Lower White Cell Count Research Articles

The Cell Expression of PML-RARa at Diagnosis Has a Marginal Correlation with Prognosis in Patients with Acute Promyelocytic Leukemia (APL).

Acute promyelocytic leukaemia (APL) is characterised by the t(15;17) leading to the fusion of the PML gene with the retinoic acid receptor a (RARa) gene. APL is associated with favourable prognosis, however, approximately 15–20% of patients ultimately relapse. With regards to pre-treatment characteristics, is now clear that long-established prognostic factors such as age and leukocyte count have a major impact on outcome. However, none of these parameters is robust enough, in order to adjust treatments strategies according to the risk of relapse. The quantification of PML-RARa fusion gene transcripts (leukemia-specific chimeric mRNA) can add important prognostic information useful for risk group stratification. However, few clinical studies have been carried out and there are discrepancies concerning the prognostic significance of the quantification of fusion gene transcripts of newly diagnosed patients. In this study we tested the PML- RARa fusion gene transcripts level in 126 newly diagnosed patients with t (15;17) in order to determine their correlation with disease characteristics at presentation and to identify a subset of patients at high risk of relapse. The presence of the PML- RARa fusion gene transcripts was analysed from 1mg of RNA by real-time quantitative RT-PCR (RQ-PCR) based on TaqMan probes and the 7700 Sequence Detector, performed according to the “Europe Against Cancer Program” (Leukemia 2003, 17:2323; 2318–2357).Results: In 121 out of 126 patients, evaluable data were obtained: 73 (60,3%) cases had bcr-1, 4 (3,3%) cases had bcr-2 and 44 (36,4%) cases had bcr-3 fusion types. The expression of the fusion gene was reported as the PML- RARa normalized quantities (NQ, number of PML- RARa copies per 1x104 ABL copies as gene control). The median of NQ was 3030 and the expression was highly variable (range of 826 to 9605). The NQ was not significantly associated with disease characteristic at diagnosis, such as age, percentage of blasts cells, fusion types and platelet counts. Nevertheless, patients with NQ above 3000 had lower white cell counts (7,4±12,1 vs 24,2±39,3x109/L, p=0,03). Therefore, the fusion transcript copy number per leukemic cell was higher in patients with lower leukocyte count. Moreover, in survival analysis, the NQ did not correlate with disease free survival or overall survival.Conclusions: Our data confirms the wide range of differences in expression activity between individual patients. The NQ did not correlate with the clinical and biological disease characteristics except for white cell counts. Neither did it correlate with principal prognostic parameters (response and survival).

Epstein-Barr virus-associated smooth muscle tumours in a patient with an immuno-osseous dysplasia

A term female baby born via a normal delivery to consanguinous parents, presented with a lower respiratory tract infection in the neonatal period. At this time the patient was noted to have a low white cell count associated with short limbs. Immunological investigation revealed lymphopenia and markedly reduced lymphocyte proliferation in keeping with a T-cell immunodeficiency. This episode of lower respiratory tract infection responded well to antibiotic therapy and the patient remained well until 15 months of age. At 15 months of age the patient developed jaundice and was noted to have haemoglobin of 3.0 g/dl, which was treated with transfusion. Laboratory indices revealed an autoimmune haemolytic anaemia. This caused repeated anaemic episodes, requiring blood transfusions on multiple occasions. In an attempt to control the autoimmune haemolytic anaemia, therapy in the form of cyclosporin A and steroids were commenced. The autoimmune haemolytic anaemia was controlled on this regimen until the age of 3 years when it was noted that the patient was developing increasing abdominal distension and breathlessness. Plain film radiography of the limbs was performed to investigate the nature of her limb shortening, which demonstrated generalized osteopenia, delayed bone age and symmetrical limb shortening. The metaphyses were noted to be flared, with under modelled, wide diaphyses and wide ribs. In the hands ivory and cone-shaped epiphyses were seen. These features were consistent with an immuno-osseous dysplasia, most likely to be metaphyseal chondrodysplasia McKusick type (Figs. 1 and 2). An abdominal ultrasound was performed which showed hepatomegaly, with multiple well-defined reduced reflectivity focal lesions throughout both liver lobes, which were hypovascular on colour Doppler. No biliary dilatation was seen and the remaining abdominal viscera had a normal ultrasound appearance. Owing to her breathlessness a chest radiograph was performed which revealed a right lower zone soft-tissue density. Computed tomography (CT) of the thorax was then performed, demonstrating multiple soft-tissue density masses within the lungs. Percutaneous biopsy of both a chest lesion and a liver lesion was performed, revealing the lesions to be leiomyomata. The tumours were demonstrated to be positive for EBV using insitu hybridization (Figs. 3–5). This case presents a grave dilemma for future management. The optimal treatment for the congenital immunodeficiency and auto-immune haemolytic anaemia is ablation of the native bone marrow, followed by bone marrow transplant. The danger of this treatment strategy in this patient is the risk of unchecked proliferation of further smooth muscle tumours, which could become overwhelming. In patients with solitary EBV-associated leiomyomata, surgical excision is a viable option. In this patient with mutiple EBV-driven leiomyomata this is not a treatment option. Currently the patient is not receiving treatment for the tumours, and they are not rapidly progressing.

