Erythroid blast crisis in chronic myelogenous leukemia

Blood or bone marrow specimens from 22 patients with chronic myelogenous leukemia in blast crisis were studied for the surface expression of glycophorin-A, a marker for early erythroid differentiation. The leukemic blasts were stained with rabbit anti- glycophorin-A antiserum. The glycophorin-A molecules detected by the rabbit antiserum were identified by polyacrylamide slab gel electrophoresis of the immunoprecipitates from the membrane lysates of surface-labeled blasts. Blasts expressing surface glycophorin-A were found in 9 of the 22 patients. In 4 patients, almost all blasts were glycophorin-A positive, and in 5 patients, less than half of the blast population expressed glycophorin-A. The present study shows that when glycophorin-A is used as a marker for erythroid blasts, involvement of the erythroid lineage during blast crisis of chronic myelogenous leukemia seems to occur more frequently than previously recognized.     

Terminal deoxynucleotidyl transferase activity and B cell markers in chronic myelogenous leukemia blast crisis.

High terminal deoxynucleotidyl transferase activities were found in blast cells having B cell markers in 3 patients suffering from chronic myelogenous leukemia. The blast cells from these patients were lymphoblastic in appearance. Two of these cases were treated with vincristine and prednisolone. They responded well to this therapy.     

Extramedullary presentation of blast crisis in chronic myelogenous leukemia

We present a case with the clinical and pathological impression of Ph1-positive chronic myelogenous leukemia in extramedullary blast crisis involving lymph nodes as demonstrated by morphological and cytogenetic studies. The hyperploid cell lines that were present in the lymph node were not present in the bone marrow. The present case demonstrates that cytogenetic and morphological studies of extramedullary organs are helpful in the confirmation of the diagnosis of blast crisis, especially when lymph nodes are the site of original presentation.     

Natural killer lymphocyte blast crisis of chronic myelogenous leukemia

We describe for the first time a case report documenting a chronic myelogenous leukemia (CML) patient who developed a blast crisis of natural killer (NK) lymphocytes. Many of the blasts exhibited large granular lymphocytic (LGL) morphology. Single parameter immunophenotyping results determined that the granulated as well as the agranulated blast cells were NK lymphocytes (CD45, NKH1, CD2, LEU 17, and CD16 positive; CD3, CD8, and LEU 7 negative). Dual parameter flow cytometric testing also determined that some of the blasts expressed the CD11b and CD11c markers as reported for some types of NK lymphocytes. Approximately 10% of the cells were in the S phase of the cell cycle as determined by a modified Vindelov DNA content analysis test and may theoretically reflect some of those cells expressing CD11b and CD11c. The cells did not express in vitro NK lymphocyte functional activity against a K562 target and therefore similar to other reported cases of presumably immature NK lymphocytic leukemias. The NK lymphocyte blast crisis was successfully treated with vincristine and prednisone. The patient's disease eventually relapsed and transformed to a progenitor stem cell before she died (CD45, 13, CD38, and CD34 positive). The flow cytometric immunophenotyping results contributed significantly as an important adjunct in determining the appropriate diagnosis, helping to select the type of therapy, and monitoring the patient with this unusual type of blast crisis.     

Lymphoid blast crisis during interferon-alpha therapy in a patient with chronic myelogenous leukemia in myeloid blast crisis

A 47-year-old woman was admitted to the hospital on March 13, 1998, because of general malaise and fever. It was determined that she had chronic myelogenous leukemia (CML) in myeloid blast crisis. Hydroxyurea was started initially, and the blasts completely disappeared from peripheral blood on day 9 of therapy. Interferon (IFN)-alpha was subsequently started, but lymphoblasts newly appeared on day 13 of administration. Treatment with adriamycin, vincristine, and prednisolone (AdVP) was immediately started, which rapidly reduced the lymphoblasts. However, the myeloblasts again began to gradually increase. Subsequent examinations showed the combined presence of myeloblasts and lymphoblasts in the marrow and peripheral blood. The ratio between myeloblasts and lymphoblasts depended on the treatment (IFN-alpha or AdVP). The patient died from respiratory failure on November 16, 1998. This patient may have had an underlying bipotential blastic clone that evolved differently in response to IFN-alpha or AdVP. In some CML patients, IFN-alpha may induce lymphoid blast crisis.     

T cell lineage involvement in lymphoid blast crisis of chronic myeloid leukemia

Cytochemical and immunologic analysis of cells obtained from two patients with chronic myeloid leukemia (CML) during blast crisis reveals markers suggestive of an immature lymphoid phenotype. Peripheral blood mononuclear cells from both patients generated spontaneous lymphoblastoid colonies in methylcellulose, a phenomenon observed in T cell acute lymphoblastic leukemias and T cell non- Hodgkin's lymphomas but not in any other type of leukemia. Colonies derived from one patient were composed predominantly of OKT3+ cells (89%), whereas those from the second patient displayed 42% OKT3+ and OKT6+ cells. In the second patient's colonies, each of five mitoses contained the Philadelphia chromosome (Ph1) and two of five displayed the same additional karyotypic abnormalities as the blast crisis cells. Cells obtained from the two patients during remission still gave rise to spontaneous T cell colonies (greater than 85% OKT3+) and Ph1 was detected in 33% and 60% of the metaphases, respectively. However, when colony growth was induced by an interleukin 2-containing conditioned medium, less than 5% of mitoses were Ph1-positive. These data suggest that: (1) the T cell lineage might be involved in CML; (2) a subset of T cells may remain unaffected by the leukemic process, as demonstrated by the virtual absence of Ph1 in induced T cell colonies; and (3) the spontaneous colony assay seems to select for the growth of malignant T cells.     

