Acute Granulocytic Leukemia Research Articles

Evaluation of Polo-like Kinase 1 inhibition on the G2/M checkpoint in Acute Myelocytic Leukaemia

Polo-Kinase 1 (PLK1) is a key cell cycle regulator that is necessary for checkpoint recovery after DNA damage-induced G2 arrest. We have examined the effects of PLK inhibition in Acute Myelocytic Leukaemia (AML) cells, whose resistance to genotoxic agents is thought to be associated with checkpoint reinforcement. We report that in U937 AML cells, PLK1 participates in checkpoint recovery, and that inhibition of PLK by the GW843682X compound results in mitotic accumulation and apoptosis. We also found that when challenged with VP-16, inhibition of PLK1 prevented U937 cells from checkpoint exit. Finally, we found that treatment with GW843682X slightly reduced genotoxic-induced inhibition of colony formation efficiency of primary leukaemia cells (CFU-L) from AML patients.

Identical Outcome Following Autologous or Allogeneic Genoidentical Hematopoietic Stem Cell Transplantation in First Complete Remission for Good Risk Acute Myelocytic Leukemia Carrying INV 16 or t(8;21): A Retrospective Comparison from the Acute Leukemia Working Party (ALWP) of the European Cooperative Group for Blood and Marrow Transplantation (EBMT).

Patients with acute myelocytic leukaemia (AML) with core binding factor mutations (CBF), bearing abnormalities of chromosome 16 or t(8;21) are classified as good risk with chemotherapy regimens including high dose cytosine arabinoside and are not subjected to hemopoietic stem cell transplantation (HSC) front line. However there are limited data from old studies indicating good outcome following HSC, autografting in particular, and there has been recently some concern about higher than expected relapse incidence following conventional chemotherapy in this patient population. From January 1990 to December 2004, a total of 325 adult patients were reported to the EBMT Acute Leukemia registry as receiving a transplant in first remission (CR1). Of these, 159 had an inversion 16, including 124 with no additional chromosome abnormality and 35 with other abnormalities. 166 had a t(8;21) translocation, as the only chromosome abnormality in 106 and associated to other abnormalities in 60. 64 patients with inv 16 and 81 patients with t(8;21) received a geno-identical allograft. 95 patients with inv 16 and 85 patients with t(8;21) translocation received an autograft. In patients with inv 16, following allogeneic and autologous transplantation respectively, the LFS were 59 ± 7% and 66 ± 5% (p=0.5), the RI 27 ± 6% and 32 ± 4% (p=0.45) and the TRM 14 ± 4% and 2 ± 2% (p=0.003). The LFS was significantly higher after January 2001. Female patients had a significantly lower incidence of relapse and a higher LFS. The existence of additional chromosome abnormalities not only did not worsen the prognosis but was associated with less relapses (12±5% vs 34 ± 4%, p= 0.01), and a better LFS (78 ± 7% vs 59 ± 5%, p=0.04). In patients with t(8;21), following allogeneic and autologous transplantation respectively, the LFS were 60 ± 5% and 66 ± 5% (p=0.69), the RI 15 ± 2% and 28 ± 3% (p=0.03) and the TRM 24 ± 3% and 6 ± 1% (p=0.003). Younger age and a lower white cell count at diagnosis were associated with a lower TRM and a better LFS.There was no difference in outcome between female and male patients. Following autologous transplantation as compared to allogeneic, the TRM was significantly lower and the relapse incidence significantly higher. For all adult CBF AML, the LFS did not differ between autologous and allogeneic transplants. Although the reasons why these patients were transplanted are unclear, considering the low TRM of autologous stem cell transplantation and the possibility to monitor in vivo purging by molecular biology, the data support the inclusion of ASCT in the front line treatment of CBF AML and suggest that a randomized prospective trial comparing high dose ARA-C and ASCT would be of interest.

Results of Non Myeloablative Geno-Identical Transplants in Adults with AML: Influence of the Doses of Peripheral Stem Cells Infused (on Behalf of the Acute Leukemia Working Party of EBMT).

