Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 48-year-old Japanese man was admitted to our hospital because of general fatigue, nasal bleeding, and petechiae on his extremities. He was diagnosed with acute myelomonocytic leukemia with trilineage myelodysplasia (T-MDS). Chromosomal analysis of bone marrow cells revealed t(7;11)(p15;p15), which has been rarely reported but known to be characteristic of Japanese patients. Although t(7;11)(p15;p15) has been reported mainly in acute myelogenous leukemia (AML), it can be occasionally found in so-called stem cell diseases such as chronic myelogenous leukemia or chronic myeloproliferative disorders. Therefore, t(7;11)(p15;p15) might affect trilineage progenitors or stem cells as well as myeloid lineage cells, subsequently resulting in AML with T-MDS, as in our case reported here.
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PMID:t(7;11) and trilineage myelodysplasia in acute myelomonocytic leukemia. 861 92

We analyzed 144 of 475 previously untreated patients with acute myeloid leukemia (AML, n = 87) and 'high-risk' myelodysplastic syndromes (MDS, n = 57) who failed to achieve a complete remission with fludarabine- and high-dose cytarabine-containing regimens between 1991 and 1994. The AML and MDS groups were comparable with regard to age, major prognostic indicators, supportive care received, type of antileukemia response and causes of death and were considered together. The causes of death of 118 evaluable patients were compared to a series of 123 AML initial remission induction failures previously reported from our institution. The induction failure rate was significantly lower (30 vs 43% P <0.001). We found a significant decrease in fatal infections (autopsied patients, P = 0.001) and a reduction in bacterial (autopsied and non-autopsied patients, P <0.005) but not fungal (non-autopsied patients, P = 0.93; autopsied patients P = 0.15) infections as causes of induction death. Pulmonary hemorrhage was twice as common in the present report (P < 0.005, with pulmonary hemorrhage almost three times as common as fatal cerebral hemorrhage. A comparison restricted to the AML patients in the present study yielded similar results. We conclude that the mortality profile in AML remission induction has undergone substantial changes at our institution since our last report, probably as a consequence of the introduction of new chemotherapy regimens and supportive care modalities.
Leukemia 1996 Apr
PMID:Causes of initial remission induction failure in patients with acute myeloid leukemia and myelodysplastic syndromes. 861 34

The option of bone marrow transplantation (BMT) significantly improved prognosis of adult patients with hematologic malignancies aged less than 50 years. Allogeneic BMT using the marrow of an HLA-identical family member still provides the most effective method of BMT. Conventional indications for this form of BMT are chronic myeloid leukemia (CML), acute leukemias presenting with adverse risk factors, myelodysplastic syndromes and severe aplastic anemia. If performed early in the disease course (e.g. during the chronic phase of CML or first remission of acute leukemia and MDS) allogeneic BMT cures 50 to 60% of patients. About 20% die of therapy related complications, e.g. graft versus host disease (GvHD), fatal infections or venoocclusive disease of the liver (VOD) and about 20% of patients succumb to relapse of their hematologic disorder. 80% presenting with severe aplastic anemia can be cured, if allogeneic BMT is performed soon after diagnosis without previous immunosuppressive therapy and blood transfusions. BMT with the marrow of a matched unrelated donor or autologous BMT are increasingly used as alternative procedures. A rate of lethal complications as high as 50% hinders rapid extension of BMT with unrelated donors. Therefore, this form of BMT should be restricted to young patients with leukemias, who cannot achieve long-term remission with conventional chemotherapy (in case of acute leukemias) or alpha-interferon (in case of CML). Reconstitution of hematopoiesis is more rapid after peripheral blood stem cell transplantation (PBSCT) compared with autologous BMT. Therefore, PBSCT will replace autologous BMT in most cases. Most favourable results of PBSCT have been reported in patients with malignant lymphomas after relapse or inferior response to primary induction therapy. Due to the higher relapse rate autologous BMT is inferior to allogeneic BMT in leukemia patients. Trials are required to clarify the potential role of myeloablative therapy with stem cell support in the treatment of patients with solid tumors. Many of the preliminary results already published are unsatisfactory and data of larger trials are still lacking. Therefore, BMT or PBSCT cannot be recommended generally for the therapy of patients with solid tumors.
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PMID:[Indications, technique and risks in bone marrow transplantation in adulthood]. 864 1