Concomitant septic and gouty arthritis--an analysis of 30 cases.

To analyse the clinical features and outcomes of gouty patients with concomitant septic arthritis in a medical centre. From the hospital database, we collected 30 hospitalized cases with concomitant septic arthritis and gouty arthritis from 1987 to 2001. All patients had positive bacterial culture and monosodium urate crystals in the affected joints. Medical records of the patients were analysed in detail. The mean age of patients was 52.8+/-12.5 yr. One-third of patients were afebrile at presentation, 30% had a normal blood leucocyte count and 10% had a synovial fluid leucocyte count less than 6000/mm3. The knee joint was the most common site of involvement, followed by the ankle, shoulder and wrist joints. Most patients had long-standing disease and subcutaneous tophi. Subcutaneous tophi rupture with secondary wound infection is the most common route of infection. Causative micro-organisms were Staphylococcus aureus (16 cases, 7 of whom were oxacillin-resistant), Streptococcus sp. (5 cases), Pediococcus sp. (1 case), and Gram-negative bacilli (9 cases). Fourteen patients received surgical debridement, among them two patients had an arthrodesis owing to severe joint destruction and one received above-knee amputation. Two patients died. One died of septic complications and the other died of acute myocardial infarction. Septic arthritis coexistent with gout presented a diagnostic difficulty. An early diagnosis requires a high level of suspicion. Prompt aspiration and analysis of the synovial fluid is imperative, regardless of the absence of fever or leucocytosis. Culture of the aspirated synovial fluid is warranted in gouty attack, even when it has a low white cell count or the Gram stain reveals no organisms.

White cell count and intensive care unit outcome.

A high white cell count on admission to the intensive care unit (ICU) is generally perceived to be associated with severe illness and poor outcome, but the implications of a low white cell count are less well recognised. We retrospectively analysed data on 4,165 patients. The white cell count on admission was split into four categories, leucopenic (< 4.0 x 10(9).l(-1)), normal (4.001-10.0 x 10(9).l(-1)), leucemoid (10.001-25.0 x 10(9).l(-1)) and an exaggerated leucemoid response (> 25.001 x 10(9).l(-1)). The mortality of patients with leucopenia on admission to the intensive care unit was higher than those with normal or moderately raised white cell count (37.5% vs. 18.9% and 23.9%, respectively). A leucopenic response, as well as an exaggerated leucemoid response, is associated with an increased mortality.

CHRONIC NEUTROPHILIC LEUKAEMIA: A DISTINCT CLINICAL ENTITY?

CHRONIC NEUTROPHILIC LEUKAEMIA: A DISTINCT CLINICAL ENTITY?

Olanzapine-induced leukopenia with human leukocyte antigen profiling

Olanzapine is an atypical antipsychotic medication frequently used in the management of psychotic states. While it has proved to be safe compared to clozapine with regard to haematotoxicity, because it has only been available for a few years, full documentation of its haematological side-effects remains incomplete. We report a case of olanzapine-induced leukopenia with associated neutropenia. Since clozapine-induced haematotoxicity has been associated with characteristic human leukocyte antigen (HLA) groups, HLA typing was determined in this patient. Following failure with typical antipsychotic medication, the patient received 10 mg/day of olanzapine. Three weeks later, he developed fever and a significant decrease in leukocyte count. Olanzapine was immediately discontinued. HLA typing was determined. The white cell count returned to normal and the fever, most probably secondary to the low white cell count, subsided with antibiotic treatment. HLA typing results were: A1 24, B7, B35, DRB1*15, DRB1*11, DRB3*01-03, DRB5*01-02. Olanzapine may induce serious leukopenia and neutropenia. HLA typing in this single patient demonstrated a distinct haplotype compared to that previously observed in clozapine-induced haematoxicity.