In adult patients with acute myelocytic leukaemia receiving a conventional myeloablative allogeneic stem cell transplantation, several studies have shown that the higher the doses of hemopoietic stem cells infused, the better the outcome, with a lower transplant related mortality (TRM), a lower relapse incidence (RI) and a better leukaemia free survival (LFS). We wondered whether this observation was transposable in the context of non myeloablative transplants with peripheral blood stem cells where graft versus leukaemia (GVL) is the only anti tumor mechanism generated by the procedure in an effort to control the disease. In this particular situation, one might postulate that increasing the doses of peripheral blood T cells infused in an effort to increase GVL might increase GVHD and TRM. Further, one might speculate on the existence of an optimal range of stem cell and T cell doses to infuse. From January 1998 to December 2003, 253 patients with de novo AML, who received a non myelo ablative transplant with peripheral blood from a genoidentical donor, were reported to the ALWP registry with the dose of cells infused available. The sex ratio of the patients was 56% male /female. Patient age was 55 years (18–72). 141 patients were transplanted in first remission (CR1), 47 in second remission (CR2) and 65 patients had refractory disease or were transplanted in relapse. The pretransplant reduced intensity regimens were variable but 91% included fludarabin and Total body irradiation (TBI) was used in 23% of the patients at a dose<5 Gy. The median dose infused was 9.09 x 108 nucleated cells/kg (1.23–24). The follow up was 17 months (2–67). The LFS of the total population at 2 years was 41± 4%. For patients transplanted in CR1, CR2 and more advanced disease, the LFS were 49 ± 6%, 50± 8% and 23± 6% and the RI 37±4%, 34±7% and 69±6% respectively. Patients transplanted in CR had a significantly lower RI (p< 10−4, RR= 0.43 (0.29–0.65)) and better LFS (p< 10−5, RR=0.49 (0.35–0.7)) than those transplanted with advanced disease. Patients receiving doses of peripheral blood nucleated cells above the median had a trend towards a lower RI (42±5% versus 47±4%; p=0.06, RR=0.67 (0.45–1.02)) and a significantly higher LFS (46±5% versus 37±5%; p=0.04, RR= 0.68 (0.48–0.98)). Higher doses of nucleated cells were associated to a higher incidence of chronic GVHD (59 ± 5% versus 41 ± 5%, p=0.01, RR= 1.75 (1.12–2.73)). Interestingly, the use of TBI was associated to a higher RI (51± 8% versus 43±4%; p=0.02, RR=1.8 (1.1–2.9)). There was no relationship with the doses expressed in CD34+ cells infused. We conclude that in the context of non myeloablative transplants for adult AML, infusing higher doses of PB nucleated cells is beneficial to the patients.

THE HIGHLY UNUSUAL CLUSTER OF CHILDHOOD LEUKAEMIA IN CHURCHILL COUNTY, NEVADA

ISEE-116 Introduction: A dramatic increase in childhood leukaemia has recently occurred in Churchill County, a rural area of about 25,000 people in western Nevada, USA. Aim: The purpose of this paper is to describe the unique nature of the cluster and the likelihood that the cluster could be due to chance. Methods: From 1999 to 2001, ten cases of acute lymphocytic leukaemia (ALL) and one case of acute myelocytic leukaemia were diagnosed in this area. An additional five cases of ALL were identified from the years 1997 to 2002 among children who were not residents at the time of diagnosis, but lived in Churchill County at some point prior to diagnosis. In the preceding twenty years, only one case of childhood leukemia was reported to the Nevada Central Cancer Registry, among Churchill County residents. We have very recently learned that one new case of ALL was diagnosed in Churchill County in 2004. The primary economic sources in this area are agriculture and the nearby Fallon Naval Air Station. Despite intensive efforts by local and national investigators, a clear cause of the cluster has not been identified. Results: Although elevated levels of arsenic, tungsten, and DDE were found community wide, no differences were found between case subjects or family members and randomly selected controls. The possibility that the cluster may be due to chance has been hypothesized. However, using national rates of leukaemia for comparison, we calculated an age standardized rate ratio (RR) for Churchill County for the years 1999 to 2001 of 12.0 [95% confidence interval (CI), 6.0-21.4; n = 11 cases]. This corresponds to a probability of 4.3 x 10-9, or about 1 in 232 million. Based on the population of Churchill County relative to the US population, a cluster of this magnitude would be expected to occur in the US by chance about once every 22,000 years. In comparison, the p -value for the cancer cluster in Woburn, Massachusetts, was 8.4 x 10-3, or about one in 120. Routine tests of statistical significance may not be appropriate in the post-hoc analysis of clusters since the specific location and time frame being assessed is defined by the cluster, not set a priori. However, an important feature of the Churchill County cluster was that the cluster continued after state authorities began their investigation and the rate ratio remained high after this time (RR = 11.2; 95% CI, 3.6-26.3). Conclusion: The dramatic rise in the number of cases, the short time frame in which the cases were diagnosed, and the small population of the source area, highlight the highly unusual nature of this cancer cluster and suggest that this group of cases is one of the most remarkable childhood cancer clusters ever reported.

