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At least 451 records · Page 25Linked to original sources
PubMed1979

Refractory anemia with excess of blast cells: prognostic factors and effect of treatment with androgens or cytosine arabinoside. Results of a prospective trial in 58 patients. Cooperative Group for the Study of Aplastic and Refractory Anemias.

The results of a prospective study of 58 patients with refractory anemia and partial blastic infiltration of the bone marrow lead to the following conclusions. The median survival (12 months from diagnosis) is shorter and the rate of acute leukemia as cause of death (60%) higher than in other retrospective series. This group of patients, however, appears to be a "continuum" of preleukemic states with more or less rapid evolution, so that the exclusion of the most severe cases appears unjustified. Based on the degree of bone marrow blastosis, and also on the degree of blood cytopenias, the anomalies of 59 Fe incorporation kinetics and the bone marrow stem-cell cultures, it is possible to derive a plausible prognosis for individual patients, which could aid the choice of therapy. Androgen therapy does not accelerate leukemic evolution, but does not improve the bone marrow insufficiency. Cytosine-arabinoside at low dosage exhibited no toxicity, but did not delay the appearance of overt leukemia.

Acute Disease↗
PubMed1980

Induced acute non-lymphocytic leukemia following long-term chemotherapy: a study of 20 cases.

Twenty individuals developed acute non-lymphocytic leukemia (ANLL) following long-term chemotherapy for other disorders. The primary disorders included non-Hodgkin's lymphoma (five), Hodgkin's disease (five), carcinoma (four), multiple myeloma (three), chronic leukemia (two), and rheumatoid arthritis. Leukemia developed from 11-132 months (mean approximately 60 months) following institution of chemotherapy and all cases have occurred since 1974. Pre-leukemic cytopenias were present in 15 individuals. Fifteen of the 20 patients had chromosome analyses and 14 were abnormal. The leukemia was invariably refractory to chemotherapy with a median survival of only two months. Of the patients autopsied, only one individual had any evidence of the primary malignancy. This study illustrates the need for surveillance for secondary ANLL following long-term chemotherapy with/without radiotherapy. Duration of optimal chemotherapy for the primary disease must be determined by control trials and weighed against the risk of developing a secondary leukemia.

Adult↗
PubMed1981

Preleukemic states in children with acute lymphoblastic leukemia.

Two cases are reported of childhood acute lymphoblastic leukemia presenting with preleukemic states and 13 other cases in the literature are reviewed. Hypoplastic anemias, which transiently resolved spontaneously or with steroid therapy, were seen most commonly. Acquired hypoplastic anemias, even when associated with spontaneous resolution, may at times represent a preleukemic state.

Anemia, Aplastic↗
PubMed1983

Proliferative activity of bone marrow cells in primary dysmyelopoietic (preleukemic) syndromes.

The proliferative activity of bone marrow cells was studied in 24 patients with primary dysmyelopoiesis by means of flow cytometry and 3H-TdR autoradiography. Abnormal DNA content was found in two cases with aneuploid karyotypes. DNA content typical of a diploid population was observed in all patients with normal karyotype and in three patients with chromosomal aberrations. The fraction of bone marrow cells in S- and G2-phase was higher in primary acquired sideroblastic anemia and refractory anemia (without excess of blasts) than in refractory anemia with excess of blasts and chronic myelomonocytic leukemia. Regardless to the diagnosis, the patients with low fraction of cells in S- and G2-phase had short survival time and showed high rate of evolution into acute nonlymphoblastic leukemia. The labeling (LI) and mitotic (MI) indexes of both erythroblasts and granulocytic cells were decreased in nearly all patients. The lowest values of LI and MI of the granulocytic compartment were found in the patients who subsequently developed acute leukemia. These data suggest that cytokinetic analysis allows investigators to achieve useful information on the stage of disease in the dysmyelopoietic syndromes.

Adult↗
PubMed1983

Ph1-positive acute myelocytic leukemia with high TdT levels.

