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)

We herein report a rare case of Ph chromosome-negative acute T-lymphoblastic leukemia (T-ALL) with a classical BCR rearrangement seen in chronic myelogenous leukemia (CML). There were no clinical or morphologic features to suggest a previous chronic phase of CML. The importance of a full analysis of the BCR gene in the case of adult acute lymphoblastic leukemia (ALL), especially in T-ALL, are discussed.
Leukemia 1994 Mar
PMID:De novo Ph-negative acute T-lymphoblastic leukemia with BCR gene rearrangement. 809 40

In a retrospective multicentre study, we analyzed 184 consecutive patients who underwent bone marrow transplantation (BMT) from identical siblings for adult acute lymphoblastic leukemia in first complete remission between March 1980 and May 1989. The main causes of transplant-related mortality were GVHD and interstitial pneumonitis. Univariate and multivariate analyses identified the mode of total body irradiation (TBI) as the only independent predictive factor of transplant-related mortality. Ninety-one patients received single-dose TBI and 93 received fractionated-dose TBI as part of the conditioning regimen prior to BMT. Transplant-related mortality was more frequent in the single dose group (p = 0.017). The incidence of interstitial pneumonitis, acute and chronic GVHD and veno-occlusive disease of the liver was not statistically different between the two irradiation groups. However, fatal interstitial pneumonitis was significantly more frequent in the single dose irradiation group (p = 0.031). These results show that transplant-related mortality is closely associated with the mode of TBI administration. The increased relapse rate in the fractionated group explains why there was no difference between the two groups in terms of overall leukemia-free survival.
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PMID:Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia in first complete remission: factors predictive of transplant-related mortality and influence of total body irradiation modalities. 813 42

Adult Philadelphia-chromosome-positive acute lymphoblastic leukemia (Ph1-positive ALL) represents about 30% of all adult ALL, and is considered a poor prognosis disease, since complete remission (CR), which can be achieved in 50-70% of cases, is usually short in patients treated with conventional chemotherapy. Presently bone marrow transplantation, performed early in first CR is becoming the treatment of choice, as it has shown to be able to cure some cases. In a ten-year period, at our department, among 108 adult ALL patients, in which cytogenetics was successfully carried out at diagnosis, 24 (22%) resulted Ph1-positive. Molecular biology was performed in 13 out of these 24 patients: 10 patients showed a p210 rearrangement and three p190. All patients have been treated at induction with conventional drugs, with a CR rate of 96%. As post-remission therapy, the first 17 cases (group 1) followed a chemotherapeutic program, like the other adult ALL; while the remaining six patients (group 2) have been enrolled in a pilot study including early BM transplantation. In group 1, the median overall duration of first CR is 7 months; 50% of relapses were recorded within the first 6 months, although in this group five patients exhibited a first CR prolonged more than 30 months. In group 2, among the six patients, three were submitted to allogeneic bone marrow transplantation (BMT), and three to autologous bone marrow transplantation (ABMT). Overall median duration of first CR is 13 months. Three patients relapsed, three are in continuous CR for 11, 31 and 32 months.
Leukemia 1994 Apr
PMID:Adult Philadelphia-chromosome-positive acute lymphoblastic leukemia: experience of treatments during a ten-year period. 815 62

Philadelphia chromosome (Ph1) is detected in more than 95% of chronic myelogenous leukemia (CML) and approximately 20% of adult acute lymphocytic leukemia (ALL). In order to discriminate Ph1-positive ALL from Ph1-positive CML as a clinical entity, I studied on biological and genetic characteristics of Ph1-positive ALL cells. Two cases out of 11 Ph1-positive ALL showed hybrid leukemia phenotypes; in one hybrid case simultaneous proliferation of lymphoid and myeloid blast cells was observed and contained rearranged alleles of heavy chain genes, thus indicating that both blast cells might originate from a common precursor. Two Ph1-positive ALL cell lines (TOM-1 and ALL-MIK) were established from two patients and were investigated for their differentiation potential in vitro. Both cell lines showed the potency to differentiate into monocytic lineage cells, thus suggesting that these Ph1-positive ALL cells might reside at the stage of multipotent progenitor cell along hematopoietic cell differentiation. As to Ph1-chromosome, 4 out of 9 Ph1-positive ALL cases showed rearrangements within the classical sequence (M-bcr), similar to those in CML cases. Two out of 5 cases without rearrangement of M-bcr showed breakpoints in the first intron of the BCR gene. In the rest of 3 cases, BCR-ABL rearrangement was not detected by Southern analysis. However, a leukemic cell line established from one of these patients (TOM-1) were contained P190bcr-abl mRNA as analyzed through RT-PCR. Thus, breakpoints of the BCR gene in Ph1-positive ALL cases were heterogenous, in contrast to those of CML. Then, I investigated whether or not the activation of transforming genes other than BCR-ABL might be involved in pathogenesis of Ph1-positive ALL. Three out of 15 Ph1-negative ALL cases showed the mutations of RAS gene by the PCR. However, no activated oncogene was detected in Ph1-positive ALL cases by both DNA transfection assay and PCR.
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PMID:[The cellular and molecular-biological studies on Philadelphia chromosome-positive acute lymphocytic leukemia]. 831 33

