Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to further improve the cure rate in AML we investigated the effect of more chemotherapy--in terms of its intensity and its duration--in 2 studies. In our 1981 study patients received TAD 1-2 courses for induction, 1 course for consolidation and randomly no further treatment or monthly myelosuppressive maintenance for 3 years. Evaluating 213 responders remission duration was clearly longer in the maintenance group with 24% CCR after 5 and 10 years. In our 1985 study the same successful strategy was further intensified by a second induction course given regardless of response to the first course to all patients up to 60 years of age while older patients received standard induction as before. This age-adapted concept resulted in a further increase of 5 years CCR in the 461 responders to as much as 34% not achieved for unselected patients in other multicenter trials. 20 patients receiving auto-BMT in first CR show the same relapse free survival as their counterparts receiving chemotherapy according to the 1985 protocol in a matched-pair analysis. We conclude that both very early intensification and prolonged maintenance contribute to a higher cure rate that is not further improved even by a maximum intensity short-term treatment. The limits of chemotherapy in AML may be overcome by modulating its myelotoxicity and antileukemic potency using GM-CSF as shown in 2 studies of our group.
Leukemia 1992
PMID:Longterm effects of prolonged maintenance and of very early intensification chemotherapy in AML: data from AMLCG. 157 46

The results of four consecutive trials designed by the GIMEMA group for the treatment of ANLL in elderly patients are reviewed. Complete remission (CR) has been achieved in 20.8% of patients older than 60 years treated with 5-day courses of ARA-C plus thioguanine, in 22.7% of patients treated with high dose ARA-C (HDARAC) plus Asparaginase, in 39.5% of patients aged 55 to 80 receiving either Idarubicin or Daunorubicin in combination with Cytarabine in a standard 3+7 protocol and in 51% of patients older than 60 years treated with intermediate dose ARA-A (IDARAC) plus Mitoxantrone. From 1988, patients ineligible for aggressive chemotherapy entered a study of palliative treatment with Thioguanine and ARA-C. This 18 year GIMEMA experience showed that: CR can be obtained only with regimens producing marrow aplasia, the inclusion of anthracyclines or Mitoxantrone improves the CR rate, without prohibitive toxicity, haematological toxicity is very high in elderly patients and account for the most frequent cause of treatment failure namely death in aplasia, palliative treatment does not improve the quality of life and prolongs median survival only slightly. When comparing the results of these trials, it appears that in the GIMEMA group the capability of offering effective treatment to elderly patients with ANLL has continuously improved and that IDARAC plus Mitoxantrone is so far the most active and best tolerated regimen. Death in aplasia remains a major problem and future trials will be aimed at exploiting the possibility of reducing the haematological toxicity by using recombinant colony stimulating factors.
Leukemia 1992
PMID:Treatment of acute non lymphoid leukemia (ANLL) in elderly patients. The GIMEMA experience. 157 48

Between 1978 and 1988 (median follow up 5 1/2 years), 396 newly diagnosed adults with AML (age range 14-59 years, median 44) received STT comprising daily Adriamycin: 25mg/m2 for 3 days, Cytosine arabinoside (ara-C): 100mg/m2 bd and 6-thioguanine: 100mg/m2 bd, each for 7 days. A maximum of 6 cycles was administered with as short an intercycle time as possible. No further treatment was given. Complete remission (CR) was achieved in 243/396 patients (62%), 71 patients (18%) having resistant leukaemia and 82 (21%) dying within 6 weeks. Antecedent myelodysplasia and advanced age correlated unfavourably with achievement of CR (p = less than 0.001 and 0.005 respectively). Sixty nine patients continue in first remission between 2 1/2 and 12 years; the median duration of remission was 1 year. M3 morphology (p = 0.005) and absence of hepatosplenomegaly (p = 0.001) correlated favourably with duration of remission. Ninety one patients remain alive with an actuarial survival of 22% at 5 years. More recently, additional consolidation comprising high-dose ara-C and total body irradiation (TBI) with autologous bone marrow transplantation (ABMT) has been evaluated in an open study. CR has been achieved in 41/66 patients under the age of 50 but only 19/41 have proceeded to ara-C + TBI + ABMT. Twenty two have not (early recurrence 10, allogeneic BMT 4, debility 6, refusal 2). 11/19 who proceeded to ablative therapy continue in remission (4 treatment related deaths, 4 recurrences) as compared to 9/22 who did not. Currently the overall median duration of remission for the 41 patients intended to proceed is identical to that of age-matched historical controls illustrating the difficulties inherent in demonstrating benefit for the use of myeloablative therapy and ABMT in patients with AML in first remission.
Leukemia 1992
PMID:Short term therapy (STT) for acute myelogenous leukaemia (AML). 157 52

