Reversible bone marrow hypoplasia in a case of male anorexia nervosa

The authors report the case of a 17 year old boy with anorexia nervosa and bone marrow hypoplasia. After a 14 kg weight loss, the patient had pancytopenia, morphological abnormalities of the red cells (acanthocytes, schizocytes), without hemolysis, and hypogonadotropic hypogonadism. Bone marrow biopsy showed a marked reduction of hematopoietic cells with striking diffuse interstitial oedema. Clinical recovery, during the next 6 months, was associated with a return of the haematological changes to normal and to a disappearance of hypogonadism. Anorexia nervosa is a rare entity in boys. In all probability, bone marrow hypoplasia is not a well known feature of this disorder. The haematological changes are reversible with improvement of nutritional status.     

Familial Erythroleukaemia: A Cytogenetic and Haematological Study

Clinical and haematological details of 2 siblings with a familial myeloproliferative disorder (erythroleukaemia) are presented. Their father is presumed to have died from a similar disease. The 2 siblings showed similar but not identical chromosomal abnormalities detected initially in marrow and later in peripheral blood. Serial studies revealed the emergence of an increasingly diverse pattern of chromosomal changes coincident with the haematological and clinical progression of the disease. Other members of the family were screened for cytogenetic and haematological changes. The paternal sibship displayed an increased incidence of cancer.     

Familial erythroleukaemia: a cytogenetic and haematological study.

Clinical and haematological details of 2 siblings with a familial myeloproliferative disorder (erythroleukaemia) are presented. Their father is presumed to have died from a similar disease. The 2 siblings showed similar but not identical chromosomal abnormalities detected initially in marrow and later in peripheral blood. Serial studies revealed the emergence of an increasingly diverse pattern of chromosomal changes coincident with the haematological and clinical progression of the disease. Other members of the family were screened for cytogenetic and haematological changes. The paternal sibship displayed an increased incidence of cancer.     

Absence of parvovirus b19 infection in chronic fatigue syndrome

Objective. To evaluate the presence of infection with parvovirus B19 in patients with chronic fatigue syndrome (CFS) who also had rheumatologic symptoms and mild hematologic abnormalities. Methods. Seven patients meeting the Centers for Disease Control and Prevention working case definition for CFS who also had mild leukopenia, thrombocytopenia, or anemia were studied. Bone marrow was aspirated from each patient, and examined for morphologic abnormalities, including features seen in marrow infections with parvovirus B19, as well as for parvoviral DNA, using polymerase chain reaction (PCR) amplification. Serum obtained at the time of marrow aspiration was also evaluated for parvoviral DNA, using the PCR method, and was examined for the presence of IgM and IgG antibodies to the virus. Results. No evidence of marrow involvement with parvovirus B19 was found in any patient. One patient had antibody evidence of a transient parvoviral infection, during which time an underlying thrombocytopenia worsened. Conclusion. Despite examining a selected group of patients thought most likely to have parvoviral infection, based on clinical and hematologic measures, no evidence of clinically important parvoviral infection was noted. Thus, it seems unlikely that parvovirus B19 plays a role in CFS, even though it has been associated with fibromyalgia, a clinically similar syndrome.     

Erythroid Aplasia in Riboflavin-Deficient Baboons and its Relation to Marasmus and Kwashiorkor

An erythroid hypoplasia characterized by falls in red cell precursors, haemoglobin, packed cell volume, reticulocytes and sometimes platelets, resembling that which occurs in marasmus and kwashiorkor, has been produced experimentally in baboons on a synthetic riboflavin-deficient diet. The red cell uptake of⁵⁹Fe on the 8th and 12th days was 40 per cent lower in the riboflavin-deprived animals and thus agreed with the low marrow activity estimated cytologically. The haematological abnormalities were accompanied by gross skin changes, falls in serum folate, and sometimes intramuscular and intestinal haemorrhages. Striking macroscopic and histological abnormalities were also present in the adrenals. All the abnormalities disappeared when riboflavin was given, and re-appeared when it was again omitted from the diet. When prednisone was given to the deprived animals instead of riboflavin, only the erythroid hypoplasia disappeared. Since the diet was adequate in all respects and contained 20 per cent of its kilocalories in the form of animal protein, the abnormalities cannot have been due to protein deficiency. The pair-fed controls on a similar diet but with added riboflavin developed no abnormalities. It is suggested that as riboflavin is an important co-enzyme in many vital metabolic processes, its absence may affect marrow activity directly or by disturbing corticosteroid metabolism, as well as being associated with serum protein changes.     