Associations between temperament, performance and immune function in cattle entering a commercial feedlot

Behavioural, endocrine and immunological measures made at weaning or feedlot entry were examined for associations amongst them and with feedlot performance with a view to identifying predictors of the suitability of cattle for feedlot finishing. The 24 animals used in this experiment were chosen to represent the extremes of temperament amongst 209 beef steer calves that were weaned at 7–9 months of age. From a subgroup of 50 animals that were paddock-weaned without handling or supplementary feeding, the 12 animals with the worst temperament were selected on the basis of flight time and crush behaviour assessment. From a matched subgroup of 100 animals that were weaned in yards and hand fed for 10 days, the 12 animals with the best temperament were selected on the basis of flight time, crush score and a novel behavioural test performed as follows. Each morning, fresh hay and a small amount of grain were offered in an adjacent pen and calves were scored on their willingness to walk past an observer standing by the gateway between the 2 pens. These 2 experimental groups were designated as ‘nervous’ and ‘calm’, respectively. Blood samples were collected at the start and end of weaning for cortisol assay. On entry to a commercial feedlot 6 months later, blood samples were collected for cortisol and immunological assays on day 1 (immediately after induction processing) and day 5 (after 4 days in the feedlot pen). The nervous group had significantly higher cortisol levels at weaning and at the feedlot and, after 85 days on feed, had significantly lower average daily gain and significantly higher morbidity than the calm group. Groups did not differ in total and differential leucocyte counts, lymphocyte proliferation, production of the cytokine interferon, natural killer cell activity, neutrophil myeloperoxidase activity, lymphocyte subsets (CD4, CD8 or WC1), and serum concentrations of IgA, but IgM was lower in the calm group. Significant correlations were found between cortisol and a number of haematological variables, flight time, and average daily gain. The correlations suggest that desirable traits at feedlot entry may include slow flight time, low crush score and high confidence score, low cortisol, low total white cell count, low neutrophil count, high CD8 + lymphocyte percentage, high lymphocyte proliferative activity and high IgA concentration. Relationships between behavioural traits and immunological measures may have utility in predicting the suitability of individuals for the feedlot environment.

Haematological toxicity of cranio-spinal irradiation

Background: To assess the frequency and severity of myelosuppression due to cranio-spinal irradiation either alone or in combination with chemotherapy and to identify patients at high risk of haematological toxicity who may require supportive therapy. Materials and Methods: Between 1965 and 1994, 210 patients received cranio-spinal axis (CSA) radiotherapy as a component of treatment for primary CNS tumours at the Royal Marsden Hospital. Full blood counts (FBC) were obtained before, during and after radiotherapy in 200 patients. Haematological toxicity was graded according to the WHO criteria and duration was measured from the onset of grades 3 and 4 toxicity until recovery to grade 2. Results: Sixty-six (33%) patients developed grades 3 and 4 haematological toxicity. Nadir occurred during radiotherapy and was most frequent during the second week of spinal radiotherapy. Low haemoglobin and white cell counts prior to radiotherapy increased the likelihood of myelosuppression. Nine patients had febrile episodes requiring antibiotic therapy. Treatment was interrupted in 49 patients but treatment time was extended beyond 12 weeks in only 17 (8%) patients of which nine were due to haematological toxicity. Chemotherapy (vincristine) during radiotherapy did not impact on haematological toxicity. Age and prior chemotherapy were independent predictive factors for haematological toxicity. The relative risk of leukopaenia in children compared to adults was 7.9 (95% CI 3.4–18.6%). Patients who received prior chemotherapy had a relative risk of toxicity of 6.1 (95% CI 2.9–12.8%). Conclusion: One-third of patients undergoing CSA radiotherapy develop grades 3 and 4 haematological toxicity. The risk is higher in children and in patients who receive chemotherapy prior to radiation. There was no treatment-related mortality and only nine of 200 patients (9/60 of those with toxicity) required supportive treatment for neutropaenic sepsis. The low incidence severe haematological toxicity does not warrant routine use of haemopoietic growth factors during CSA irradiation and future studies should target high risk sub-groups.