Philadelphia-chromosome-positive pre-B-cell leukemia presenting as blast crisis of chronic myelogenous leukemia.

Cytogenetic studies of chronic myelogenous leukemia (CML) have shown that the majority of hemopoietic cells originate from pluripotential stem cells affected in this disease. Evidence that lymphocytes are also progeny of these stem cells, however, has been indirect. Philadelphia-chromosome-positive leukemic blasts from a 4 10/12-yr-old boy with CML in blast crisis had features characteristic of pre-B leukemic cells, including expression of cytoplasmic IgM and absence of surface immunoglobulin. Additional immunologic, enzymatic, and pharmacologic characterization of these cells supported their pre-B-cell phenotype. Together, these features provide direct evidence for CML stem cell ancestry to lymphocytes of the B-cell lineage.     

High incidence of meningeal leukemia in lymphoid blast crisis of chronic myelogenous leukemia

Fifteen patients with lymphoid blast crisis of chronic myelogenous leukemia (LyBC-CML) and five patients with acute lymphoblastic leukemia converting to Philadelphia-positive (Ph+) chronic myeloid leukemia (ALL Ph + CML) were followed. Seven of 15 (46.7%) LyBC-CML patients developed meningeal leukemia within a median period of 6 months (range 2–11 months), while there was no medullary relapse. Five of these responded well to triple intrathecal therapy. In the ALL Ph + CML patients, in spite of central nervous system (CNS) prophylaxis with IT MTX and 18 Gy cranial radiation, two of five patients (40%) experienced meningeal leukemia, one isolated and the other with medullary relapse. The data confirm that LyBC-CML patients experience a high incidence of meningeal leukemia. The role of CNS prophylaxis is not very clear, but its use may delay development and reduce morbidity due to CNS disease.     

Complex chromosomal abnormalities in a patient with lymphoid blast crisis of chronic myelogenous leukemia

A 46-year-old Chinese man underwent lymphoid blast crisis (Ia+, CALLA+, TdT+) after 5 years of chronic phase, Philadelphia-chromosome positive chronic myelogenous leukemia. Chromosome analysis revealed a hyperdiploid karyotype, including two Philadelphia chromosomes--55,XY,t(9;22) (q34;q11), +2, +5, +5, +6, +10, +18, +19, +21, +del(22)(qll----qter)--in the majority of the leukemic blasts. The constellation of a lymphoid blast crisis and complex chromosomal abnormalities usually associated with myeloid blast crisis as well as the clinical data are discussed.     

Lymphoid blast crisis of chronic myelogenous leukemia occurring more than 11 years after receiving an allogeneic bone marrow transplant for chronic myelogenous leukemia in myeloid blast crisis at onset

A 25-year-old male developed lymphoid blast crisis (BC) of chronic myelogenous leukemia (CML) more than 11 years after receiving an allogeneic bone marrow transplant (alloBMT) for CML with myeloid BC at presentation from his HLA-identical brother. The lymphoid BC of CML probably occurred without a preceding chronic phase of CML. This case illustrates the difficulties involved in determining the appropriate length of follow-up after alloBMT.     

Rearrangement and expression of p53 in the chronic phase and blast crisis of chronic myelogenous leukemia

We tested a population of over 60 patients with chronic myelogenous leukemia (CML) for changes in the structure and expression of the p53 gene, which is located on chromosome 17. Six of 27 (22%) blast crisis samples and 3 of 5 (60%) accelerated phase samples had rearrangements of chromosome 17, whereas only 3 of 42 (7%) chronic phase patients had cytogenetic changes in chromosome 17. There was no loss of heterozygosity during the transition to blastic crisis among seven individuals who were informative for polymorphic probes for regions in or around the p53 gene on 17p. One patient in the chronic phase and one patient in the blastic phase of the 61 CML patients studied exhibited rearrangements of the p53 gene that were detectable by Southern analysis. One p53 allele was rearranged in the chronic phase patient and both p53 alleles were rearranged in the blastic phase patient. The p53 messenger RNA (mRNA) was of normal size (2.8 kb) in chronic phase and blast crisis, and the expression of the p53 gene was at least as high or higher in blast crisis as in the chronic phase of CML. The high incidence of abnormalities of chromosome 17 in blast-crisis CML found in our studies and the discovery of rearrangements of the p53 gene in two CML patients studied suggest that further study with probes for the p53 gene and anonymous polymorphic sites in chromosome 17 should be conducted in CML.     

Lymph node blast crisis in chronic myeloid leukemia mimicking T-immunoblastic lymphoma.

BACKGROUND: Chronic myeloid leukemia arises from a somatic mutation in a pluripotent stem cell. It generally terminates with a blastic crisis (BC). One third of BC are lymphoid, and most have a pre-B phenotype. Few cases of T-lymphoid BC have been reported. Here we describe a lymph node blast crisis mimicking T-immunoblastic lymphoma. METHODS: Bone marrow and lymph nodes were histologically examined by standard methods and by an immunoperoxidase technique. Cytogenetic studies were also performed on lymph node and blood cells. Analysis of T-cell receptor genes and BCR rearrangements were performed on DNA extracted from both frozen bone marrow and lymph-node cells. RESULTS: Lymph-node histology showed an infiltration by large lymphoid blasts, consistent with a diagnosis of immunoblastic lymphoma. Blast cells were CD2, CD7, TDT positive, and negative for myeloid and mature lymphoid antigens. The Ph1 chromosome was found in both bone marrow and lymph-node cells. BCR rearrangement was found in the DNA from both bone marrow and lymph-node cells. TCR genes were not rearranged. DISCUSSION: The present study provides strong evidence that the lymph-node blast crisis of CML can assume the morphological appearance of immunoblastic lymphoma and may retain the immunological phenotype and genetic features of early T cells with BCR rearrangements.