T lymphocyte function in hairy cell leukaemia.

Eosinophils were isolated from the mammary gland of Fasciola hepatica-infected cattle by intramammary infusion with a crude extract from adult F. hepatica. Up to 5 x 10(9) eosinophils with a purity of over 90% could be obtained from a single quarter of the gland. The major contaminating cells were monocytes which reached their peak several days following the eosinophil peak. Two major proteins were isolated from bovine eosinophil granules, a high molecular weight peroxidase-active protein and a smaller molecular weight predominantly basic protein. This smaller protein was thought to be the bovine equivalent of guinea-pig and human major basic protein (MBP), although it possessed an unusually high concentration of cysteine. The bovine MBP had a profound effect on juvenile F. hepatica in vitro causing damage and death at concentrations down to 1 x 10(-6) M. The damage was detected by a 51Cr release assay and/or a viability assay involving microscopical examination of the flukes. Other cations, especially protamine sulphate, were also shown to kill flukes, although both lysozyme, found in neutrophils, and the peroxidase-positive peak from bovine eosinophils were unable to mediate any detectable damage.     

Chromosome abnormalities in hairy cell leukaemia variant

We describe chromosome abnormalities in 6 patients with hairy cell leukaemia (HCL) variant, a rare B-cell disorder with clinical and laboratory features intermediate between HCL and B-prolymphocytic leukaemia (B-PLL). All but one had marked splenomegaly and a raised white blood cell count (median 40 × 10⁹/l) with over 80% nucleolated hairy cells. These cells had a B-cell immunophenotype distinct from that of typical HCL. All patients but one are alive with stable disease with a median follow-up of 60 months. Numerical chromosome changes included loss of chromosomes 2, 3, 4, 6, 10, 19, 21, and X. Three cases had translocations involving the immunoglobulin gene regions: t(14;17)(q32;q11), t(14;22)(q32;q11), and t(2;8)(p11.12;q24). Immunocytochemistry demonstrated the presence of the MYC protein in cells from the case with t(2;8) but not in two others. Other structural abnormalities included t(3;10)(q27;q22) and t(3;12)(q27;q13) in the same patient, der(17)t(7;10;17) (p11;q27;q22), t(1;3)(q25;p21), t(8;21)(p12;q11), t(17;21)(p11;p11), del(6)(q15), del(7)(q34), and del(14)(q24). Genes Chromosom Cancer 10:197–202 (1994). © 1994 Wiley-Liss, Inc.     

Natural killer cell function and malignant cell phenotype in hairy cell leukaemia.

We have followed for 33 months the changes that occurred in natural killer (NK) cell numbers and activity in a patient (A) with hairy cell leukaemia (HCL), using a single cell assay and a microcytotoxicity assay. The composition of the peripheral blood mononuclear cell population and malignant cell phenotype were also analysed. During this period he received treatment with interferon and his grossly enlarged spleen was removed. Four further patients were also studied, two were splenectomized and all had received treatment with interferon. In four of the five patients studied there was an apparent link between low NK activity and presence of a tumour-infiltrated spleen, and in the fifth patient, who was aleukemic and had no splenomegaly, NK function was related to disease activity. There was no correlation between NK activity and the number of target binding (TB) cells in these five patients. IFN had little direct effect on overall NK activity, but the proportion of killing cells among TB cells was increased. Three patients showed binding of several cells to a single target. Further analysis revealed that in the patients most of the TB cells were not CD56-positive NK cells, in contrast to TB cells from normal subjects. In patient A a large proportion (84%) of TB cells were identified as malignant cells and in patient E 15% of TB cells were malignant cells. The phenotype of the malignant cells was: CD19+, HLA-DR+ and CD25(Tac)+, except for patient A. In this patient the hairy cells were positive for the NK marker CD56 as well as the monocyte marker CD14. Furthermore, a change occurred in phenotype as only later samples carried CD25. It is concluded that the level of NK function correlates closely with disease activity in HCL and that competitive target cell binding by malignant cells may be one cause of depressed NK-cell function in hairy cell leukaemia.     