Clinical features and indicators of prognosis of herpes simplex and varicella-zoster hepatitis in non-pregnant patients

Herpes simplex (HSV; type I and II) and varicella-zoster virus (VZV) form the alpha herpesvirus subfamily, characterized by latency in sensory nerve ganglia, a short replicative cycle, rapid cell to cell spread, characteristic skin lesions and, rarely, development of fulminant hepatitis. Dissemination of HSV type II from the genitourinary tract may explain the high frequency of this type in pregnant women with herpesvirus hepatitis. AIM: To characterize the clinical features of HSV and VZV hepatitis in a series of non-pregnant patients. METHODS: A retrospective review of cases diagnosed at the Mayo Clinic with HSV or VZV hepatitis by liver histopathology or culture techniques during life or at autopsy. RESULTS: From 1979 to 1996, 13 new cases (9 male, 4 female) ofHSV and VZV hepatitis were diagnosed with a mean age of 39 years (range 2-76). Most had fever (maximal temperature 38.4 _+ 0.3°C; Mean 4SE) and a low white cell count (nadir 3.2 _+ 1.0*109/L). All had evidence of severe hepatocellular necrosis (maximal AST 3400___ 1200 U/mL; maximal ALT 14004-500 U/mL). Cholestasis and jaundice were absent until late in the disease (maximal alkaline phosphatase 600_ 140 U/mL; maximal bilirubin 4.2_ 2.3 mg/dL) and renal function remained intact (maximal creatinine 1.6 40.5 mg/dL). Eight cases were due to HSV type I, 5 were due to VZV. Five patients survived (2/8 or 25% with HSV; 3/5 or 60% with VZV). None of the survivors had evidence of underlying immuno-compromise or malignancy. Six of the 8 (75%) nonsurvivors were immuno-compromised secondary to chemotherapy and died within days from liver failure or disseminated disease (5 patients had HSV; 1 VZV); the other 2 were not immuno-compromised and died from liver failure and a CVA complicating the hepatitis. Survivors differed from nonsurvivors in the maximal AST level (1100_+ 100 U/mL vs 4900_+ 1700; p=0.03) and the nadir of the white cell count (6.2 _+ 1.6109/L vs 1.4 _+ 0.6; p=0.005). CONCLUSIONS: 1) HSV and VZV hepatitis are characterized by fever, very high serum aminotransferase levels, a low white cell count and late, mostly mild, cholestasis; 2) HSV type II hepatitis is rare in non-pregnant patients; 3) HSV type I and immunocompromise are associated with high mortality; and 4) survival is associated with significantly lower transaminase levels and higher white cell counts.

Monitoring of patients on high dose antipsychotic medication

In the light of recently published Royal College of Psychiatrists' guidelines on the use of high dose antipsychotic medication, electrocardiographic and blood investigations were performed on 11 patients with learning disabilities receiving such treatment. All patients had normal electrocardiograms (ECGs). Four patients had asymptomatic low white cell counts and mild anaemia was detected in three individuals. Three patients were hyponatraemic; liver function tests were essentially normal. Issues around routine monitoring of such patients are discussed.

Reply from Clozaril Patient Monitoring Service

EDITOR,—We have been aware for some time that the strict haematological limits used by the Clozaril Patient Monitoring Service may exclude patients who normally have low white cell counts from receiving clozapine. Lawton et al reported “normal neutropenia” in an Afro-Caribbean patient taking clozapine and expressed similar concerns to those raised by Nigel Fisher and Barbara Baigent.1 In answering Lawton et al we explained why the safety limits were set so strictly and provided data to support …

