Generalized Monocyte Deficiency in Leukaemic Reticuloendotheliosis

Examination of the blood of 40 patients with leukaemic reticuloendotheliosis (LRE) revealed a drastic reduction in monocyte numbers (mean 74/μl) when compared to a normal group of 33 (mean 442/μl). Repeated blood studies in 8 LRE patients were made over periods of 2 months to 5 years and monocytopenia was observed to be a persistent phenomenon. Similarly, tissues from 29 patients showed an overall decrease in numbers of monocytes/histiocytes when compared with those of 73 control subjects. Skin window examinations in all 11 patients so studied showed marked reduction or absence of monocyte response to inflammation. 2 exceptional cases to this trend are noted. In one, circulating monocyte levels remained normal over a 14-month period while examinations of blood and marrow in this case showed few hairy cells. In another case, severe and persistent monocyte deficiency was noted during a 2-year period of unsuccessful treatment. When he eventually responded to low dose chlorambucil and his Hb rose from 40–140 g/1 and WBC became normal, the number of circulating monocytes also became normal.     

Defective Monocyte Function in Legionnaires' Disease Complicating Hairy Cell Leukaemia

ABSTRACT We describe a case of Legionnaires' disease in a 64-year-old man, in which hairy cell leukaemia was diagnosed after the onset of the infection. Immunological studies revealed a complete suppression of blood monocyte chemotactic and oxidative burst activities. We suggest that in hairy cell leukaemia both monocytopenia and defective functions of monocytes underlie the increased susceptibility to intracellular infections including Legionnaires' disease.     

Granulocyte transfusions in neutropenic patients: beneficial effects proven?

Despite the huge armamentarium of modern antibiotics and anti-fungals infections remain life-threatening events in patients with profound neutropenia. For decades, the value of granulocyte transfusions (GT) has been explored and results are still not conclusive. However, it has been shown that GT increase peripheral blood neutrophil counts of recipients and lead to migration of functional neutrophils into inflamed tissues. A favourable increment of absolute neutrophil counts is observed after concentrates from technically up-to-date apherese from granulocyte-colony stimulating factor-stimulated donors. Most studies indicated a potential positive effect on infection elimination with a minimum cell content of GT (1·5–3 × 10⁸/kg recipient body weight). Although to date the beneficial effect of GT is not proven in prospective randomized trials, in specific situations GT is an option to treat infections along with antibiotics when there is profound neutropenia. However, these patients in critical situations need to be treated within carefully designed studies based on the best known methods for providing granulocyte concentrates in sufficient dose and frequency, standardized similar to other blood product transfusions. That includes definition of minimum cell content, maximum interval between apheresis and application, storage conditions, methods of donor stimulation according to patient's body weight and frequency of GT. This review considers the results of recent studies using GT from cytokine-stimulated donors and the consequences and effects in recipients and donors.     

Kinetics of 111In-Labelled Leukaemic Cells in Blast Crisis of Chronic Myelocytic Leukaemia

The distribution within the body of autologous leukaemic cells labelled with ¹¹¹In oxine was studied in 4 patients with blast crisis of chronic myelocytic leukaemia (CML) by means of serial samples and gamma camera imaging. Leukaemic cells of the blood initially entered the spleen and liver, and the major site of localization was the former rather than the latter. A portion of leukaemic cells, which rapidly entered the liver, left temporarily 3 h after reinjection. Leukaemic cells entered the spleen maximally at 3 or 24 h and then continued to leave gradually or rapidly up to 48 h. The majority of leukaemic cells in acute myelocytic leukaemia did not leave the spleen for up to 48 h. It is suggested that the destruction of sinusoidal structures of the spleen due to marked infiltration of leukaemic cells in CML impairs the effects of filtration in endothelial cells of sinusoids and facilitates the entry of leukaemic cells into sinusoids from splenic cords.     

