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.     

Hypercalcemia associated with blast crisis of chronic myeloid leukemia

We describe a patient with CML who developed hypercalcemia in his course of blast crisis. A 25-years-old man was diagnosed as CML with priapism in April 1985, and controlled with BHAC-DVP, VMP, busulfan therapy. In December 1987, he readmitted to our hospital with abdominal pain. Investigations at that time showed: white blood cell count 11600/microliters (blast cells 9%); hemoglobin 8.4 g/microliters; platelets 19.0 X 10(4)/microliters; serum calcium 13.2 mg/dl; BUN 44 mg/dl; creatinine 2.7 mg/dl. Treatment with predonine, 6-MP and vincristine was begun. But serum calcium level rose gradually up to 16.5 mg/dl. So we tried middle dose Ara-c therapy, serum calcium decreased to 6.8 mg/dl. At once he was in a chronic phase, but he relapsed and died of heart failure. Necropsy showed extensive leukemic blast-cell infiltration of the bone marrow, liver, spleen, lung, and kidney. The cause of hypercalcemia in our case was suspected of local osteolytic hypercalcemia, because multiple bone destruction was found.     

T-lymphoid blast crisis in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is considered to be a pleuripotential stem cell disorder with the capacity to differentiate into myeloid, erythroid, megakaryocytic, and lymphoid cell lines. Consequently, blast crisis (BC) involving each of the above lineages has been well described. Among lymphoblastic crises, differentiation frequently occurs along B-cell lineage. We report four patients of CML who terminated in T-cell extramedullary BC in lymph nodes after a variable duration of chronic phase. The T-lineage was established by characteristic cytochemical staining and reactivity with a panel of anti-T-cell monoclonal antibodies. All four cases were Philadelphia (Ph) chromosome positive and demonstrated the Ph chromosome and associated anomalies (extra Ph, +19) in the lymph nodes. Our data adds to the growing evidence that CML is a disorder of the common stem cell from which T, B, and myeloid precursors originate.     

Treatment of chronic myeloid leukemia blast crisis with vindesine and prednisone

Sixteen patients in chronic myeloid leukemia blast crisis entered a phase II trial with vindesine and prednisone. Median duration of the chronic phase was 29 months in 13 patients, one previously had polycythemia vera, and two presented with a primary blast crisis. Eleven patients had myeloblastic features, as evidenced by morphology, cytochemistry, and cell surface antigens; three had a mixture of myeloid and lymphoid blast cells with lymphoblastic predominance; one had blast cells which displayed lymphoid characteristics; and one was classified as undifferentiated. Three patients had complete remissions lasting 1 month (myeloid), 3 months (mixed), and 5 months (lymphoid). Eleven patients had minor responses, with a median duration of 3 weeks (eight with myeloid, two with mixed, and one with undifferentiated). Two patients did not respond to vindesine. Leukopenia and thrombocytopenia were severe and prolonged independent of their morphologic or immunologic phenotype.     

Analysis of 30 cases of chronic myeloid leukemia with non-myeloid blast crisis

30 cases of chronic myeloid leukemia (CML) with non-myeloid blast crisis from 1966 to 1986 in PUMC Hospital were investigated. Morphologically 18 cases were lymphoblastic, 4 histiocytic, 3 basophilic, 2 erythro-leukemic, 2 megakaryocytic, and 1 monocytic, the ratio between male and female was 3.3:1, and their age ranged from 16 to 55 years. These results suggest that blast crisis of CML may involve many other cellular derivatives than the myeloid series of the pluripotential stem cells, Spleen was not palpable among half of the patients with lymphoblastic crisis, but all the cases with blast crisis of other morphological types had enlarged lives and spleen, especially those with histiocytic and monocytic crisis of CML. Most of cases of CML with non-myeloid blast crisis had poor prognosis with survival time of less than 6 months. However, cases of CML with lymphoblastic crisis had longer survival duration than those with non-myeloid blast crisis of other types.     

Megakaryocytic blast crisis as first presentation of chronic myeloid leukemia

We describe an extremely rare case of megakaryocytic blast crisis as first presentation of chronic myeloid leukemia. The patient had a very high platelet count and developed an ischemic stroke with seizures. She was treated with hydroxyurea, platelet apheresis, ARA-C, and idarubicin in order to obtain a prompt reduction of thrombocytosis and then with imatinib 600 mg/die PO. The therapy induced a complete hematological remission with a resolution of neurological signs within 4 weeks.     