ARE SLOW-ACTING ANTI-RHEUMATIC DRUGS MONITORED TOO OFTEN? AN AUDIT OF CURRENT CLINICAL PRATICE

Rheumatologists usually recommend monthly blood monitoring when patients with rheumatoid arthritis (RA) are treated with slow-acting anti-rheumatic drugs (SAARDs). Is monthly monitoring needed or could its frequency be reduced? We audited the opinions of UK rheumatologists and reviewed clinical experience at three centres. To ascertain the interval at which patients are monitored and the determinants of monitoring policy we sent a questionnaire to 193 consultant rheumatologists; 143 (74%) replied. The majority use monthly monitoring for most SAARDs except sulphasalazine, chloroquine and hydroxychloroquine. There is extensive variation, which is not related to the type of rheumatology unit or whether a shared scheme with general practitioners is used. Reviewing experience in 390 patients treated with SAARDs at three adjacent rheumatology units in London showed that haematological adverse reactions were infrequent. During 1560 patient-years of treatment involving 18,720 monthly monitoring visits there were 13 haematological adverse reactions (11 thrombocytopenias and two leucopenias). Five thrombocytopenias developed after 6 months of treatment; five occurred gradually over 5 months or more and one borderline low platelet count was seen once. The two leucopenias were borderline low white cell counts occurring gradually over 3-6 months. Such frequent monitoring is expensive. The total cost of monitoring 390 patients for 1560 patient-years was 420,000 pounds. The cost of detecting each adverse reaction was 32,000 pounds. Three-monthly monitoring when therapy is established after an initial stabilizing period would have identified seven out of eight late adverse reactions. Monitoring policies are mainly based on clinical consensus with few prospective studies of their value; they need re-evaluation.

Acute promyelocytic leukemia toluidine blue subtype.

In the hypergranular group of acute promyelocytic leukemia (APL) a rare subvariant with basophilic granules, metachromatic for toluidine blue, is recognizable. To evaluate the incidence as well as the biological and clinical significance of this subtype, we studied 53 consecutive untreated patients with APL with morphological, cytochemical, immunological and cytogenetic methods. In 10 cases (19% of the total) granules stained metachromatically in percentages of promyelocytes ranging from 16 to 60. In these cases peroxidase positivity was weaker than in the classic hypergranular and microgranular M3 and activities of esterases were usually present; at the ultrastructural level granules contained particulate material. Immunophenotypic and cytogenetic characteristics seemed not to differ from those of other M3 cases. Coagulopathy was usually life-threatening, notwithstanding the low white cell count, and the median survival was short. Hyperhistaminemia-related symptoms were not observed. Cytochemical, immunologic and cytogenetic findings are useful to differentiate this form from M2 with basophilic differentiation and from mast cell leukemia.

Preliminary results of a prospective randomized controlled clinical trial with hydroxyurea and cisplatinum as radiosensitizers in advanced carcinoma of the cervix

AbstractSixty‐three patients with cervical carcinoma were randomized prospectively to receive radiation therapy alone, or hydroxyurea (HU) and cisplatinum as radiosensitizers. All patients were treated by a four field box technique, 2.5 Gy daily, 4 days per week, to a total dose of 50 Gy (TDF 90). A central boost by high dose rate intracavitary therapy (HDR‐ICT), 4.2 Gy daily × 4 was given on the same days (with a 6 hr gap between fractions) during the last 4 days of external beam therapy. This reduced the overall treatment time from 6 to 5 weeks. The Indwelling Intrauterine Tube technique was used. The summated dose at point A is 66.8 Gy (TDF 130). Twenty patients (group A) received radiation therapy (RT) only; 21 (group B) received cisplatinum 15 mg/m2 on alternate days, plus RT; 22 patients (Group C) received HU 80 mg kg/body weight on alternate days, plus RT. The median time of follow‐up is 14 months for group A and 19 months for the other two groups. The survival probability for patients with at least 20 months follow‐up (Kaplan‐Meier method) is 0.61, 0.88, and 0.84; disease‐free survival is 0.42, 0.63 and 0.62 for groups A, B, and C, respectively, which are not statistically significantly different. Early complications: Moderate to severe cystitis was seen in 15,4.76, and 9.09%; proctitis in 5,0, and 4.5%, and diarrhoea in 5, 14.29, and 13.64% for groups A, B, and C; for a total of 25, 19.05, and 27.28%, respectively. Late moderate to severe complications: Cystitis occurred in 0,9.5, and 4.55%, and proctitis in 10,4.76, and 9.09% in groups A, B, and C, respectively. One patient in group B (4.76%) and two patients in group C (9.09%) developed chronic diarrhoea giving a total late complication rate of 10, 19.04, and 22.7%, respectively. In addition, vaginal stenosis occurred in 15, 23.81, and 9.09% in groups A, B, and C, respectively. No rectovaginal fistulae developed in any of the three groups. All except 1 of the 63 patients completed their treatment. Three patients out of group A, 2 out of group B, and 1 out of group C were lost to follow‐up. One out of the 63 patients, 1.56% (group C) needed a colostomy for a grade III late proctitis. Drug related toxicity was not severe and proved that the regimens could be tolerated. Treatment had to be interrupted in group A, because of treatment related morbidity, for 2 days in one patient, 2 weeks in a second, and terminated in a third after 45 Gy teletherapy due to unrelated problems. There were no treatment interruptions in group B. In group C, 2 patients were rested for 7 days each as a result of a low white cell count (WCC). The incidence of metastatic disease was the lowest in group B; the complication rate the highest in group C. The results indicate that cooperative controlled studies based on these results should be considered. © 1993 Wiley‐Liss, Inc.