Therapeutic transfusions of granulocytes collected by simple bag method for children with cancer and neutropenic infections: results of a single-centre pilot study

BACKGROUND AND OBJECTIVES: Granulocyte transfusion therapy (GTX) can be effective for life-threatening infections unresponsive to conventional antimicrobial therapies in severely neutropenic children with cancer. We developed a new granulocyte collection method, named the 'bag method', in which apheresis, hydroxyethyl starch (HES) or dexamethasone are not used. We undertook a pilot study to determine the feasibility and the safety of GTX collected by the bag method for children with cancer and life-threatening infections. MATERIALS AND METHODS: A total of 25 GTX were administered to 13 patients (median age 3 years, range: 0.3-17; median weight 10.6 kg, range: 4.5-49.8) with neutropenia-related infections. Thirteen blood-relative donors received granulocyte colony-stimulating factor (G-CSF) (5-10 microg/kg), subcutaneously, 14 h before collection. Major end-points were granulocyte yields, post-transfusion absolute neutrophil counts (ANC) in patients, donor and patient safety, and clinical outcome on day 30. RESULTS: The median yield of ANC per 400 ml of processed whole blood was 6.2 x 10(9) (range: 2.5-15.0 x 10(9)). Patients received a mean of 6.4 +/- 0.8 x 10(8) granulocytes per kg of body weight per transfusion. The 1-h and 24-h post-transfusion ANC rose to 607 +/- 124/microl and 704 +/- 300/microl, respectively, from the baseline of 21/microl before the first GTX. Adverse reactions were observed in five of 13 donors (bone pain, headache, vasovagal reaction; all < or = grade 2) and in two of 25 transfusions of 13 patients (transient hypoxia; grade 3). Ten patients had favourable responses, and infection resolved in nine patients. CONCLUSIONS: The bag method without apheresis relieves the physical load of donors and enables patients with a low body weight to provide an adequate dose of granulocytes.     

Ultrastructural Aspects of Leukaemic Cells in Acute Myeloblastic Leukaemia

Ultrastructural aspects of leukaemic cells in a case of myeloblastic leukaemia are described. Changes concerning of mitochondrial ultrastructure, but primarily the presence of vast numbers of fibrillar structures in the cytoplasm of the examined cells were observed. These structures were spreading through their gradual widening to cover almost the whole cell cytoplasm, damaging its organellae and internal architecture. The nature of the observed changes remains unknown.     

Granulocyte transfusions for neutropenic patients with life-threatening infections: a single centre experience in 47 patients, who received 348 granulocyte transfusions

INTRODUCTION: The role of granulocyte transfusions (GT) in patients with neutropenia-related infections remains controversial. MATERIALS AND METHODS: A retrospective analysis of 47 neutropenic patients, treated with 348 consecutive GTs for life-threatening infections between 1999 and 2004, is presented. RESULTS: The only grade III-IV toxicity observed in GT recipients was respiratory deterioration (n = 6, 12.8%). The overall infection-related mortality (IRM) approached 38%. Achievement of a neutrophil count of > 700 cells per microl after at least 50% of days of GTs (n = 33, 70%) significantly correlated with reduced IRM (27.3% vs. 64.3%, P < 0.02). GT doses of > 2 x 10(10) neutrophils per bag appeared to increase both neutophil and platelet counts following transfusion. CONCLUSION: GTs are safe and should be considered for patients with life-threatening neutropenic infections. However, prospective randomized studies of GTs are the only way to establish the true role of GTs.     

Community‐acquired Legionnaires' disease in a renal transplant recipient with unclear incubation period: the importance of molecular typing

Transplant recipients are at risk of developing Legionnaires' disease (LD) because of impaired cellular immunity. Here, we describe a renal transplant recipient who developed LD at least 10 days after hospital admission and transplantation. The hospital water network was initially suspected, but further testing determined that the probable source was the patient's domestic water supply. Our report also suggests that the patient's immunosuppressed state may have switched potential colonization to pneumonia.     

The role of granulocyte transfusions in neutropenic patients

The precise role for donor granulocyte infusions remains to be delineated, partly because of the lack of defined clinical trials. The aim of this article is to summarize the studies undertaken so far and highlight the logistical problems associated with undertaking future studies. We also aim to provide a practical guide to the application of this therapeutic approach.     

Blood Transfusion in Sickle Cell Disease

Sickle cell anemia is an inherited disease that causes chronic hemolytic anemia. Its pathognomonic signs and symptoms are caused by hemoglobin (Hb) S, which results from a single nucleotide substitution in the β-globin gene that places the amino acid valine with glutamic acid at codon 6 of the β-globin chain. Hb S is an insoluble Hb that crystalizes at low oxygen tension and other precipitating conditions leading to rigidity of red cells and clumping in small blood vessels.

