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

The important advances made in recent years in the therapy of adult ALL have been reviewed. The definition of bad-prognosis patients has been improved and includes those with T-ALL, ABLL, and Ph1+ALL, in addition to those presenting with evidence of extensive disease. In contrast to childhood ALL, induction chemotherapy should include another drug (or drugs) in addition to VCR and prednisolone, and one of the anthracycline drugs (ADR or DNR) has been employed most frequently in this context. Such therapy should result in a CR rate of 70 to 75%. Similar to the experience in childhood ALL, the improvement in haematological response rate has led to an apparent increase in CNS leukaemia, and the need for adequate CNS prophylaxis is stressed. Despite these improvements, the outlook for adults with ALL is not yet as good as it is for childhood ALL. Controlled studies involving large numbers of patients are urgently needed to provide answers to a number of questions. In induction therapy, the use of higher drug dosage, the use of more and other drugs, and the use of an individual patient's risk factors to determine drug dosage, must be assessed. The benefits of consolidation therapy and the optimal duration and intensity of maintenance therapy have yet to be established. Methods of CNS prophylaxis other than cranial irradiation and IT MTX must be carefully studied. These important questions require that adult patients with ALL should be concentrated in centres capable of providing optimal overall care and, at the same time, able to conduct the necessary clinical trials.
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PMID:The management of adult acute lymphoblastic leukaemia. 36 95

Blast cells from a female patient with acute lymphoblastic leukemia-hand mirror variant were examined using various techniques, including light and ultrastructural morphologic examination, cytochemical analysis, surface antigen characterization, cytogenetic analysis, and gene rearrangement studies. The blast cells were found to be pre-B cells (CD19+ and Tdt+) that also expressed the myeloid antigens CD13 and CD33 and demonstrated a heavy chain immunoglobulin gene rearrangement. Cytogenetic studies revealed a t(11;19) translocation previously described in biphenotypic leukemias. A subset of acute lymphoblastic leukemia-hand mirror cells has been previously defined and includes predominately female patients with an indolent course. The authors' findings place this case, a mixed leukemia, within that subgroup. The possibility of mixed lineage should be considered in future cases of hand mirror variants of adult acute lymphoblastic leukemia. Furthermore, hand mirror morphologic features in any case of acute leukemia should alert the hematopathologist/hematologist to the possibility of mixed lineage.
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PMID:Hand mirror variant of adult acute lymphoblastic leukemia. Evidence for a mixed leukemia. 128 57

Forty patients with Ph-positive blastic phase (BP) (28 patients) or chronic phase (CP)-CML (3 patients) and relapsed adult acute lymphoblastic leukemia (ALL) (9 patients) with cytogenetical translocations [t(8;14):2 patients; t(4;8):2 patients; t(4;11):3 patients; t(9;22):2 patients], received an intensive conventional chemotherapy. During early recovery from marrow aplasia, when WBC reached 0.3-1.5 x 10--9/L, peripheral blood stem cells (BSC) were collected by 4-8 leukapheresis consecutively. BSC collected from the 2/3 patients with CP-CML resulted Ph-negative and PCR negative. In 8 out of 26 BP-CML patients, BSC resulted Ph-negative and in two cases PCR negative. Of the nine ALL patients, 6 patients lost the cytogenetic translocations, one patient died during aplasia, two patients did not have cytogenetic modifications and died in few weeks of leukemia and one patient out of six responding patients relapsed before transplant. After complete recovery, 15 patients (BP-CML:8 patients; CP-CML:2 patients; ALL:5 patients) were subsequently given high-dose therapy (VP-16 +/- Cy+TBI in single dose) followed by reinfusion of "normal" BSC. Both the patients in CP-CML and 5/5 patients with ALL maintain clinical and cytogenetic remission; all the patients transplanted in BP-CML relapsed 5-18 months post-transplant. It is concluded that intensive conventional chemotherapy employed in CML and ALL can lead to a precocious overshoot of cytogenetically normal BSC.
Leukemia 1992 Nov
PMID:Intensive conventional chemotherapy can lead to a precocious overshoot of cytogenetically normal blood stem cells (BSC) in chronic myeloid leukemia and acute lymphoblastic leukemia. 135 2

