Circulating Micromegakaryocytes Signaling Blast Transformation of Chronic Myeloid Leukaemia

A patient with chronic myeloid leukaemia had numerous micromegakaryocytes in the peripheral blood and bone marrow appearing coincidentally with the onset of blast crisis. These cells were initially confused with lymphocytes because of their size, configuration and scanty cytoplasm. The true identification of these cells can be suspected by careful scrutiny of well prepared Wrights stained preparations and proven electronmicroscopically. Such marked dysplasia of the megakaryocyte series appears to be a poor prognostic sign in chronic myeloid leukaemia.     

Emperipolesis Observed in Immature Cells in Blast Crisis of Chronic Myelogenous Leukaemia

In a 62 year-old male with chronic myelogenous leukaemia, an acute phase developed with appearance of large immature cells in the bone marrow. A significant proportion of these cells was found to have engulfed autologous immature and polymorphonuclear neutrophils, erythroblasts, red cells and platelets. These abnormal cells were Philadelphia chromosome positive, and considered to be derived from the leukaemic cell line. Electron microscopic examinations revealed, in the cytoplasm of engulfed cells, no lysosomes or phagosomes which are typically seen in phagocytic cells, nor any evidence of degenerative changes in either engulfing or engulfed cells. These findings suggest that this phenomenon be considered as emperipolesis rather than phagocytosis. The pathophysiological mechanism of this phenomenon is uncertain.     

Chromosomal,Morphological and Clinical Correlations in Blastic Crisis of Chronic Myeloid Leukaemia A Study of 69 Cases

The karyotypic pattern in 69 patients with Ph¹-positive chronic myeloid leukaemia (CML) was investigated during the blastic phase (BC) and correlated with survival and certain parameters of potential prognostic significance, including blast morphology, basophilia and thrombocytopenia. There was no difference in median survival in BC between patients with and without aberrations in addition to the Ph¹. Nor were there any differences in this respect among patients with the specific aberrations +Ph¹, +8, iso(17q), or other abnormalities. There was no correlation between the incidence of thrombocytopenia and any particular karyotypic change. However, the incidence of basophilia was a characteristic feature for patients with an iso(17q). The survival time in BC was considerably longer in patients with a lymphoid morphology of the blastic cells compared to the myeloid varieties, and within the myeloid varieties the survival in BC was longer in patients with granular differentiated blasts than in those with granular atypical blast cells. No obvious correlation was apparent between blast morphology and karyotypic pattern. However, a pattern was discernible regarding survival and certain chromosomal changes within some morphologic groups: in patients with granular differentiated and lymphoid morphology, the median survival in BC was considerably longer when the bone marrow cells had a Ph¹ as the sole abnormality compared to patients who had additional aberrations.     

Vincristine and Prednisolone Therapy in Blast Crisis of Chronic Myelogenous Leukaemia in Childhood

6 cases of chronic myelogenous leukaemia (CML) blast crisis in childhood were treated with vincristine and prednisolone (V-P). In 3 terminal transferase (TdT)-positive cases, blast cells were lymphoid in appearance. All 3 TdT-positive patients entered a complete remission but developed meningeal leukaemia. The mean duration of survival from the onset of blast crisis was 32 months. In 3 TdT-negative cases, V-P therapy was ineffective. The results of this study suggest that V-P therapy is more effective for CML blast crisis in childhood with TdT positive blast cells and that prophylactic central nervous system treatment is necessary to prevent meningeal leukaemia.     

Experience on the Treatment of Chronic Myelocytic Leukaemia (CML) in Blastic Crisis

A group of 50 patients with chronic myelocytic leukaemia in blastic crisis were treated with different chemotherapeutic regimens. A total of 19 remissions (6 CR + 13 PR) were achieved with an overall and complete response rate of 38 % and 12 % respectively. Of the 4 patients presenting with a lymphoblast-like appearance of the blasts, the 3 treated with the combination of vincristine and prednisone all achieved remission (2 CR + 1 PR). Duration of survival was significantly longer in responding patients (median 11.5 versus 4.5 months). Either more effective therapeutic regimens or prevention by aggressively approaching the chronic phase are to be sought in order to improve the prognosis of blastic crisis of CML.     

Arabinosyl Cytosine in Chronic Myeloid Leukaemia: Evidence for High Cytokinetic Sensitivity of Myeloblasts