Patients with sickle cell disease have a variable Hb level that may range from 7.0 to 11.0 g/dL in their steady state condition. The most common cause of hospital presentation is due to acute painful crisis that results from vaso-occlusion by sickled cells. These episodes are treated with hydration and analgesia and do not require blood transfusion. Blood transfusion should be aimed to increase tissue delivery of oxygen. Hb S is known to be a low affinity Hb and so delivers oxygen at a lower partial pressure of oxygen compared to Hb A. Even with adequate pre transfusion testing and precautions, blood transfusion is never totally safe and short or long term complications may occur.

Blood transfusion in patients with sickle cell disease has only limited indications such as acute hemolytic, aplastic or sequestration crises. Chronic transfusion protocols are implemented in cases of strokes or high cerebral blood flow ultrasonic studies as a prophylactic measure. Exchange blood transfusion is used in some complications of the disease such as acute chest syndrome (ACS), priapism or peri operatively. Once it is decided to transfuse blood, the transfused blood should be Hb S negative, Rh and Kell antigen matched.     

A community-acquired Legionnaires’ disease outbreak caused by Legionella pneumophila serogroup 2: an uncommon event,Italy, August to October 2018

In September 2018 in Brescia province, northern Italy, an outbreak of Legionnaires'' disease (LD) caused by Legionella pneumophila serogroup 2 (Lp2) occurred. The 33 cases (two fatal) resided in seven municipalities along the Chiese river. All cases were negative by urinary antigen test (UAT) and most were diagnosed by real-time PCR and serology. In only three cases, respiratory sample cultures were positive, and Lp2 was identified and typed as sequence type (ST)1455. In another three cases, nested sequence-based typing was directly applied to respiratory samples, which provided allelic profiles highly similar to ST1455. An environmental investigation was undertaken immediately and water samples were collected from private homes, municipal water systems, cooling towers and the river. Overall, 533 environmental water samples were analysed and 34 were positive for Lp. Of these, only three samples, all collected from the Chiese river, were Lp2 ST1455. If and how the river water could have been aerosolised causing the LD cases remains unexplained. This outbreak, the first to our knowledge caused by Lp2, highlights the limits of UAT for LD diagnosis, underlining the importance of adopting multiple tests to ensure that serogroups other than serogroup 1, as well as other Legionella species, are identified.     

Beneficial Effect of Granulocyte Transfusions in Patients with Defects in Granulocyte Function and Severe Infections

A 3-year-old boy (patient A) with a congenital and a 24-year-old man (patient B) with an acquired granulocyte function defect received supportive granulocyte transfusions for the management of severe infections. The boy had suffered from recurrent infections since birth. His granulocytes showed in vitro almost no chemotactic responsiveness, an impaired phagocytosis and reduced intracellular killing of Candida albicans. Family studies suggested that it was an inherited autosomal recessive defect. The child developed a Pseudomonas pneumonia at the age of 3 years, which did not respond to antibiotic therapy. Granulocyte transfusions were then started and soon after the fever and pneumonia disappeared. Patient B showed the haematological signs of a preleukaemic state. He had 3 recurrent episodes of furunculosis which led each time to cellulitis and septic temperatures accompanied by symptoms of an enterocolitis. Tests of granulocyte function in vitro showed reduced intracellular killing of Staphylococcus aureus. Granulocyte transfusions were started, since no clinical improvement could be attained by antibiotics. With transfusion therapy, fever, cellulitis and enterocolitis disappeared each time.     

Serum granulocyte colony-stimulating factor levels in patients with chronic neutropenia of childhood: modulation of G-CSF levels by myeloid precursor cell mass

The serum G-CSF levels of eight patients with severe congenital neutropenia (SCN) were found to be significantly higher than those of 22 patients with chronic benign neutropenia (CBN). The relative number of cells expressing the G-CSF receptor in light density bone marrow cells (LDBMC) was lower in patients with SCN than in patients with CBN or in normal subjects. When recombinant human G-CSF was incubated with LDBMC, G-CSF levels were decreased by LDBMC from normal subjects and CBN patients, but not by those from SCN patients. Serum G-CSF concentrations, which are affected by mature neutrophils, may also be modulated by myeloid precursor cells in the bone marrow.     

