304
Letters and Correspondence
REFERENCES I. Asakura H, Jokaji H, Saito M, Uotani C , Kumabashiri I,Morishita E, Yamazaki M, Matsuda T: Changcs in plasma levels of tissue-plasminogen activatorhhibitor complex and active plasminogen-activator in paticnts with disseminated intravascular coagulation. Am J Hemato1 36:176-183, 1991. 2. Lorente JA, Garcia-Frade J , Landin L, Garcia-Avello A, de Pablo R. Renes E, Liste D: Coagulation and fibrinolysis activation in carly sepsis. Am Rev Rcspir Dis 143:A677, 1991. 3. Garcia-Frade LJ, Sureda A, Tornado MC. Garcia-Avello A: High plasma uPA levels are present in patients with acute non-lymphohlastic leukemia. Acta Hcmato1 (in press). 4. Bennett B, Booth NA, Croll A, Dawson A: The bleeding disorder in acute promyelocytic leukemia: Fihrinolysis due to uPA rather than dcfibrinafion. Bri J Hematol 71:511. 1989. 5. Pralong G , Calandra T, Glauser MP, Schellekens J, Verhoof J. Bachmann F, Kruithof EKO: Plasminogen activator inhibitor I: A new prognostic marker of septic shock. Thromb Haeinostas 61:459, 1989. 6. Colucci M , Paramo JA, Collen D: Generation in plasma of a fast-acting inhibitor of plasminogcn activator in response to endotoxin stimulation. J Clin Invest 75:818, 1985. 7. Shoemaker W, Appel PL, Krain HB: Tissue oxygen dcbt as a determinant of lethal and nonlethal postoperative organ failure. Crit Care Med 16:1I17, 1989.
rearrangement in Lugassy and Farhi’s [4] and our report suggest that the bcr-abl hybrid is not involved in the pathogenesis of CNL.
JANSTOREK Division of HematologylOncology, Department of Medicine, UCLA School of Medicine, Los Angeles, California
REFERENCES I . You W, Wcisbrot IM: Chronic Neutrophilic leukemia. Report of two casts and review of litcrature. Am J Clin Pathol 72233, 1979. 2. Wang J-S. Ho C-H, Lin C-K: Chronic neutrophilic leukemia. Report of a case and review of the literature. Chin Mcd J (Taipei)46:109, 1990. 3. lurlo A, Foa P, Maiolo AT, Luksch R. Capsoni F, Polli E E Polycythemia Vera terminating in chronic ncutrophilic leukemia: Report of a case. Am J Hematol 35:139. 1990. 4. Lugassy G, Farhi R: Chronic neutrophilic leukemia associated with polycythemia Vera. Am J Hematol31:300, 1989 (addendum in Am J Hematol 35:140, 1990). 5. Sanz MA: Long-term survival in chronic neutrophilic leukemia. Am J Clin Pathol 74:717. 1980.
