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

Immune mechanisms superimposed to the myeloablative conditioning regimens exert an additional powerful effect in eradicating leukemia and in achieving immunological control of minimal residual disease. The impact of GVHD-independent GVL has been evaluated to be absent, or near absent, in ALL, about 30% in AML and about 40% in CML. While until little time ago most of the evidence in favor of an immune antileukemia mechanism exerted by allo BMT in CML was indirect, based on the lack of GVL, there is now solid evidence of a positive type, based on the antileukemia effect of donor lymphocyte infusions in patients having relapsed after transplant. There are three lines of indirect clinical evidence for GVL in CML: they include the classical linkage between GVHD and reduced relapse rate, increased relapse rate after identical twin allografts, and increased relapse risk after effective GVHD prophylaxis, with T lymphocyte depletion in the foreground. The eradicating effects of donor lymphocyte infusions in relapsed patients are the ultimate demonstration that allogeneic immune competent cells are capable of recognizing and destroying the Ph-positive clone. However the frequency of irreversible aplasia indicates that donor lymphocytes act in the same way on residual host hematopoiesis, so that a second graft, without repeat conditioning, should be programmed for such cases.
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PMID:The graft versus leukemia (GVL) effect after allogeneic bone marrow transplantation for chronic myelogenous leukemia (CML). 825

Bone marrow transplantations have a definite role in treatment of leukemias and lymphomas. In acute myeloid leukemia and CML an allogeneic transplant using an HLA identical donor certainly provides a far superior survival than chemotherapy. Patients with Ph' chromosome need to be transplanted in first remission if a suitable donor is available. In recurrent lymphomas the best results are achieved if the patient is transplanted in complete remission. Transplantation done using minor mismatched family donors or unrelated donors are still considered experimental and more data is needed before final recommendations can be made. Availability of supportive services is an absolute must prior to establishing transplant program. Selection of patients for transplantation should be done after carefully reviewing the indications and discussing with the family the emotional, financial and physical burden of the procedure. For selected indications in leukemias and lymphomas, BMT may be the only viable treatment option and therefore must be considered.
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PMID:Bone marrow transplantation. 826 90

Over the past decade infections from food-borne Listeria monocytogenes have become an important cause of septicaemia and meningitis and immunocompromised patients are at particular risk. We report three cases of Listeria meningitis occurring post-BMT. The patients were aged 53, 51 and 56 years and presented 4, 7 and 90 months post-transplant, respectively. The first patient had undergone allogeneic BMT for myelodysplasia and the other two patients had ABMT for AML in second and first CR, respectively. All the patients presented with classical features of meningitis and L. monocytogenes was cultured from cerebrospinal fluid. All made a full recovery with appropriate antibiotic therapy. We have not seen cases of meningitis due to other organisms in our transplant programme and the cases represent a risk of one episode per 59 surviving patient years. None of the patients was receiving prophylactic post-BMT antibiotics and the episodes may strengthen the case for using prophylactic penicillin. Recent epidemics of septicaemia and meningitis caused by L. monocytogenes-contaminated milk and cheese suggest that these patients should be informed about potential sources of infection.
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PMID:Listeria meningitis after bone marrow transplantation. 829 66

Current progressive chemotherapy and transplantation induce not only remission but complete cure. By this reason, the detecting system for MRD must be established in complete remission phase. In this study, we showed the detecting for MRD by molecular biology techniques in the patients with non-Hodgkin's lymphoma, CML, B-ALL and AML. 1) Malignant cells could be detected in peripheral blood or bone marrow cells by Southern blot analysis in 15 of 30 patients with non-Hodgkin's lymphoma. 2) In CML patients, BCR/ABL fusion gene was positive by RT-PCR for 6 months after BMT, 4 patients became undetectable for 7 months after BMT. 3) Rearrangement of Ig H has been disappeared in 12 months after achieved complete remission the patients with B-ALL. In conclusion, the detection for MRD remain an important goal for therapy including chemotherapy and bone marrow transplantation in hematopoetic malignancy.
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PMID:[Detection of residual malignant cells in patients with hematopoietic malignancy]. 831 24