Recurrent abortions and circulating anticoagulant. Relation to lupic disease: 6 cases

Six women, aged 16 to 27 years old at the beginning of their illness suffered recurrent spontaneous abortion (two to eight episodes) and three of them had arteriolar venous thrombosis. These symptoms led to the finding of an antiprothrombinase type of circulating anticoagulant. In two cases, positive dissociated syphilitic serology was observed and all patients presented other haematological abnormalities: thrombocytopaenia and/or autoimmune haemolysis. The diagnosis of disseminated lupus erythematosis was established after an average period of 11 years (range 1 to 27 years) based on at least 4 of the ARA criteria (five out of six cases) and/or characteristic immunological abnormalities (five out of six cases). Thrombosis is more common in lupus when there are associated haematological abnormalities. It is probably directly related to the presence of circulating anticoagulant which inhibits the production and/or secretion of prostacyclin by the endothelial cells.     

Haematological aspects of HIV infection.

Multiple interacting factors contribute to the haematological manifestations of HIV disease. The effects of HIV-1 infection influence all haemopoietic cell lineages resulting in a spectrum of haematological abnormalities. Even in the absence of other pathological processes, bone marrow morphology is invariably abnormal, and anaemia, neutropenia and thrombocytopenia are all common during the course of disease. Intercurrent opportunistic infections may cause bone marrow suppression or induce specific cytopenias. Therapies used to treat HIV and its complications are frequently implicated as the cause of haematological dysfunction, and many have significant myelotoxic side-effects. Insights into the molecular basis for many of these abnormalities have permitted a clearer understanding of the pathophysiology of HIV-1 infection. Recombinant human growth factors that may be used to treat isolated cytopenias or to ameliorate the myelotoxic effects of other essential therapies. Lymph opoietic growth factors and the use of gene modified cells provide future therapeutic strategies that may alter the course of HIV disease.     

Acquired amegakaryocytic thrombocytopenic purpura associated with immunoglobulin deficiency

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a haematological disorder characterized by severe thrombocytopenia due to an immunologically induced absence of megakaryocytes in an otherwise normal-appearing bone marrow. A 57-year-old male with a 6-month history of rectal and cutaneous bleeding is reported. Platelet count was 10 X 10(9)/l, while other haematological values were within the normal range, except for the presence of hypogammaglobulinaemia with decreased IgA and IgG. Both platelet median volume and half-life span were normal, and antiplatelet IgG determinations were negative. Bone marrow aspiration and biopsy showed no megakaryocytes, with a normal appearance of erythroblastic and granulopoietic series. An in vitro culture for megakaryocytic progenitor cells did not show any growth of megakaryocyte colonies. No inhibitory effect on the growth of normal marrow megakaryocytic colonies was observed when serum and lymphocytes of the patient were added. Following 4 weeks of prednisone therapy, the platelet count rose to 127 X 10(9)/l and the bone marrow aspirate showed some megakaryocytes. The possible pathogenetic mechanisms of this entity are discussed.     

Chronic neutropenia of childhood: frequent association with parvovirus infection and correlations with bone marrow culture studies

Summary. Children with neutropenia of more than 3 months duration often have evidence of immune-mediated destruction of mature neutrophils and variable abnormalities of myeloid precursors in their bone marrow. These patients often have anti-neutrophil antibodies which persist for several months. To further investigate the aetiology of neutropenia in such patients, bone marrow cells were evaluated for the presence of common viruses. Fifteen of 19 patients tested had evidence for parvovirus infection by PCR amplification of bone marrow DNA with parvovirus specific primers. Of these 15, six also had serologic evidence of parvovirus infection. Anti-neutrophil antibodies were identified in nine of 12 patients with parvovirus infection. Bone marrow culture studies done on six patients revealed varying degrees of myeloid and erythroid inhibition by patient plasma. These studies indicate that parvovirus may be a common cause of immune-mediated neutropenia in children.     

Chromosome Studies on Bone Marrow from a Male Control Population

Summary Chromosome analyses of bone marrow cells prepared by the direct method were carried out on 32 male patients, who had no primary haematological disease. One patient was found to have a pericentric inversion of the Y chromosome, which was also present in a skin fibroblast culture and in a lymphocyte culture. Three cases were found to have a high percentage of bone marrow cells with a ₄₅,X chromosome constitution and one case had a ₄₅, X?Y - or G- cell line. The high degree of aneuploidy was not found on examination of cells from leucocyte cultures. This observation is discussed in relation with other similar findings in patients with haematological diseases. The remaining 27 patients had a normal male karyo-type and showed only small deviations from the modal chromosome number. The percentage of bone marrow cells with either chromatid aberrations or stable chromosome abnormalities was not significantly different from previous observations on lymphocyte cultures. However, the proportion of cells with unstable chromosome abnormalities was found to be substantially reduced in comparison with results from cultured lymphocytes examined in their first in vitro division.     