Chronic myeloid leukaemia occurring in a patient with hairy cell leukaemia

Occurrences of second malignancies in hairy cell leukaemia are well recognised. Most of these malignancies are either solid tumours or lymphoproliferative disorders. The association of myeloproliferative disorders with hairy cell leukaemia (HCL) is very rare. This report describes a case of a patient with HCL who after remaining in remission developed Philadelphia chromosome positive chronic myeloid leukaemia (CML), which rapidly transformed to acute lymphoblastic leukaemia with further cytogenetic abnormalities.     

Macrophages in non-hodgkin lymphomas and hairy cell leukaemia

Methods used in the study of human mononuclear phagocytes in vitro were applied to surgical specimens from 49 patients with non-Hodgkin lymphomas and eight patients with hairy cell leukaemia. Two of the tumours (both classified as “true histiocytic” neoplasms by the Kiel criteria) were distinguished by the presence of atypical macrophages in the in vitro system. In one the atypical cells were adherent; In the other example they were non-adherent. These tumours were the only examples of mononuclear phagocyte neoplasia identified in this series. All the remaining 47 cases of non-Hodgkin lymphoma were judged to be of lymphoid origin. While initial observations on hairy cell leukaemia-derived spleen cells suggested macrophage neoplasia, this impression does not stand up to more detailed analysis. The findings are more in keeping with a B lymphoid cell lineage. In hairy cell leukaemias and low grade lymphoma the proportion of macrophages per gram weight of tissue is diminished. This suggests a deficiency of macrophage functional activity compared with normal; the nature of this defect is not clear.     

A clinico-pathological study of six cases of hairy cell leukaemia.

Clinicopathological findings of six cases of Hairy cell leukaemia are presented. All the patients were males, the age ranged between 32-57 years. Complications of anaemia and neutropenia were common modes of presentation. Hepatomegaly and splenomegaly were present in all the cases whereas only 2 patients had lymphadenopathy. Severe pancytopenia was detected in 3 cases and circulating hairy cells were present in all the cases. Trephine biopsy done in all six patients was found to be diagnostic. Tartrate resistant acid phosphatase was detected in the hairy cells of 2 cases.     

Histometry of splenic microvascular architecture in hairy cell leukaemia

In this study we investigated the splenic microvascular architecture in hairy cell leukaemia, in order to provide a morphological basis for the haemodynamic modifications occurring in the disease. When compared with controls, the four leukaemic spleens examined showed a set of changes involving both the arterial and the venous system. A real increase in the absolute volume, surface and length of pulp arterial vessels was present. This increase was not so great as the enlargement of the spleen, thus resulting in a reduced density of distribution of arterial vessels in the infiltrated pulp. Enlargement of pulp cords and sinuses was also present: the pulp cord enlargement was apparent in the unit volume, which resulted in a disproportionately higher increase of the absolute volume, compared with that of sinuses. The sinus-cordal rearrangement and, particularly, the increase in the volume of pulp cords may cause a slowing down of blood cell circulation with resultant increased phagocytosis and hypersplenism. Moreover, it is suggested that the changes observed in the arterial bed of the spleen in hairy cell leukaemia involve both a reduced blood supply per unit volume of splenic pulp and a more marked conditioning of blood cells prior to their screening by cordal macrophages.     

Altered basement membrane structure of the spleen in hairy cell leukaemia. Demonstration of laminin in hairy cells

Changes in five spleens affected by hairy cell leukaemia were characterized using immunohistochemical staining for the basement membrane (BM) components laminin and type IV collagen. The ring fibres had not been totally destroyed, and were well preserved in places. The spaces filled by abnormal blood or hairy cells were assigned to the categories of altered sinus and two types of pseudosinus. In an altered sinus the staining pattern of the ring fibres had gained attenuations and the sinus was sometimes lined by a continuous BM of uneven thickness. The number of altered sinuses was related to the size of the spleen. The pseudosinuses were larger than normal sinuses and usually also larger than altered sinuses. One of the two types seemed to be derived from ruptured Billroth's cords and entailed spaces of irregular size and shape bounded by strips of fibres containing BM proteins. No ring fibres were seen in the wall. The other type of pseudosinus occurred in those spleens where no white pulp remained. These spaces were large, located around arteries and bounded by irregular strips of BM material. In three cases a number of hairy cells could be demonstrated which showed positive staining for laminin either in the surface or in the cytoplasm. Adhesive properties of hairy cells would be conceivable on the basis of the presence of laminin on the surface of the cells.     

