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

Relapse after marrow transplantation occurs despite total body irradiation and high doses of chemotherapy used to prepare the recipient. Recurrence rate is particularly high after autologous transplantation. In order to eliminate minimal residual disease persistent after marrow grafting, immunotherapy is currently being explored as a treatment modality that is non-cross-reactive with radiation and chemotherapy. This review describes first clinical results on the use of interferons and interleukin-2 in marrow transplant recipients as well as attempts to induce graft-versus-leukemia effects.
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PMID:Trying to overcome residual disease after bone marrow transplantation for hematologic malignancies. 128 96

Differences in tumor cell burden among acute lymphoblastic leukemia (ALL) patients are largely unexplored, because methods of detecting residual malignant cells have not been sufficiently sensitive. Using the polymerase chain reaction (PCR) amplification of rearranged T-cell receptor delta(TCR delta)-chain junctional sequences for the preparation of clonospecific probes, we performed a retrospective PCR study of remission bone marrow (BM) samples in seven pediatric patients with ALL who subsequently relapsed (the largest series studied so far) and in 10 patients who were in longterm (greater than 39 to greater than 72 months) remission. Following two rounds of PCR primed by nested amplimers, 1 x 10(-4) to 1 x 10(-6) cells could be identified in 16 out of 17 cases. PCR analysis of 39 BM and peripheral blood samples obtained from ALL patients considered to be in complete remission according to morphological criteria revealed the following results. In BM remission specimens of all 10 patients in continuous complete remission for a long time (median 55 months), no residual leukemic cells could be identified in the latest remission sample available for PCR analysis. In three patients the persistence of residual leukemic cells, or the continuous increase of residual blasts to the point of clinical manifestation, were indicative of impending relapse. In three patients PCR analysis failed to identify residual leukemic cells in BM samples obtained 2, 6 and 16 months respectively before clinical relapse. Differences in the duration of minimal residual disease were not associated with distinct clinical-hematological features. In one patient a different pattern of V delta 2 recombination occurred in leukemic cells from diagnosis to relapse, thus preventing the further monitoring of the patient by the initial clonospecific probe.
Leukemia 1992 Apr
PMID:Minimal residual disease in childhood acute lymphoblastic leukemia: analysis of patients in continuous complete remission or with consecutive relapse. 131 78

Soluble Interleukin-2 Receptor (sIl-2R) and Tumor Necrosis Factor-alpha (TNF-alpha) have been found significantly increased in serum samples of patients with HCL at diagnosis and a strict correlation with leukemic burden has been reported. Furthermore, following therapy, serological monitoring of these cytokines may be considered a useful tool for controlling therapeutic efficacy and for detection of minimal residual disease. Eighteen HCL patients, treated with 2-Chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg daily for 7 days, entered the study all of them showing increased levels of sIL-2R and TNF-alpha prior to therapy. After therapy, serum levels were reassessed and a remarkable decrease was recorded in all cases. In particular, after 1 month by the end of treatment sIL-2R and TNF-alpha decreased from 3,377 +/- 2,303 to 149 +/- 96 pM/ml (p = 0.00003) and from 38 +/- 41 to 18 +/- 18 pg/ml (p = 0.015) respectively. The only 3 patients who did not normalize sIL-2R and TNF-alpha levels showed also an evident persistence of the disease in the marrow. In conclusion, 2-CdA leads to a rapid normalization of the increased levels of sIL-2R and TNF-alpha in the majority of HCL patients. Furthermore, monitoring of these cytokines represents a useful tool for detecting minimal residual disease.
Leukemia 1992 Nov
PMID:Biological markers and minimal residual disease in hairy cell leukemia. 135 4

Polymerase chain reaction (PCR) is a highly sensitive technique to detect minimal residual disease (MRD) of hematological malignancy by amplifying tumor specific nucleotide sequences. When breakpoint is located over large lesions of genomic DNA, like t(9;22) leukemia, PCR amplifying cDNA of chimeric mRNA, called reverse transcriptase PCR (RT-PCR), can be utilized. We applied this method for the detection of MRD in patients with t(1; 19) acute lymphoblastic leukemia. RT-PCR detection of MRD in patients with leukemia might be useful for estimating of the depth of remission, for disclosing preclinical relapse, and for evaluating the efficacy of in vitro purging in autologous bone marrow transplantation.
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PMID:[Detection of minimal residual disease using reverse transcriptase polymerase chain reaction technique]. 138 48

