the patient actually had CLL – it could have been mantle cell lymphoma or a variant. A study from Sweden published in 1992 said this:
In order to evaluate the effects of different cell types of leukaemic cell origin on skin capillary circulation we have studied patients with (a) chronic lymphocytic leukaemia (CLL) (n = 6) and (b) acute non-lymphocytic leukaemia (ANLL) (n = 6) or chronic granulocytic leukaemia (CGL) (n = 5). Capillary blood cell velocity (CBV) in fingernail-fold capillaries was measured by videophotometric capillaroscopy. After a 1-min arterial occlusion at the finger base, the post-occlusive reactive hyperaemia was evaluated by measuring the peak (p) CBV and the time to pCBV. In patients with ANLL/GGL, both resting CBV and pCBV were lower than in healthy control subjects. In the CLL patients these values were not significantly different compared to controls.
More recently there have been occasional patients with very high white counts due to CLL that have caused either hyperviscosity or leukostasis, but they are so rare that they are almost certain to be reported in the literature.
In Paris in 1988:
A 50 year old man with chronic lymphocytic leukemia (CLL) and extreme hyperleukocytosis (600 x 10(9)/liter) presented with a respiratory distress syndrome, congestive heart failure with cardiomegaly, endotoxic shock and anuria. Examination revealed nodes in all areas and hepatosplenomegaly; laboratory studies showed hypoxemia and a chest X-ray diffuse bilateral alveolar infiltrates. He was treated twice by leukapheresis using a cell separator. This procedure removed 10.1 x 10(10) white blood cells with marked clinical improvement and resolution of air-space diseases over the subsequent 48 hours.
In Germany in 1991
An 82-year-old woman with CLL developed acute neuropsychiatric signs (confusion, disorders of speech and vision) together with ataxic gait and left hemiparesis mainly affecting the lower limb. Her white count was 1,300, most of the cells being morphologically atypical lymphocytes. Significant reduction of leucocyte count with considerable improvement in clinical signs was achieved after three doses of vincristine and prednisone together with one cycle of COP
In the Netherlands in 1996
The authors mistook pulmonary infiltrates with CLL cells for leukostasis. The white count was only 153.
In Poland in 1999
A severe leukostasis syndrome was observed in a case of CLL with peripheral lymphocyte count of 1,120. Typical symptoms of respiratory and central nervous system were developed (tachypnoe, hypoxia, headache, slurred speech, somnolence and confusion). Leukapheresis decreased the lymphocyte count to 305 rapidly and reversed the leukostasis syndrome.
And in Israel in 2002
We describe a 73-year-old woman who presented with newly diagnosed CLL, leukostasis, and hyperleukocytosis (2000 x 10(9)/l), affecting the respiratory and nervous system. We hypothesize that in our patient the extreme number of circulating lymphocytes resulted in an abnormal accumulation of lymphocytes possibly causing stasis and occlusion of a larger vessel, which resolved after leukapheresis.
In CLL patients with high white counts there are usually other reasons to begin treatment, but in patients without symptoms there should be no urgency to begin treatment just because the white count has reached 100 or 200 or 300 or 400 or even 500 because of the possibility of leukostasis or hyperviscosity. This makes CLL different from other types of leukemia, where a high white count carries its own dangers.