The authors have determined TdT levels in a case of Ph1-positive AML. Peripheral blood cells and bone marrow cells taken during the various phases of the disease were examined. Liquor cells were analyzed when symptomatic central nervous system involvement occurred. High TdT levels were found in all of the phases of the disease including the liquor. TdT eluted at various isoelectric points indicating a shifting of the activity to greater molarity during progress of the disease. Two different forms of TdT were present in the liquor. The authors speculate about the existence of a relation between TdT levels and Ph1-positive leukemia. They point out the importance of TdT levels as functional criterion of remission in acute leukemia. Finally, the existence of different forms of TdT could be the expression of a clonal selection caused by therapy or of a spontaneous clonal competition.

Adolescent↗
PubMed1984

Evolution of oligoleukemia.

Chronic lithium administration to 22 patients with oligoleukemia did not alleviate cytopenia or stimulate bone marrow proliferative activity. The authors identified, however, pretreatment characteristics discriminating two evolutionary endpoints of oligoleukemia (marrow failure, 10 patients; overt acute leukemia, 12 patients): higher marrow leukemic infiltrate, normal myeloid precursor proportion, platelet count, and female sex all favored eventual transition to overt leukemia which, in comparison with marrow failure, was associated with a significantly longer survival duration from symptoms. For patients developing overt leukemia, survival from diagnosis was inversely correlated with the degree of marrow leukemic infiltrate. The lack of lithium responsiveness in oligoleukemia is consistent with the concept of differentiated leukemia with abnormalities either at the level of a lithium-responsive adherent cell elaborating colony stimulating activity (CSA) or at the level of CSA-responsive CFUs.

Acute Disease↗
PubMed1985

Low-dose cytosine arabinoside (Ara-C) therapy in the myelodysplastic syndromes and acute leukemia.

Twenty-two patients with either a myelodysplastic syndrome or acute nonlymphocytic leukemia were treated with 10-21 days of subcutaneous cytosine arabinoside (Ara-C) (5-10 mg/m2 every 12 hours). There were two complete remissions and ten partial responses. Clinically significant improvements in peripheral blood counts persisted for periods of 8 weeks to greater than 21 weeks. Responses were seen even in patients who had previously proven refractory to conventional induction regimens or high-dose Ara-C. The toxicity, however, was considerable. Nearly all patients developed significant thrombocytopenia. Platelet and red cell transfusion support was required in many cases. The response to low-dose Ara-C therapy seen in patients with the leukemic and myelodysplastic disorders may be mediated by the induction of cell differentiation or a direct cytotoxic effect on a sensitive population of cells. Low-dose Ara-C may provide an alternative therapy in the selected patient with acute nonlymphocytic leukemia or a myelodysplastic syndrome.

Acute Disease↗
PubMed1985

Myelodysplastic syndromes. A clinical and pathologic analysis of 109 cases.

A total of 109 patients with myelodysplastic syndromes (MDS) was analyzed to determine the clinical and pathologic features of the five recently defined French-American-British Cooperative Group (FAB) subtypes, and to assess the utility of this classification system in predicting survival, evolution to acute nonlymphocytic leukemia (ANLL), and cause of death. All patients with MDS presented with anemia; additional cytopenias were present in patients with refractory anemia with excess blasts (RAEB), chronic myelomonocytic leukemia (CMML) and refractory anemia with excess blasts in transformation to ANLL (RAEB/Tr). Thirty-two patients received some form of antileukemic therapy for MDS. ANLL developed in 16 of the 77 remaining untreated patients, including 18% (2/11), 0% (0/21), 22% (5/23), 33% (2/6), and 44% (7/16) of patients with refractory anemia (RA), refractory anemia with ring sideroblasts (RARS), RAEB, CMML, and RAEB/Tr, respectively (P = 0.02). The FAB subtype was highly predictive of survival with median survivals ranging from 71 months for RARS to 5 months for RAEB/Tr (P = less than 0.0001). Patients with RAEB, CMML, and RAEB/Tr frequently died of direct consequences of MDS, while patients with RA and especially RARS generally survived or died from unrelated disorders (P = less than 0.0001). MDS encompass a spectrum of disorders. RA and RARS, are relatively indolent and often do not lead to the patient's demise. RAEB, CMML, and RAEB/Tr are aggressive disorders which are often responsible for the patient's death whether or not actual progression to overt leukemia occurs. FAB subtype predicts survival, evolution to ANLL, and cause of death, although the five morphologic subtypes appear to separate into only two disease groups, especially with regard to survival and cause of death.