The epipodophyllotoxins, etoposide and teniposide, have been used in leukemias and malignant lymphomas for the past 15 years. Although etoposide has acquired a place in many first-line protocols for lymphomas and, more recently, for leukemias, the role of teniposide has remained limited. Teniposide is a more potent inhibitor of topoisomerase II than etoposide, and has a less toxic effect on hematopoietic progenitor cells. Both drugs have been regarded as equitoxic and cross-resistant. The role of teniposide in front-line treatment of leukemias has only been established in childhood acute lymphoblastic leukemia (ALL). Some promising results have been obtained in small numbers of patients with refractory adult ALL and acute monoblastic leukemia. However, the remission rates and remission duration were not significantly different from those of other combination regimens. Data on teniposide in untreated acute nonlymphoblastic leukemia are very scarce. In non-Hodgkin's lymphoma, the antineoplastic activity of teniposide has been demonstrated in studies by the European Organization for Research and Treatment of Cancer and in two large studies conducted by the Australian and New Zealand Lymphoma Co-operative Chemotherapy Study Group. In these studies, teniposide had comparable but not significantly better activity than vincristine. The dose-dependent antineoplastic activity of teniposide has led to its use in several conditioning regimens in bone marrow transplantation for leukemias and lymphomas. The limited clinical data currently available on teniposide seem to warrant further clinical trials with this agent in leukemias and lymphomas.
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PMID:Teniposide in lymphomas and leukemias. 141 40

The Philadelphia (Ph1) chromosome, or its molecular counterpart, the BCR-ABL fusion gene, is a rare but important prognostic indicator in childhood acute lymphoblastic leukemia (ALL), but its impact on adult ALL has not been well ascertained. A prospective study of the BCR-ABL fusion gene was begun on patients entered on clinical trials conducted by the Cancer and Leukemia Group B (CALGB). All patients received intensive, multiagent chemotherapy that included daunorubicin. Over 2 years, 56 patients were studied for molecular evidence of a BCR-ABL gene using Southern blot and pulsed-field gel hybridization analysis. Results were compared with cytogenetic detection of a Ph1 chromosome, and clinical features were compared for the BCR-ABL-positive and -negative groups. Molecular methods detected the BCR-ABL gene in 30% of cases compared with cytogenetic detection of the Ph1 chromosome in only 23%. The majority of cases (76%) showed the p190 gene subtype similar to pediatric ALL; the BCR-ABL-positive cases displayed a more homogeneous immunophenotype than the BCR-ABL-negative cases and were predominantly CALLA positive (86%) and B-cell surface antigen positive (82%). The rate of achieving complete remission was similar in the BCR-ABL-positive and -negative groups (71% and 77%, respectively, P = .72). There were more early relapses in the BCR-ABL-positive group, resulting in a shorter remission duration that was especially marked in the CALLA-positive and B-cell antigen-positive populations. These preliminary data suggest that the impact of the BCR-ABL gene on clinical outcome in ALL may be on maintenance of complete remission (CR) rather than achievement of CR when aggressive, multiagent chemotherapy is used. This study identifies the BCR-ABL gene as an important factor in adult ALL and demonstrates the utility of molecular methods for its accurate diagnosis.
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PMID:Clinical significance of the BCR-ABL fusion gene in adult acute lymphoblastic leukemia: a Cancer and Leukemia Group B Study (8762). 146 14

Acute lymphocytic leukaemia (ALL) has a bimodal age incidence. It constitutes the majority of leukaemias diagnosed in childhood but less than 5% of adult leukaemia. Distinction between lymphocytic and myeloid forms of acute leukaemia in routine statistics has only been possible since 1968. There is no adequate study on the aetiology of acute lymphocytic leukaemia in adults. Apart from ionizing radiation and certain genetic conditions, risk factors for ALL are poorly understood. While Greaves' biological hypothesis offers some insight into childhood ALL, the causes of adult ALL are obscure. An epidemiological study of adult ALL is proposed, with particular emphasis on environmental risk factors and recent biological markers of ALL, in order to advance understanding of this leukaemia.
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PMID:[Epidemiology of acute lymphoid leukemia]. 148 Aug 9