Activating ras mutations are frequent (25-60%) in chronic myelomonocytic leukemia (CMML) and in acute myeloid leukemia (AML) (30%), in contrast to chronic myeloid leukemia (CML) in which the incidence is very low (0-3%). This might reflect that the leukemic cell in CML is at a level of differentiation in which ras gene activation is not involved or, alternatively, might be due to the presence in CML of the bcrlabl fused gene. We have analyzed the presence of point mutations in codons 12, 13, 59, 61 and 63 of N-, K-, and H-ras genes, in 26 cases of Philadelphia-chromosome-positive, bcrlabl-positive acute leukemia (Ph+ AL), and in eight CMML cases by using the polymerase chain reaction. Aberrant ras genes were detected in a single Ph+ AL case, and in four out of eight CMML patients. The Ph+ AL showing altered ras allele had an unusual point mutation in H-ras gene, substituting leucine for glutamine. This mutation has not been previously found in any hematological disease. Our findings suggest that ras mutations are probably not involved in the pathogenesis of those leukemias in which blast cells contain bcrlabl oncogene activation.
Leukemia 1992 Apr
PMID:Low frequency of ras oncogene mutations in Philadelphia-positive acute leukemia and report of a novel mutation H61 Leu in a single case. 158 96

To determine whether serial examinations of the peripheral blood can replace regular bone marrow punctures in the diagnosis of a relapse of acute myelogenous leukemia (AML), the peripheral blood of 40 AML patients in remission undergoing regular bone marrow punctures was studied. Within three months prior to bone marrow examination proving relapse in 97% of the relapses, at least one of the following values of the peripheral blood was pathological: blasts (84%), neutrophil granulocytes (72%), thrombocytes (64%), and hemoglobin (58%). The simultaneous appearance of abnormalities in the peripheral blood and the bone marrow occurs in such high incidence that routine bone marrow punctures are rendered obsolete in the follow-up of AML patients. Needless pain and anxiety can therefore be avoided for many AML patients.
Leukemia 1992 May
PMID:Routine bone marrow punctures during remission of acute myelogenous leukemia. 159 5

We have examined the effect of a combined 24 h exposure to cytosine arabinoside (ara-C) and the protein kinase C activator bryostatin 1, either alone or in conjunction with recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), on the clonogenic growth of 14 primary samples from acute myelogenous leukemia (AML) patients, as well as normal human committed and early hematopoietic progenitors. Incubation of blasts with 1 microM ara-C and 12.5 nM bryostatin 1(+/- 1.25 ng/ml rGM-CSF) resulted in a heterogeneous pattern of inhibitory effects toward primary leukemic colonies, ranging from 32-98%, and subadditive to synergistic drug interactions. However, exposure of blasts to ara-C and bryostatin 1, either with or without rGM-CSF, eliminated leukemic cell self-renewal in 80-93% of samples, and very substantially reduced growth in the remainder. Exposure of normal human bone marrow mononuclear cells to identical concentrations of ara-C and byostatin 1 permitted the survival of 23% of committed myeloid progenitors (granulocyte-macrophage colony-forming units), and greater than 50% when rGM-CSF was included. Finally, exposure of bone marrow populations highly enriched for progenitor cells (CD34+, DR-, CD71-) to ara-C and bryostatin 1 +/- rGM-CSF for 24 h led to minimal reductions (e.g. 10-15%) in the survival of early hematopoietic progenitors (high proliferative potential colony-forming cells). Together, these findings indicate that combined exposure in vitro to ara-C and bryostatin 1, both with and without rGM-CSF, effectively inhibits the growth of leukemic cells with self-renewal capacity, while sparing a significant fraction of normal committed and primitive hematopoietic progenitors.
Leukemia 1992 May
PMID:Effect of a combined exposure to cytosine arabinoside, bryostatin 1, and recombinant granulocyte-macrophage colony-stimulating factor on the clonogenic growth in vitro of normal and leukemic human hematopoietic progenitor cells. 159 8

We analysed data from 114 recipients of HLA-identical sibling transplants who relapsed and received a second transplant between 1978 and 1989. Twenty-nine patients had acute lymphoblastic leukemia, 46 acute myeloid leukemia and 39 chronic myelogenous leukemia. Median (range) interval between first and second transplants was 15 (1-80) months. Following the second transplant, graft failure occurred in 2%, acute graft-versus-host disease (GVHD) in 27% and chronic GVHD in 21% of patients at risk. Risks of interstitial pneumonia and hepatic veno-occlusive disease were higher after the second than the first transplant. Two-year probabilities (95% confidence interval) of treatment-related mortality, relapse and leukemia-free survival were 41% (30-53%), 65% (53-75%) and 21% (14-30%), respectively. Leukemia-free survival was 7% (2-19%) among patients relapsing less than 6 months after their first transplant, with high rates of both relapse, 77% (49-92%), and treatment-related mortality 69% (46-85%). In contrast, leukemia-free survival was 28% (19-41%) in those relapsing more than 6 months after the first transplant; in this group the probability of relapse was 59% (45-72%) and treatment-related mortality 30% (20-43%). Factors correlated with better outcome included a diagnosis of chronic myelogenous leukemia, relapse more than 6 months after the first transplant, acute leukemia in remission prior to the second transplant and good performance status.
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PMID:Second HLA-identical sibling transplants for leukemia recurrence. 160 Apr 15