Two-year incidence of tuberculosis in cohorts of HIV-infected and uninfected urban Rwandan women.

To determine the prevalence of Mycobacterium tuberculosis infection and the incidence of tuberculosis in HIV-infected and uninfected urban Rwandan women, 460 HIV-positive and 998 HIV-negative childbearing women were recruited from pediatric and prenatal care clinics and were enrolled in a prospective study in 1988 and followed for 2 yr. Tuberculin testing was administered 12 to 18 months after enrollment. Fifty-three percent of HIV-negative women had positive tuberculin tests (induration > or = 10 mm), with higher rates among older women and among women who had received BCG vaccine. Only 21% of HIV-positive women had positive tuberculin tests, with no relationship to BCG vaccine. Follow-up was available for 93% of subjects. Tuberculosis was diagnosed in 20 HIV-positive women and in two HIV-negative women. Features associated with an increased risk of tuberculosis among HIV-positive women included: age > or = 30, body mass index in the lowest quartile, low income, erythrocyte sedimentation rate > 75, positive tuberculin test, and chronic cough, chronic fever, and weight loss. Among Rwandan women who are infected with HIV, approximately half of those who are infected with M. tuberculosis do not have positive tuberculin tests. The rate ratio for development of tuberculosis among HIV-positive women was 22 (95% CI, 5 to 92). New algorithms are needed to improve the early detection of tuberculosis among HIV-positive patients in Africa.

High frequency of antibodies to Mycoplasma penetrans in HIV-infected patients

Mycoplasma penetrans, a novel mycoplasma isolated from HIV-1-infected patients with AIDS, has pathogenic properties associated with in-vivo virulence. Enzyme-linked immunosorbent assay and western blotting detected a more than 100 times higher frequency of antibodies to the mycoplasma in serum from HIV-1-infected patients with AIDS (40%) than from HIV-negative controls (0·3%). Serum from 20% of HIV-1-infected, symptom-free individuals also had M penetrans specific antibodies. The antibodies' major immunoreactivity was directed against P35 and P38, the two main lipid-associated membrane protein antigens of the organism. Patients attending sexually transmitted disease clinics had a low frequency of antibody (0·9%). None of 178 HIV-negative patients with different non-AIDS diseases, many associated with immune dysfunction and/or low white cell counts, tested positive for the antibodies. M penetrans, apparently not a commensal and not a simple opportunist, is uniquely associated with HIV-1 infection and AIDS.

ERYTHROPOIETIN (EPO) TREATMENT OF PROTEIN AND IRON SUPPLEMENTED PREMATURE AGA INFANTS

Preterm AGA infants with birth weights 900-1400 g are studied in this controlled randomized multicentertrial. The infants are followed from 3 to 8 weeks of age with a further assessment at the age of 16 weeks. Only “healthy preterms” are included. Human milk is given throughout the study, and both treatment group and controls receive extra protein and iron to ensure sufficient supply for increased red cell production. Milk protein (0.9 g/100 ml human milk) and oral iron (18 mg Fe++/day increasing to 36 mg/day if serum iron falls below 16 μmol/l) are given. EPO (Eprex, Cilag AG) is given s.c. thrice weekly; 100 IU/kg/dose from week 3 to week 7. Until now 24 children have been included (10 treated & 14 controls). Preliminary data show : BW of the groups are similar (1294 g and 1244 g). There is a significant increase in reticulocyte count after one week of EPO-treatment (8.5% vs. 4.5%, p < 0.01). Mean Hb concentrations after 3 and 4 weeks of EPO-treatment are 11.6 g/dl and 12.1 g/dl respectively. Similar control values are 10.1 g/dl and 9.8 g/dl, which are significantly lower (p<0.05). The calculated total red cell production increased rapidly and significantly (p<0.01) during the first week of EPO treatment, and remained higher than that of the control group during EPO treatment. Three children in the control group needed blood transfusions during the study, none in the treatment group. No adverse effects have been seen, particularly no low white cell counts or increased trombocytes.