IL-2 has been used after autologous BMT (ABMT) with the aim of inducing graft versus leukemia (GVL) effect. Our studies in mice have shown that IL-2 therapy induces GVL effect when employed after BMT with bone marrow (BM) that has been activated with IL-2 in vitro (ABM). The present study was carried out to define the time of optimal GVL effect after BMT so that the immunomodulatory approaches could be concentrated at the time of maximum GVL effect. Our data show that GVL effect was induced if IL-2 was instituted immediately after BMT with ABM in mice with acute myeloid leukemia; institution of IL-2 1 week after BMT with ABM did not induce GVL effect. IL-2 therapy instituted immediately or 1 week after BMT with fresh bone marrow (FBM) did not induce any GVL effect. A significant increase in the NK activity was noticed whether IL-2 was instituted immediately or 1 week after BMT, either with FBM or with ABM. To evaluate the ability of IL-2 in the eradication of residual disease from the autograft and the host, BM with variable infiltration with leukemia was activated with IL-2 and used for BMT in leukemic mice. The GVL effect of BM with minimal leukemic infiltration (absence of morphologically demonstrable disease) was comparable to the GVL effect of normal BM. These findings suggest that: (a) maximum GVL effect after BMT with ABM is concentrated in the early post-transplant period possibly because of minimal residual disease during this time; (b) an increase in the NK activity induced by IL-2 therapy may not predict for an improved GVL effect; and (c) for optimum GVL effect, BM with minimal leukemic infiltration should be activated with IL-2 before BMT.
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PMID:Graft versus leukemia effect after transplantation with interleukin-2-activated bone marrow. Correlation with eradication of residual disease. 833 64

The very rapid development in the last few years of techniques based on use of the polymerase chain reaction (PCR) for characterizing molecular lesions in leukaemia and lymphoma now offers the opportunity for monitoring residual disease at a sensitivity of one malignant cell in 10(5) or 10(6) normal cells. Maximal specificity is presumably achieved when the DNA sequences amplified are truly leukaemia-specific, such as BCR/ABL in chronic myelogenous leukemia, RARA PML/RARA in t(15;17) acute myelogenous leukemia, DEK/CAN in t(6;9) AML, PBX1/E2A in t(1;19) acute lymphoblastic leukemia (ALL), or TAL-1 deletions in other T-ALLs. Comparable sensitivity may be achieved by using immunoglobulin heavy chain (IGH) and T-cell receptor (TCR) gene rearrangements if a clonospecific probe can be generated. However, the presence of similar sequences in IgH genes from normal B lymphocytes may decrease the specificity. For clinical purposes the crucial issues are the following. Can PCR techniques be used for confirmation of diagnosis and evaluation of extent of disease? Can PCR data obtained in remission provide information about the probability of cure or of relapse? Can techniques be developed to quantitate the PCR product and thereby increase its predictive value? These and other issues were addressed at the 4th Workshop of the Molecular Biology/BMT Study Group that took place in Bristol UK on 9-10 May 1992.
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PMID:Molecular evidence of minimal residual disease after treatment for leukaemia and lymphoma: an updated meeting report and review. 835 Jun 33

One hundred and fifty children with AML in first remission were treated with allogeneic BMT in two sequential studies of the Childrens Cancer Group. The absence of differences in baseline variables justified comparison between the two studies. In the initial study (CCG-251), patients received GVDH prophylaxis with MTX alone (17 doses over 102 days). In an attempt to diminish the morbidity and mortality of acute GVDH, a second study (CCG-213) employed stronger GVHD prophylaxis with 6 months of CYA and short-course MTX (four doses over 11 days). Outcome was compared between these two non-randomized populations of children with AML transplanted in first remission. Augmented GVHD prophylaxis substantially diminished treatment-related mortality from 31% to 11% (p = 0.0033), but this effect was counterbalanced by an increase in the relapse risk from 22% to 35% (p = 0.29). Event-free survival at 2 years was 54% on CCG-251 and 59% on CCG-213 (p = 0.21). We observed a marginal diminution of relapse risk among patients with chronic GVHD compared with those without chronic GVHD (19% vs. 35%, respectively; p = 0.10). No anti-leukemic effect of acute GVHD was observed.
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PMID:Outcome of BMT during first complete remission of AML: a comparison of two sequential studies by the Children's Cancer Group. 837 37

