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PubMed1979

Myelofibrosis in chronic granulocytic leukaemia.

Serial trephine biopsies were performed in 45 cases of chronic granulocytic leukaemia (CGL) in order to determine the frequency and significance of secondary myelofibrosis in the evolution of the disease. Histological changes were graded 1-5b, ranging from no increase in reticulin to dense osteomyelosclerosis. Many cases showed a progressive increase from Grade 1 to Grade 3, and accelerated disease, or blast crisis, often supervened when Grade 3 changes were present. However, a significant number of cases showed Grade 4 and 5 changes, which were indistinguishable histologically from those found in agnogenic myeloid metaplasia (AMM) (idiopathic myelofibrosis), at the time of diagnosis. These patients did not always show a rapidly fatal course and may be considered as an example of 'transitional myeloproliferative disorder', with features intermediate between CGL and AMM.

Adult↗
PubMed1979

The reticulin content of bone marrow in acute leukaemia in adults.

Marrow reticulin was studied by trephine biopsy in 44 patients with adult acute leukaemia at presentation and subsequently during the course of their illness. The findings indicate that: (1) an increase in marrow reticulin is common at presentation in patients with both acute lymphoblastic and acute non-lymphoblastic leukaemia; (2) effective anti-leukaemic therapy results in resolution of some or all of the increased marrow reticulin and is not contraindicated, even in patients with a marked increase in marrow reticulin; and (3) reappearance of an increase in marrow reticulin may be a sign of relapse of the leukaemia.

Acute Disease↗
PubMed1984

Bone marrow histology in myelodysplastic syndromes. II. Prognostic value of abnormal localization of immature precursors in MDS.

A study has been performed of 40 bone marrow trephine biopsies from patients with myelodysplastic syndromes (MDS). Histology, more specifically the abnormal localization of immature precursors (ALIP), cytology and karyotype analysis were correlated with survival time and the prognostic value of these factors was determined. The presence or absence of ALIP proved to be highly significant in predicting the duration of survival (P = 0.007): the presence of ALIP predisposes patients to early death with high probability of developing acute myeloid leukaemia (AML), whereas the absence of ALIP carries a better prognosis with more long-term survivors and low probability of transformation to AML. The presence or absence of ALIP was not correlated with increased mortality from infection and/or bleeding. In contrast with ALIP, the main histological parameter, we were not able to obtain statistically significant prognostic information for cytology (FAB classification) or karyotype analysis (normal or abnormal chromosomes). We conclude that bone marrow biopsy provides useful information for the prognosis of MDS and that the presence of ALIP has greater predictive value than the more commonly used parameters deduced from cytology and karyotype.

Adult↗
PubMed1986

Bone lesions in chronic granulocytic leukaemia.

Radiographic abnormalities in bone are unusual during the stable phase of chronic granulocytic leukaemia (CGL). A rare situation is reported in which a patient developed three distinctive skeletal lesions simultaneously in different anatomical sites. Firstly, in both fibulae symmetrical punched out and permeative lesions were present throughout much of the shafts, being most prominent in the mid-diaphyseal regions. Secondly, the tibiae were slightly porotic and showed localized periosteal reactions, whereas in the fibulae there was extensive cloaking by a similar but much more intensive reaction. Thirdly, multiple osteosclerotic lesions were present in the pubic bones and in the proximal ends of the femora and humeri. Concurrently, fluctuant, culture negative swellings were present on the extremities. Histological examination of the material from the subcutaneous and lytic lesions showed only areas of fibrosis with islands of haematopoietic tissue, including scanty megakaryocytes. Bone marrow trephine biopsy showed the presence of myelofibrosis with islands of haematopoietic tissue typical of CGL without any evidence of blastic transformation.

Adult↗
PubMed1986

Myelofibrosis in chronic granulocytic leukaemia: clinicopathologic correlations and prognostic significance.

We performed 221 marrow trephine biopsies in 139 patients with Ph1-positive (Ph1+) chronic granulocytic leukaemia (CGL) in order to assess the incidence, degree and prognostic significance of marrow fibrosis (MF) at various stages of the disease. We also attempted to elucidate the relationship between development of MF and the various clinical and haematological features of CGL. A significant correlation was found between the amount of fibrosis (graded from 0 to 3) and the stage of CGL, indicating that major fibrotic changes are associated with accelerated or blastic disease. Survival studies performed to assess the prognostic significance of the various degrees of MF, showed a progressively worse life-expectancy from grade 0 to grade 3 fibrosis. Multivariate regression analysis indicated Hb level, age, number of marrow megakaryocytes (MKs), time from diagnosis as the features most significantly correlated with the degree of MF. This study demonstrates that the natural history of CGL involves a progressive increase in reticulin deposition towards severe MF, although the rate of this progression varies widely. Monitoring changes of fibrosis with sequential biopsies could give a measure of the rate of progression of the disease and help in prognostic assessment of CGL patients. Our findings also confirm that among marrow features the number of MKs is the cytological variable most significantly correlated with MF.