T Cell-Mediated Inhibition of Erythropoiesis in Myelodysplastic Syndromes Chronic Neutrophilic Leukemia: Case Report Documenting the Absence of bcr-abl Rearrangement To the Editor: Chronic neutrophilic leukemia (CNL) is a rare disorder characterized by unexplained neutrophilia, increased bone marrow myeloidmythroid ratio without a marked leftward shift, and elevated neutrophi1 alkaline phosphatase score. Philadelphia chromosome (Ph) has been absent in 12 of 13 cases studied cytogenetically so far [ 1 4 1 . The rearrangement of bcr and abl genes was negative in one studied patient [4]. Here we report another case of Ph- and bcr-abl-negative CNL. A 48-year-old male with no chronic inflammatory or neoplastic disease was found to have leukocytosis of 18 X I0’1liter in 1988, 27 X I0’1liter in 1989, 32-33 X I09/literin 1991, and 33-38 X IO‘1literin April, 1992. His symptoms included fatigue and night sweats since at least June, 1991. Past medical history was remarkable for Legionella pneumonia in February, 1991, and genital herpes in February, 1992, but there was no history of other infections, bleeding, thromboembolism, or arthritis. On physical examination, there was no lymphadenopathy, and the spleen and liver were not palpable. Abdominal ultrasound was normal in 1989, but there was mild splenomegaly (12.6 cm) in April, 1992. Laboratory results from April, 1992, showed platelets 403 X IO‘/Iiter, hemoglobin 156 giliter, reticulocytes 1.6%, leukocyte alkaline phosphatase score 166 (normal 25125), vitamin B,, 1,184 pmoliliter (1600 ng/liter), uric acid 0.44 mmol1 liter (7.3 mg/dl), lactate dehydrogenase 146 Uiliter (normal 45-95), and normal serum protein electrophoresis. Blood smear revealed marked leukocytosis composed or75% segments, 12% bands, 3% eosinophils, 9% lymphocytes, and I % monocytes along with mild anisocytosis. Bone marrow was hypercellular, with a differential of 1 % blasts, 4% promyelocytes, 19% myelocytes, 10% metamyelocytes. 29% bands, 19% segments, 2% eosinophils, 3% lymphocytes, 2% monocytes, and 8% normoblasts. Plasma cells were scarce; rnegakaryocytes were slightly increased. Karyotype was normal (46,XY in 20120 mitoses). bcr-abl hybrid gene was not present (Southern blot). Treatment with hydroxyurea resulted in less leukocytosis but no improvement in symptoms. Currently, the patient is on no medication, and allogeneic bone tr,arrow transplantation is being contemplated, since the longest reported survival of a patient with CNL is 7 years [ 5 ] .The absence of Ph in the vast majority of reported cases and the absence of bcr-abl
To the Editor: Recently, high-dose methylprednisolone has been shown to be effective in some patients with myelodysplastic syndromes (MDS) [I]. Moreover, the effect of antilymphocyte globulin has also been reported in MDS patients [2]. Thus, there is a possibility of immune-mediated inhibition of hematopoiesis as the etiology of MDS. This study was designed to investigate the mechanism of immune-mediated hematopoietic inhibition in MDS through the inhibitory activity of T cells on autologous erythroid colony-forming units (CFU-E). The ten previously untreated patients with MDS and 15 normal subjects as controls gave informed consent to their participation in this study. The diagnosis and classification of MDS was established by blood and bone marrow examinations according to the criteria of the French-AmericanBritish (FAB) Cooperative Group [ 3 ] . They included seven patients with refractory anemia (RA) (cases 1-7). two patients with RA with excess of blasts (RAEB) (cases 8, 9), and one patient with RAEB in transformation (RAEB-T) (case 10). Preparation of T and non-T cells was performed as previously described [4]. CFU-E assays were performed in quadruplicate according to the method described by Tepperman et al. 151 with some modifications. Data are expressed as mean f SD. Data were evaluated by Student’s t-test. CFU-E was lower in MDS patients when compared to normal controls. It was absent in one RA patient (case 2) and one RAEB patient (case 8). Figure I presents the results of investigation of the inhibitory activity of T cells on autologous CFU-E in patients. CFU-E in patients were varied upon addition of bone marrow or peripheral blood T cells. CFU-E decrease by the addition of bone marrow and peripheral blood T cells was significant (P < 0.01) in two (cases 5 and 7) out of 10 patients. T cells are well known to function as regulators of hematopoietic cell growth and differentiation [6]. In this report, to explore the possible role of T cell-mediated inhibition of erythropoiesis in MDS, we studied the effect of bone marrow and peripheral blood T cells from 10 patients with MDS on CFU-E by autologous bone marrow in vitro. Two of the 10 patients with MDS caused significant reduction of CFU-E. Smith et al. [7] described a population of hematopoietic inhibitory T cells which occurred in a population of patients with MDS using autologous CFU-GM (glanulocyte-macrophage colony-forming units) assay. Their study has demonstrated that hematopoietic inhibitory T cells are CD8-positive and occur in 28% of the MDS patients.