Aged↗
PubMed1986

DNA aneuploidies in adult patients with acute myeloid leukemia. Incidence and relation to patient characteristics and morphologic subtypes.

Analyses of the cellular DNA content were carried out by flow cytometry (FCM) in 148 adult patients with acute myeloid leukemia (AML) to assess the incidence of DNA aneuploidies and its relation to patient characteristics and morphologic subtypes. DNA aneuploidies were found in 54 of 131 patients with de novo AML (41.2%) and in 4 of 17 patients with AML after preleukemic syndromes. Subclassification according to morphology revealed the lowest rate of DNA aneuploidies in M1 leukemias (25%) and a significantly lower degree of DNA aneuploidy in M1 and M2 cases as compared to M4 and M5 subtypes (P less than 0.05). Within the group of M4 and M5 leukemias, patients less than or equal to 40 years of age had a higher frequency of aneuploid DNA stemlines (71.4%) than older patients (33.3%) (P less than 0.025). No differences between patients with and without DNA aneuploidy were identified for the initial leukocyte count, serum LDH, bone marrow S-phase index, bone marrow cell count/mm3 bone marrow nor the initial response to the induction regimen of 6-thioguanine, cytosine arabinoside, and daunorubicin (TAD). For remission duration a tendency towards a higher proportion of lung remissions was observed in patients with DNA aneuploidy.

Adolescent↗
PubMed1986

Preleukemic changes in cases of nonlymphocytic leukemia secondary to cytotoxic therapy. Analysis of 105 cases.

Peripheral blood changes preceding therapy-related leukemia were studied in 105 patients who had received cytotoxic therapy, 53 for Hodgkin's disease and 52 for other cancers. Preleukemic anomalies were observed in 74.3% of the cases, appearing after a mean interval of 68.7 months after diagnosis of the initial cancer. This interval was only 57.5 months in patients aged 50 years or older and only 42.3 months in patients with Hodgkin's disease having received cytotoxic therapy for 6 months or less. The first changes most frequently observed were pancytopenia (24.8%) and isolated erythrocyte abnormalities such as anemia or macrocytosis (18.1%). Involvement of two cell lines, isolated thrombocytopenia or leukopenia, circulating immature cells, monocytosis, leukocytosis, or thrombocytosis were also observed. Therapy-related myelodysplastic syndrome was recognized in 19 patients and myelofibrosis in 3. Median duration of the preleukemic phase was 6 months; 9 months in cases of isolated erythrocyte involvement and 5 months in the other cases. Myelomonocytic or monoblastic leukemia appeared less frequently when the first sign involved erythrocytes only. Hematological surveillance thus appears necessary in all patients having received cytotoxic therapy. Bone marrow study with cytogenetic examination should be performed in cases of persistent peripheral blood abnormalities.

Adolescent↗
PubMed1986

Significance of chromosome 14 anomaly at band 14q11 in Japanese patients with adult T-cell leukemia.

The chromosomes of leukemic blood cells in eight Japanese patients with acute adult T-cell leukemia (ATL) were examined by a direct method or short-term culture method without any mitogens. Six patients showed a chromosome 14 anomaly with a break at band q11-13: inv(14)(q11q32) in two patients, t(11;14)(p13;q13) in one patient, t(14;14)(q11;q32) in addition to del(14)(q11q13) in another, and only del(14)(q11q13) in two patients. Thus, a proximal 14q rearrangement exists in ATL as in other types of T-cell malignancies. Based on these facts, the pathogenesis of ATL is discussed in reference to the literature.

