The main diagnostic criteria of CNL are chronic neutrophilia in the blood, expansion of neutrophilic granulopoiesis in the bone marrow, and splenomegaly in the absence of any form of BCR/ABL translocation or leukaemoid reaction.1
These criteria were sufficiently fulfilled in our 14 patients with CNL. The spectrum of fatal complications we saw in our patients was very similar to that described in the literature.2
The haemorrhagic diathesis seen in patients with CNL may be the result of thrombocytopenia and thrombocyte dysfunction,6
or it may be caused by leukaemic infiltration of vascular walls.7
With rare exceptions,8
CNL is a disease of older adults (fig 1). At the time of diagnosis, 88% of the patients with CNL in the literature were older than 50 years. The sex distribution in CNL is nearly equal.
Distribution of patients with chronic neutrophilic leukaemia in the literature (including the Freiburg cases) according to sex and age.
There is doubt about whether all of the CNL cases in the literature represent true CNL. Some authors1,2,5
have suggested that those cases of CNL that occurred in association with plasma cell dyscrasias like myeloma were in fact neutrophilic reactions. Moreover, it was suggested that cases of CNL showing dysplastic features would be better classified as a myelodysplastic entity. Thus, reviewing the data of all CNL cases in the literature, Reilly5
defined a group of 33 cases of true CNL, including one unpublished case of his own. This group of 33 selected patients with CNL also showed a high mean age (62.5 years) and short survival times (mean survival, 30 months), but had a 2 : 1 male to female ratio. The term true CNL used by Reilly reveals the need for an even more precise definition of CNL as an entity. Thus, the diagnostic criteria of CNL should be applied in a strict manner, especially for the conditions mentioned above.
“To date, because of the rarity of the disease, no therapeutic standard has been determined in chronic neutrophilic leukaemia”
In the differential diagnosis of CNL, patients with CML usually show a higher degree of leucocytosis (white blood cell count, ~ 170 × 106
/litre), with more immature granulopoietic forms, a decreased NAP score, and basophilia.1
In the bone marrow, granulopoiesis is far more left shifted, and micromegakaryocytes are present. The most important criterion of CML is the presence of a BCR/ABL translocation. There is a rare form of CML (neutrophilic chronic myeloid leukaemia)9
that shares some of the morphological features of CNL, but is characterised by an uncommon type of BCR/ABL translocation (BCR e19/ABL a2). Like CNL, leukaemoid reactions are BCR/ABL negative and show identical morphological changes, including raised NAP scores, making a distinction difficult or even impossible. Because CNL is a clonal disorder,10
clonality studies of the neutrophils in the future may help to distinguish between cells of leukaemic or reactive origin.
To date, because of the rarity of the disease, no therapeutic standard has been determined in CNL.2
Chemotherapeutic agents, such as hydroxyurea, may temporarily control leucocytosis and splenomegaly, and the use of interferon α may induce long standing clinical remission.4
So far, allogeneic bone marrow transplantation represents the only treatment modality with curative potential.2,6
Take home messages
- Chronic neutrophilic leukaemia (CNL) is a rare myeloproliferative disease, mainly found in elderly patients
- This disease has a mostly fatal outcome—three quarters of our patients died within two years of diagnosis, mainly as a result of severe cerebral haemorrhage
- Two younger patients were successfully treated with allogeneic bone marrow transplantation or interferon, which resulted in haematological remission for years
- Thus, it is important to recognise CNL and to develop appropriate therapeutic strategies for affected patients
We conclude that it is important to recognise CNL as a rare, but distinct, disease entity different from CML, and in particular to distinguish CNL from leukaemoid reactions, because patients with CNL generally have a poor prognosis. To gain a better understanding of the nature of true CNL the reporting of new cases must be encouraged.