Evi-1 is a transforming gene originally identified in a common integration site of murine leukemia retrovirus and mapped in human chromosome 3q26. It is not normally expressed in either human or murine hematopoietic cells, but is overexpressed in retrovirus-induced murine myeloid leukemias as well as human myeloid leukemias with 3q26 abnormalities, and thus thought to be responsible for both human and murine leukemogenesis. In this study, possible involvement of the Evi-1 gene in human leukemias was evaluated by Northern blot analysis in a total of 73 patients with various types of leukemias. We found that increased expression of the Evi-1 gene was most frequently observed in patients with CML in blastic crisis. It was found in 10 of 14 (71.0%) samples from CML in blastic crisis, three of 15 (20.0%) from acute myelocytic leukemia, three of 11 (27.3%) from MDS-derived leukemia, and one of 11 (9.1%) from acute lymphoblastic leukemia. Among 18 patients showing increased Evi-1 expression, none of 17 informative patients showed cytogenetic abnormalities involving 3q26. In addition, Southern blot analysis revealed neither amplification nor rearrangements of the Evi-1 gene in 11 Evi-1-positive patients whose DNA samples were available. Our results suggest that increased expression of the Evi-1 gene may play an important role in development of human leukemias, especially in progression from chronic phase to blastic crisis of CML even without 3q26 abnormalities.
Leukemia 1996 May
PMID:Increased Evi-1 expression is frequently observed in blastic crisis of chronic myelocytic leukemia. 865 73

The recognition of distinct cytoimmunological subsets of pre-leukaemia and overt AML has been accomplished by morphological, immunological and ultrastructural studies. In many cases, a strong association has been documented between distinctive cytological features and specific chromosome changes. The primary genetic event underlying malignant transformation was also elucidated in a number of acute leukaemias and, as a matter of fact, assessment of these biological parameters has now an established role in the diagnostic work-up and in the monitoring of residual disease. On a more general basis, biological research in MDS is gradually clarifying the fundamental pathophysiological mechanisms of altered cell growth, and differentiation and therapeutic decision making in leukaemia is becoming increasingly dependent on the precise characterization of blast cells. Further refinement of the cytoimmunological classification of acute leukaemias and MDS is warranted in order to provide the physician with an updated framework of reference for the categorization of these heterogeneous haematological disorders and to improve the reproducibility of current morphological diagnosis among different centres (Castoldi et al, 1993).
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PMID:Special cytological subtypes of acute myeloid leukaemias and myelodysplastic syndromes. 873 May 49

Immunophenotyping improves both accuracy and reproducibility of the FAB classification and is considered particularly useful for identifying poorly differentiated FAB subtypes of AML, such as AML with minimal differentiation (M0), microgranular promyelocytic leukaemia (M3V), and megakaryoblastic leukaemia (M7). Immunological studies of myeloid leukaemic blasts has become critical also in identifying biphenotypic leukaemias and AML expressing lymphoid-associated markers (Ly+ AML). At present, while the prognostic value of individual antigen expressions is still controversial, due to technical questions, the immunological detection of MRD seems to be important in monitoring AML patients in remission and, perhaps, in detecting leukaemic cell contamination into bone marrow or peripheral blood progenitor cells collected for autologous transplantation. In addition, the relationship established between genetic abnormalities and certain phenotypes within different FAB subtypes suggests that, in the future, immunophenotypical studies could be used for the screening of AML cases carrying specific genetic aberrations. Compared to acute leukaemias, little information is available concerning immunological patterns in MDS, and the role of the immunophenotype in diagnosis, subclassification, and prognosis of MDS is currently not well established.
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PMID:Immunophenotyping of AML and MDS and detection of residual disease. 873 May 50

