Development of PH Positive Chronic Myeloid Leukemia in a Patient with Chronic Lymphocytic Leukemia Treated with Total Body Irradiation: A Rare Association

Philadelphia (ph) chromosome positive chronic myeloid leukemia developed in a patient treated for chronic lymphocytic leukemia after treatment with total body irradiation. The role of radiation in the development of CML is discussed.     

Parameters of Predictive Value in Chronic Myeloid Leukemia—The Prognostic Impact of Histopathological Variables in a Multivariate Regression Analysis

The prognostic significance of disease features at the time of diagnosis was examined in 113 patients (75 males/38 females, median age 49 years) with chronic myeloid leukemia (CML) using multivariate regression analysis. In the course of this study we tested the validity of the prognostic model described by Sokal and coworkers³, the predictive value of histopathological variables, and determined the disease-specific loss in life expectancy. The median survival time was 35 months in our patients. By using Cox's proportional hazards model for covariate analysis of censored survival data²⁶'³² two prognostic models were derived. The first consisted of the following parameters—age, presence of pseudo-Gaucher cells in the marrow, spleen size and the product of myeloblasts and normoblasts in the peripheral blood. The second model included age, the presence of myelofibrosis, the number of megakaryocytes in the bone marrow and the liver size. Both models provided a risk status that showed an excellent predictive relationship to relative survival rates and life expectancy. Application of the Sokal model³ to our subpopulation of CML patients failed to reveal a significant segregation of the intermediate group from the other risk groups, even when assessing the disease-specific loss in life expectancy. Our results suggest that an amendment of the generally accepted model for prognostic evaluation of survival in CML should be made by inclusion of histological variables and the determination of relative survival rates.     

Acute Myeloid Leukemia in the Elderly: A Critical Review of Therapeutic Approaches and Appraisal of Results of Therapy

In the elderly, acute myeloid leukemia (AML) is characterized by a poorer prognosis than in younger patients, due to either host related factors (poor performance status, co-morbid diseases, organ function impairment) or the biology of leukemia itself (high incidence of adverse cytogenetic abnormalities, high frequency of preceding myelodysplastic syndromes, intrinsic resistance to cytotoxic drugs). Current therapeutic results are mostly unsatisfactory and studies reporting high rates of complete remission are probably influenced by selection biases as suggested by the low rate of elderly patients inclusion into cooperative trials. Availability of intensive support including hematopoietic growth factors could stimulate clinicians to manage an increasing number of elderly patients with AML with aggressive programs. However, chemotherapy in the elderly is difficult, costly and usually associated with high morbidity and mortality rate. Therefore, all efforts should be made to identify those subset of elderly patients in whom aggressive treatment may result in a true improvement of disease free and overall survival. The critical analysis of our five years experience, as reported here, seems to suggest that older AML patients displaying unfavourable prognostic factors at diagnosis (i.e., adverse karyotype and high serum LDH levels), but clinically eligible for intensive chemotherapy, do not actually benefit from an aggressive approach. A blind attempt to treat these patients aggressively may be associated with a life threatening toxicity not counterbalanced by an actual survival advantage. We suggest therefore that aggressive treatment should be reserved for elderly AML cases in whom the presence of good prognostic factors at diagnosis predicts that the loss of some patients due to toxicity may be balanced by the achievement of a substantial proportion of long term survivors. Finally, given the biological and clinical heterogeneity of elderly AML patients, a more precise prognostic categorization of these patients would be particularly useful in interpreting future therapeutic results.     

Inversion of chromosome 16 in accelerated phase of chronic myeloid leukaemia: report of a case and review of the literature

A patient with a Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) developed a blast crisis (FAB subtype AML-M2) without a monocytic involvement. Karyotype showed the presence of inv(16)(p13;q22) in addition to Ph, in 16/20 marrow metaphases.     