The effect of a single and of repeated i.v. push dose(s) of Arabinosyl Cytosine (ARA-C) has been investigated in 9 chronic myeloid leukaemia (CML) patients in non-blastic phase. This was done by determining separately the relative compartment size, the mitotic index (IM), and the in vitro ³H-TdR labelling index (IL) of marrow and blood myeloblasts (MB) and promyelocytes plus myelocytes (PMC + MC), before and at intervals after the drug. After a single dose of ARA-C, the IL of marrow MB declines rapidly, and recovers thereafter, often with an overshoot at 15 h. After 2 to 4 doses of ARA-C, the IL of marrow and blood MB rises by a factor of 2 to 3, and is maintained at a plateau during further treatment. The behaviour of the IL of blood MB is not always the same as that of marrow MB. The IM of marrow MB does not rise proportionally to the IL, and sometimes is even found to be decreased. It is suggested that these kinetic perturbations reflect an accumulation of MB in S-phase where many but not all of them are trapped and sooner or later die off. With a few exceptions, ARA-C induces only milder kinetic perturbations in marrow and blood PMC + MC. The overall results of this study are in agreement with the generally accepted mechanism of action of ARA-C (S-phase specific effector agent), and with studies that indicate that the effect of ARA-C depends on the growth pattern and on the degree of maturation of the target cells. It is suggested that a proper evaluation of ARA-C on a cell population should take into account the existence of different cell pools, provided with different proliferative activity and potential, and with variable degrees of maturation.     

Non-Randomness in Complex Translocations of Chronic Myeloid Leukaemia

A new case of chronic myeloid leukaemia with a complex translocation involving chromosomes No. 1, 9 and 22 is reported. The striking similarity of this case with another previously reported case and the involvement of band 9q34 in chromosome rearrangements in CML patients indicates clearly a non-randomness of chromosome abnormalities in this blood disease, even when the translocation is different from the usual t(9;22) one. The usefulness of R-banding techniques is emphasized in these cases.     

Mitotic Activity of the Granulopoietic Precursor Cells in the Peripheral Blood in Chronic Myeloid Leukaemia

The mitotic indices (MI) of granulopoietic precursor cells in peripheral blood and bone marrow were studied in 38 patients with typical chronic myeloid leukaemia (CML) in the chronic phase. The MI in the peripheral blood were very low, in the median 0.07 %, compared to those in the bone marrow with a median of 1.07 %. The blood MI were significantly increasing with raising WCC and the values of the MI above the median were combined with short survival times. The bone marrow MI were negatively correlated to the blood MI and it is suggested that this is a sign of an increased exchange of cells between bone marrow and blood.     

Kinetics of 111In-Labelled Leukaemic Cells in Blast Crisis of Chronic Myelocytic Leukaemia

The distribution within the body of autologous leukaemic cells labelled with ¹¹¹In oxine was studied in 4 patients with blast crisis of chronic myelocytic leukaemia (CML) by means of serial samples and gamma camera imaging. Leukaemic cells of the blood initially entered the spleen and liver, and the major site of localization was the former rather than the latter. A portion of leukaemic cells, which rapidly entered the liver, left temporarily 3 h after reinjection. Leukaemic cells entered the spleen maximally at 3 or 24 h and then continued to leave gradually or rapidly up to 48 h. The majority of leukaemic cells in acute myelocytic leukaemia did not leave the spleen for up to 48 h. It is suggested that the destruction of sinusoidal structures of the spleen due to marked infiltration of leukaemic cells in CML impairs the effects of filtration in endothelial cells of sinusoids and facilitates the entry of leukaemic cells into sinusoids from splenic cords.     

Isozymes of Amino Acid Naphthylamidase in Chronic Myeloid Leukaemia and Erythroleukaemia

Isozymes of amino acid naphthylamidase were investigated in 11 patients with chronic myeloid leukaemia (CML) and 1 patient with erythroleukaemia. Two isozymes were found in all cases (isozymes A and C) which also occur in normal granulocytes. An isozyme with intermediate mobility appeared in all the patients in two main forms (isozymes B_F and B_S), which both differed from the isozyme B found in normal granulocytes. This may therefore support the diagnosis. In 3 patients a shift occurred between isozymes B_F and B_S, the possible significance of which is discussed.     

Non-Random and Random Chromosomal Abnormalities in Transformed Chronic Granulocytic Leukaemia

Chromosome abnormalities, identified using a banding technique and additional to the Ph, are reported in 10 consecutive cases of transformed chronic granulocytic leukaemia. In most of the cases the abnormalities were non random. In 2 cases serial studies were performed and additional abnormalities found, antedating transformation by one week and two months respectively. In 2 others the Ph status had been established during the chronic phase of the disease. In the remaining cases the first chromosome analysis was performed at the time of transformation.     

The Incidence and Characteristics of Acute Myeloid Leukaemia Arising in Hodgkin's Disease

In 201 consecutive patients with Hodgkin's disease treated from 1964 through 1975 with intensive irradiation and/or combination chemotherapy 3 cases of acute myeloid leukaemia were observed. The observed number of cases was 75 times over the expected (P < 0.01). An analysis of 47 reported cases of acute myeloid leukaemia arising in Hodgkin's disease shows that these cases differ considerably from ‘spontaneous’ cases of acute myeloid leukaemia by appearing in a much younger age group, by a very poor response to anti-leukaemic chemotherapy, and by a relatively low male/female ratio (0.84). The intensification of radiotherapy and cytostatic therapy of Hodgkin's disease during the last decade is considered the explanation of the increased incidence of acute myeloid leukaemia in these patients.     