The translocation (6;9)(p23;q34) is mainly found in specific subtypes of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The diagnosis of this translocation is not easy since the cytogenetic change is quite subtle. The two genes involved in this translocation were recently isolated and diagnosis at the DNA-level became an additional option. Both the dek gene on chromosome 6 and the can gene on chromosome 9 contain one specific intron where breakpoints of t(6;9) patients were found to cluster. The translocation results in a consistent chimeric dek-can mRNA which is generated from the 6p- derivative. Five centers participated in a study to estimate the incidence of t(6;9) in leukemic patients using conventional Southern blot analysis. Patients (n = 320) with either acute undifferentiated leukemia (AUL), AML, MDS or acute lymphoblastic leukemia (ALL) were screened for rearrangement of the genes involved in this translocation. Four of these 320 patients showed rearrangement of the can gene on chromosome 9, of which one also had a rearranged dek gene on chromosome 6. A further 20 patients were studied with karyotypic aberrations in which either the short arm of chromosome 6 or the long arm of chromosome 9 were specifically involved. Both conventional Southern blot analysis and contour-clamped homogeneous electric field (CHEF) analysis failed to show dek-can rearrangement in any of these patients. The results of our study indicate that the incidence of the t(6;9) is a low as reported based on cytogenetic data and that rearrangement of the dek and can genes is mainly restricted to this specific translocation.
Leukemia 1992 Jun
PMID:Dek-can rearrangement in translocation (6;9)(p23;q34). 160 86

Bone marrow samples collected from acute myeloblastic leukemia (AML) patients in complete clinical and hematological remission were studied for the persistence of cytogenetic abnormalities. AML patients from the three favorable cytogenetic categories [inv 16, t(8;21) and t(15;17)] and patients from the unfavorable cytogenetic categories (+8, -5, -7 and Philadelphia-positive) were studied. Seventy-one patients had evaluable metaphase spreads in remission marrows and 20 (28%) had one or more abnormal metaphases identical to that present in the pretreatment marrow. All 20 of these patients relapsed within 78 weeks, thus there were no false positive studies. Fifty-one patients had only diploid metaphases in their complete remission marrow, 25 relapsed, and 21 remained in continuous complete remission. Thus there was a 49% false negative rate of this study. These data indicate that the failure to detect residual chromosomally abnormal cells in the bone marrow does not guarantee continuous complete remission. Cytogenetic study was most useful in the favorable cytogenetic groups and least useful in the unfavorable groups. The persistence of normal metaphases in pretreatment marrows did not affect outcome or risk of recurrence. Twenty-five of 34 evaluable patients who relapsed after remission had either the identical cytogenetic abnormality present in the pretreatment marrow or showed the identical abnormality with additional chromosomal changes. Thus study indicates that cytogenetic examinations of complete remission bone marrow samples in patients with AML provides an objective method for detecting residual leukemia, and identifies patients with a potential for prolonged disease-free survival.
Leukemia 1992 Jun
PMID:Cytogenetics for detection of minimal residual disease in acute myeloblastic leukemia. 160 88

The t(9;11)(p21;q23) has been associated with characteristic clinical features and a superior treatment outcome in previously untreated pediatric acute myeloblastic leukemia (AML), but has not been well studied in children with secondary AML. This translocation was detected in 6.7% of de novo and 46% of secondary AML patients treated at St Jude Children's Research Hospital over an 11-year period. Clinical, immunophenotypic, and morphologic characteristics were examined for the cases of t(9;11) secondary AML (n = 12) and compared with findings for children with t(9;11) de novo AML (n = 12). Patients with t(9;11) secondary AML were older at diagnosis, had higher hemoglobin levels, and central nervous system leukemia or hepatosplenomegaly was less frequent. These differences probably reflect survival of the first malignancy and close clinical scrutiny during post-treatment follow-up. Whereas the t(9;11)(p21;q23) occurred exclusively in the French-American-British (FAB) M5 subtype in de novo AML, the FAB M0 and M4 subtypes were also represented in secondary cases. The complete remission rate was somewhat higher for the de novo AML group (91 vs 58%; p = 0.16); their event-free survival was clearly superior to that for children with t(9;11) secondary AML (p = 0.003). Host differences related to the previous malignancy or its treatment could explain the poorer clinical outcome for patients with t(9;11) secondary AML. Alternatively, there could be critical differences at the translocation site or additional, hidden molecular events, that explain the different outcomes.
Leukemia 1992 Jun
PMID:Translocation t(9;11)(p21;q23) in pediatric de novo and secondary acute myeloblastic leukemia. 160 90


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