Adolescent↗
PubMed1987

Peripheral blood and bone marrow abnormalities in patients with HIV related disease.

Between February 1983 and April 1986 we studied peripheral blood and bone marrow samples from 20 patients with human immunodeficiency virus (HIV) related disease. 14 patients had AIDS, three had ARC, two had PGL and one had ITP as a sole manifestation of HIV related disease. Peripheral blood abnormalities included marked anisocytosis and poikilocytosis, rouleaux formation, neutropenia, lymphopenia, monocytopenia, a left shift in the granulocyte series and, in the patients with AIDS, vacuolated monocytes. The most frequent bone marrow abnormalities were reticuloendothelial iron block, dyserythropoiesis, megaloblastic change and erythroid hypoplasia. Excess histiocytes were noted in four marrows, one exhibiting haemophagocytosis. None of the bone marrows showed lymphopenia. Eight of the 20 marrows were difficult or impossible to aspirate. None of the trephine biopsies showed increased reticulin. The causes of these abnormalities are probably multiple and include opportunistic infections, drug therapy, immune mechanisms and possibly direct insult by the HIV virus.

AIDS-Related Complex↗
PubMed1988

Histology of neuroblastoma involving bone marrow: the problem of detecting residual tumour after initiation of chemotherapy.

One hundred and eighty bone marrow trephine biopsies obtained during 68 staging procedures before and during treatment of 20 children with Stage IV neuroblastoma were reviewed. A primitive cell infiltrate with prominent fibrous stromal reaction and increased reticulin characterized the marrow at presentation. Once treatment had begun, primitive cells became difficult to find but fibrosis and a marked increase in reticulin persisted in most cases. Distortion in marrow architecture and the continuation of abnormal stromal reactions may reflect failure to eradicate tumour despite absence of detectable primitive cells. If current therapeutic options are to be assessed properly, uniformly accepted criteria to define continuance of marrow infiltration in children with neuroblastoma are needed. A scheme for classifying marrow histological appearances is presented which may prove to be of more value than a simple distinction between 'involved' and 'uninvolved'.

Adolescent↗
PubMed1989

In situ immunophenotyping of lymphocytes in human bone marrow: an immunohistochemical study.

Lymphoid cells in human bone marrow are either assembled focally or occur in a diffuse, loosely scattered infiltrate. While the focal lesions are easily detected, the lymphoid cells of the diffuse infiltrate are hardly recognizable with conventional stains. Quantitative immunohistological analysis of 103 trephine biopsies, including cases with reactive disorders (e.g. myeloid hyperplasia, aplastic anaemia) and neoplastic processes (e.g. myeloproliferative disorders, B-cell non-Hodgkin's lymphomas) and some specimens with normal architecture yielded the following results: (1) Various antibodies recognizing B cells (L26, 4KB5, MB1, Ki-B3), T cells (UCHL1, MT1) and NK cells (Leu-7) are effective in paraffin-embedded bone marrow sections, thus enabling analysis of the in situ distribution of normal lymphocyte subsets and subtyping of lymphomatous infiltrates. (2) The lymphocytes of the diffuse infiltrate constituted about 1-5% of all nucleated cells in normal bone marrow. (3) In the diffuse infiltrate, T lymphocytes were regularly observed in higher numbers than B cells, and Leu-7+ cells were rare or virtually absent, irrespective of the diagnosis. (4) The focally assembled lymphoid cells were mainly B lymphocytes, but many T cells were always intermingled. This was true for both reactive follicles and neoplastic lymphomatous infiltrates, which generally cannot be differentiated on the basis of immunohistological findings alone.

Antibodies, Monoclonal↗
PubMed1991

Congenital spherocytosis, B19 parvovirus infection and inherited interstitial deletion of the short arm of chromosome 8.