The role of mixed hematopoietic chimerism in engraftment and relapse after allogeneic BMT remains unclear. To better evaluate post-transplant chimerism we used polymerase chain reaction (PCR) in vitro amplification of four single locus simple repetitive DNA sequences, all of which vary extensively in their repeat number among different individuals: variable number of tandem repeats D1S80, APOB and D17S5, and the tetranucleotide repeat F8VWF. We tested 13 cases of CML, four of multiple myeloma (MM), three of ANLL and one of B-CLL. In a sequential analysis protocol with the different loci, the donor could be distinguished from the recipient in 14 of 20 (70%) pairs with the first marker used (D1S80). When a donor of opposite sex was involved, karyotyping and Y chromosome-specific PCR were also used. With the use of the four markers, chimerism was identified in all the pairs. Mixed chimerism was present in 5 patients, and complete chimerism in 15. No patients relapsed. The application of PCR for documenting post-transplant chimerism has several advantages over Southern blotting: increased sensitivity, use of small amounts of sample, ease of preparation of DNA, elimination of restriction enzyme analysis and of radioisotopes, and speed.
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PMID:In vitro amplification of hypervariable DNA regions for the evaluation of chimerism after allogeneic BMT. 840 55

Forty-seven patients with poor-prognosis myeloid leukemias received induction therapy with high-dose cytosine arabinoside (HDara-C), 1.5-3.0g/m2 for 8-10 doses, and mitoxantrone (DHAD), 12-15 mg/m2 for 3 doses. Complete remissions were achieved in 21 [45%, 95% confidence interval (CI) 30.2-59.9%] of the patients, including 11 of 14 with acute myelogenous leukemia (AML) in first relapse (79%, 95% CI 49.2-95.3%), 4 of 8 with refractory anemia with excess blasts in transformation (RAEBiT) (50%, 95% CI 15.4-84.6%), and 4 of 6 (67%, 95% CI 22.3-95.7%) previously untreated elderly AML patients. Patients with secondary AML and advanced chronic myelogenous leukemia had a very low response rate. The incidence of reversible toxicity was low and only 3 treatment-related deaths occurred. After reinduction, 8 of 9 AML patients < or = 60 years of age were ultimately able to undergo intensive therapy and either autologous 4-hydroperoxycyclophosphamide-purged bone marrow (7 patients) or peripheral blood stem cell (1 patient) transplantation with satisfactory hematological recovery. We conclude that HDara-C and DHAD is an effective antileukemic regimen in selected AML and RAEBiT patients, and that its use may allow subsequent successful autologous BMT in appropriate patients.
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PMID:Chemotherapy with high-dose cytosine arabinoside and mitoxantrone for poor-prognosis myeloid leukemias. 840 19

Recommendations for the treatment of ANLL in general, and in pediatrics more specifically, are still conflicting. Overall, a child diagnosed with ANLL has a 35-50% of remaining alive long term, without disease. Induction chemotherapy with cytarabine and daunorubicin will achieve remission in about 80% of children with ANLL. So far, intensifying induction chemotherapy by adding more agents has not changed this result significantly. Major changes in induction chemotherapy may come from either new chemotherapeutic agents or biological agents that hasten bone marrow recovery after treatment. Such an approach might allow more dose-intensive drug administration without increased toxicity. Another question that is slowly being answered with the ongoing trials is the one concerning maintenance. So far, all the pediatric trials that have tried to shorten the maintenance therapy of this disease were able to do so without jeopardizing the final outcome. The final optimal minimal duration of therapy has yet to be established. The best therapy for a patient who has achieved a remission is still the most difficult question regarding the treatment of this disease. So far, allogeneic BMT has yielded the best results, with a disease-free interval varying between 55 and 65%. However, one-third of these patients have chronic GvHD and, therefore, a somewhat diminished quality of life. As preparative regimens and marrow purging protocols evolve, the results of autologous bone marrow transplantation seem to be improving, with disease-free intervals of 35-50% reported.
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PMID:Treatment of childhood acute nonlymphoblastic leukemia: a review. 840 23


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