Plasma lipids in juvenile chronic granulocytic leukaemia

Plasma lipid parameters (triglycerides, total cholesterol and high density lipoprotein cholesterol) were measured in 7 children with juvenile chronic granulocytic leukaemia, of whom 3 were with and 4 without xanthomas. In all cases, whatever the stage of the disease, these parameters were extremely altered. Plasma triglycerides were generally increased, total and HDL cholesterols were very low. No relationship seems to exist between these values and the occurrence of xanthomas.     

Plasma fibronectin in acute leukaemia

In acute leukaemia, low plasma fibronectin was seen at diagnosis and when the disease relapsed. This was not directly related to tumour load, chemotherapy or neutropenia, but correlated well with episodes of intercurrent infection. In severe infections, fibronectin fell rapidly to very low levels, and was sometimes not restored to normal up to 2 weeks later. Preliminary attempts at replacement therapy were successful and the possible importance of this is discussed.     

Granulopoiesis in chronic granulocytic leukaemia

Summary: The disappearance from the blood was studied of (1) leucocytes of patients with chronic granulocytic leukaemia labelled in vitro with DF³²P and irradiated with 1500 rad, and (2) in vitro labelled normal marrow leucocytes. These studies made it possible to estimate the intravascular phase of the lifespan of mature leukaemic neutrophils and to compute the granulocyte turnover rate when immature leucocytes (myelocytes) were present in the blood. The studies support the hypothesis that immaturity of the leucocytes per se may result in their sequestration from the blood stream. The results suggest that granulocyte production is increased in chronic granulocytic leukaemia in relapse, and that the tendency for the leucocytosis to occur may be potentiated by a prolongation of the lifespan of the mature neutrophils. However, this prolongation is only manifest in the presence of leucocytosis.     

Papilloedema in chronic granulocytic leukaemia

Five of 75 patients with chronic granulocytic leukaemia seen over a 25 year period had papilloedema at presentation. These patients had unusually high leucocyte counts and the papilloedema may be a manifestation of leucostasis. The fundal abnormalities resolved in all five patients–in four after conventional treatment with busulphan only.     

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.     

Plasma fibronectin in acute myeloid leukaemia

In 13 patients with acute myeloid leukaemia (AML), plasma fibronectin (P-FN) was measured before, during and after chemotherapy. Pre-treatment concentrations of P-FN were within the reference range and significantly higher than the nadir value (p less than 0.05). A rise in body temperature by more than 1 degree C induced a significant fall in P-FN (p less than 0.05) and transfusion with freshly drawn blood products could prevent this fall. P-FN concentrations were significantly higher in patients obtaining complete haematological remission than in patients in whom remission could not be induced (p less than 0.001). This difference could not be attributed to transfusion or febrile episodes.     

Histological classification of chronic granulocytic leukaemia

On the basis of the trephine marrow histology at presentation, 52 Ph1 positive cases of chronic myeloid leukaemia were divided into two subgroups, classical chronic granulocytic leukaemia (CGL) and chronic megakaryocytic granulocytic myelosis (CMGM). In 24 cases in which conventional therapy had preceded trephine biopsy, the distribution of cases between the two groups was found to have been significantly altered. Subsequent analysis was therefore confined to the remaining 28 untreated cases; of these 15 were classified as CGL and 13 as CMGM; no statistically significant difference was found between the two groups in respect of patient's age, leucocyte counts, platelet counts, NAP scores or of occurrence of 'blast' crisis. The differential diagnosis between idiopathic myelofibrosis (IMF) and CMGM subgroup is discussed. It was concluded that classification of chronic myeloid leukaemia on the basis of marrow histology should be restricted to Ph1 positive cases in order to obviate the possible inclusion of cases of IMF within the CMGM subgroup.     

Iron stores in chronic granulocytic leukaemia at presentation

In 87 patients with Ph¹ positive chronic granulocytic leukaemia (CGL), the bone marrow iron content was studied on smears obtained at diagnosis. A low sideroblast score and a decreased or absent marrow iron on semiquantitative estimation were found in 91 % and 85 % of cases, respectively. These findings did not correlate with blood parameters reflecting iron status such as Hb concentration, mean corpuscular volume, mean corpuscular haemoglobin, serum iron, total iron-binding capacity and transferrin saturation, which were normal in most cases. In 30 patients, initial serum ferritin was estimated, normal or slightly increased levels being as a rule found. In 24 of such patients, serum ferritin was again measured in remission following busulphan and, although values remained normal, a significant decrease was observed with respect to the initial levels (P < 0.001). Thus, in spite of the consistent marrow pattern of iron depletion, initial iron stores appear to be normal in CGL. It seems, however, that the disease activity may partially influence the serum ferritin levels.     

