Two color flow cytometric analysis of concomitant acute myeloid leukemia and chronic lymphocytic leukemia

Abstract

Key terms: Concomitant leukemia, two-color flow cytometry, immunophenotypingThe development of acute leukemia during the course of chronic lymphocytic leukemia (CLL) is rare but is being reported with increasing frequency. To our knowledge, 18 cases have been reported since 1970 where CLL and acute myeloid leukemia (AML) or myeloproliferative disorder were detected simultaneously (1-3, 5, 9-1 1, [13][14][15][16][17][18][19]. A larger number of the reported cases are associated with cytotoxic treatment of CLL and the subsequent detection (or development) of acute myeloid leukemia ( 4 2 0 ) . We report a case of simultaneous detection of CLL with AML and demonstrate the use of two-color flow cytometry in the discrimination of the two malignant cell types. CASE REPORTA 74-year-old woman was referred to UNC Hospitals, Chapel Hill, NC, with macrocytic anemia, thrombocytopenia, leukocytosis, fatigue, shortness of breath, and a 20 pound weight loss during the preceding 6 months.Two weeks prior to admission she presented to her local emergency room with blood specks in her sputum. She was noted to have a decreased hematocrit with an increased mean corpuscular volume (MCV), which was refractory to multiple vitamin B-12 injections. Past medical history was remarkable for non-insulin dependent diabetes mellitus, hypertension, and recurrent urinary tract infections. Past surgical history included bilateral breast reduction and total abdominal hysterectomy. On physical examination the patient appeared well. She had a few 0 1 9 9 4 Wiley-Liss, Inc.small petechiae on her palate, abdomen, and legs. N o lymphadenopathy or hepatosplenomegaly was noted. Rectal exam showed trace guaiac positive stool. Laboratory data included the following complete blood count (CBC) results: hematocrit 17%, hemoglobin 5.6 gdl, platelets 29 X 107/L, and white blood cells (WBC) 15.6 X 107/L. The white blood cell differential showed 3% neutrophils, 7596 lymphocytes, 2% monocytes, < 1 o/u eosinophils, 1 % basophils, and 19% peroxidase-negative (large unstained cells, "LIJC").A diagnostic bone marrow aspirate and biopsy were performed and a portion of the aspirate material was submitted for flow cytometric analysis. Results of these studies were positive for both acute myeloid leukemia and chronic lymphocytic leukemia.The patient's hospital course was relatively uncomplicated. She was started on a chemotherapeutic regimen of vincristine and prednisone. A more rigorous induction chemotherapeutic regimen was not attempted due to the patient's age. Supportive therapy with packed red blood cells and apheresis donor platelets was given as needed over the following 2 months.

Acute leukemia in patients with untreated chronic lymphocytic leukemia: A report of two cases with remarkably similar time cluster

“…Our results support the other authors' suggestions that the use of full panel of monoclonal antibodies for immunophenotyping is recommended to provide the information about cell heterogeneity, as well as the information of an unexpected second malignancy presence [6,7].…”

Concomitant chronic lymphocytic leukemia and acute myeloid leukemia with an uncommon immunophenotype

“…On the other hand, cytogenetic studies were described in only three previous cases of concomitant AML and CLL, reporting no recurrent anomaly [11,13,19]. Additionally, in no case has the same cytogenetic aberration been reported in both the CLL and AML populations, a finding that would support the hypothesis of a common aberrant pluripotent progenitor developing along two different pathways, as has been suggested by some authors [11,12,15,16,19]. Other hypotheses have been made in an attempt to explain the association of AML and untreated CLL.…”

“…Clonality of the lymphocyte population defined as restriction in the pattern of expression of light chains has therefore seldom been demonstrated [8,11,14,15,17] and immunophenotype of the blast population reported in few cases [13][14][15]18]. The large panel of MoAbs studied in our case defined the typical B-cell CLL phenotype (B cell markers with coexpression of CD5, CD23, and CD43) and the following phenotype in the blast population: CD33+, CD13+, CD56+, cMPO+, CD34−, HLA-DR−, CD16−, CD57−.…”

“…It has been suggested that AL may occur as a secondary leukemia following treatment with chemotherapy and/or radiotherapy [1,2] or in some cases of lymphoblastic leukemia, sharing the same monoclonal surface immunoglobulin, as part of the natural history of CLL [3,4]. In some patients, acute myeloid leukemia (AML) has been diagnosed simultaneously with CLL [5][6][7][8][9][10][11][12][13][14][15] or during the course of an untreated case of CLL [5,[16][17][18][19]. Most of these cases have been diagnosed on the basis of morphology and cytochemistry and little information is available about the immunophenotypic profiles of these two cell populations.…”

Concurrent acute myeloid leukemia with inv(16)(p13.1q22) and chronic lymphocytic leukemia: Molecular evidence of two separate diseases

“…There are approximately 30 cases of AML occurring concurrently with or after untreated CLL in the literature since the 1970s [1,, 17 of which contain immunophenotypic data [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Nevertheless, none of the previous reports drew a conclusion regarding whether AML and CLL cells share the same clonality in those patients.…”