Cases Of Chronic Granulocytic Leukemia Research Articles

Chronic granulocytic leukemia: Reassessment of morphologic and cytogenetic characteristics in Ph1-positive and Ph1-negative cases

33 cases of chronic granulocytic leukemia (CGL) were reassessed to determine if, by strict morphologic criteria. Philadelphia chromosome (Ph1)-negative CGL exists as a diagnostic entity and if Ph1-positive CGL could be distinguished from Ph1-negative CGL. Cases were reassessed using published criteria and, of 11 Ph1-negative cases, only 4 could be reclassified as myelodysplastic syndromes or undifferentiated chronic myeloproliferative disorder. Of the morphologic parameters evaluated, peripheral blood basophilia and bicytopenia proved to be good discriminators between Ph1-positive and Ph1-negative cases. As a group, Ph1-negative cases were more heterogeneous and tended to have lower hemoglobin, WBC, platelet count and absolute eosinophilia. Chromosomal abnormalities other than Ph1 were seen only in the Ph1-positive cases. Based on these findings, we conclude that Ph1-negative CGL constitutes a heterogeneous group, a subgroup of which is morphologically identical with the Ph1-positive CGL. The parameters that best discriminate between Ph1-positive and Ph1-negative cases are peripheral blood absolute basophilia and bicytopenia.

Chronic Granulocytic Leukaemia and Sickle Cell Anaemia: A Case Report

The occurrence of haematological malignancies in patients with sickle cell anaemia is uncommon. We hereby present a case of Chronic Granulocytic Leukaemia [CGL] in a 36 year old Nigerian with sickle cell anaemia. The modalities of treatment common to both diseases are discussed. NQJHM Vol. 14 (1) 2004: pp.49-50

Fine needle aspiration cytology diagnosis of extramedullary leukemic infiltration

To assess the diagnostic accuracy of fine needle aspiration cytology (FNAC) in extramedullary leukemic infiltration. The results of FNAC from 65 cases of extramedullary leukemic infiltration were reviewed and analyzed. In the 65 cases studied, there were 24 cases of acute lymphoblastic leukemia (ALL), 25 cases of acute myelogenous leukemia (AML), 6 cases of chronic lymphocytic leukemia (CLL) and 10 cases of chronic granulocytic leukemia (CML). The commonest site of infiltration was lymph node, which accounted for 73.8% of all cases. Accurate cytologic diagnosis of extramedullary leukemic infiltration relies on detailed morphologic assessment as well as correlation with clinical examination and other relevant laboratory findings, especially in patients whose initial symptom being a local mass. Leukemic infiltration, which represents proliferation of primitive cells, should be distinguished from non-Hodgkin's lymphoma. Morphologic assessment by oil immersion lens and examination of peripheral blood smears is useful in this respect.

Twelve cases of malignant hematopathy treated by combined therapy of hematopoietic stem cell transplantation and Chinese herbal medicine

To evaluate the effect of hematopoietic stem cell transplantation combined with Chinese herbal medicine in treating malignant hematopathy. Allo-bone marrow transplantation (Allo-BMT) or alloperipheral blood stem cell transplantation (Allo-PBSCT), with conditioning regimen of TBI + Cy or Bu + Cy, was used to treat 4 cases of chronic granulocytic leukemia (CGL, 3 of chronic phase and 1 of acceleration phase) and one case of acute non-lymphocytic leukemia (ANLL). And auto-BMT or auto-PBSCT, with conditioning regimen of MAC or MAC + VP16, was used to treat 7 cases of hematopathy, including 5 cases of ANLL (3 of CR1 and 2 of CR2) and 2 cases of malignant lymphoma (1 of first occurring and 1 of relapse). Chinese herbal medicine was given orally to all the 12 patients after' transplantation according to TCM Syndrome Differentiation. All patients were successfully engrafted. Within the median follow-up period of 18 (4-70) months, one patient (8.3%) died of transplantation-related death, 3(25.0%) relapsed and 8 (66.7%) survived free of original disease. The transplantation effective rate was 88.8% as counting by ANLL CR1 and CGL chronic phase. Auto-BMT or auto-PBSCT in CR1 stage of acute leukemia could reduce the relapse rate, when there was no matched bone marrow donor; allo-BMT or allo-PBSCT in chronic stage could result in long-term disease-free survival of patients; Chinese herbal medicine administration in patients of malignant hematopathy might reduce the complications and plays certain role in promoting recovery of hematopoietic function.