Monoclonal gammopathy in chronic myeloproliferative disorders

Summary The incidence of monoclonal gammopathy in 61 patients with chronic myeloproliferative disorders (CMPD) was studied. The distribution of patients among the CMPD subgroups was: chronic myelocytic leukemia, 24 patients; myelofibrosis, 11; polycythemia vera, 15; essential thrombocythemia, 7; unclassified MPD, 4 patients. Monoclonal gammopathy was found in 5 patients (8.2%). Two of these patients (1 IgA/k and 1 IgM/k) had myelofibrosis and 3 (2 IgG/k and 1 IgG/) polycythemia vera.The presence of monoclonal gammopathy indicates an involvement of the lymphoplasmatic system in CMPD.     

Uncontrolled thrombocytosis in chronic myeloproliferative disorders

S ummary . A retrospective study was performed to examine the natural course of uncontrolled thrombocytosis associated with chronic myeloproliferative disorders. Thirty-eight patients with polycythaemia rubra vera (PV), myelofibrosis/myeloid metaplasia (MM), chronic myelogenous leukaemia (CML) or essential thrombocythaemia (ET) had platelet counts greater than 1000 × 10⁹/1 and were followed closely for a total of 246 patient years. Eleven of the patients experienced haemorrhagic episodes. Bleeding was twice as frequent in patients over 59 years old as in those younger and no bleeding occurred in those less than 51 years of age. There was no correlation between frequency of bleeding and extent of thrombocytosis. Bleeding events occurred concurrently with use of anti-inflammatory agents in 32% of episodes. The gastrointestinal tract was the most frequent site. Documented thrombotic events occurred in three patients, two of whom had PV with haematocrits greater than 53%. This study suggests that the thrombocytosis of myeloproliferative processes may pose a less serious threat than originally thought and that aggressive lowering of the platelet count may not be indicated in all cases.     

Cytogenetic studies in chronic myeloproliferative disorders

Cytogenetic studies were performed on 113 patients with the clinical diagnosis of a chronic myeloproliferative disorder: 70 were classified as chronic myelocytic leukemia (CML), 8 as polycythemia vera (PV), 10 as osteomyelofibrosis/sclerosis (OMS), and 15 as unclassified myeloproliferative disorder (UMPD). 2 patients, 1 with UMPD and 1 with subacute leukemia, were reclassified as CML after the cytogenetic study. In the group comprising PV, OMS, and UMPD, 28% (9/32) had a chromosomally abnormal clone. The chromosomes affected involved those reported to show nonrandom alterations in myeloproliferative disorders, namely the chromosomes, 1, 7, 8, and 9.4 patients exhibited a loss of the Y-chromosome.     

Thrombocythaemic erythromelalgia in chronic myeloproliferative and myelodysplastic disorders

Erythromelalgia, which is specific for primary thrombocythaemia or polycythaemia with thrombocythaemia, is reported in a case of primary myelofibrosis at platelet counts of between 350 and 450 X 10(9)/l. In addition, the unexpected occurrence of thrombocythaemic erythromelalgia associated with Ph1 chromosome positive micromegakaryocytic myelofibrosis and with myelodysplastic syndrome type II is described. Therefore it is concluded that erythromelalgia may occur in all variants of myeloproliferative disease as well as myelodysplastic syndrome as long as they present with thrombocythaemia.     

Unexplained pulmonary hypertension in chronic myeloproliferative disorders

AIM: To investigate the potential association between the chronic myeloid disorders (CMDs), including the chronic myeloproliferative disorders, and pulmonary hypertension (PH). METHODS: Retrospective chart review of patients who had received diagnoses of both CMD and PH. Patients with a known cause of PH were excluded. The diagnosis of a CMD was based on established criteria. The diagnosis of PH was based on echocardiographic data or right heart catheterization data. RESULTS: Twenty-six patients satisfied the criteria for both a CMD and PH. Twelve patients had myeloid metaplasia with myelofibrosis (MMM), 5 patients had essential thrombocythemia (ET), 6 patients had polycythemia vera, 2 patients had a myelodysplastic syndrome, and 1 patient had chronic myeloid leukemia. Twenty-two patients (92%) received treatment for their CMDs, which included therapy with hydroxyurea (18 patients), anagrelide (7 patients), and busulfan (3 patients). PH was diagnosed a median of 8 years after recognition of the CMD (range, 0 to 26 years). The median right ventricular systolic pressure (RVsys) was 71 mm Hg (range, 32 to 105 mm Hg). RVsys correlated with the platelet count in patients with MMM (r = 0.30) and ET (r = 0.6) and with the hemoglobin levels in patients with PV (r = 0.77). Treatment of CMD did not seem to affect the severity of the pulmonary artery pressures as measured by serial echocardiography. With a median survival time of 18 months after the diagnosis of PH, the cause of death in the majority of the patients was cardiopulmonary. CONCLUSIONS: The current study suggests a higher than expected incidence of PH in patients with MMM, PV, and ET. Prognosis in such a setting is poor and may not be influenced by aggressive treatment of the underlying hematologic disorder.