Chronic neutrophilic leukaemia: an Egyptian case -- Elbahrawy et al. 2009 (241): bcr1120081277 -- BMJ Case Reports
Published 24 June 2009 Cite this as: BMJ Case Reports 2009 [doi:10.1136/bcr.11.2008.1277] Copyright © 2009 by the BMJ Publishing Group Ltd.
Rare disease Chronic neutrophilic leukaemia: an Egyptian case Ashraf Elbahrawy1,3, Mahmoud Hamdy2, Mohamed Hanafy Morsy2 and Ramadan Ragab3 1
Graduate School of Medicine Kyoto University, Gastroenterology and Hepatology, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan 2
Al-Azhar University, Clinical Pathology, Nasr City, Cairo, 11256, Egypt
3
Al-Azhar University, Internal Medicine, Nasr City, Cairo, 11256, Egypt
Correspondence to: Ashraf Elbahrawy,
[email protected]
SUMMARY Chronic neutrophilic leukaemia (CNL) is a rare myeloproliferative disorder of elderly patients characterised by sustained neutrophilia. The diagnosis of CNL requires the exclusion of BCR/ABL positive chronic myelogenous leukaemia and leukemoid reaction. We present here a case of a 61-year-old Egyptian man with CNL and 21 months of follow-up. The main symptom of our patient was purpura. Splenomegaly, hepatomegaly and lymph node enlargement were not detected at presentation or throughout the patient’s course. Thrombocytopenia was a considerable problem in our patient, causing recurrent bleeding and affecting the hydroxyurea dose adjustment. While hydroxyurea decreased the total leucocytic count, it could not affect the fatal course of the disease. The survival course of our patient extended to 21 months after presentation. The cause of death was attributed to disease progression.
BACKGROUND Chronic neutrophilic leukaemia (CNL) is a rare chronic myeloproliferative disorder that has been identified as a distinct entity by the World Health Organization.1 CNL is characterised by sustained, mature neutrophilic leucocytosis with few or no circulating immature granulocytes, monocytosis or basophilia.2 Bone marrow histology reveals granulocytic hyperplasia without evidence of dysplasia or striking reticulin fibrosis.3,4 Cytogenetic and molecular analysis are negative for Philadelphia chromosome (Ph chromosome) and/or its molecular counterpart, fusion of BCR and ABL genes.2 Clinical evaluation should exclude malignancy or infection capable of causing leukemoid reaction. Although most reported cases had common clinical manifestations, splenomegaly, hepatomegaly and lymph node enlargement are not universal. Thrombocytopenia was reported as a cause of bleeding tendency in CNL.5 The course of CNL is heterogeneous; an accelerated phase and a blast phase can be recognised. The median survival of patients with CNL is 23.5 months (range 1–106 months). Treatment has consisted largely of cytoreductive agents such as hydroxyurea. No haematological complete remission has been
第2页 共6页
Chronic neutrophilic leukaemia: an Egyptian case -- Elbahrawy et al. 2009 (241): bcr1120081277 -- BMJ Case Reports
reported following induction chemotherapy for accelerated or blast phase in CNL.2 In the view of low frequency, uncertain optimal treatment and fatal course of this haematological disease, we believe that continued reporting and investigation of specific therapeutic strategies and responses must be encouraged.
CASE PRESENTATION On 6 July 2006, a 61-year-old Egyptian man presented to us with recurrent purpura involving both lower limbs of 2 weeks duration, which was not associated with bleeding from any orifice, or a history of deep bleeding. The condition was associated with fatigue, but at presentation there was no history to suggest an infection. The patient had no significant history of recent cytotoxic or growth factor therapy, exposure to chemicals or relevant medical history, apart from mild hypertension. The family history was not relevant. On examination the patient had mild pallor, and multiple ecchymotic patches scattered in both lower limbs. There was no gum hypertrophy, hepatomegaly, splenomegaly or peripheral lymph node enlargement.
INVESTIGATIONS On 6 July the patient’s haemoglobin was 10.3 g/dl, platelet count 77x109/l, and leucocyte count 50x109/l (segmented 87%, staff 4%, lymphocyte 5.37%, monocyte 1.31%, eosinophil 0.3%, basophil 0.3%, myelocyte 1%, juvenile 0.7%). International normalised ratio (INR) and partial thromboplastin time (PTT) were 1.3 and 29s (normal range (NR) 32–38 s), respectively. On 12 July, the results of biochemical investigations were: alanine transaminase (ALT) 17/31 IU, aspartate transaminase (AST) 13/31 IU, serum bilirubin 0.9 mg/dl, serum albumin 4.7 g/dl, serum globulin 1.4 g/dl, alkaline phosphatase 184/129 units/l, serum creatinine 1.4 mg/dl, prostate specific antigen (PSA) 0.65/4 ng/ml. Abdominal ultrasonography was unremarkable. Bone marrow aspirate was done on the 16 July and revealed notable hypercellular marrow with granulocytic hyperplasia. Erythroid and megakaryocytic series were depressed with normal morphology. The myeloid/erythroid ratio was 20/1.
DIFFERENTIAL DIAGNOSIS At that time the suggested differential diagnosis included: (1) chronic myeloid leukaemia (CML), (2) CNL, and (3) leukemoid reaction. Ph chromosome, BCR/ABL and neutrophil alkaline phosphatase (NAP) score were done to rule out CML. Ph chromosome by conventional method as well as BCR/ABL was negative, and NAP score was 170 (NR 20–130) U/109. In the absence of any evidence suggesting infection or solid malignancy, a diagnosis of CNL was made.
TREATMENT On 19 July, treatment with hydroxyurea 500 mg twice daily was started.
OUTCOME AND FOLLOW-UP Three weeks later, on 14 August, the leucocytic count had decreased to 4x109/l. By that time the patient had stopped the hydroxyurea treatment due to the cost. Ten days after stoppage of hydroxyurea the leucocytic count increased to 42x109/l (segmented 76%, staff 9%, lymphocyte 11%, monocyte 4%, eosinophil 0%, basophil 0%). The patient was treated with hydroxyurea again (500 mg/day) and the leucocytic count decreased to 16x109/l. On 14 September the dose of hydroxyurea was decreased to 500 mg every other day due to progressive thrombocytopenia, and the patient continued with this regimen for
第3页 共6页
Chronic neutrophilic leukaemia: an Egyptian case -- Elbahrawy et al. 2009 (241): bcr1120081277 -- BMJ Case Reports
another 17 months. During this period, increased susceptibility to bacterial infection and increased frequency of bleeding episodes (including haematuria and subconjunctival haemorrhage) were recognised. In addition, the leucocytic count showed a fluctuating course and the hydroxyurea dose adjustment was difficult due to progressive thrombocytopenia (figs 1 and 2). On February 2008, the patient died as a result of disease progression.
View this figure (13K): in this window | in a new window | PowerPoint for Teaching Figure 1 Leucocytic count throughout the disease course.
View this figure (11K): in this window | in a new window | PowerPoint for Teaching Figure 2 Platelet count throughout the disease course.
DISCUSSION Diagnosis of the non-classic myeloproliferative neoplasms in general requires the absence of BCR/ABL, dyserythropoiesis, granulocyte dysplasia or monocytosis ( 1x109/l).1 Chronic neutrophilic leukaemia is considered in the presence of 25x109/l leucocytes in the peripheral blood accompanied by >80% segmented neutrophils or bands,