Accuracy of Immunohistochemistry and Flow Cytometry in Estimating the Proportion of Leukemic Cells in S Phase in Chronic Myeloid Leukemia Patients

We compared the proportion of S phase cells in bone marrow and peripheral blood samples obtained from 17 patients with chronic myeloid leukemia (CML). Before sampling all patients received a one hour IV infusion of iododeoxyuridine (IdUrd). The proportion of S phase cells was studied by immunohistochemistry (IHC) in bone marrow biopsies, and by flow cytometry (FCM) in bone marrow aspirates and peripheral blood samples. The IdUrd labelling index (LI) in bone marrow biopsy sections (27.5 ± 1.8%) was significantly higher than the proportion of IdUrd labelled cells in bone marrow aspirate (15.1 ± 2.0%). The percentage of S phase cells in peripheral blood was approximately the same as that in the aspirate (12.4 ± 1.3%) and was correlated with that of bone marrow aspirate indicating a high degree of the aspirate dilution by peripheral blood. It is likely that the differences in % S phase cells in the aspirate and the biopsy result from this dilution. Estimates of the % S phase cells in the peripheral blood study by IHC and FCM were essentially the same. Samples labelled for one hour in vitro resulted in 1.5 fold higher LI than the same samples labelled in vivo. We conclude that estimates of the 8% S phase cells in the bone marrow of patients with CML should be made by infusing patients with IdUrd or BrdUrd with immunohistochemical evaluation of a marrow biopsy. Additionally in vitro labelling is not reflective of the percent S phase cells in vivo in patients.     

Characteristics of Granulocyte-Macrophage Colony Formation in Chronic Myelomonocytic Leukemia: A Comparative Study with Other Myelodysplastic and Myeloproliferative Disorders

We studied granulocyte-macrophage (GM) colony formation in chronic myelomonocytic leukemia (CMML, 6 cases), as compared with that in myelodysplastic syndromes (MDS, 6 cases) and myeloproliferative disorders (MPD, 12 cases). GM colony formation of bone marrow cells by colony-stimulating factor (CSF) was normal in CMML and MPD patients, but was decreased in MDS patients. Circulating granulocyte-macrophage progenitors (CFU-GM) were detected in CMML and MPD patients, but not in MDS patients. GM colony formation without CSF was observed in CMML patients, but not in MDS or MPD patients. These endogenous colonies decreased markedly after adherent cell (AdC) depletion, but AdC did not form endogenous colonies in sufficient numbers to explain their marked decrease after AdC depletion. In CMML patients, the numbers of circulating CFU-GM and endogenous colonies correlated with leukocyte and monocyte counts, respectively. The cellular composition of GM colonies was normal in MDS and MPD patients, whereas granulocytic colonies predominated in all CMML patients but one. The CSF-producing capacity of peripheral blood cells was also studied and was found to be increased in CMML patients. This capacity was markedly decreased by AdC depletion; and AdC could produce CSF only in CMML patients. CSF produced by CMML patients supported granulocytic colonies to a greater extent than CSF produced by MDS or MPD patients. These results suggest that enhanced granulopoiesis in CMML patients is closely associated with the possible hyperproduction of granulocytic CSF by their adherent monocytes.     

A Clone with a Chromosome Abnormality, i(17q), in the Myeloid Crisis of Chronic Myeloid Leukemia Is Able to Differentiate into Neutrophil, Basophil and Eosinophil Lineages

Simultaneous cytogenetic and morphologic observations of singlecolonies derived from granulocytic precursor cells were performedon a patient with chronic myelogenous leukemia (CML) duringthe myeloid crisis. Colonies having a Ph¹ chromosome and i(17q)were found to consist of neutrophilic/basophilic, eosinophilic/basophilicor basophilic granulocytes. These findings led to the conclusionthat cells having the additional abnormality, i(17q), are stillable to differentiate into neutrophil, basophil and eosinophillineages. In other words, this chromosome abnormality does notgive a proliferative advantage to a restricted cell lineage.     

Study of the levels of expression of two oncogenes, c-myc and c-myb, in acute and chronic leukemias of both lymphoid and myeloid lineage

Total cellular RNA from a series of leukemic cell populations, both myeloid and lymphoid, as well as from normal circulating lymphocytes was analysed for the expression of two cellular oncogenes, c-myc and c-myb, by Northern blot hybridization assay. Expression of c-myc but not of c-myb was observed in unstimulated normal lymphocytes. Stimulation by PHA was shown to activate the expression of both genes. Remarkably different levels of expression of c-myc were observed in ALL, whereas in CLL the expression of c-myc was uniformly low or absent. Differential expression of c-myc was detected in AML as well as in CML, c-myb was differentially expressed in AML and ALL, and absent in CLL and CML. Other single cases of hemopoietic disorders were studied, but the expression of the two oncogenes was low or absent. Neither evident genome amplification nor genome rearrangements were detected in the cell DNAs digested with restriction endonucleases.