Maturation of B-lineage blast crisis cells in chronic myeloid leukemia

A 44 year-old Chinese male presented with lymphoid blast crisis of chronic myeloid leukemia, in which the blast cells exhibited a pre-pre-B cell phenotype (B4+B1-J5+12+smIg-). There was a phenotypic transition during the course of the disease to a more mature B cell phenotype (B4+B1+J5+12+smIgG lambda+). The maturation of blast crisis cells may be related to the chemotherapeutic agents used in the treatment of the disease.     

Treatment of juvenile chronic myeloid leukemia with sequential subcutaneous cytarabine and oral mercaptopurine.

Three cases of the juvenile type of chronic myeloid leukemia are described, all of which have shown a clinical and hematologic response to repeated cycles of sequential subcutaneous cytarabine and oral mercaptopurine. It appears that this regime, as described, may afford some control of a disease process previously supposed to be unresponsive to chemotherapy. This control, however, is likely to be reflected in an improvement in well-being, rather than overall survival time. Patient 1 survived 26 mo from diagnosis, and patients 2 and 3 are alive and well 12 and 9 mo from diagnosis, respectively.     

Epidural myeloid sarcoma as the presenting symptom of chronic myeloid leukemia blast crisis

Clinical Rheumatology - Epidural myeloid sarcoma revealing chronic myeloid leukemia is scarce. Herein, we describe a patient that presented with back pain and bilateral sciatica secondary to root...     

Vindesine-prednisone in the treatment of blast crisis of chronic myeloid leukemia

Eight patients with chronic myeloid leukemia in blast crisis were treated with a combination of vindesine and prednisone. Complete remission was achieved in three patients; partial remission was achieved in three. All six responders received maintenance treatment with hydroxyurea and 6-mercaptopurine. The median duration of survival was 9 months. Two patients had long-term survival: one survived 32 months and the other is alive after 30 months. These data suggest that vindesine-prednisone polychemotherapy might improve the prognosis of blast crisis in chronic myeloid leukemia.     

T-cell surface antigens in a patient with blast crisis of chronic myeloid leukemia

There is little evidence to suggest that T lymphocytes are involved in the leukemic process in chronic myeloid leukemia (CML). A case of CML in blast phase is described in which T-cell surface antigens were detected by immunofluorescence on the patient's blasts using monoclonal antibodies. In order to determine that the T-cell blasts were derived from the original CML clone, cells bearing the T3 antigen were isolated by fluorescence-activated cell sorting and chromosome analysis was performed. All metaphases examined had the Philadelphia chromosome, confirming their origin from CML.     

High-dose cytosine arabinoside and idarubicin treatment of chronic myeloid leukemia in myeloid blast crisis

Chronic myeloid leukemia in myeloid blast crisis (CML-MBC) is highly resistant to standard induction chemotherapy regimens. Anecdotal results from previous clinical trials support the concept of dose escalation in patients with CML-MBC. Eight patients with CML-MBC were treated with cytosine arabinoside (Ara-C) 1.5-3.0 g/m2 intravenously over 1 hr every 12 hr for 12 doses and idarubicin 12 mg/m2 intravenously daily for 3 days. Sixteen previous reports describing the use of Ara-C-based chemotherapy regimens in patients with CML-MBC were also reviewed. Our patients' median age was 62 years (range, 42-69 years). One patient achieved complete hematologic remission (95% confidence interval, 0.3%, 53%). The median survival for our patients was 7.3 months. These results were not different from previous published reports using Ara-C-based chemotherapy regimens to treat CML-MBC. In summary, the combination of high-dose Ara-C and idarubicin did not improve the overall prognosis of patients with CML-MBC. Innovative approaches need to be explored for this patient population.     

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.     

Cigarette smoking, blast crisis, and survival in chronic myeloid leukemia

We reviewed the records of all patients with chronic myeloid leukemia (CML) seen in the CML Clinic of the University of Colorado Health Sciences Center between 1968 and 1987 for a history of cigarette smoking. Patients who smoked for five or more pack/years within the ten years preceding, or after the diagnosis of CML, were defined as smokers. Adequate smoking histories were obtained on 122 patients. Eighty-seven of these were non-smokers and 35 were smokers by the above criteria. The smoking group had a higher predominance of males, an older median age, and were diagnosed earlier in the course of the 20 year study. Seventy-two patients had died at the time of analysis. All but one, a non-smoker, died from the development of blast crisis. The overall median actuarial survival was significantly reduced for smokers (35 months) as compared to non-smokers (47 months). This was particularly striking for patients who had succumbed to the disease, with a median survival of 30 months in smokers versus 46 months in non-smokers. Although various explanations could explain the differences noted, we conclude that cigarette smoking has an adverse effect on the development of blast crisis and survival in chronic myeloid leukemia.     

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.