Detection of WT1 Expression in Bone Marrow Cells of Acute Leukemia Patients and during Their Follow-Up after Allo-BMT Using Real-Time Quantitative RT-PCR.

WT1, a tumor suppressor gene originally found to be responsible for the development of childhood kidney tumor, is now thought to be also involved in the pathogenesis of human leukemia. Since WT1 is reported to be expressed at much higher level in bone marrow cells from MDS and all subtypes of leukemia comparing to the normal blood cells, it is proposed to be a “panleukemic marker” for the diagnosis of leukemia. The expression level of WT1 may also have significance in predicting prognosis and monitoring relapse. However, this notion on the usage of WT1 is somehow still remaining controversial because WT1 is also expressed to a certain level in a small population of CD34+cells. To measure more accurately the expression level of WT1 in bone marrow cells of acute leukemia patients (ALs). Real-time quantitative reverse transcription polymerase chain reaction (RQ-RT-PCR) method was established for detecting WT1 and GAPDH expression levels in BM of 108 ALs and 23 non-leukemias patients by LightCycler. Besides, BM cells of 15 AL patients, including a total of 111 BM specimen taken during the follow-up after allo-BMT were also subject to RQ-RT-PCR. Normalized WT1 expression level (WT1N) was determined as a ratio between WT1 and GAPDH times 104. The expression levels of WT1N in 70 newly diagnosed ALs and 11 relapsed ALs were statistically higher than those of 23 ALs with complete remission(CR) and 23 non-leukemic controls (108.50±137.08 and 135.00±107.87 vs 3.88±3.09 and 2.23±3.19). Statistical differences were found neither between the CR group and control group, nor between the newly diagnosed group and relapsed group. Of the 70 newly diagnosed ALs, WT1N expression level of acute granulocytic leukemias was significantly higher than that of acute monocytic leukemias, but there were no statistic differences among the M1, M2, M3 and ALL subtypes. Furthermore, the WT1N levels were not correlated to WBC counts in peripheral blood, the blast ratio in the BM and the expression of MDR-1 at presentation, but do correlated to the leukemia cell chromosome karyotypes. The dynamic changes of WT1N levels in 2 patients during treatment suggested that WT1 expression levels could be used to monitor the disease outcome and predict relapse. In gereral, the dynamic curves of WT1 level following allo-BMT were consistemt with the tendnecy of changes in expression levels of corresponding fusion genefor MRD monitoring. A re-increment of WT1 expression level during follow-up could be detected 40 to 180 days earlier to hematological relapse. These studies have provided strong evidence suggesting that WT1 expression levels in cells of AL patients were markedly higher than an undetectable or a marginal level expressed in non-leukemias patients. WT1 can indeed be a marker for evaluating therapy efficacy in leukemias. WT1 expression levels in leukemia patients following allo-BMT measured by real time RT-PCR can be a useful tool for monitoring MRD and warning the clinical relapse during follow-up.

Density of Demodex folliculorum in haematological malignancies.

We aimed to investigate the incidence and density of Demodex folliculorum in adults with leukaemia or lymphoma. Fifty patients with haematological malignancy and 50 healthy controls were studied. Patients had been diagnosed with acute lymphocytic leukaemia (12%), acute myelocytic leukaemia (32%), chronic lymphocytic leukaemia (4%), chronic myelocytic leukaemia (10%), Hodgkin's lymphoma (4%) or non-Hodgkin's lymphoma (38%). Standardized skin surface biopsies were taken and > or = 5 living parasites/cm2 of skin was defined as an infestation. The difference in infestation rates between patients and controls was statistically significant. The highest incidences of D. folliculorum were found in patients with acute myelocytic leukaemia (10%), non-Hodgkin's lymphoma (6%), acute lymphocytic leukaemia (4%), chronic lymphocytic leukaemia (4%) and chronic myelocytic leukaemia (4%). Demodicidosis should be included in the differential diagnosis of facial eruptions in patients with haematological malignancies who are receiving chemotherapy, and a standardized skin surface biopsy should be performed.