Leukaemic pulmonary infiltrates in adult acute myeloid leukaemia: a high-resolution computerized tomography study

Leukaemic infiltration of the lungs may occur in acute myeloid leukaemia (AML). Pulmonary infiltrates are usually microscopic and invariably associated with hyperleucocytosis. Four AML patients with respiratory symptoms and low leucocyte counts underwent standard chest radiography, bronchoscopy with bronchoalveolar lavage and high-resolution computerized tomography (HRCT) of the lungs. HRCT scans showed pulmonary infiltrates with alveolar, interstitial, mixed and peribronchial/perivascular patterns in all patients, including one with negative standard radiographic findings. Infectious agents were excluded. Histology of the lung biopsy/autopsy specimens showed leukaemic infiltrates. Pulmonary leukaemia may be the cause of pulmonary infiltrates, even in non-hyperleucocytosic AML patients with low blast counts.     

Increase of Proliferative Activity of Leukaemic Blast Cells from Human Peripheral Blood in Liquid Culture

The proliferative behaviour of leukaemic blast cells from the peripheral blood of 12 patients suffering from acute leukaemia was investigated in short term liquid culture. In 3 cases of AML an increase of the blast cell number was observed exceeding the initial value whereas in 9 other cases the cell number decreased more or less rapidly. In 9 of these patients the proliferation kinetics of the cultured leukaemic blast cells were studied with ³H-thymidine labelling. In all these cases the labelling index increased during the first days of culture, in 3 cases to values of 48 %, 45 % and 38 % on day 3. Only in 5 cases, however, did an absolute increase of the blast cells incorporating ³H-thymidine occur. Here the doubling times of the proliferating leukaemic blast cells were estimated to be 12, 13, 14, 28 and 55 h. Since a doubling time of 12 to 14 h seems to be too short to be explained only by an exponential growth of the initially proliferating cells it is postulated that leukaemic blast cells in a G₀- or long G₁-phase were present in the peripheral blood of these patients and that these entered the cell cycle during liquid culture.     

The spectrum of Fusarium infection in immunocompromised patients with haematological malignancies and in non-immunocompromised patients: a single institution experience over 10 years

Fusarium is a newly emerging fungal pathogen associated with significant morbidity and mortality in the immunocompromised host. We have reviewed our hospital's experience with Fusarium between 1985 and 1995. Fusarium species were isolated from 22 specimens, representing 11 patients. Cases were not clustered by time period. The median age of the patients was 36.5 years (range 17-69 years). The sources of the organism were 12 skin lesions from eight patients, seven blood cultures from two patients and one specimen each from a Hickman catheter tip, nail clippings and a bronchoalveolar lavage. Seven of the patients had chemotherapy-induced neutropenia when the Fusarium was isolated. Five of them developed invasive fusarosis during acute leukaemia induction treatment. They remained neutropenic, and none survived. The other two patients recovered from neutropenia and were treated successfully for this infection. The remaining four patients were not neutropenic or immunocompromised. Three grew Fusarium from skin or nail clippings and one from bronchial alveolar lavage (BAL). There was no evidence of invasive disease in any of the four. None of them received antifungal therapy, and they were all alive at last follow-up. We conclude that Fusarium is a newly emerging infection in neutropenic patients. A high index of suspicion, especially for skin lesions, will help in early diagnosis before systemic and visceral dissemination. Excision of the initial focus of infection and antifungal therapy, aided by speedy neutrophil recovery, are likely to protect patients threatened with these fatal infections. Fusarium isolated from non-neutropenic, non-immunosuppressed patients is not significant and does not merit systemic antifungal treatment.     

The place of myeloid growth factors in the treatment of hairy-cell leukaemia

A patient with hairy-cell leukaemia was treated with granulocyte colony stimulating factor lenograstim (Granocyte) 300 μg daily by subcutaneous injections. His pre-existing neutropenia remitted and the therapy was continued for a total of 4 months. When the therapy was discontinued the neutropenia returned. There was no evidence that the growth factor itself had any disease modifying activity.