Chromosome Aberrations↗
PubMed1988

Down's syndrome and acute myelofibrosis. Time study of DNA content during the progression to leukemia.

Flow cytometry (FCM) for the determination of cellular DNA content was performed on multiple bone marrow biopsy specimens from a 3-year-old boy with Down's syndrome and myelofibrosis. A rapidly fatal acute nonlymphocytic leukemia developed within 3 months after initial bone marrow evaluation. The clinical and morphologic changes corresponded to the development of aneuploidy as determined by FCM and cytogenetic analysis. These findings support the clinical observations of the premalignant potential of myelofibrosis in Down's syndrome.

Antibodies, Monoclonal↗
PubMed1991

Exposure histories in acute nonlymphocytic leukemia patients with a prior preleukemic condition.

A subset of patients with acute nonlymphocytic leukemia (ANLL) have evidence of a myelodysplastic syndrome (MDS), low infiltrate leukemia, or other preleukemic condition that may be present for several months before onset of disease. The hypothesis that these conditions act as markers for environmentally induced cancer was examined in 270 ANLL patients, 46 with a preleukemic phase and 224 with an acute onset. Although the effects of previously identified risk factors (male sex, age older than 50 years, prior cytotoxic therapy) were demonstrated, no associations with common environmental conditions (cigarette smoking, alcohol use, occupations with exposure to chemicals or radiation) were present with the exception of hobbies involving potential chemical exposure, odds ratio (OR) and 95% confidence intervals = 4.2 (1.4 to 12.3) and self-reported exposure to pesticides, OR = 10.2 (1.8 to 63.1). These may be chance associations although a previous case-control study of MDS reported similar findings.

Age Factors↗
PubMed1994

Significance of soluble interleukin-2 receptor levels for evaluation of the progression of adult T-cell leukemia.

BACKGROUND: The authors conducted a survey of a large cohort of patients with adult T-cell leukemia (ATL) and a group of human T-cell leukemia virus type 1 (HTLV-1) carriers to elucidate whether measurements of soluble interleukin-2 receptor (sIL-2R) levels are indicative of ATL tumor burden and correlate with clinical progression. METHODS: Using a sandwich enzyme immunoassay, the authors determined sIL-2R in the serum of 135 patients with ATL diagnosed and subclassified according to the Japan Lymphoma Study Group criteria and in the serum of healthy HTLV-1 seropositive persons. Also included were patients in the preleukemic state of ATL (pre-ATL), which is characterized by only slight blood changes but does not fit the diagnostic criteria of ATL. In the five subjects who finally advanced to overt ATL, the authors prospectively performed serial measurements of the receptor. RESULTS: Serial measurements of sIL-2R levels taken until overt ATL developed showed that these levels in the initial samples were higher than those of control subjects, even when subjects were asymptomatic or in the pre-ATL state. The serial levels of the five subjects gradually increased despite being in a clinically stable condition, finally reaching markedly high levels at the time ATL became overt. The mean sIL-2R levels of the smoldering, chronic, acute, and lymphoma subtypes of ATL were 1680 U/ml, 6680 U/ml, 45,940 U/ml, and 34,620 U/ml, respectively (P < 0.01). The sIL-2R levels of each subtype at the time of diagnosis were more correlated with tumor burden, malignant behavior, and prognosis than lactate dehydrogenase (LDH) levels. In the low, moderate, and high sIL-2R subgroups, the median survival time and percent survival probability at 2 years was 30.2 months (46.0%), 16.5 months (25.0%), and 7.7 months (15.3%), respectively. CONCLUSIONS: Serial measurements of sIL-2R levels are of clinical importance because changes of the levels correlate with disease progression, especially in early phase of ATL. The data suggest that sIL-2R may be more useful than LDH. In addition, emphasis may be placed on sIL-2R as an indicator of ATL progression status and prognosis for survival. The value of this marker in clinical practice should be confirmed prospectively.