Immunological parameters were evaluated in patients treated with cytokine-mediated immunotherapy (CMI) consisting of low doses of recombinant human interferon alpha 2a (rIFN alpha) and recombinant human interleukin-2 (rIL-2) administered either concomitantly or sequentially by subcutaneous self-injections in an outpatient setting. Twenty-six patients with hematological malignancies and 2 metastatic melanoma patients in a progressive stage were enrolled in this clinical trial. Of the 26 patients, 24 were at a stage of minimal residual disease, including 14 patients who had received autologous bone marrow transplantation (ABMT) 2-5 months previously, 7 chronic myelogenous leukemia (CML) and 3 acute myeloid leukemia (AML) patients. Two patients (1 CML and 1 mult. myeloma) were treated at a stage of progressive disease. Non-MHC-restricted cytotoxicity directed against natural-killer(NK)-resistant (Daudi) and NK-sensitive (K562) target cells was assessed before, during and after CMI, either in fresh peripheral blood samples (spontaneous activity) or after in vitro rIL-2 activation (induced activity). Spontaneous killing activity was low prior to treatment, but increased upon termination of treatment in 10/15 evaluated cycels. rIL-2-activated cytotoxicity in vitro was markedly elevated in 8/12 and 6/8 patients after one and two cycles, respectively, of sequential treatment, as well as in 3/8 CML and 5/6 patients after one and two cycles, respectively, of concomitant treatment. Activation of the T cell mitogenic response was demonstrated in 6/9 patients after concomitant CMI, while no such effect was observed throughout a sequential treatment in lymphoma and leukemia patients after ABMT. Although a direct correlation between immune stimulation and the in vivo antitumor response cannot yet be determined, our clinical observations support a beneficial therapeutic effect in a substantial number of patients. These results indicated that the ambulatory CMI protocol of rIL-2 and rIFN alpha could stimulate the host defense immune system and may be helpful in mediating the in vivo antitumor response in patients with minimal residual disease.
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PMID:Immunological evaluation of patients with hematological malignancies receiving ambulatory cytokine-mediated immunotherapy with recombinant human interferon-alpha 2a and interleukin-2. 139 43

Autologous bone marrow transplantation (ABMT) is a therapeutic approach that permits the administration of high-dose chemoradiotherapy followed by the infusion of the patient's own marrow, previously collected during remission and cryopreserved. In recent years, ABMT has been increasingly used as a treatment for acute leukemias. The mechanisms underlying leukemic relapse represent the most exciting and controversial aspects of ABMT. At least three factors may be responsible for leukemic relapse in patients receiving ABMT: (a) minimal residual disease; (b) leukemic cells reinfused with the graft; and (c) the lack of a graft-versus-leukemia effect. Techniques for pharmacological marrow decontamination, clinical results obtained with ABMT, and new perspectives opened by growth factors and cytokines are reviewed.
Leukemia 1992 Nov
PMID:Autologous bone marrow transplantation in acute myelogenous leukemia. 143 91

The genetic sequence of the third complementarity determining region (CDR III) of the immunoglobulin heavy chain (IgH) gene was analysed in 55 rearranged alleles from 36 children presenting with B-lineage acute lymphoblastic leukaemia (ALL). This confirmed the unique nature of these rearrangements. However, contrary to the hypothesis that the CDR III is produced by a random process of rearrangement, biased utilisation of diversity (D) segments and of joining (J) regions 4, 5 and 6 was demonstrated. Moreover, preferred sequence boundaries were seen in J regions 1 to 5 and were suggested at the 3'-end of certain D regions, notably D21/9 and DK1. Similar patterns of rearrangement have been noted in normal B-lymphocyte clones. Together with relatively limited N nucleotide addition, these factors may restrict the potential sequence variability at the D-N-J junction. The occurrence of clonal progression by secondary gene rearrangements, such as V-V replacement, favours the use of this site when designing clone-specific oligonucleotide probes for use in monitoring minimal residual disease (MRD). In cases where biased features of D-J rearrangement are shared by both the leukaemic and normal B-lymphocyte clones this could reduce the sensitivity of these probes in detecting low levels of residual disease.
Leukemia 1992 Nov
PMID:Third complementarity determining region (CDR III) sequence analysis in childhood B-lineage acute lymphoblastic leukaemia: implications for the design of oligonucleotide probes for use in monitoring minimal residual disease. 143 6

