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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty patients are described who received chemotherapy for the diagnosis of acute myeloid leukemia but who were subsequently reclassified as having dysmyelopoietic syndrome using the French-American-British criteria. Thirteen patients had refractory anemia with excess blast cells (RAEB) (age range, 23-82 years; median, 68) and seven had chronic myelomonocytic leukemia (CMML) (age range, 44-79 years; median, 70). Three patients (two with RAEB and one with chronic myelomonocytic leukemia) had previously been treated with cytotoxic therapy for another malignancy. In 15 patients the antileukemic therapy was a chemotherapy regimen that was highly active in acute nonlymphoblastic leukemia (ie, containing daunorubicin and/or cytarabine). These patients achieved complete remission lasting 14, 34+, and 36+ months and survival times of 31, 35+, and 37+ months. All three patients were from a subgroup of four patients characterized by RAEB, younger age, no previous cytotoxic therapy, and treatment with an aggressive chemotherapy regimen. The median survival time of the patients not achieving remission was 1 month (range, less than 1-22). Our results suggest that while most patients with the dysmyelopoietic syndrome appear to have their life shortened by chemotherapy, there is a subgroup characterized by younger age, absence of previous cytotoxic therapy, and the morphologic picture of RAEB who can have a favorable response to aggressive treatment.
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PMID:Effect of chemotherapy for the dysmyelopoietic syndrome. 694 53

Clinical and cytogenetic findings in 10 patients with deletions of the long arm of chromosomes 5 (5q-) are reported. Five cases had refractory anemia, the preleukemic syndrome, or refractory anemia with an excess of blasts; in all but one, the 5q- was the single initial abnormality. Three patients had overt leukemia; in all, the 5q- was accompanied by additional anomalies. Two patients had a myeloproliferative disorder. In one of these, a case of polycythemia vera, the 5q- appeared secondarily to other karyotypic abnormalities and concomitantly with transformation into a "spent phase." The deletions were interstitial in most cases, and even if the size of the deletion varied, the region q15-q31 was lost in all cases except 2. Bone marrow from all cases except one showed a marked increase in the number of megakaryocytes. A survey of the literature yielded a total of 69 evaluable patients with 5q- deletions, including the present series. The 5q- has now been observed in a wide spectrum of hematologic disorders. However, most cases had either preleukemia (39%) or leukemia (46%). When detected during preleukemia, the 5q- usually appeared alone (74%), while during overt leukemia it regularly was accompanied by other abnormalities (88%).
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PMID:On the 5q- deletion: clinical and cytogenetic observations in ten patients and review of the literature. 694 80

The clinical and laboratory features of 37 patients with variants of acute monocytic leukemia are described. Three of these 37 patients who had extensive extramedullary leukemic tissue infiltration are examples of true histiocytic "lymphomas." Three additional patients with undifferentiated leukemias, one patient with refractory anemia with excess of blasts, one patient with chronic myelomonocytic leukemia, one patient with B-lymphocyte diffuse "histiocytic" lymphoma and one patient with "null" cell, terminal deoxynucleotidyl transferase-positive lymphoblastic lymphoma had bone marrow cells with monocytic features. Another patient had dual populations of lymphoid and monocytoid leukemic cells. The true monocytic leukemias, acute monocytic leukemia (AMOL) and acute myelomonocytic leukemia (AMMOL), are closely related to acute myelocytic leukemia (AML) morphologically and by their response to chemotherapy. like AML, the leukemic cells from the AMMOL and AMOL patients form leukemic clusters in semisolid media. Cytochemical staining of leukemic cells for nonspecific esterases, presence of Fc receptor on the cell surface, phagocytic ability, low TdT activity, presence of surface "ruffles" and "ridges" on scanning EM, elevations of serum lysozyme, and clinical manifestations of leukemic tissue infiltration are features which accompanied monocytic differentiation in these cases.
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PMID:The acute monocytic leukemias: multidisciplinary studies in 45 patients. 700 98

