On admission to the UPMC, the patient was treated with leukopheresis and hydroxyurea to lower the WBC. His respiratory status remained unstable with continued dyspnea, and his O2 status was closely monitored. He developed petechiae on his arms; a subsequent DIC screen revealed active DIC, and he was started on low molecular weight heparin. The patient's respiratory status improved somewhat, but on the day he was to start induction chemotherapy, he was found pulseless in bed. Resuscitation efforts could not revive him.
The morphologic and immunophenotypic data support the presence of two hematologic malignancies: chronic lymphocytic leukemia, T-cell type and acute myeloid leukemia. In this case, the presence of a marked leukocytosis of small lymphocytes with irregular nuclei, inconspicuous nucleoli and mature CD4+ T cell phenotype without antigen loss are characteristic of T-CLL.
Although some controversy exists as to its precise classification, some agree that it is indeed a separate entity with features distinct from other T-cell chronic lymphoproliferative disorders. Bona fide T-CLL is very rare and probably accounts for less than 1% of all CLL. Unlike patients with B-CLL, these patients do poorly, with only minimal responses to chemotherapy in a minority of patients. (1,2,3) Although this patient's HTLV-1 status was not known, this virus has been only rarely associated with T-cell CLL. (13,14) T-CLL should be differentiated from other chronic T-cell lymphoproliferative disorders. In T-cell prolymphocytic leukemia the prolymphocytes are larger with a prominent nucleolus, and a lower nuclear:cytoplasmic ratio with a similar immunophenotype to T-CLL. Mycosis fungoides/Sezary syndrome would typically have antigen loss immunopenotypically. Sezary cells in the peripheral blood of patients with mycosis fungoides demonstrate deeply indented convoluted or "cerebriform" nuclei without marrow involvement. Most cases are CD7 negative. In adult T-cell lymphoma/leukemia the cells demonstrate a hyperlobated or "cloverleaf" nucleus and most are CD4+ and CD7+. HTLV-1 genomes are found in all cases. Large granular lymphocytic leukemias are commonly CD4 and CD7 negative, with CD8+, CD16+, and CD57+/-. Natural killer cell large granular lymphocytic leukemias do not demonstrate T-cell receptor gene rearrangements, are CD3-, CD8+/-, CD16+, CD56+/- and CD57+/-. The lack of positivity for B cell associated antigens, monoclonal light chains, and coexpression of CD19+/CD5+ would rule out B-CLL. In this case, the morphologic, immunophenotypic and clinical features were most consistent with T-CLL. The identification of a T-cell receptor gene rearrangement supported the clonal nature of the T-cells and was of benefit in distinguishing the T-cells from a reactive process.
Immunophenotypically, the myeloblasts were positive for CD13, CD33, CD14, CD15, and myeloperoxidase. Tdt and CD34 were negative. The blasts strongly expressed non-specific esterase and peroxidase, the latter finding not characteristic but can be seen in acute monoblastic leukemia. These findings, together with the morphology and flow cytometric immunophenotypic studies favored a diagnosis of AML-FABM5a.
The incidence of secondary cancers in B-CLL patients is increased, with higher rates of lung carcinoma, melanoma, and Hodgkin's disease, presumably due to impaired immune surveillance mechanisms. (4) Others have noted an increase in diffuse large cell lymphomas in this same patient population. (5) Although the incidence of acute leukemia in patients with B-cell CLL varies from 0-6.9%, recent studies indicate that it may be much less frequent than previously thought. (5) Most often acute leukemias associated with B-CLL are therapy related (5,6) but acute leukemias representing blastic transformation of existing B-CLL (8), and simultaneous coexistent acute myeloid leukemia with B-CLL (9,11) including AML developing in untreated B-CLL have also been reported. (7,10) The prognosis of AML developing in patients with B-CLL appears to be similar to AML in other patients. The current case may represent a therapy related AML, as the patient was treated with alkylating agents including Fludarabine, which has well documented leukemogenic potential. (12)
Cytogenetic findings demonstrated an 8;22 translocation, which has been reported in AML FAB type M4 or M5. The presence of a subclone with 2;22 translocation would suggest progression of disease. Typical cytogenetic findings for T-CLL involve abnormalities of chromosome 14, which were not present in this case. Whether this abnormal karyotype was derived from the T-cells or the myeloid blasts could not be determined.
This case was unusual for the presence of a T-CLL, and it may represent the first case of a therapy related AML in a patient with T cell CLL.
Contributed by Peter Christakos, MD and Lydia Contis, MD