Letters and Correspondence
REFERENCES I. Asakura H, Jokaji H, Saito M, Uotani C , Kumabashiri I,Morishita E, Yamazaki M, Matsuda T: Changcs in plasma levels of tissue-plasminogen activatorhhibitor complex and active plasminogen-activator in paticnts with disseminated intravascular coagulation. Am J Hemato1 36:176-183, 1991. 2. Lorente JA, Garcia-Frade J , Landin L, Garcia-Avello A, de Pablo R. Renes E, Liste D: Coagulation and fibrinolysis activation in carly sepsis. Am Rev Rcspir Dis 143:A677, 1991. 3. Garcia-Frade LJ, Sureda A, Tornado MC. Garcia-Avello A: High plasma uPA levels are present in patients with acute non-lymphohlastic leukemia. Acta Hcmato1 (in press). 4. Bennett B, Booth NA, Croll A, Dawson A: The bleeding disorder in acute promyelocytic leukemia: Fihrinolysis due to uPA rather than dcfibrinafion. Bri J Hematol 71:511. 1989. 5. Pralong G , Calandra T, Glauser MP, Schellekens J, Verhoof J. Bachmann F, Kruithof EKO: Plasminogen activator inhibitor I: A new prognostic marker of septic shock. Thromb Haeinostas 61:459, 1989. 6. Colucci M , Paramo JA, Collen D: Generation in plasma of a fast-acting inhibitor of plasminogcn activator in response to endotoxin stimulation. J Clin Invest 75:818, 1985. 7. Shoemaker W, Appel PL, Krain HB: Tissue oxygen dcbt as a determinant of lethal and nonlethal postoperative organ failure. Crit Care Med 16:1I17, 1989.
rearrangement in Lugassy and Farhi’s [4] and our report suggest that the bcr-abl hybrid is not involved in the pathogenesis of CNL.
JANSTOREK Division of HematologylOncology, Department of Medicine, UCLA School of Medicine, Los Angeles, California
REFERENCES I . You W, Wcisbrot IM: Chronic Neutrophilic leukemia. Report of two casts and review of litcrature. Am J Clin Pathol 72233, 1979. 2. Wang J-S. Ho C-H, Lin C-K: Chronic neutrophilic leukemia. Report of a case and review of the literature. Chin Mcd J (Taipei)46:109, 1990. 3. lurlo A, Foa P, Maiolo AT, Luksch R. Capsoni F, Polli E E Polycythemia Vera terminating in chronic ncutrophilic leukemia: Report of a case. Am J Hematol 35:139. 1990. 4. Lugassy G, Farhi R: Chronic neutrophilic leukemia associated with polycythemia Vera. Am J Hematol31:300, 1989 (addendum in Am J Hematol 35:140, 1990). 5. Sanz MA: Long-term survival in chronic neutrophilic leukemia. Am J Clin Pathol 74:717. 1980.