We performed cytogenetic and molecular analysis of the BCR-ABL rearrangement by polymerase chain reaction (PCR) in 39 consecutive cases of adult acute lymphoblastic leukemia (ALL). Eleven patients had a Philadelphia (Ph) chromosome. Thirteen patients had a BCR-ABL rearrangement, involving minor breakpoint cluster region (m-bcr, situated in intron 1 of the BCR gene) in 11 cases, and major breakpoint cluster region (M-bcr, 'specific' of chronic myeloid leukemia) in the remaining two cases. All of the 12 BCR-ABL cases studied immunologically were of early B, CALLA-positive immunophenotype. The 13 BCR-ABL positive cases included the 11 Ph-positive cases, and two patients with normal karyotype at diagnosis. In the two Ph-negative BCR-positive cases, seven (patient 1) and 18 (patient 2) mitoses had been examined at diagnosis. In patient 1, Ph negativity at diagnosis could certainly be explained by the small number of mitoses analyzed, as a Ph chromosome was found at relapse. This was less probable in patient 2, who raised the issue of whether authentic Ph-negative BCR-ABL-positive ALL exists (as in the chronic myeloid leukemia model) or not. Whatever the explanation, our results suggest that molecular detection of BCR-ABL should be more widely used in B-lineage ALL.
Leukemia 1993 Jul
PMID:Philadelphia negative, BCR-ABL positive adult acute lymphoblastic leukemia (ALL) in 2 of 39 patients with combined cytogenetic and molecular analysis. 832 Oct 20

A total of 55 previously untreated adults with acute lymphocytic leukemia (ALL), median age 38 years (range 15-73 years), were treated with MOAD (methotrexate, vincristine, L-asparaginase, and dexamethasone). This regimen includes five phases--induction, consolidation, cytoreduction, maintenance, and central nervous system (CNS) prophylaxis with parenteral high-dose methotrexate. Of the 55 evaluable patients, 42 achieved complete remission 76%), with a median CR duration of 12+ months (range 0.5-195+ months). The median survival in remission is 22+ months (range 1-198+ months), with 33% of remitters continuing in long-term remissions (> 5 years). Two out of four patients who developed CNS leukemia did so without marrow relapse, were successfully treated for that complication, and continue in total complete remission at 8+ and 16+ years. Another patient with extramedullary relapse (breast) was treated with radiation to that site and remains in total CR at 16+ years. Expected toxicities included myelosuppression during the induction phase of treatment, with 65% of patients requiring intravenous antibiotics. Mucositis was the next most frequent toxicity and required dose-reduction in seven patients. Minimal toxicity was seen during the post-remission phases of treatment. L-Asparaginase toxicity was more prominent during intravenous administration (24 patients) than when the intramuscular route of administration (30 patients) was used. The remission rate and long-term survivorship achieved with this regimen, without the use of an anthracycline, is comparable to that of other regimens for adult ALL. MOAD was well-tolerated by young and old adults with ALL. Aseptic necrosis of bone, successfully treated in each instance, occurred in four long-term disease-free survivors. The effect of this complication and its treatment on quality of life has been negligible.
Leukemia 1993 Aug
PMID:Long-term follow-up of treatment and potential cure of adult acute lymphocytic leukemia with MOAD: a non-anthracycline containing regimen. 835 Jun 24