Tremendous advances in our understanding of acute leukemia have been made through the development of new technologies and close collaboration between immunologists, molecular biologists, and clinical oncologists. These technological advances have included the development of monoclonal antibodies (MoAb) reactive with surface antigens on leukemic cells which can help confirm the lineage and diagnosis of acute leukemia. More importantly, MoAb in conjunction with morphology and cytochemical stains have led to the identification of FAB-MO and the more common recognition of FAB-M7. MoAbs have also helped define prognostic groups, e.g., T-cell leukemia, mature B-cell leukemia, and rare groups such as CD7+ AML. However, the greatest advances in our understanding of acute leukemia has occurred with the application of genetic techniques. Disregulation of genes responsible for normal growth and differentiation initiates the molecular events that lead to the transformation and proliferation of cells recognized clinically as leukemia. Non-random cytogenetic abnormalities apparently contribute to this gene disregulation and specific abnormalities are associated with clinically important subgroups. In acute lymphoblastic leukemia (ALL), the t(9;22), t(1;19), and t(4;11) appear to have a poor prognosis. In acute myeloblastic leukemia (AML), -7/7q-;-5/5q-, 11q23 abnormalities have poor outcomes while t(15;17) and in some series t(9;11), t(8;21), and inv(16) have a good response to therapy. Molecular studies of somatic cell (immunoglobulin and T-cell receptor) gene rearrangements have assisted in the diagnosis and classification of ALL. The application of the polymerase chain reaction technique to specific gene rearrangements has provided a useful approach to minimal residual disease. Specific gene activation (N-myc, evi-1) or fusion genes such as the alpha retinoic acid receptor (alpha RAR) and pml have been identified as the specific cause of some cases of leukemia. The cloning of specific chromosomal breakpoints identified in leukemia (as has been done for CML) will result in specific probes which can be used to make the diagnosis rapidly at the molecular level. Because of the tremendous number of recent developments, this paper will focus only on major developments that will soon have a clinical impact.
Leukemia 1992 Nov
PMID:Pathology and immunology of acute leukemia. 143 16

Recent investigations in animal models of human lymphoid and myeloid leukemia suggest that induction of immune-mediated antitumor effects is feasible at the stage of minimal residual disease (MRD) using allogeneic immunocompetent lymphocytes following initial reconstitution with T cell depletion and/or activation of reconstituting syngeneic or allogeneic immune cells by recombinant interleukin-2 (rIL2). Pilot clinical trials in patients with leukemias and lymphomas at high risk to relapse following autologous bone marrow transplantation (BMT) suggest that beneficial antitumor effects may be achieved at the stage of MRD by home immunotherapy as soon as hematopoietic reconstitution occurs using rIL2 (Cetus) and alpha interferon (Roferon A) (Hoffmann LaRoche). Although results obtained from our open trial seem encouraging, prospective randomized trials and longer observation periods are needed in order to confirm immune-mediated antitumor effects in conjunction with autologous BMT in patients with malignant hematological disorders at high risk to relapse. Likewise, it seems that amplification of anti-leukemia effects following allogeneic BMT is feasible by post-transplant infusion of donor's peripheral blood lymphocytes for prevention and/or treatment of relapse.
Leukemia 1992 Nov
PMID:Immunotherapy of minimal residual disease in conjunction with autologous and allogeneic bone marrow transplantation (BMT). 143 23

Based on pre-clinical findings and on more recent preliminary in vivo data it has been suggested that immunotherapy with Interleukin 2 (IL2) may be employed in the treatment of acute leukemia patients. Here we shall discuss the biological and clinical observations which indicate that this innovative therapeutic approach may play a role in the management of minimal residual disease.
Leukemia 1992 Nov
PMID:Has IL2 a role in the management of minimal residual disease for acute leukemia? 143 44


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