Defective monocyte function in Legionnaires' disease complicating hairy cell leukaemia

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.     

Phenotypic and functional characterization of the circulating NK compartment in hairy cell leukaemia.

A phenotypic and functional analysis of the circulating natural killer (NK) cell population was carried out in a series of patients with hairy cell leukaemia (HCL). The overall mean NK activity of both the mononuclear and T cell fractions was reduced compared to that of normal controls (466 lytic units (lu) v 573 lu and 226 lu v 381 lu, respectively), though this difference did not reach statistical significance (P less than 0.05). Individual analysis of the data showed that in five out of 15 and in seven out of 16 cases the K562 killing by the mononuclear and T cells respectively was below the lowest s.d. limit for normal subjects. This reduced NK function was associated with a decreased ability of the effector cells to bind the target. The NK response to exogenous human leucocyte interferon was also generally depressed in cases with a low basal NK activity. The functional studies were complemented with the evaluation of the membrane expression of NK associated antigens. The percentage of circulating T cells recognized by the monoclonal antibody (MoAb) Leu-7 was significantly higher (P less than 0.001) in HCL than in normal blood (25.2% +/- 10.2 v 11.9 +/- 5.9 s.d.). However, the reactivity with two other NK-related MoAb, Leu-11 and AB8.28, was significantly lower (7.1% +/- 6.9 and 9.8% +/- 8.5; P less than 0.002) than with Leu-7 and moderately reduced compared with that of normal circulating T cells (11.7% + 6.1 & 12% + 5.5). These findings suggest that in a proportion of patients with HCL there is an impairment of the NK compartment, which may contribute towards the occurrence of the infective complications which are the primary cause of death in this disease.     

Enzyme histochemical demonstration of hairy cell leukaemia in paraffin-embedded tissue sections

Summary Hairy cell leukaemia is a form of leukaemia difficult to diagnose since pancytopenia is often present. Hairy cells contain tartrate-resistant acid phosphatase, and this factor is utilised in the diagnosis of the condition. This study confirms that it is also possible to demonstrate tartrate-resistant acid phosphatase in leukaemic infiltrates in formalin fixed paraffin-embedded tissue sections.     

Bone marrow trephines. Findings in patients with hairy cell leukaemia before and after treatment

Bone marrow trephine biopsies from 20 patients with hairy cell leukaemia were reviewed at diagnosis and during therapy with alpha-interferon (IFN) and with 2-chlorodeoxyadenosine (2-CdA). At time of diagnosis the trephines revealed classical features of hairy cell leukaemia and profound alterations of haematopoiesis. All three lines showed dysplastic features with architectural, qualitative and quantitative changes. Review of consecutive trephine biopsies in patients that received IFN showed that a complete remission with disappearance of the tumour was never achieved and that the dysplastic features persisted. An improvement of haematopoiesis was noted, but recovery, especially of the myelopoiesis, was never completely achieved. By contrast, patients treated with 2-CdA de novo and previously treated with IFN achieved a complete remission in all but three cases. The trephine biopsies showed an improvement of haematopoiesis with progressive disappearance of the dysplastic features and a good recovery of myelopoiesis. A residual lymphocytosis was present, but as it was also present in age-matched control cases it could not be considered as a residual tumour. The disappearance of the leukaemic infiltrate probably constitutes a prerequisite for the recovery and normalization of haematopoiesis, while the dysplastic changes present at diagnosis could be the result of cytokine production by the leukaemic cells.