Most approaches to demonstrating immunoglobulin heavy chain gene rearrangements are relatively laborious for routine follow-up of acute lymphoblastic leukemia (ALL). Here the use of a simple polymerase chain reaction (PCR) approach to monitor ALL disease activity has been validated. In the dilution experiments the method revealed a detection sensitivity 0.5% clonal cells in a background of 99.5% normal cells. To validate the immunoglobulin heavy chain gene PCH (IgH-PCR) in practice, we monitored the disease activity of 26 adult ALL patients showing a B-cell lineage component in immunophenotyping at the diagnosis of the disease. In 18 of those 26 patients, an IgH-PCR product could be demonstrated in the samples taken either at diagnosis or in relapse. These 18 patients were followed with a total of 158 consecutive samples by IgH-PCR. The mean follow-up time for the IgH-PCR-positive patients was 13.6 months (range 4 to 26 months). Eleven of these patients underwent altogether 18 relapses. In nine patients (81.8%), ten relapses (55.6%) could be predicted using the IgH-PCR approach. The mean time of IgH-PCR clonality detection, preceding a cytologic relapse, was 9.1 weeks (range 1.0 to 30.7 weeks). It seems that in three patients the predictive value of the IgH-PCR was remarkable, showing a repetitive positivity in spite of a cytologic remission, even one year prior to the relapse. We find that IgH-PCR provides a straightforward additional tool for monitoring B-cell lineage ALL. Due to the straightforward technical performance the method has low running costs and it is thus suitable for a routine service laboratory. Even if a negative finding in IgH-PCR does not rule out a forthcoming relapse in the patient, a positive finding is a definitive warning signal. All of the patients that showed an IgH-PCR clonality in the follow-up samples relapsed sooner or later.
Leukemia 1993 Sep
PMID:Monitoring of adult B-cell lineage acute lymphoblastic leukemia: validation of a simple method for detecting immunoglobulin heavy chain gene clonality. 837 95

Age has long been recognized as an important factor in predicting response to treatment for acute lymphocytic leukemia (ALL). Specifically, the results of treatment of childhood ALL have been far superior to the treatment of what appears to be the same disease in adults. However, from an analysis of the clinical and biological prognostic factors known to be predictive in childhood ALL, there is a striking difference in their distribution in adults with ALL. It appears that there is a special form of ALL seen in children of some populations with a peak incidence of three to seven years. This treatment responsive leukemia appears to be different clinically, biologically, and epidemiologically from adult ALL.
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PMID:Adult and childhood acute lymphocytic leukemia: are they different diseases? 841 87

Modern chemotherapy can cure more than 70 per cent of children with standard risk acute lymphoblastic leukaemia (ALL). Encouraging results are also reported in children with high risk ALL receiving intensive chemotherapy. Results in adults with ALL are less satisfactory, the long term survival is less than 35 per cent. Further dose intensification as possible in the setting of bone marrow transplantation (BMT) has increased the cure rate to 50 per cent in adult ALL. Allogeneic BMT has, however, besides the enhanced antileukaemia activity related to high dose therapy, additional antileukaemia effect related to immune mechanisms. Immune effects may be separated into three elements viz., an antileukaemia effect of graft vs host disease (GvHD), a separate antileukaemia effect of T cells and possibly a specific graft vs leukemia effect (GvL). These immune mediated antileukaemic effects offer a new potential therapeutic modality. For instance, the T cell antileukaemic effect of transplant could be achieved by transfusing radiated T cells or administering lymphokines. Alternatively autologous bone marrow could be manipulated in vitro prior to reinfusion. Manipulation might include activation of natural killer (NK) cells or lymphokine activated killer (LAK) activity. Another newer approach to treat ALL is the use of hemopoietic growth factors. Use of these factors prior to chemotherapy may increase the proportion of proliferating leukaemic stem cells. This would increase the efficacy of many drugs since most are active against proliferating cells. Hemopoietic regulatory factors could also be used to directly inhibit leukemic cell growth or to promote differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Emerging concepts in the management of acute lymphoblastic leukaemia. 849 83

Treatment of adult acute lymphoblastic leukemia (ALL) consists of two parts: induction of complete remission (CR) using a triple chemotherapy with prednisone, vincristine and one anthracycline associated in the majority of protocols with either asparaginase or cyclophosphamide or cytosine arabinoside. A CR rate of 75% can be obtained. The second part is the treatment during remission with 3 phases: early intensification or consolidation by chemotherapy, prevention of leukemia in the central nervous system and maintenance. Alternative strategies are allogeneic or autologous transplantation after myeloablative therapy. Overall long term survival is between 25 and 40%, for less than in children. Future direction of treatment are: better definition of heterogeneous forms of the disease with standard or high risk of relapse allowing adjustment of the treatment. Karyotype analysis, and molecular biology are mandatory to define high risk ALL such as Ph1 + ALL and also to know the level of residual disease during remission. For treatment strategy efficacy of transplantation must be improved (less toxicity for allogeneic BMT, less relapse for autologous BMT and more efficient chemotherapy regimen).
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PMID:[Treatment of acute lymphoid leukemia in adults]. 859 92


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