T Cell-Mediated Inhibition of Erythropoiesis in Myelodysplastic Syndromes Chronic Neutrophilic Leukemia: Case Report Documenting the Absence of bcr-abl Rearrangement To the Editor: Chronic neutrophilic leukemia (CNL) is a rare disorder characterized by unexplained neutrophilia, increased bone marrow myeloidmythroid ratio without a marked leftward shift, and elevated neutrophi1 alkaline phosphatase score. Philadelphia chromosome (Ph) has been absent in 12 of 13 cases studied cytogenetically so far [ 1 4 1 . The rearrangement of bcr and abl genes was negative in one studied patient [4]. Here we report another case of Ph- and bcr-abl-negative CNL. A 48-year-old male with no chronic inflammatory or neoplastic disease was found to have leukocytosis of 18 X I0’1liter in 1988, 27 X I0’1liter in 1989, 32-33 X I09/literin 1991, and 33-38 X IO‘1literin April, 1992. His symptoms included fatigue and night sweats since at least June, 1991. Past medical history was remarkable for Legionella pneumonia in February, 1991, and genital herpes in February, 1992, but there was no history of other infections, bleeding, thromboembolism, or arthritis. On physical examination, there was no lymphadenopathy, and the spleen and liver were not palpable. Abdominal ultrasound was normal in 1989, but there was mild splenomegaly (12.6 cm) in April, 1992. Laboratory results from April, 1992, showed platelets 403 X IO‘/Iiter, hemoglobin 156 giliter, reticulocytes 1.6%, leukocyte alkaline phosphatase score 166 (normal 25125), vitamin B,, 1,184 pmoliliter (1600 ng/liter), uric acid 0.44 mmol1 liter (7.3 mg/dl), lactate dehydrogenase 146 Uiliter (normal 45-95), and normal serum protein electrophoresis. Blood smear revealed marked leukocytosis composed or75% segments, 12% bands, 3% eosinophils, 9% lymphocytes, and I % monocytes along with mild anisocytosis. Bone marrow was hypercellular, with a differential of 1 % blasts, 4% promyelocytes, 19% myelocytes, 10% metamyelocytes. 29% bands, 19% segments, 2% eosinophils, 3% lymphocytes, 2% monocytes, and 8% normoblasts. Plasma cells were scarce; rnegakaryocytes were slightly increased. Karyotype was normal (46,XY in 20120 mitoses). bcr-abl hybrid gene was not present (Southern blot). Treatment with hydroxyurea resulted in less leukocytosis but no improvement in symptoms. Currently, the patient is on no medication, and allogeneic bone tr,arrow transplantation is being contemplated, since the longest reported survival of a patient with CNL is 7 years [ 5 ] .The absence of Ph in the vast majority of reported cases and the absence of bcr-abl
To the Editor: Recently, high-dose methylprednisolone has been shown to be effective in some patients with myelodysplastic syndromes (MDS) [I]. Moreover, the effect of antilymphocyte globulin has also been reported in MDS patients [2]. Thus, there is a possibility of immune-mediated inhibition of hematopoiesis as the etiology of MDS. This study was designed to investigate the mechanism of immune-mediated hematopoietic inhibition in MDS through the inhibitory activity of T cells on autologous erythroid colony-forming units (CFU-E). The ten previously untreated patients with MDS and 15 normal subjects as controls gave informed consent to their participation in this study. The diagnosis and classification of MDS was established by blood and bone marrow examinations according to the criteria of the French-AmericanBritish (FAB) Cooperative Group [ 3 ] . They included seven patients with refractory anemia (RA) (cases 1-7). two patients with RA with excess of blasts (RAEB) (cases 8, 9), and one patient with RAEB in transformation (RAEB-T) (case 10). Preparation of T and non-T cells was performed as previously described [4]. CFU-E assays were performed in quadruplicate according to the method described by Tepperman et al. 151 with some modifications. Data are expressed as mean f SD. Data were evaluated by Student’s t-test. CFU-E was lower in MDS patients when compared to normal controls. It was absent in one RA patient (case 2) and one RAEB patient (case 8). Figure I presents the results of investigation of the inhibitory activity of T cells on autologous CFU-E in patients. CFU-E in patients were varied upon addition of bone marrow or peripheral blood T cells. CFU-E decrease by the addition of bone marrow and peripheral blood T cells was significant (P < 0.01) in two (cases 5 and 7) out of 10 patients. T cells are well known to function as regulators of hematopoietic cell growth and differentiation [6]. In this report, to explore the possible role of T cell-mediated inhibition of erythropoiesis in MDS, we studied the effect of bone marrow and peripheral blood T cells from 10 patients with MDS on CFU-E by autologous bone marrow in vitro. Two of the 10 patients with MDS caused significant reduction of CFU-E. Smith et al. [7] described a population of hematopoietic inhibitory T cells which occurred in a population of patients with MDS using autologous CFU-GM (glanulocyte-macrophage colony-forming units) assay. Their study has demonstrated that hematopoietic inhibitory T cells are CD8-positive and occur in 28% of the MDS patients.