The Haematological and Histological Findings in 18 Patients with Clinical Features Resembling those of Myelofibrosis

S ummary . The presentation and haematological abnormalities in 18 patients with splenic and hepatic enlargement and a leukaemoid or leucoerythroblastic blood picture have been reviewed. The clinical features in each case were consistent with a diagnosis of myelofibrosis. Histological examination of the bone marrow showed myeloid proliferation of various types for which no underlying cause was apparent. On the basis of the bone marrow histology, it was possible to divide the 18 patients in this study into two groups.
The first group of four patients presented with a splenomegaly and a marked leucocytosis. Bone marrow aspirate and biopsy specimens showed marked granulocytic proliferation akin to chronic myeloid leukaemia, from which these cases were separated by the findings of a normal or raised leucocyte alkaline phosphatase score. Other distinguishing features these patients had in common were that they were all elderly and their illness appeared to follow a prolonged course, with little need of active treatment.
The second larger group of 14 patients were less uniform. The histological and haematological appearances were variable. Excess bone marrow reticulin was present in each case, and marrow fibrosis was noted in eight. Prominent aggregations of large primitive stem cells were a histological feature in all 14 instances. Correlation between the clinical, haematological and histological features was poor and in particular the marrow aspirate gave little indication of the marrow morphology as found in the bone marrow sections.     

Corticosteroid Therapy in Felty''s Syndrome and its Effect on Hypersplenic Rats

S ummary . A patient with Felty's syndrome was treated with prednisone with resulting improvement in anaemia. This was due to a decrease in an expanded plasma volume; it occurred rapidly and was not associated with any apparent change in the size of the spleen.
A contrasting form of hypersplenism was induced in rats, splenic enlargement being due to storage of methylcellulose in the organ. Corticosteroid treatment of these animals produced haematological changes similar to those in the patient although they occurred much more abruptly. The nature of the changes brought about by steroid therapy was investigated by isotope studies.
It is concluded that corticosteroid therapy can improve the anaemia of hypersplenism by reducing an expanded plasma volume and that this effect may occur without parallel improvement in the other haematological changes of hypersplenism. The decrease in plasma volume does not appear to result from a steroid-induced lymphoid involution and a reduction in splenic size. Instead, it seems likely that this treatment affects an intermediary mechanism by which plasma volume is increased in hypersplenic states. The possible nature of this is discussed.     

Specificity of haematological indicators for '5q- syndrome' in patients with myelodysplastic syndromes

83 patients with myelodysplastic syndromes were analyzed for the presence of three haematological features: (1) macrocytic anaemia, (2) normal or high platelet count and (3) megakaryocytic hypolobulation in most megakaryocytes. In 10 of the 83 patients, a 5q- chromosome was the only clonal aberration; 31 patients had other chromosomal aberrations (including 6 patients with 5q- chromosome and other abnormalities in the same clone) and 42 patients had a normal karyotype in their bone marrow cells. 9 patients displayed all three haematological features investigated. In 8 of these patients the 5q- chromosome was the only clonal aberration. The 9th patient had a karyotype of 47,XX, + 8. None of the 6 patients with 5q- chromosome and additional abnormalities in the same clone fulfilled all criteria. The '5q- syndrome', a situation with the 5q- chromosome as a sole aberration, should be accepted as a diagnostic entity within the macrocytic anaemias. This syndrome can be suspected on the basis of the above haematological indicators and the diagnosis confirmed with bone marrow karyotype analysis.     

Competition between recipient and donor cells after bone marrow transplantation for chronic myeloid leukaemia

The cytogenetic and clinical course of three patients allografted for Ph positive chronic myeloid leukaemia are reported. All patients had a peculiar pattern of relapse. Two out of three patients had donor marrow graft pretreated with monoclonal antibody for graft versus host prevention. The cytogenetic relapse was invariably associated with major morphological changes in the marrow indicating that these were also haematological relapses. However, no changes in the peripheral blood count were observed. When relapse occurred in these patients, Ph positive marrow metaphases and host red blood cells ranged from 75% to 100% of the total cell population: thereafter they spontaneously reverted to complete chimaerism. Therefore the presence of leukaemic cells even in considerable amount was not sufficient, per se, to prevail over normal marrow. In addition these observations indicate that relapse was not associated with elimination of the graft: while haemopoiesis was entirely of recipient origin the donor normal stem cells were present and vital although functionally silent. These data suggest that, although TBI remains the more effective tool for eradicating the majority of leukaemic cells, haemopoietic competition between host and donor marrow may have a major impact on leukaemic relapse.     