Amplification of mitochondrial DNA in acute myeloid leukaemia.

There is a long-standing interest in the possible role of mitochondria in malignancy. We sought to discover whether amplification of mitochondrial DNA (mtDNA) occurred in leukaemia, and found it was often remarkably amplified in the blast cells of acute myeloid leukaemia (AML). We used gene dosage experiments to quantify the amount of mtDNA relative to nuclear DNA. DNA extracted from peripheral blood leucocytes or bone marrow of healthy individuals or patients was simultaneously hybridized with a probe for the mitochondrial genome and a control probe for the renin gene on human chromosome 1. Comparative densitometric ratios of approximately 1 were obtained between the two signals in 20 normal control peripheral blood samples. In contrast, comparative ratios in the range of 2-50 were observed in 25 AML samples and 13 of these showed 8-fold or greater amplification of mtDNA relative to normal peripheral blood controls. An additional four cases of AML were investigated at both presentation and remission and showed 3-10-fold amplification of mtDNA at presentation, but no amplification when in clinical remission. 18 cases of chronic granulocytic leukaemia (CGL) were also studied in chronic phase and showed mtDNA dosage levels equivalent to normal peripheral blood controls. However, 8/9 CGL patients showed mtDNA amplification during transformation from chronic phase. We conclude that amplification of mtDNA is an invariable feature of acute myeloid leukaemia and that it may be a useful marker for detecting transformation of CGL.

Chronic granulocytic leukaemia/ eosinophilic leukaemia in a dog?

ABSTRACTA suspected case of chronic granulocytic leukaemia (chronic myelogenous leukaemia) with eosinophil differentiation and hepatic involvement is described in a 3–5‐year‐old rottweiler dog. Neoplastic eosinophilic infiltrates were also present in the lungs, kidneys, mesenteric lymph nodes and peribronchial and prester‐nal lymph nodes. Both pleural and abdominal effusions contained predominantly eosinophils and their precursors. The bone marrow showed an increase in the myeloid to erythroid ratio and an increase in the marrow granulocyte reserve. The majority of cells identified within the bone marrow were of the eosinophil series. Myelocytes and promyelocytes predominated.

Chronic granulocytic leukaemia in a dog with associated bacterial endocarditis, thrombocytopenia and preretinal and retinal haemorrhages

ABSTRACTThe clinical, haematological and pathological features of a case of chronic granulocytic leukaemia (CGL) associated with valvular bacterial endocarditis are described in a nine‐year‐old male Springer Spaniel. The disease was characterized clinically by lethargy, weight loss, hepatosplenomegaly, anaemia and leucocytosis. Severe thrombocytopenia resulted in preretinal and retinal haemorrhages. A diagnosis of CGL was based on the finding of a hypercellular bone marrow with increased M: E ratio and morphologically abnormal myeloid precursors. The dog terminally became leucopenic and bacteraemic. Necropsy revealed invasion of liver, spleen and bone marrow with a pleiomorphic population of myeloid blast cells, consistent with transition to a blast cell crisis.

Myeloid lineage specificity and high sensitivity of monoclonal antibody GM 58/8 proves its usefulness as a diagnostic reagent in acute leukemia

Monoclonal antibody (MoAb) GM 58/8 was earlier reported to be directed against an antigen expressed by myeloid progenitors (CFU-GM), myeloid precursors, granulocytes, and monocytes. Immunophenotyping of 216 cases of acute leukemia [acute myeloblastic leukemia (AML) = 147 and acute lymphoblastic leukemia (ALL) = 69] and 18 cases of chronic granulocytic leukemia in blast crisis (CGLBC) with this antibody showed that GM 58/8 reacted with 92% of AML cases (M1-M5) and 100% of myeloblastic crisis in CGL cases. All cases of ALL, lymphoblastic crisis in CGL, erythroleukemia, and erythroblastic crisis in CGL were unreactive with GM 58/8. The antibody revealed the myeloid phenotype in an additional 15 cases of otherwise unclassifiable acute leukemia and six cases of CGLBC. Eleven cases of acute "mixed lineage" leukemia were also diagnosed with the help of GM 58/8. The high specificity (100%) and sensitivity (92%) of MoAb GM 58/8 for myeloblastic leukemia is unmatched by almost all previously described myeloid MoAb and proves its usefulness as a single diagnostic reagent for AML and myeloblastic crisis in CGL.

