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.     

Double Philadelphia masquerading as chromosome 20q deletion--a new recurrent abnormality in chronic myeloid leukaemia blast crisis

Summary. The most common abnormality of chromosome 20 in haematological malignancy is deletion of the long arm [del(20q)]. These interstitial deletions are variable in size and are seen in both premalignant haematological conditions and acute myeloid neoplasia. A commonly deleted region (CDR), mapped within the 20q11.2/q13.1 segment with an estimated size of 1·7 Mbp, is considered to present a primary genetic lesion marking a gene(s), the loss of which is responsible for the pathogenesis of these haematological disorders. While a small number of recurrent translocations involving chromosome 20 have also been reported, no recurrent aberration of this chromosome has been associated with myeloid disease progression. We present nine cases of Philadelphia (Ph)-positive chronic myeloid leukaemia (CML) in which deletions of chromosome 20 were also detected by conventional karyotyping. In six cases, fluorescent in situ hybridization (FISH) mapping confirmed a del(20q) which corresponded to the myeloid CDR. In the remaining three cases however, the presumed del(20q) marker was shown to be the result of an unbalanced translocation between band 20p11 and a second copy of the Ph chromosome. This new abnormality, termed dic(20;Ph) for short, was identical to a del(20)q by G-banding, and combined duplication of the breakpoint cluster region and Abelson murine leukaemia viral oncogene homologue (BCR-ABL) fusion with loss of the 20p11-pter segment. In all three cases, the dic(20;Ph) was associated with disease progression and therefore represents a new recurrent abnormality in CML blast crisis.     

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) translocation, 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.     

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.     

Emergence of Philadelphia positive chronic myeloid leukaemia during treatment with hydroxyurea for Philadelphia negative essential thrombocythaemia

A 58-yr-old male patient with essential thrombocythaemia (ET) developed chronic myeloid leukaemia (CML) after continuous uneventful treatment with hydroxyurea for 18 yr. G-banding analyses of bone marrow cells had repeatedly demonstrated normal male karyotype before this event, but t(9;22)(q34;q11) was demonstrated after the event. An unrelated allogeneic stem cell transplantation was performed. Blood and bone marrow morphology, and the karyotype were normalised and the patient is in good health 1 yr post-transplant. There are no previous reports in the literature about the emergence of CML during treatment with hydroxyurea.     

E rosette-positive agar colonies containing the Philadelphia chromosome in chronic myeloid leukaemia

In an attempt to document possible T-cell involvement in chronic myeloid leukaemia, E rosette-positive colonies (ERPC) were grown in agar culture using a T-cell-conditioned medium. Colonies were grown from whole mononuclear cells (WMN), nonadherent E rosette-positive (NAT+) and nonadherent E rosette-negative (NAT-) cells. Cells collected from the colonies after 10 d in culture were 99-100% E rosette-positive. 8 metaphases were obtained from both NAT+ and NAT- ERPCs. In NAT- ERPCs, 5 out of 8 metaphases were positive for the Philadelphia (Ph1) chromosome as compared to 1 Ph1 positive out of 8 metaphases in the NAT+ ERPCs. These results suggest that, at least in this particular patient we studied, a subpopulation of E rosette-positive cells derived from the NAT- cell fraction express the Ph1 chromosome.     

T-cell acute lymphoblastic leukaemia with late developing Philadelphia chromosome

A case of childhood T-cell acute lymphoblastic leukaemia (ALL) is presented in which the only chromosome abnormality at diagnosis was a deletion of part of the short arm of one chromosome 9 (9p-). Cytogenetic studies at relapse showed, in addition to 9p-, a partial deletion of the long arm of one chromosome 6 (6q-) and the Philadelphia chromosome (Ph1) produced as a result of the classical translocation t(9q+;22q-). All metaphases from haemopoietic colonies grown from a cryopreserved specimen of this patient's marrow at relapse were normal, in contrast to haemopoietic colonies cultured from patients with chronic myelogenous leukaemia (CML) which contained the Ph1. A hypothesis which incorporates T-cell ALL with late development of the Ph1 into the overall family of Ph1 positive diseases is suggested.     