We report two siblings with congenital spherocytosis, multiple phenotypic abnormalities and an inherited interstitial deletion of the short arm of chromosome 8 (8p). The propositus came to our attention with acute bone marrow hypoplasia secondary to B19 parvovirus infection. The bone marrow trephine biopsy appearances of intranuclear eosinophilic degeneration in the erythroblasts may be pathognomonic of B19 parvovirus induced acute bone marrow aplasia. The presence of B19 parvovirus DNA was demonstrated in erythroblasts by in situ hybridization. Chromosome analysis of peripheral blood lymphocytes from both siblings showed an interstitial deletion of the short arm of chromosome 8, del (8) (p11p21). This abnormal chromosome was inherited from their mother, who showed this deletion as well as a small fragment representing the deleted 8p chromosome portion, del (8) (p11p21), +f. Centromeric material from chromosome 8 was detected in this chromosome fragment by in situ hybridization using an alpha satellite probe (pJM 128), but not by C banding. Chromosome analysis of skin fibroblasts from the mother and a third sibling with a similar karyotype showed the deleted fragment in over 80% of cells. Cells in which the fragment was absent exhibited the deleted 8p, suggesting there was no mosaicism. The mother and the third sibling were phenotypically normal without spherocytosis. A fourth sibling and the father were normal. The chromosome abnormality was not observed in five of the mother's siblings, suggesting that it arose de novo in the mother. Our findings strongly support a locus for congenital spherocytosis on the short arm of chromosome 8. The frequency of defects at this locus is unknown.

Adolescent↗
PubMed1992

Argyrophilic nucleolar organizer region counts and prognosis in multiple myeloma.

The prognostic significance of argyrophilic nucleolar organizer regions (AgNORs) has been evaluated in bone marrow trephine biopsies from 64 patients with multiple myeloma (MM) prior to therapy. The univariate Kaplan-Meyer survival analysis showed a significant correlation between survivals and AgNOR counts (median of survival 51.3 months for cases with < or = 4.62 AgNORs per plasma cell (PC) versus 16 months for cases with > 4.62 AgNORs per PC; P = 0.0000) or AgNOR distribution in PC nucleus (AgNOR configuration) (median of survival 71.67 months for cases with tightly grouped AgNORs, 16.26 for partially grouped and 11.74 for dispersed AgNORs; P = 0.001). Significant prognostic correlations were also found for monoclonal immunoglobulin type (P = 0.008), platelet counts (P = 0.0078), serum creatinine level (P = 0.0001), Durie's clinical stage (P = 0.02), percentage of plasma cells in bone marrow biopsies (BMPC%) (P = 0.005), pattern of medullary involvement (P = 0.003) and PC atypia (P = 0.009). Borderline result was detected for the percentage of PCs in aspirates (P = 0.06). No significant correlation was found between prognosis and patients age, sex, haemoglobin level, serum albumin or calcium level, marrow cellularity and excess of haemosiderin. Multivariate survival analysis showed that only two variables were significantly correlated with prognosis: AgNOR counts (P = 0.003) and AgNOR configuration (P < 0.001). In addition, the analysis of variance showed significant association between AgNOR number and platelet counts, haemoglobin level, calcaemia, creatininaemia, clinical stage, percentage of PCs in aspirates, BMPC%, pattern of medullary involvement, PC atypia, marrow cellularity and configuration of AgNORs. Our results indicate that AgNOR counts and configuration have prognostic and diagnostic value and therefore they are useful independent parameters to assess the pretherapeutic aggressiveness of multiple myeloma.

Adult↗
PubMed1993

Proliferating normal bone marrow cells do stain for Ki-67 antigen.

The normal human bone marrow has been investigated in the past for the presence of the proliferation associated antigen detected by the Ki-67 antibody and aberrantly low scores for this antigen have been reported. We used a new Ki-67 equivalent antibody (MIB 1) and a formalin fixation of smears and trephine biopsies, and we report 52.8% +/- 9.2 SD of the normal BM cells to stain for MIB 1. Late forms of the maturing blood cells compartment such as metamyelocytes and megakaryocytes were stained in cytokine-treated marrows.

Bone Marrow↗
PubMed1993

BCR rearrangement in apparent essential thrombocythaemia.

The presence of the Philadelphia chromosome is a major determinant of the prognosis of patients with myeloproliferative disorders. We describe a case of apparent essential thrombocythaemia in whom cytogenetic analysis was normal. However, the presence of basophilia, the absence of abnormal megakaryocytes in a trephine biopsy and the female sex of the patient prompted Southern analysis of peripheral granulocyte DNA. This revealed a BCR rearrangement and the patient has therefore undergone allogeneic bone marrow transplantation. This case emphasizes the importance of both cytogenetic and molecular analysis of patients with apparent essential thrombocythaemia.

Blotting, Southern↗
PubMed1994

Detection and significance of bone marrow infiltration at the time of autologous bone marrow transplantation in Hodgkin's disease.

Bilateral iliac crest biopsies were performed at the time of bone marrow (BM) harvest in patients with poor-risk Hodgkin's disease (HD) undergoing autologous bone marrow transplantation (ABMT). 67 consecutive patients with normal trephine biopsies (58 unilateral; nine bilateral) taken 2 weeks prior to harvest were studied. Nine (13%) of patients had BM infiltration with HD on the harvest biopsies. These patients had all previously had only unilateral biopsies. Three patients did not proceed to ABMT because disease progression became clinically apparent, but the remaining six patients were infused with involved marrow. One patient died 6 weeks post ABMT, with no evidence of disease at post-mortem. One patient showed no response to ABMT and four patients either had a partial or complete response to ABMT. Of the responders, three patients are now in complete remission at 53, 39 and 33 months past ABMT.