The Philadelphia chromosome (Ph1) was the first genetic change to be associated consistently with leukemia, and it is one of the best understood on the molecular level. Because of this, it is an excellent model to investigate the application of molecular techniques to the clinical setting. These techniques are reviewed as are their clinical use in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), and transplantation. The Ph1 is caused by the fusion of two genes on chromosomes 9 and 22, resulting in the BCR-ABL fusion gene. This new gene is believed to be the cause of these Ph1-positive leukemias. The ability to detect the BCR-ABL fusion gene evolved from cytogenetic detection to Southern blot analysis, and now includes sophisticated techniques such as polymerase chain reaction (PCR) methods and pulsed-field gels. Diagnosis of the BCR-ABL fusion gene by Southern blot detection of bcr genetic rearrangements is the prototype of molecular cancer diagnosis. The sensitivity and clinical uses of this test are reviewed, especially its application to monitoring the response to treatment. PCR methods enable the researcher to detect 1 CML cell in a population of 10(5) cells. Clinical experience with PCR, especially in transplantation medicine, is providing a better understanding of the meaning of the terms "remission" and "cure." Newer techniques using fluorescent in situ hybridization have considerable potential for BCR-ABL detection, but no clinical experience has been gained with these techniques currently. The diagnosis of the BCR-ABL fusion gene in ALL has important clinical implications because it is the most common molecular genetic change in adult ALL and is associated with short remissions and poor outcome in all age groups. Diagnosis of the BCR-ABL fusion in ALL is difficult because the molecular findings are more heterogeneous than they are in CML. The methods available and their accuracy and sensitivity are compared. A review of their clinical impact is included.
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PMID:The role of molecular techniques in the clinical management of leukemia. Lessons from the Philadelphia chromosome. 151 23

In January 1987 we started a multicenter study in order to evaluate in adult ALL patients the results of an intensive chemotherapy effected early after CR, and to compare the efficacy of allogeneic BMT vs autologous BMT vs prolonged intensive chemotherapy in the attempt to eradicate minimal residual leukemia. To September 1990 ninety-six patients entered this study; of the 87 evaluable for induction 25 were at low risk and 62 at high risk; 67 (77%) achieved CR by an induction chemotherapy including vincristine, adriamycin, cyclophosphamide, dexamethasone. Fifty-six out of 67 remitters were enrolled for the early intensification, which consisted of HDAra-C+amsacrine (or IDAra-C+mitoxantrone) followed by vincristine+adriamycin+cyclophosphamide and etoposide+Ara-C. During the early intensification an unexpectedly high number of relapses (10/56) was observed, showing that very intensive treatment with myelosuppressive agents is not useful at this point of the post-remission therapy. One patient suffered toxic death. Out of 45 patients who completed the early intensification 16 had a related well-matched donor and were selected for allogeneic BMT (performed in 11); of the remaining 29 patients, 14 were randomized for autologous BMT (performed in 9) and 15 for a second intensification. The overall DFS at 3 years is 35%. The high number of early relapses makes it difficult to draw conclusions from the comparison of the three eradication modalities. The best results, although without statistical significance, were obtained after allogeneic BMT; in high-risk patients this procedure should be effected as soon as possible after attainment of CR. Autologous BMT and prolonged intensive chemotherapy gave results similar to each other; both were sometimes followed by delayed relapses.
Leukemia 1992
PMID:Early intensification followed by allo-BMT or auto-BMT or a second intensification in adult ALL: a randomized multicenter study. 157 35

The Philadelphia (Ph) translocation is the most common cytogenetic abnormality in adult acute lymphoblastic leukemia (ALL) and is associated with an adverse prognosis. Using polymerase chain reaction (PCR) technology we recently observed a remarkably high incidence (55%) of BCR-ABL rearrangements in adult common ALL patients. In the present study we asked whether a subset of Ph-negative cALL, similarly to Ph-negative chronic myelocytic leukemia (CML) patients, exhibit BCR-ABL transcripts. PCR analysis of 58 adult Ph-negative cALL patients, including 47 cases with a normal karyotype revealed no evidence of chimeric BCR-ABL genes. We conclude that Ph-negative BCR/ABL-positive ALL is very rare entity if existing at all.
Leukemia 1992 May
PMID:Polymerase chain reaction analysis of BCR-ABL sequences in adult Philadelphia chromosome-negative acute lymphoblastic leukemia patients. 159 11

The expression of myeloid surface markers was investigated in 41 cases of untreated adult acute lymphoblastic leukemia (ALL). Nineteen cases (46%) reacted with at least one myeloid monoclonal antibody (CD15 in 16 cases, CD13 in 10 cases, CD14 in five cases, and CD33 in four cases). Double-staining confirmed the coexpression of myeloid and lymphoid markers. In addition, 35 samples were tested for CD34 expression. Fourteen of the 17 myeloid-positive cases tested were positive for CD34 vs. eight of 18 negative cases (p less than 0.05). A t(9;22) translocation was found in eight cases, and a t(4;11) translocation in two cases, all expressing CD34 and myeloid antigens. These findings confirm the high frequency of myeloid markers on the surface of adult ALL blasts, and suggest that these leukemias may originate in a poorly differentiated precursor cell with mixed differentiation capacities.
Leukemia 1990 Sep
PMID:Myeloid surface antigen expression in adult acute lymphoblastic leukemia. 169 40


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