Carrier State↗
PubMed1981

Auer rod positive dysmyelopoietic syndrome.

Twenty-five patients with refractory anemia with excess blasts (RAEB) were studied. Five of these patients showed Auer rods in their myeloblasts, but met other criteria for RAEB. Median survival of the Auer rod-positive group was 14 months (range 2-27) from diagnosis with survival of 7 months after Auer rods were first observed. Median survival for the Auer rod-negative group was 12 months. Two patients developed overt acute leukemia, both from the Auer rod-negative group. The clinical course of Auer rod-positive RAEB, like that of Auer rod-negative RAEB, was one of progressive bone marrow failure complicated by infection, serious bleeding and the development of absolute transfusion requirement. These findings suggest that Auer rod-positive RAEB is a morphologic variant dysmyelopoietic syndrome that may pursue a similar clinical course to Auer rod-negative disease. Formulation of a separate treatment approach for those RAEB patients who possess Auer rods would appear ill advised.

Aged↗
PubMed1982

Childhood monosomy 7 syndrome.

In recent years, chromosomal aberrations in various hematologic disorders have raised a great deal of interest. In fact, several nonrandom chromosomal abnormalities are now recognized to be responsible for a specific type of dyshemopoiesis while others are closely associated with characteristic hematologic features. Monosomy C, later shown to be monosomy 7 by different banding methods, has been described in children in relation to a peculiar myeloproliferative disorder. Retrospective analysis of early cases published in the literature and a recent observation that we wish to report suggest that the most consistent phenotypic expression of monosomy 7 is an increased susceptibility to bacterial infections related to a preleukemic dyshemopoiesis. Acute nonlymphocytic leukemia is the terminal event of this peculiar preleukemic syndrome, and thus suggests that monosomy 7 involves a stem cell already committed to myeloid differentiation.

Anemia, Aplastic↗
PubMed1985

Terminal deoxynucleotidyl transferase-positive acute leukemias evolving from a myelodysplastic syndrome.

We have analyzed the distribution of terminal deoxynucleotidyl transferase (TdT) in 30 patients with myelodysplastic syndromes (MDS), in connection with morphology, cytochemistry, and cytogenetics. All cases in preleukemic phase were strictly TdT-negative. At variance, 4 (19%) of 21 cases with subsequent leukemia were TdT-positive and showed a pure lymphoid (one case) or a mixed lymphoid-myelomonocytic (three cases) morphology. The TdT enzymatic activity ranged from 2 to 21 U/10(8) cells and the percent of positive cells in the immunofluorescence test ranged from 10 to 80% of total. All cases were Philadelphia chromosome-negative. The clonal origin of MDS from the pluripotent stem cell, capable of originating both a lymphoid and myeloid progeny, is further corroborated.

Acute Disease↗
PubMed1985

Low-dose arabinosyl cytosine in acute leukemia after a myelodysplastic syndrome and in elderly leukemia.

Low-dose arabinosyl cytosine (ARA-C) was tested in 15 patients with acute leukemia after a myelodysplastic syndrome (MDS) and in six elderly patients with acute nonlymphoid leukemia (ANLL). The drug was given subcutaneously at 10 mg/m2, every 12 hr for 2 weeks, every 28 days. The overall response rate was 19% (one complete remission, three partial responses), and the median duration of response was 4 months. No particular features at diagnosis were predictive of response. Pancytopenia and marrow hypoplasia occurred after 44 (78%) of 56 courses of therapy and were more severe in nonresponders. Four patients died during the aplasia following ARA-C therapy. Subcutaneous low-dose ARA-C was of limited benefit and bore a noticeable hematologic toxicity.

Acute Disease↗