Oncogenes, cancer and analytical cytology.

Oncogenes, cancer and analytical cytology.

Characterization of myeloid leukemias with monoclonal antibodies 3C5 and MY9.

The expression of two membrane antigens identified by the monoclonal antibodies (McAb) My9 and 3C5 has been investigated in cells from 80 acute leukemias. My9 was positive in the blasts of 33 out of the 38 (87 per cent) cases of acute myeloid leukemia (AML) tested, regardless of FAB subtype, and in 13 of 18 (72 per cent) cases of chronic granulocytic leukemia (CGL) in myeloid blast crisis. The reactivity of 3C5 was confined to myeloblastic (M1) AML, 85 per cent of cases, and to lymphoblastic leukemia (ALL) of B-lineage, 70 per cent of cases, including CGL in lymphoid transformation. My9 was negative in ALL except for an unusual case. The phenotype My9+, 3C5+ was seen exclusively in M1 (69 per cent) and M2 (14 per cent) AML. Ultrastructural analysis with the immunogold method in combination with the myeloperoxidase (MPO) reaction showed that expression of My9 increased in parallel with MPO activity whereas 3C5 was expressed mainly in myeloblasts with little MPO content. We conclude that the use of these two McAb will contribute to the diagnosis and classification of AML and may throw some light to the pathogenesis of biphenotypic acute leukemias, including TdT + AML.

A sensitive method for immunophenotyping stored leukemia and lymphoma cells with preservation of morphological detail

We describe a method by which density-separated mononuclear preparations of blood and bone marrow may be stored and batch-processed for immunophenotyping by the indirect immunoperoxidase (IP) technique. The method gives excellent preservation of cellular detail thus permitting clear morphological categorization of IP-positive and IP-negative cells. We compared the immunofluorescence (IF) and IP techniques for estimation of the proportions of cells displaying a variety of antigens; with normal blood cells the results were closely similar but with chronic lymphocytic leukemia (CLL) cells, IP was superior to conventional IF. Using 910 D7, a new anti-la antibody, we were able to observe directly the presence of la-positive lymphocytes and monocytes in normal peripheral blood and la-positive granulocyte precursor cells from 2 cases of chronic granulocytic leukemia (CGL) in transformation. The method is useful for immunophenotyping of cases of lymphoproliferative disorder (LPD) and for morphological identification of specific antigen-positive cells.

人工透析導入後5年目に発見された慢性骨髄性白血病の1剖検例

尿毒症患者または慢性透析患者における悪性腫瘍の合併についての報告は多いが, 慢性骨髄性白血病の合併の報告は3例のみである.私達は慢性透析開始後に腫瘤形成性急性転化をきたして死亡した慢性骨髄性白血病の1症例を経験したので, 輿味深い経過とともに剖検所見を合わせて報告する.症例は45歳男性で, 昭和58年8月30日右前頭部痛と全眼球麻痺を主訴として当科に入院した.患者は51年3月より慢性透析を受けていたが, 55年7月白血球増多, 白血病裂孔を伴わない過形成性骨髄, アルカリフォスファターゼ・スコアーの低値, フィラデルフィア染色体の検索より, 慢性骨髄性白血病と診断され, その後特に自覚症状なく, busulfanにより白血球数も30,000-50,000/cummに維持されていた. 頭痛出現時の58年7月のCTでは, トルコ鞍近傍の腫瘤が認められた.入院時の骨髄所見および末梢血所見は慢性期の像を呈していたが, 造影剤を用いてCTを再検したところ腫瘤は海綿静脈洞に存在し, さらにトルコ鞍, 蝶形骨洞にまで及んでいたため, 慢性骨髄性白血病の腫瘤形成性急性転化と診断した.頭部照射により症状はすみやかに改善したが, その後皮下腫瘤が多発し, 骨髄所見も急性転化を示し, 消化管出血とこれに続発した高カリウム血症のため死亡した.剖検では, 腫瘤は皮下, 骨髄, 縦隔, 甲状腺, 消化管など全身臓器に及び, その光顕所見は大細胞型悪性りンパ腫様の所見を呈していた.

A Case of Chronic Granulocytic Leukemia with Neutropenia and t(8q-; 22q+) at Onset

A Case of Chronic Granulocytic Leukemia with Neutropenia and t(8q-; 22q+) at Onset

Significance of Phi bodies in acute leukaemia.