Now that a substantial group of cancer patients has such a favourable prognosis, it has become increasingly important to evaluate the long-term complications of treatment. Of all late effects of treatment, secondary leukaemia is one of the most serious. Increased risk of AML has been observed both after RT and after CT; however, several types of CT have much stronger leukaemogenic properties than RT. Limited field radiation in the therapeutic dose range is associated with very little or no increased risk of leukaemia, which has been attributed to cell killing at the higher radiation doses. With respect to CT, two different syndromes of treatment-related AML have been recognized. Risk of alkylating agent-related AML is highest in the 5-10 year follow-up period and seems to decrease afterwards. This type of leukaemia is often preceded by MDS, and is characterized by deletions of chromosomes 5 and 7. Leukaemias related to treatment with the topoisomerase II inhibitors are characterized by a short induction period, presentation as myelomonocytic or monocytic leukaemia (rather than MDS) and balanced chromosomal translocations involving bands 11q23 and 21q22. This review addresses the risk of secondary AML and MDS following treatment of HD, NHL, testicular cancer, ovarian cancer, breast cancer and paediatric malignancies. In patients with HD, the risk of AML is higher with an increasing number of mechlorethamine-procarbazine-containing cycles, a greater number of CT episodes, and after splenectomy. The majority of data shows that RT does not add to the leukaemia risk from CT, but this issue is still surrounded by some controversy. ABV(D)-treated patients have a very low risk of AML. Generally, patients with NHL, testicular cancer and breast cancer experience much lower risk of AML than patients with HD. NHL and breast cancer treatment regimens with cumulative cyclophosphamide doses of 20 g or less do not confer an appreciable increase of AML. Recently, strongly increased AML risk has been observed following autologous bone marrow transplantation and other dose intensification strategies. Risk factors for this excess remain to be defined. PVB treatment for testicular cancer is not followed by increased leukaemia risk, but modern etoposide-containing regimens do confer excess risk, of which the magnitude at conventional drug doses is not yet well known. High risk of leukaemia has been reported in children treated with epipodophyllotoxins. The leukaemogenic hazards of cancer treatment should be weighed against their therapeutic benefits.
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PMID:Risk of acute myelogenous leukaemia and myelodysplasia following cancer treatment. 873 May 51

In a retrospective analysis we assessed occurrence, contributing factors and outcome of patients experiencing granulocytic sarcoma as a localized extramedullary relapse after allogeneic BMT. EBMT members were asked to report the number of patients transplanted for leukemia between January 1981 and December 1992 and the number of patients with granulocytic sarcoma. Of a total of 5824 patients transplanted for AML, CML or MDS by 86 teams, granulocytic sarcoma was observed in 26 patients (0.45% occurring 4-56 months after BMT. Granulocytic sarcoma occurred after allogeneic BMT in 20 out of 3071 patients grafted for AML (0.65%), and in the CML/MDS subgroup in six out of 2753 grafted patients (0.22%). Granulocytic sarcoma can involve any site of the body, presenting as a soft tissue mass; it occurred in body cavities (eg pleural cavity, abdominal cavity, spinal canal, stomach and bladder), the head and neck region (orbit, ear, skull base, peripheral nerves), the trunk and limbs, and mammary and sex glands. Granulocytic sarcoma predicts an additional hazard to outcome after BMT. Nine of 26 patients (33%) were alive 15-151 months after the onset of granulocytic sarcoma. Advanced disease stage at grafting adversely affected survival and all patients died. The best treatment option still needs to be defined.
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PMID:Granulocytic sarcoma after allogeneic bone marrow transplantation: a retrospective European multicenter survey. Acute and Chronic Leukemia Working Parties of the European Group for Blood and Marrow Transplantation. 873 1