Since all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF) not only enhance proliferation and differentiation of normal myeloid cells but also synergistically promote the differentiation of myeloid leukemic blast cells in vitro, we have started a pilot study of combined treatment with ATRA and G-CSF in patients with myelodysplastic syndrome, to analyze the effect of these drugs on hematopoietic differentiation. ATRA was given at 45 mg/m2/day p.o. from week 1-12 and G-CSF at 5 micrograms/kg/day s.c. from week 5-12 with dose modifications according to the absolute neutrophil counts (ANC). A total of 15 patients, predominantly with refractory anemia, were treated. During initial ATRA therapy, a bilineage response with increases of both ANC and platelet counts occurred in three patients. During combined ATRA/G-CSF therapy, ANC increased in all patients, and platelets increased in three out of 14 evaluable patients. An increase in hemoglobin concentration and a decrease in transfusion requirements occurred in one patient each. In the bone marrow, the myeloid-to-erythroid ratio increased during ATRA treatment and remained increased during concomitant G-CSF administration, while the maturation index of myeloid cells increased only in response to ATRA therapy, but returned to baseline during ATRA/G-CSF treatment. Cytogenetic analysis demonstrated persistence of the abnormal clones in all patients. The number of circulating progenitor cells CFU-GM increased in all patients studied. Serum concentrations of the soluble TNF receptor and IL-2 receptor both increased, while TNF-alpha--already elevated prior to therapy--and soluble ICAM-1 concentrations did not significantly change. Adverse effects included dermatitis and cheilosis in most patients, and a drop in platelet counts related to G-CSF in one patient. The pilot study demonstrates that the combination treatment with ATRA/G-CSF is well tolerated, leading to normalization of ANC in most, and improvement of platelets and red blood cells in a subgroup of patients.
Leukemia 1994 Mar
PMID:Effect of combination therapy with all-trans-retinoic acid and recombinant human granulocyte colony-stimulating factor in patients with myelodysplastic syndromes. 751 Mar 54

Activation of the N- and K-ras proto-oncogenes is the most common molecular abnormality in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). In retrospective studies, approximately 3-36% of MDS patients were reported to harbor a mutated ras proto-oncogene, with some series suggesting the presence of ras-mutations are associated with progressive disease and a poor prognosis. Since hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) are currently used for therapy in MDS but may stimulate the proliferation of leukemic cells, we assessed the frequency and significance of ras mutations in 27 MDS patients, 15 of whom underwent G-CSF therapy. Patients were analyzed for the presence of mutations in codons 12, 13, and 61 of the N- and K-ras proto-oncogenes. Only three patients (11%, two refractory anemia with excess of blasts (RAEB), one RAEB in transformation (RAEB-T)) harbored activated ras oncogenes with the mutations localized in N-ras codons 12 and 61. Patients were followed for periods of up to 4 years or until death supervened. Patients exhibiting ras mutations were no more likely to develop AML compared to ras-negative patients (1/3 vs. 10/24) or to have decreased survival (p = 0.64). These data indicate that, in this group of MDS patients, ras mutations do not appear to correlate with a poor prognosis, and do not adversely interact with exogenously administered G-CSF.
Leukemia 1994 Apr
PMID:Mutations in the ras proto-oncogenes in patients with myelodysplastic syndromes. 751 75

The in vitro colony-forming capacities of marrow CD34-positive (CD34+) cells from 25 patients with myelodysplastic syndromes (MDS) were studied. In all patients this purified cell population showed erythroid (burst-forming unit erythroid; BFU-E) or non-erythroid colony growth, both of which were more restricted than non-purified mononuclear cell population under stimulation with erythropoietin (EPO) or granulocyte/macrophage colony-stimulating factor (GM-CSF) alone. MDS patients examined were put into two groups; refractory anemia (RA) or RA with ringed sideroblasts (RA/RARS) and RA with excess of blasts (RAEB) or RAEB in transformation (RAEB/RAEB-t). The CD34+ cells of both RA/RARS and RAEB/RAEB-t exhibited a similarity to the cells of normal individuals in their responsiveness to the addition of interleukin 6 (IL-6), IL-3 or stem cell factor (SCF). SCF caused powerful but highly variable responses in both erythroid and nonerythroid colony formation as compared with IL-6 or IL-3. We demonstrated that MDS marrow hematopoietic progenitor cells reactive to GM-CSF or EPO were additionally stimulated with early-acting hematopoietic growth factors including IL-6, IL-3 and SCF in a fashion similar to those of normal individuals.
Leukemia 1994 May
PMID:Growth analysis of marrow CD34-positive hematopoietic progenitor cells in patients with myelodysplastic syndromes. 751 49

The c-mpl proto-oncogene which encodes a member of the hematopoietic cytokine receptor superfamily has been recently shown to be the receptor for thrombopoietin (TPO), which stimulates megakaryocyte progenitor expansion and differentiation. We studied c-mpl expression by Northern blot analysis, in a large series of 58 MDS. No expression was found in 14 patients with refractory anemia (RA) or with refractory anemia with ring sideroblasts (RARS). In contrast 11/26 (42%) patients with refractory anemia with excess of blasts (RAEB), or with RAEB in transformation (RAEBt), and 8/18 (44%) patients with chronic myelomonocytic leukemia (CMML) expressed c-mpl. In CMML patients, no correlation was found between c-mpl expression and any prognostic factor tested, nor with the course of the disease. In contrast, in RAEB and RAEBt, expression of c-mpl was correlated with high Bournemouth scoring (P < 0.005) and poor survival (P = 0.02) due to leukemic transformation. Forty-five per cent (5/11) of the c-mpl positive patients evolved towards AML with a mean follow-up of 10.5 months, while 13% (2/15) of the c-mpl negative patients developed a secondary leukemia, with a mean follow-up of 21.1 months. Moreover, in RAEB and RAEBt, a significant correlation was observed between c-mpl, CD34, megakaryocyte glycoprotein IIb (GPIIb) expression, and the presence of dysmegakaryopoiesis. These results indicate that patients with RAEB and RAEBt, with high expression of the c-mpl, CD34, and GPIIb genes, may identify a subgroup of patients with particularly poor prognosis, due to an increased risk of secondary leukemia. More aggressive therapy could be justified in these patients.
Leukemia 1995 May
PMID:Prognostic value of c-mpl expression in myelodysplastic syndromes. 753 13