Marrow versus peripheral blood for geno-identical allogeneic stem cell transplantation in acute myelocytic leukaemia: influence of the dose and the source of stem cells; better outcome with rich marrow. On behalf of the acute leukaemia working party (ALWP) of the european cooperative group for blood and marrow transplantation (EBMT)

Marrow versus peripheral blood for geno-identical allogeneic stem cell transplantation in acute myelocytic leukaemia: influence of the dose and the source of stem cells; better outcome with rich marrow. On behalf of the acute leukaemia working party (ALWP) of the european cooperative group for blood and marrow transplantation (EBMT)

Cost analysis of HLA-identical sibling and voluntary unrelated allogeneic bone marrow and peripheral blood stem cell transplantation in adults with acute myelocytic leukaemia or acute lymphoblastic leukaemia.

Allogeneic stem cell transplantation (SCT) is one of the most expensive medical procedures. However, only a few studies to date have addressed the costs of HLA-identical sibling transplantation and only one study has reported costs of unrelated transplantation. No recent cost analysis with a proper follow-up period and donor identification expenses is available on related or voluntary matched unrelated donor (MUD) SCT for adult AML or ALL. Therefore, we calculated direct medical (hospital) costs based on 97 adults who underwent HLA-identical sibling bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT), and patients who received a graft from a MUD between 1994 and 1999. The average costs per transplanted patient were Euro 98,334 (BMT), Euro 151,754 (MUD), and Euro 98,977 (PBSCT), including donor identification expenses, 2 years follow-up and costs of patients who were not transplanted after they had been planned to receive an allograft. The majority of these costs was generated during the hospitalisation for graft infusion. For MUD transplants, nearly one-third of these costs was spent on the search for a suitable donor. For patients who were alive after 2 years, cumulative expenses were calculated to be Euro 103,509 (BMT), Euro 173,587 (MUD), and Euro 105,906 (PBSCT).

Epidemiology of invasive aspergillosis in France: a six-year multicentric survey in the Greater Paris area

Invasive aspergillosis is the most prevalent mould infection. An epidemiological surveillance network was set up in 18 teaching hospitals in Paris and the Greater Paris area. Prospective surveillance was conducted between 1994 and 1999. Between 1994 and 1997 cases were categorized as proven or probable aspergillosis and then the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria were used. The authors analysed 621 cases (115 proven, 506 probable). No seasonal variation was found. Haematological disorders (73%) including stem-cell transplantation (36%), solid-organ transplantations (10%) and AIDS (9%) were the main underlying conditions. The crude mortality was 63%. Incidence of IA was 8% (CI95: 6.5–9.5) in acute myelocytic leukaemia and 6.3% (CI95: 4.3–8.3) in acute lymphocytic leukaemia. Incidence was 12.8% (CI95: 10.8–14.8) following allogeneic stem-cell transplantation and 1.1% (CI95: 0.7–1.5) following autologous stem-cell transplantation. In solid-organ recipients incidence ranged from 11% following heart–lung transplantation and small bowel to 0.4% following kidney transplantation. Incidence in HIV infected patients ranged from 0.02 to 0.13% per annum. This large series confirmed that patients with haematologic disorders and transplantations are the most at risk for IA.

Leucemia cutánea aleucémica: presentación de un caso

Abstract—The term aleukemic leukemia cutis describes the invasion of the skin by leukemic cells in the absence of peripheral blood and/or bone marrow involvement. Although the pathogenic mechanisms of this disease are still unknown, it is widely recognized its poor prognosis. Most of the reported patients completely developed the hematologic disease (the majority acute granulocytic or monocytic leukemias) in 10-14 months after diagnosis of aleukemic leukemia cutis, and they had a median survival of 22 months.We report on a case of a 77-year-old man with aleukemic leukemia cutis who presented with numerous erythematous to violaceous papulonodular lesions, mainly located on the trunk and head, lack of peripheal blood involvement and very early alterations in the bone marrow aspirate. Inmunohistochemical stains of skin and bone marrow biopsies revealed the infiltration of both tissues by blast cells of monocyte-histiocytic lineage. Our patient presented spontaneous resolution of skin lesions and his hematological disease showed no progression during 9 months after diagnosis, although he did not undergo any treatment.We emphasize the low incidence of association between myelodysplastic syndromes and aleukemic leukemia cutis as well as the surprising spontaneous remission of cutaneous lesions in our patient.