Improvement of resting myocardial asynergy with cessation of upright bicycle exercise

Exercise generally aggravates ischemic myocardial dysfunction, presumably by increasing tissue oxygen demand out of proportion to the increase in supply. Nevertheless, resting left ventricular (LV) wall motion abnormalities can improve dramatically after upright exercise. To investigate this "paradoxical" phenomenon, we performed upright bicycle exercise equilibrium radionuclide ventriculography in 93 patients with angiographic coronary artery disease. Immediately after exercise, LV end-diastolic volume was similar to the resting level (1 +/- 22% of rest value), but end-systolic volume (ESV) was significantly below (p less than 0.05) that at rest (-11 +/- 32%) and LV ejection fraction increased significantly compared with rest (0.57 +/- 0.16 vs 0.51 +/- 0.13, p less than 0.05). Improvement in resting myocardial asynergy was frequent (115 of 330 abnormal segments), and was observed more commonly in patients without pathologic Q waves and in segments manifesting mild rather than severe asynergy. In 60 additional patients with resting asynergy who were also studied after nitroglycerin (NTG), there was 89% concordance of wall motion response in asynergic segments after exercise and NTG: 71 of 85 segments manifesting improvement with NTG also improved after exercise, and 157 of 172 segments without improvement with NTG also failed to improve after exercise. Despite the similar wall motion response, the mechanism of improvement is probably different from that produced by NTG. With NTG, preload (end-diastolic volume) and afterload (systolic blood pressure) were significantly lower than their resting control levels (p less than 0.05). These changes did not occur after exercise. Instead, an isolated, significant reduction in ESV was noted. These data support the hypothesis that catecholamine stimulation is responsible for paradoxical wall motion improvement after upright exercise.     

A new translocation,t(3;6)(q12;24) associated with chronic myelomonocytic leukaemia and marrow fibrosis

This report describes a 75-year-old man with chronic myelomonocytic leukaemia (CMML) and marked marrow fibrosis associated with t(3;6)(ql2;24). Although structural abnormalities of 3q occur in haematological neoplasia, this particular chromosomal translocation has not been previously described in CMML. Karyotypic abnormalities involving 3q and marrow fibrosis may affect prognosis in CMML.     

Ineffective Erythropoiesis in Haemoglobin Eβ -thalassaemia: an Electron Microscope Study

S ummary. Electron microscope studies have been performed on the bone marrow cells of two non-splenectomized patients and the circulating erythroblasts and reticulocytes of three splenectomized patients with HbE/β-thalassaemia. Some intracellular precipitates (probably consisting of α-chains) and mild dyserythropoietic changes were found in the early polychromatic erythroblasts within the bone marrow. Larger quantities of precipitate and more marked dyserythropoietic changes were found in the late polychromatic erythroblasts and reticulocytes both within the marrow and within the circulation. The bone marrow macrophages contained phagocytosed erythroblasts within their cytoplasm. These data indicate that the anaemia in HbE/β-thalassaemia results largely from dyserythropoiesis and ineffective erythropoiesis. The ultrastructural abnormalities encountered in the cases of HbE/β-thalassaemia were qualitatively and quantitatively similar to those seen in homozygous β-thalassaemia.     

Haemopoiesis of transplanted patients with autologous marrows assessed by long-term marrow culture

Summary. We assessed the effect of antitumoural therapy at intensive doses on the haemopoietic system using long-term marrow cultures (LTMC) established from 33 patients (25 with haematological diseases and eight with solid tumours) after autologous bone marrow transplantation (ABMT). When compared to 42 pre-graft patients, a decreased CFU-GM Production and a defect in stromal layer (SL) confluence were found after ABMT on day 90 but also on day 365. However, these abnormalities were observed only in patients with haematological diseases and no differences between pre-graft and post-graft results were found in patients with solid tumours. Among the patients with haematological diseases, on day 90 those with acute lymphoid leukaemias showed lower CFU-GM production whereas patients with non-Hodgkin's lymphomas developed more frequently subconfluent or confluent SL. Other factors studied such as sex, patient age, disease status, marrow purging and post-graft administration of growth factors did not appear to influence post-graft LTMC results. Multivariate analysis including all the patients has shown (a) that solid tumours were associated with higher CFU-GM production, and (b) that conditioning regimens with total body irradiation (TBI) or busulfan led more frequently to non-confluent SL. In conclusion, high-dose therapy followed by ABMT can induce a persistent impairment of the stem cell and stromal cell compartments, particularly in patients with haematological diseases conditioned with TBI, despite the absence of any alloimmune reaction and post-graft immunosuppressive therapy.