A 19-year-old male who suffered from severe aplastic anemia had been treated with granulocyte colony stimulating factor (G-CSF) from September 1991. Marked increase of hematopoietic cells in his bone marrow was observed, and maintenance administration of G-CSF was continued. 15 months later, myeloblasts with nuclear abnormality increased, and 22 months later, myeloblasts with chromosomal abnormality presenting 46, XY, -7, +21 exceeded 20%, and aplastic anemia seemed to be transformed into refractory anemia with excess of blasts in transformation (RAEB in T). The usefulness of G-CSF in the treatment of aplastic anemia is now established, but there are some reports questioning the effect of long-term administration, especially transformation to MDS with monosomy 7. Leukemic transformation from aplastic anemia is very complex, but in some cases, long term administration of G-CSF may affect the natural course and may lead to the earlier development of leukemia.
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PMID:[RAEB in T with monosomy 7 after treatment of severe aplastic anemia with long term G-CSF]. 754 Feb 27

Because the cells previously designated plasmacytoid T cells share major immunophenotypic features with cells of the mononuclear-phagocyte system, they have been re-named and are now known as plasmacytoid monocytes (PM). We describe a unique case of chronic myelomonocytic leukemia with circulating PM. The patient, a 48-year-old man, presented initially with refractory anemia. Four years later his general condition deteriorated, accompanied by an increase in leukocytes to 200,000/microliters blood. The bone marrow histology was interpreted as compatible with a diagnosis of chronic myelomonocytic leukemia. Two months before he died, the patient developed generalized lymphadenopathy clinically simulating malignant lymphoma. Histologic examination of an axillary lymph node revealed diffuse infiltration by PM. The PM in the lymph node and some circulating cells closely resembling PM expressed L-selectin, a finding that could be interpreted as a morphologic correlate of their marked lymphotropism. The detection of large numbers of CD56/CD33 double-positive circulating blast cells by FACS analysis strongly supported the diagnosis of a leukemia of myelogenous origin. The patient died of tumor cachexia. Autopsy revealed widespread leukemic infiltrates (always containing clusters of PM) in bone marrow, spleen, liver, lymph nodes, and mucosa-associated lymphoid tissue of the oropharynx. The final diagnosis was one of chronic myelomonocytic leukemia with marked lymphotropism and partial differentiation towards PM. We consider that the rare instances of a hematologic tumor with differentiation towards PM should be classified amongst the myelogenous leukemias.
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PMID:Evidence for a lymphotropic nature of circulating plasmacytoid monocytes: findings from a case of CD56+ chronic myelomonocytic leukemia. 754 May 56

The t(8;21) is a frequent chromosome abnormality in acute myeloid leukemia (AML), particularly associated with M2 of the French-American-British (FAB) classification, but also found in a few patients with myelodysplastic syndrome (MDS). The two genes involved in the t(8;21) have been recently isolated and the cDNA of the AML1/ETO fusion gene identified. We have investigated a series of AML and MDS patients by a reverse transcriptase-polymerase chain reaction (RT-PCR) and analyzed the clinical and laboratory features of leukemia with t(8;21). The t(8;21) was only found in a subset of M2, which had the clinical and hematological features distinct from those M2 without t(8;21). M2 with t(8;21) was associated with a significantly higher myeloid differentiation and with a good response to chemotherapy. Moreover, among the patients with refractory anemia with excess of blasts in transformation (RAEB-T) the t(8;21) was also significantly associated with a higher myeloid differentiation and a good response to chemotherapy. M2 patients with t(8;21) could be distinguished on a number of hematological parameters, eg white blood cell count and percentage of bone marrow myeloblasts and promyelocytes, from RAEB-T carrying the t(8;21). Based on these findings we suggest that leukemia patients carrying t(8;21) can be grouped into two types; overt acute myeloid leukemia (M2) and smoldering or slowly evolving myeloid leukemia.
Leukemia 1995 Jul
PMID:High degree of myeloid differentiation and granulocytosis is associated with t(8;21) smoldering leukemia. 763 Jan 88


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