Adolescent↗
PubMed2005

Essential thrombocythaemia: challenges and evidence-based management.

Essential thrombocythaemia was first described over 70 years ago. This condition is dominated by thrombotic and haemorrhagic complications and, in the long-term, by risk of transformation to myelofibrosis and/or acute leukaemia. However, it is heterogeneous both clinically and biologically. Here, a review of current concepts in disease aetiology and management is offered with reference to recent focused reviews where appropriate. In addition, five specific areas are discussed in detail: the role of the trephine biopsy, the disease entity prefibrotic myelofibrosis; the recently described Janus kinase 2 (JAK2) mutations; the leukaemogenicity of hydroxyurea (hydroxycarbamide); and lastly, the implications of the results of the Medical Research Council Primary Thrombocythaemia 1 study are explored.

Evidence-Based Medicine↗
PubMed1986

Aplastic anaemia in the Northern Region 1971-1978 and follow-up of long term survivors.

An attempt has been made to identify and review everyone who was admitted to hospital in the Northern Region between the years 1971 and 1978, and was diagnosed as having aplastic anaemia. The hospital activity analysis scheme was used as the source of the patients. Of the 537 cases recorded, the notes of 404 (75%) were traced and reviewed. We considered that 230 (57%) had been mis-classified. The incidence of aplastic anaemia was fairly constant with an average of 25 cases per year. Prognosis in the 174 cases of aplastic anaemia remaining was found to be poor with a 5-year survival of 39%. Mortality was similar in cases with an apparent cause, and those without. A follow up study of 27 long term (greater than 3 years) survivors is also reported. Seventeen (63%) had normal blood counts. There was very poor correlation between anterior iliac crest trephine findings and peripheral blood count.

Adrenal Cortex Hormones↗
PubMed1993

Bone marrow fibrosis: histomorphometric analysis and interobserver reproducibility of a simple optical method of assessing its intensity.

A histomorphometric analysis of the length of reticulin fibres per area of haemopoietic bone marrow was performed on 59 trephine iliac crest biopsies. The values obtained were found to correlate with the degree of fibrosis as determined by a simple optical method based on the degree of microscopic magnification required for recognition of the presence of reticulin fibres. The mean length of fibre (microns/10,000 micron2) for the three degrees of fibrosis defined by the optical method were: 241.8 +/- 16.6 for grade I, 713 +/- 85.6 for grade II, and 1827.9 +/- 230.4 for grade III (P < 0.001). In a series of 67 biopsies, the overall interobserver agreement of the optical method was found to be good (Spearman's r = 0.99; P < 0.001) and there was good individual agreement for each of the three degrees of fibrosis (improved kappa test). There was a small amount of overlap between the extreme values of adjacent optical degrees. These results suggest that the optical method described here can be recommended as a practical technique for the routine evaluation of myelofibrosis.

Biopsy↗
PubMed2004

Report on slide session, British Society for Haematology, 43rd Annual Scientific Meeting, Glasgow, 2003.

Seven patients who had a diagnostic problem were presented at the British Society for Haematology, Annual Scientific Meeting in 2003. The likely diagnosis was discussed on the basis of a synopsis of the history and blood film and trephine biopsy features and forms the basis of this report. Diagnostic problems dealt with included lymphoproliferative and myeloproliferative disorders and haemolytic anaemia.

Adult↗
PubMed2004

Performing bone marrow biopsies with or without sedation: a comparison.

Although intravenous sedation (ISED) in addition to a local anaesthetic (LA) is commonly used in the performance of a bone marrow aspirate and trephine (BMAT), it is not clear under what circumstances and in which way sedation may be most beneficial. In this study, information was gathered using a questionnaire, from 112 patients shortly after undergoing BMAT; the duration of the procedures and the length of the biopsy cores were measured and any complications noted. Most patients (68%) chose to receive LA only, and almost all (74/76) were happy with their decision. Patients who received sedation gave lower pain scores than patients receiving LA only (1 vs. 3) and were found to have lower levels of apprehension at the thought of having a repeat procedure. Patients having a repeat BMAT showed a slightly increased preference for having sedation compared with patients who were undergoing it for the first time. There is some concern that guidelines regarding the use of ISED for procedures other than BMAT are not always adhered to, and current practice may be best revealed by a large-scale audit of sedation practice for the performance of BMAT. Patients should be given the choice of having ISED if the appropriate resources are available, but in most cases the additional small risk of receiving sedation can be avoided.

Adult↗