Comments on the paper: Microsatellite instability in acute myelocytic leukaemia developed from A-bomb survivors

Comments on the paper: Microsatellite instability in acute myelocytic leukaemia developed from A-bomb survivors

Case Report. Disseminated infection of Blastoschizomyces capitatus in a patient with acute myelocytic leukaemia

Case Report. Disseminated infection of Blastoschizomyces capitatus in a patient with acute myelocytic leukaemia

BCL-1 rearrangement in acute lymphocytic leukemia and its clinical significance.

BCL-1 rearrangement (BCL-1/IgH gene rearrangement) in acute lymphocytic leukemia and its clinical significance was investigated. In 38 patients with acute lymphocytic leukemia (ALL), the genomic DNA of mononuclear cells isolated from peripheral blood and bone marrow was amplified by using hemi-nested polymerase chain reaction (PCR) technique and the expression of cyclin D1 protein of mononuclear cells was detected by using immunohistochemical method. Ten patients with acute granulocytic leukemia, 2 with chronic granulocytic leukemia and 10 with normal bone marrow served as control group. The results showed that BCL-1 rearrangement was detectable in 3 of 38 ALL patients (7.9%) and cyclin D1 protein positive expression was detected in 4 ALL patients (10.5%). Three ALL patients with BCL-1 rearrangement were all B-cell leukemia (B-ALL) and accompanied by cyclin D1 protein expression. No BCL-1/IgH rearrangement or cyclin D1 protein expression was detected in 12 patients with granulocytic leukemia and 10 cases of normal bone marrow. Leukocyte counts in peripheral blood of B-ALL patients with BCL-1 rearrangement and (or) cyclin D1 protein expression were significantly increased and the patients had bad reaction to chemotherapy. It was concluded that: 1) BCL-1/IgH gene rearrangement were detected in acute B lymphocytic leukemia; 2) B-ALL patients with BCL-1 rearrangement and (or) cyclin D1 protein expression had poor prognosis.

Chun Wang on oncology in China

Professor Chun Wang obtained his medical degree at Wannan Medical College, Wuhu, Anhui Province, China. He went on to do postgraduate training at Shanxi Medical University and then Tongji Medical University, where he was awarded a MSc and a PhD, respectively. In 1986, he joined the Department of Internal Medicine and Hematology at the Second Teaching Hospital of Shanxi Medical University. During this period, his research interests included ultrastructure of haemopoietic cells, effects of haemopoietic growth factors on the growth of acute myelocytic leukaemia cells in vitro, and autologous and allogeneic bone-marrow transplantation in leukaemia.

Micellar electrokinetic capillary chromatography quantification of cytosine arabinoside and its metabolite, uracil arabinoside, in human serum

Cytosine arabinoside (Ara-C) is widely used to induce remission in adult granulocytic leukemia. High doses can be infused in refractory leukemia or in relapse. After injection, Ara-C is quickly metabolized to uracil arabinoside (Ara-U), the main inactive metabolite. We here described a micellar electrokinetic capillary chromatography (MECC) method to simultaneously determine Ara-C/Ara-U in human serum using 6- O-methylguanine as an internal standard. The assay was linear from 6.25 to 200 μg/ml with a quantification limit between 3 and 6 μg/ml. The analytical precision was satisfactory between 2 and 4.3% (within-run) and 3.7 and 7.3% (between-runs). This assay was applied to the analysis of serum from acute granulocytic leukemia patient treated by high doses cytarabine (3 g/m 2 body surface).

Microsatellite instability in acute myelocytic leukaemia developed from A-bomb survivors

Purpose : Genetic alterations, including microsatellite instability (MSI), are ultimate steps toward malignant process. To investigate MSI in A-bomb survivors, leukaemic cells were analysed from 13 acute myelocytic leukaemia patients with a history of radiation exposure and also in 12 de novo patients. Materials and methods : To assess the microsatellite changes, a fluorescent system in 10 loci (BAT40, D3S643, D5S107, IRF1, MYC, D9S171, WT1, TP53, DM, D17S855) was used. Results : MSI analysis revealed a high frequency of multiple microsatellite changes in the exposed patients (84.6%) compared with non-exposed patients (8.3%). There was a significant difference (p <0.001) between the two groups. Conclusions : These analyses clearly demonstrate that leukaemic cells from heavily exposed patients contain a number of genetic instabilities that may strongly influence the development of leukaemia among people exposed to the Hiroshima A-bomb radiation.

Feasibility of peripheral blood stem cell rescue as intensification in elderly patients with acute myelocytic leukaemia: a pilot study from the Gimema Group. Gruppo Italiano Malattie Ematologiche Maligne Dell'Adulto.