Soluble receptors have been identified for most members of the TNF-receptor/NGF receptor superfamily. CD95 (Fas/Apo-1) is of particular importance, since its triggering may induce apoptosis in sensitive cells. Recently, a soluble form of the CD95 molecule was described which interacts with the CD95-CD95 ligand death pathway. Increased concentrations of soluble CD95 (sCD95) were previously detected in some patients with T and B cell leukemias and lymphomas. In the present study we investigated sCD95 in the serum of patients with myeloid leukemias, myeloproliferative and myelodysplastic syndromes. A total of 72 patients was studied (29 AML, 17 MDS, 20 CML and six other myeloproliferative disorders). In AML with active disease, the levels of sCD95 tended to be elevated, but did not correlate with defined clinical or laboratory parameters. In the other disorders, the levels of sCD95 were not generally increased, although some patients had elevated levels. These data strongly suggest that sCD95 in AML patients is not derived from leukemic cells, but is possibly secreted or shed from reactive or stromal cells. This hypothesis is also supported by a group of eight patients with septicemia but not leukemia who had elevated sCD95 (P < 0.05). Furthermore, all three patients with elevated sCD95 who had undergone chemotherapy for AML had major infections. Taken together, this study shows that measuring soluble Fas-receptor in myeloid leukemia is not diagnostically useful, but increased sCD95 may be associated with clinical complications like septicemias.
Leukemia 1996 Sep
PMID:Soluble FAS (CD95) is not elevated in the serum of patients with myeloid leukemias, myeloproliferative and myelodysplastic syndromes. 875 76

Previous studies in pediatric patients with acute myelogenous leukemia (AML) have suggested that 2-chlorodeoxyadenosine (2CdA) is an effective therapeutic agent. Santana et al (J Clin Oncol 1992; 10: 364-370) reported a CR rate of 8/17 (95% Cl 23-72%) in children with relapsed AML and a median first CR of 21 months. The activity of 2CdA in adults with relapsed or refractory leukemia was therefore investigated in a phase I study. In the phase II study, based on biochemical modulation rationale, 2CdA was combined with Ara-C for adults with relapsed AML to test the effectiveness of this combination therapy. In the phase I study 27 patients (25 AML and two MDS) with a median first CR duration of 21 weeks, received 2CdA at doses ranging from 5 to 13 mg/m2/day by continuous infusion (CI) for 7 days. In vitro and ex vivo pharmacologic studies performed to determine the effect of pretreatment with 2CdA on Ara-CTP accumulation in leukemic blasts demonstrated a 50-65% increase in the rate of Ara-CTP accumulation. Based on this biochemical modulation, 2CdA (12 mg/m2/day x 5 days by CI) was combined with Ara-C (1 g/m2/day over 2 h) in a phase II study. Seventeen patients (15 AML, two MDS) with relapsed AML (median 1st CR of 19 weeks) were treated. In the phase I study two patients died before the day 14 marrow (ED). Marrow hypoplasia developed in 16 of the remaining 25. Leukemic regrowth occurred in nine after a median hypoplastic period of 2 weeks (range 1-3 weeks). The other seven patients died with aplastic marrows, median duration of hypoplasia was 2 weeks, range 1-4 weeks. None achieved CR and the median survival was 10.5 weeks. Toxicity generally was mild except for three late occurring cases of grade III or IV renal dysfunction and two cases of tumor lysis syndrome. The MTD was 10.8 mg/m2/day x 7 days. In the phase II study two patients, both with AML, achieved CR (95% CI 1-33%). In both cases leukemia relapsed after 10 weeks and 17 weeks. There was one ED. Most (11/16) cleared their marrow although leukemic infiltrate regrew in six cases. Toxicity was generally mild, with two episodes of grade 2 GI bleeding, one episode of severe renal dysfunction and one case of grade 2 CNS toxicity. We conclude that as a single agent 2CdA at the MTD is a cytoreductive agent but is not sufficient to achieve CR in adults with relapsed AML. While combination of Ara-C with 2CdA increases the Ara-CTP uptake in these heavily treated patients this regimen does not appear to be an improvement over existing modalities.
Leukemia 1996 Oct
PMID:Clinical and laboratory studies of 2-chlorodeoxyadenosine +/- cytosine arabinoside for relapsed or refractory acute myelogenous leukemia in adults. 884 90


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