Inhibitory Ability of Adherent Blood Cells from Patients with Chronic Myeloid Leukaemia on DNA-Synthesis in Non-Adherent Leukaemic Cells and PHA-Stimulated Lymhpocytes

Mononuclear blood cells were isolated from patients with different types of leukaemia and studied in vitro with regard to cell functions – adhesiveness, phagocytosis, DNA synthesis and inhibitory effects of adherent cells on non-adherent leukaemic cells and PHA stimulated lymphocytes. Cells from patients with chronic myeloid leukaemia (CML) adhered to the plastic surface of the culture dishes and showed esterase staining reactions as monocytes/macrophages. They showed a normal capacity to ingest Candida albicans, while the digestion capacity appeared reduced. Non-adherent cells from CML showed a high ability to incorporate thymidine, indicating DNA synthesis. Adhesive cells from patients with CML inhibited DNA synthesis in non-adherent CML cells and in PHA-stimulated lymphocytes to about the same extent as adhesive cells from normal donors. Blood cells from acute myeloid leukaemia and chronic lymphocytic leukaemia showed no adhesiveness and a very low spontaneous thymidine incorporation.     

Chromosome Banding Studies in Philadelphia Chromosome Positive Myeloid Leukaemia

A cytogenetic study of Ph¹ positive myeloid leukaemia in both chronic and acute phases had been made by a chromosome banding technique. The translocation {t(9;22) (q34;q11)}, designated t(Ph¹) was present in the myeloid cells of 43 of 44 patients; the exceptional case had normal number 9 chromosomes and a different translocation {t(19;22) (q13;q11)}. A translocation additional to that involving the Ph¹ was found as a stable abnormality present in all myeloid cells in 4 patients, chromosome 17 being involved in 2. The association of isochromosome number 17 with blast crisis was confirmed. New data were obtained concerning the significance of duplicated or dicentric Ph¹ chromosomes and their relationship with the 9q + anomaly. Monoclonal origin of Ph¹ was confirmed in cases with polymorphic number 22 or 9 chromosomes.     

Serum Beta2-Microglobulin in Acute and Chronic Leukaemia

The serum concentration of beta₂-microglobulin (beta₂-m) was measured in 69 patients with acute or chronic lympho- and myeloproliferative disorders. Serum beta₂-m was found significantly increased in 12 out of 14 patients with chronic lymphatic leukaemia. The serum concentration was proportional to the estimated lymphatic infiltration of tissues but inversely related to the number of circulating lymphocytes. Cytostatic treatment was followed by a decrease in serum beta₂-m, but normalization of the serum concentration was not observed. 11 patients with chronic granulocytic leukaemia all had significantly elevated serum concentrations of beta₂-m and increased serum concentrations were also found in patients with acute leukaemias. Thus, 12 out of 25 patients with acute myeloid leukaemia and all of 5 patients with acute myelomonocytic leukaemia as well as 4 out of 5 patients with acute lymphatic leukaemia had increased serum beta₂-m levels. In acute leukaemia no correlation could be demonstrated between the blood lymphocyte concentration and serum beta₂-m. Also no significant changes in serum beta₂-m were found in either remission or relapse of the acute leukaemia. It is concluded that serum beta₂-m in patients with chronic leukaemia may reflect the total amount or turn-over of leukaemic cells in the body and that repeated determinations of serum beta₂-m in these patients might be useful as an estimate of the residual leukaemic cell mass after therapy. Apart from this the determination of serum beta₂-m seems to be of little, if any, clinical use in leukaemia.     

Acute Myeloid Leukaemia with the Philadelphia Chromosome

A case report of serial chromosome studies on a 26-year-old male with acute myeloid leukaemia (AML) is presented. The classic Philadelphia chromosome (Ph¹) transloca-tion, t (9; 22) was found in 77 % of the metaphases at diagnosis and in 100 % in relapse; during a 3-month remission period the cytogenetic picture was normal or the Ph1 was present in a minor cell population only. The clinical and morphologic features of this case indicated that it was really a case of AML and less likely chronic myeloid leukaemia (CML) presenting in blast crisis. It is suggested that the oncogen producing the 9; 22-translocation and CML may also induce AML in rare instances.     

Trisomy 8 in Acute Myeloid Leukaemia: A Non-Random Event

6 cases of AML with a supernumerary chromosome 8 as the only aberration in practically all bone marrow mitoses and 10 cases with a normal chromosome composition of the marrow cells were investigated in order to evaluate the possible influence of trisomy 8 on some clinical and cytokinetic parameters. No significant differences between the groups were found. In our laboratory a supernumerary chromosome 8 is present in 36% of AML cases with chromosomal aberrations.     

Trisomy 8 in Acute Myeloid Leukaemia

Two cases of acute myeloid leukaemia with trisomy 8 in all examined bone marrow cells are reported. The occurrence and the prognostic significance of trisomy C in myeloproliferative disorders are discussed. The published reports of myeloproliferative disorders with chromosomal abnormalities identified by the banding technique are reviewed. It is to be noted that among group C anomalies in the acute myeloid leukaemias, only involvement of chromosome no. 7, 8 and 9 have been reported so far.