Acute myeloblasts leukaemia without Philadelphia chromosome developing after interferon therapy for chronic myelocytic leukaemia with Philadelphia chromosome

Summary. We report a patient who developed Philadelphia chromosome negative acute myeloblastic leukaemia with trisomy 8 and trisomy 11 after receiving treatment with alkylating agents and interferon for chronic myelocytic leukaemia positive for Philadelphia chromosome. Leukaemic cells were positive for myeloperoxidase and expressed CD13, CD33 and DR; some expressed CD2, CD4 and CD34. The fluorescence in situ hybridization method revealed that bcr-abl fusion genes were absent from > 90% of the bone marrow cells. The major bcr rearrangement was not detected by Southern blot analysis. We conclude that the leukaemic cells negative for Philadelphia chromosome may have developed as a result of treatment with alkylating agents and interferon in the present case.     

Early T-cell features in blast crisis of Ph1-positive chronic myeloid leukaemia

A patient with Ph1-positive chronic myeloid leukaemia (CML) presented in extramedullary blast crisis. Whereas the peripheral blood and bone marrow features were consistent with the chronic phase of CML, study of the enlarged lymph nodes demonstrated massive replacement by Ph1-positive blast cells of lymphoblastic morphology. Such blast cells showed diffuse acid phosphatase positivity, were positive for TdT, and had an enzyme pattern (adenosin-deaminase, purine-nucleosidephosphorilase and lactate-dehydrogenase) typical of immature T-cells. To further characterize the phenotype of the blast cells, they were analyzed for surface markers using a panel of monoclonal antibodies selected to identify differentiation antigens of T cells, B cells and myeloid cells. The results of the latter analysis were consistent with an early T-cell origin of the blast cells, since they were positive for TdT, CRIS1 (T1), E rosettes and OKT10, and were negative for OKT3, Leu3 and OKT8. These features demonstrate that T-cell markers may also be expressed in blast crisis of CML and provide evidence that T-cells may share a common stem cell with myeloid and B-cells in CML.     

Lymphoid blast crisis in a patient with Philadelphia-chromosome-negative chronic myelocytic leukemia

A 24-year-old man with Philadelphia-chromosome (Ph)-negative chronic myelocytic leukemia (CML) developed lymphoid blast crisis. In the chronic phase, karyotype was normal and the clinical and hematological features were indistinguishable from those of Ph-positive CML. Rearrangement of the breakpoint cluster region (bcr) was observed. In the blast phase, blast cells showed early B-cell phenotype (CALLA+, Ia+, TdT+) with a rearranged immunoglobulin heavy-chain gene joining region (JH). By using an immunoblotting method and antiphosphotyrosine sera, P210bcr-abl protein was detected. The patient responded well to vincristine and prednisolone (VP) therapy. These findings support the concept that Ph-negative bcr+ CML can behave in a very similar fashion to Ph-positive CML, not only in the clinical features of the chronic phase but also in the manner of the blast crisis.     

Neutrophilic myelofibrosis presenting as Philadelphia chromosome negative BCR non-rearranged chronic myeloid leukemia

Chronic myeloid leukemia consists of Philadelphia chromosome positive disease in 90% of cases, and a further 5%, although Philadelphia chromosome negative, exhibit bcr gene rearrangements consistent with the disease. The remaining 5% of cases have a heterogeneous clinical picture with a course unlike that of classical chronic myeloid leukemia, and may belong to different pathologic entities. We report five cases belonging to the latter group, initially identified as Philadelphia chromosome negative, bcr non-rearranged chronic myeloid leukemia, that developed progressive leucocytosis, absolute monocytosis, myelodysplasia, extramedullary hematopoiesis, and had evidence of myelofibrosis. These cases may represent a distinct clinical entity characterized by neutrophilic myelofibrosis, which can be identified prospectively by clinical and pathologic criteria. Standard therapy for treating chronic myeloid leukemia or idiopathic myelofibrosis may not be appropriate for this group.     

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.     

Eosinophilic blast crisis in a case of chronic myeloid leukaemia

A case of typical chronic myeloid leukaemia (CML) is described, of which the terminal blast crisis was characterized by an impressive proliferation of atypical eosinophils and by the simultaneous complete deficiency of neutrophilic myeloperoxidase. Since eosinophilic cells preserved a strong peroxidase positivity, a high number of immature non-granular eosinophilic precursors could be recognized among the leukaemic blast cells, thus supporting the diagnosis of eosinophilic blast crisis of CML.