Material from 39 patients with acute leukaemia was investigated with the peroxidase cytochemical reaction using 3,3'diaminobenzidine (DAB) and other substrates in order to test their sensitivity in detecting myeloid differentiation. The proportion of positive blasts and of cases with Auer rods in acute myeloid leukaemia (AML) was significantly greater with DAB than with benzidine. In addition, Phi bodies were demonstrated in AML blasts only when DAB was used; Phi bodies were also observed in two out of seven cases of chronic granulocytic leukaemia in "myeloid" blast crisis but were not seen in any case of acute lymphoblastic leukaemia. Phi bodies were more numerous when the reaction was carried out at pH 9.7, and their number was significantly reduced in the presence of 3-amino 1,2,4-triazole. Both findings suggest that the Phi bodies derive from catalase-containing granules (microperoxisomes) and are distinct from Auer rods, which derive from peroxidase-containing (primary) granules. Like Auer rods, Phi bodies appear to be characteristics of immature myeloid cells in leukaemia but are seen with a higher frequency than Auer rods in acute myeloid leukemia.

A Case of Chronic Granulocytic Leukemia with 3 Types of Abnormal Chromosomes in Addition to Ph1) Chromosome at the Blastic Crisis

A Case of Chronic Granulocytic Leukemia with 3 Types of Abnormal Chromosomes in Addition to Ph¹⁾ Chromosome at the Blastic Crisis

The Significance of Ph1 Mosaicism: a Report of Six Cases of Chronic Granulocytic Leukaemia and Two Cases of Acute Myeloid Leukaemia

Six cases of chronic granulocytic leukaemia (CGL) and two cases of acute myeloid leukaemia (AML) with dual populations of karyotypically normal and Philadelphia (Ph1) chromosome-positive cells are described. GTG and QF-banding characterized the Ph1 as resulting from a 9/22 translocation in all eight cases. Four of the patients suffering from CGL presented with 100% Ph1-positive bone marrows, and after receiving intensive chemotherapy, karyotypically normal cells were demonstrated. The other two patients with CGL showed Ph1 mosaicism at presentation. The two patients with AML exhibited Ph1 mosaicism at presentation and throughout the course of the disease. In both of these patients, a marker No. 10 chromosome was found in some of the Ph1-positive cells and in one hyperdiploidy was observed to have developed only in the clone with the additional chromosome anomaly.

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.

The Blast Crisis of Chronic Granulocytic Leukaemia: Megakaryoblastic Nature of Cells as Revealed by the Presence of Platelet‐Peroxidase—A Cytochemical Ultrastructural Study

The origin of cells in the blast crisis of some cases of chronic granulocytic leukaemia (CGL) remains controversial. Difficulties arise from the lack of cytochemical characteristics of differentiation. This report concerns the nature of cells in the blast crisis of a case of CGL in which blast cells exhibited an undifferentiated or lymphoid appearance by light and electron microscopy. The majority (90%) of such cells contained a peroxidase in the endoplasmic reticulum distinct from myeloperoxidase. In addition, some micromegakaryocytes could be recognized among the peroxidase reactive cells, by the presence of typical granules and demarcation membranes. Since this peroxidase exhibited identical characteristics to that of normal megakaryocytic precursors, these blast cells could be identified as megakaryoblasts. These data emphasize the possible megakaryoblastic nature of cells occurring in other cases of CGL blast crisis.

Chronic granulocytic leukemia following successful renal transplantation

The use of immunosuppressive therapy has markedly increased over the past several years, and concomitant with its use has been an increased frequency of associated neoplasia. The patient presented is a 22-year-old white male who, following two renal transplants and prolonged immunosuppressive therapy with azathioprine and methylprednisolone, developed chronic granulocytic leukemia. Chromosome karyotyping demonstrated the somewhat unusual development of a Philadelphia chromosome with translocation to the No. 7 of the C group. A review of transplantation centers revealed that five cases of chronic granulocytic leukemia have occurred in a population of 25,000 renal transplant patients, a 5-fold increased incidence over the general population. Possible etiologies that may be responsible for the development of chronic granulocytic leukemia in patients on immunosuppressive therapy are discussed. It is our hope that by the introduction of these reports of chronic granulocytic leukemia into the medical literature, the need for caution in the use of immunosuppressive drugs in nonmalignant disease will again be emphasized.

A Case of Chronic Granulocytic Leukemia with ALL Features at Onset

A Case of Chronic Granulocytic Leukemia with ALL Features at Onset