Heterogeneity of T cell lymphoblastic leukaemias.

Twenty eight out of 170 consecutive cases of acute lymphoblastic leukaemia (ALL) were examined. They were of T cell origin, with the following distribution: seven (28%) cases had pre-T or prothymic features; nine (36%) cases showed early thymocytic features, six (24%) had cortical features; and three (12%) had a "mature" phenotype. The remaining three cases could not be sub-classified. A striking finding was that pre-T ALL differed from intrathymic ALL not only in the absence of both E rosettes and intrathymic differentiation antigens, but also in the expression of two non-lineage specific antigens HLA-DR and CD10. Both antigens appear in the bone marrow from the very first stages of lymphoid differentiation, implying that the origin for pre-T ALL is bone marrow. A comparison of the clinical features of pre-T and thymic ALL showed that pre-T ALL disease showed a pattern more similar to non-T ALL disease: a lower incidence of mediastinal mass, absence of extrahaematopoietic disease, lower white cell counts and haemoglobin concentrations, and a higher incidence of bone pain. No obvious difference in response to treatment was apparent. The results show that T-ALL is not only a heterogeneous immunological group but also suggest that it may have different origins: bone marrow for pre-T ALL and the thymus for thymic ALL.

Clinical Importance of Myeloid-Antigen Expression in Acute Lymphoblastic Leukemia of Childhood

Leukemic cells in 15 to 25 percent of patients with acute lymphoblastic leukemia (ALL) express myeloid antigens as well as lymphoid antigens (the latter reflecting B-cell or T-cell lineage). The relations of myeloid-antigen expression to other features of ALL and to prognosis have been controversial. We analyzed clinical and laboratory features present at diagnosis in 236 consecutive cases of ALL in children. Immunophenotyping, including single- and dual-fluorescence analyses, was used to classify leukemic cells as B or T lymphoblasts and also to identify myeloid-antigen expression--the simultaneous expression of lymphoid-associated antigens and at least one of three myeloid-associated antigens (CD33, CD13, and CD14) on cells classified as L1 or L2 according to the French-American-British system. Forty-five of 185 patients with B-lineage ALL had myeloid-antigen expression, as did 8 of 41 patients with T-lineage ALL. In 10 patients, the lineage could not be determined. Myeloid-antigen expression was associated with L2 morphology (P less than 0.05), but it did not correlate with other prognostic features recognized previously. Multivariate analysis showed that myeloid-antigen expression was an important predictor of relapse in childhood ALL and the most significant prognostic factor statistically (P less than 0.0001). A white-cell count greater than or equal to 50 x 10(9) per liter at diagnosis was also an important and highly significant prognostic feature (P less than 0.001). After 40 months, the estimated disease-free survival for patients with ALL was 84 percent for those without myeloid-antigen expression and with a low white-cell count, 57 percent for those without myeloid-antigen expression and with a high white-cell count, 47 percent for those with myeloid-antigen expression and a low white-cell count, and 26 percent for those with myeloid-antigen expression and a high white-cell count (P less than 0.00001). Myeloid-antigen expression is an important independent predictor of a poor response to chemotherapy in childhood ALL.

White Cell Count During Maintenance Chemotherapy for Standard-Risk Childhood Acute Lymphoblastic Leukemia: Relation to Relapse Rate

In a retrospective study of 84 children with standard-risk acute lymphoblastic leukemia diagnosed in 1981-1986, mean white cell count (mWBC) during maintenance chemotherapy (MT) was found to be significantly related to risk of hematological relapse, giving patients with the higher mWBC the poorer outcome. The only other significant relapse-related risk factor was white-cell count at diagnosis. mWBC was not significantly related to white cell count at diagnosis, sex, age, or dose of methotrexate or mercaptopurine. Patients with low mWBC also had relatively low white-cell counts after cessation of therapy when compared with patients with high mWBC.