Elderly patients with untreated acute myeloid leukaemia (AML, n = 47) tested the feasibility of out-patient consolidation therapy and post-consolidation treatment (for patients aged < 71 years) with autologous peripheral blood stem cell transplantation (APBSCT). Overall, 13 patients out of 24 (51%) who achieved complete remission (CR) were eligible for further treatment after consolidation. Five patients were primed with granulocyte colony stimulating factor (G-CSF); a suitable number of CD34+ cells were harvested in three patients and were actually autotransplanted. The toxicity of APBSCT was negligible. Psychosocial problems impaired treatment of some patients on an out-patient basis. Resistant disease, toxicity and logistic problems reduced the number of patients to whom this procedure could actually be applied.

Feasibility of peripheral blood stem cell rescue as intensification in elderly patients with acute myelocytic leukaemia: a pilot study from the Gimema Group

Elderly patients with untreated acute myeloid leukaemia (AML, n = 47) tested the feasibility of out‐patient consolidation therapy and post‐consolidation treatment (for patients aged &lt; 71 years) with autologous peripheral blood stem cell transplantation (APBSCT). Overall, 13 patients out of 24 (51%) who achieved complete remission (CR) were eligible for further treatment after consolidation. Five patients were primed with granulocyte colony stimulating factor (G‐CSF); a suitable number of CD34+ cells were harvested in three patients and were actually autotransplanted. The toxicity of APBSCT was negligible. Psychosocial problems impaired treatment of some patients on an out‐patient basis. Resistant disease, toxicity and logistic problems reduced the number of patients to whom this procedure could actually be applied.

Mutational analysis of the tumour suppressor gene MMAC1/PTEN in malignant myeloid disorders.

The candidate tumour suppressor gene MMAC1/PTEN located at chromosome 10q23.3 has been reported to be frequently mutated in a number of solid tumours. Less is known about its status in leukaemia. In the present study we first analysed 13 leukaemia cell lines for mutations and homozygous deletions in MMAC1/PTEN using PCR and denaturing gradient gel electrophoresis (DGGE). We identified an intragenic deletion including MMAC1/PTEN exons 2-5 in an acute myelocytic leukaemia cell line, HL-60 blast, and an insertion of four nucleotides in exon 5 in an acute monocytic leukaemia cell line, U937. Analysis of 59 patients with acute myeloid leukaemia (AML), 26 patients with myelodysplastic syndromes (MDS) and 10 patients with chronic myeloid leukaemia (CML) only revealed a polymorphic base substitution in codon 44 in one AML patient, suggesting that mutations in the MMAC1/PTEN gene are infrequent genetic aberrations in myeloid leukaemia.

Surgical and laboratory findings in children with neutropenic enteropathy

Abstract Background The term neutropenic enteropathy (NE) is used to describe inflammatory conditions of the gastrointestinal system in patients who receive chemotherapy for haematological malignancy. Although the initial treatment of choice in NE is non-operative, with bowel rest, decompression, nutritional support and broad-spectrum antibiotics, operative intervention is needed in patients with the advent of the disease. The surgical and laboratory findings of seven patients with NE who required surgical treatment are presented. Methods Patients' medical records were reviewed to obtain age, sex, diagnosis, laboratory findings with neutrophil counts, blood cultures and the surgical findings. The onset of neutropenia and the diagnosis of NE were recorded for each patient. Results There were four girls and three boys, with a mean age of 6 years (range 9 months to 16 years). The primary diseases were acute myelocytic leukaemia in two, acute lymphocytic leukaemia in one and lymphoma in four patients. In all but two patients, the neutrophil counts were less than 1000 mm−3, with positive blood cultures at diagnosis. The onset of the NE was determined as mean(s.d.) 3(2) days after the onset of neutropenia. Haemorrhage, marked oedema, patchy inflammation and multiple adhesions of the bowel, perforation and localized abscess were the main operative findings. The lesions were mostly localized in the terminal ileum and the ascending colon. After resection of the affected segment of bowel, stomas (three) and end-to-end anastomoses (three) were performed. Primary repair of the perforation site was performed in one patient with gastric perforation. Four patients recovered with rapid resolution of neutropenia, while three patients with persistent neutropenia died. Conclusion A favourable outcome for patients with NE is related to early recognition of the intra-abdominal infection, appropriately timed surgical intervention and a prompt postoperative return of normal circulating levels of neutrophils.