Marked hypodiploidy in blast phase chronic myelogenous leukemia: report of a case and review of the literature

The emergence of a near-haploid clone of cells in blast phase chronic myelogenous leukemia is an unusual event. We report such a case and review eight other cases described in the English literature. The significance of the substantial loss of genetic material is discussed as is the phenotypic and genotypic heterogeneity observed in this group of patients.     

Differential diagnosis from isolated lymphoid extramedullary blast crisis from secondary non-Hodgkin lymphoma in chronic myelogenous leukemia: a case report and literature review

Case: Extramedullary blast crisis (EBC) is a special kind of blast crisis of chronic myelogenous leukemia (CML). It is more likely to be misdiagnosed as lymphoma when EBC cells are of lymphoid cell lineage and lymphadenopathy is the only symptom before the final diagnosis. In this study, we presented a patient with an unusual presentation of CML transformation as a rapid growth of generalized lymphadenopathy that appeared 5 months after the initial diagnosisof CML. The patient underwent the left supraclavicular lymph node biopsy and repeat bone marrow aspiration. The revealed CD3+, terminal deoxynucleotidyl transferase (TdT)+, CD5+, CD23+, myeloperoxidase (MPO)-, CD20-, cyclin D1-, CD10-, which was consistent with the diagnosis of T-cell lymphoblastic lymphoma (T-LBL). Fluorescence in situ hybridization (FISH) verified the BCR-ABL rearrangement, and T-cell EBC of CML was finally diagnosed. Our report suggested that the FISH was necessary to distinguish isolated lymphoid extramedullary blast crisis from secondary NHL in CML.     

Hyperdiploidy of 54 chromosomes with double Ph1 chromosome in lymphoid chronic myelocytic leukemic blast crisis

Cytogenetic analysis of bone marrow cells in a 40-year-old man revealed a mosaic of two cell lines during blast crisis: one diploid with typical Ph1 chromosome (46 XY Ph1) and one with hyperdiploidy of 54 chromosomes with double Ph1 chromosome, trisomy 4, 6, 8, 18, 21 and duplication of the sex chromosomes X and Y. Immunological characterization showed common acute lymphoblastic leukemia antigen in 90% of the blasts. In spite of intensive chemotherapy the patient died in a third blast crisis 15 months after the first blast crisis, 3 months after successfully treated central nervous system relapse.     

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.     

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.     

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.     

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.     

Myeloid/natural killer cell precursor blast crisis of chronic myelogenous leukemia with two Philadelphia (Ph-1) chromosomes

We report on a 30-year-old patient with blast crisis of a chronic myelogenous leukemia (CML) that shows immunophenotypic features similar to those of the myeloid/natural killer (NK) cell precursor leukemia previously described. Expression of CD13/CD33/CD65 as well as MPO+/LF- blasts was classified as a myelogenous blast crisis of a CML. In addition, the blasts were positive for CD7/CD56. Other lymphoid markers were not expressed. Cytogenetic and molecular cytogenetic examinations showed two Philadelphia (Ph-1) chromosomes and a trisomy 8. Similar to expression of the myeloid/NK cell precursor phenotype in acute myelogenous leukemia (AML), it is possible to exhibit this phenotype in Ph-1-positive CML. Only one case report of myeloid/NK precursor phenotype blast crisis of CML was found in the literature. Therefore, it is not clear whether this phenotype is a distinct biologic and clinical disease entity of CML, as is the case in the respective AML phenotype.     

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.