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

Supernatants from human lymphoblastoid and plasma cell lines were added to cultures of normal cells stimulated with pokeweed mitogen (PWM) with the aim of providing an in vitro model for light chain isotype suppression (LCIS). Supernatants from the kappa-secreting cell line LICR-LON-HMY2 were specifically able to block the secretion of kappa-associated immunoglobulin and supernatants from the lambda-secreting cell line U266 were specifically able to block the secretion of lambda-associated immunoglobulin without any effect on the secretion of the other light chain isotype. Supernatant from a human leukemia line, HL60, did not block either kappa or lambda immunoglobulin secretion. Purging studies where kappa or lambda light chains were removed from supernatants of these cell lines suggest that this is a direct effect of light chain and not due to any other nonspecific inhibitory material which may be present.
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PMID:Multiple myeloma: evidence that light chains play an immunoregulatory role in B-cell regulation. 251 54

Important insights into leukocyte differentiation and the cellular origins of leukemia and lymphoma have been gained through the use of monoclonal antibodies that define cell surface antigens and molecular probes that identify immunoglobulin and T-cell receptor genes. Results of these studies have been combined with markers such as surface membrane and cytoplasmic immunoglobulin on B lymphocytes, sheep erythrocyte receptors on T lymphocytes, and cytochemical stains. After using all of the aforementioned markers, it is now clear that acute lymphoblastic leukemia (ALL) is heterogeneous. Furthermore, monoclonal antibodies that identify B cells, such as the anti-CD20 and anti-CD19 antibodies in combination with studies of immunoglobulin gene rearrangement, have demonstrated that virtually all cases of non-T-ALL are malignancies of B-cell origin. At least six distinct subgroups of non-T-ALL can now be identified. T-ALL is subdivided by the anti-CD7, anti-CD5, and antibodies that separate T lymphocytes subsets into three primary subgroups. Monoclonal antibodies are also useful in the subclassification of non-Hodgkin's lymphoma, and certain distinct markers can be correlated with morphological classification. Although monoclonal antibodies are useful in distinguishing acute myeloid from acute lymphoid leukemias, they have less certain utility in the subclassification of acute myelogenous leukemia (AML). Attempts to subclassify AML by differentiation-associated antigens rather than by the French-American-British (FAB) classification are underway in order to document the potential prognostic utility of surface markers. Therapeutic trials using monoclonal antibodies in leukemia and lymphoma have been reported. Intravenous infusion of unlabeled antibodies is the most widely used method; transient responses have been demonstrated. Antibodies conjugated to radionuclides have been quite successful in localizing tumors of less than 1 cm in some studies. Therapy trials with antibodies conjugated to isotopes, toxins, and drugs have shown promise. Purging of autologous bone marrow with monoclonal antibodies and complement in vitro has been used in ALL and non-Hodgkin's lymphoma; preliminary data suggest that this approach may be an effective therapy and may circumvent many of the obstacles and toxicities associated with in vivo monoclonal antibody infusion.
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PMID:Laboratory and clinical applications of monoclonal antibodies for leukemias and non-Hodgkin's lymphomas. 265 57

Important insights into leukocyte differentiation and the cellular origins of leukemia and lymphoma have been gained through the use of monoclonal antibodies that define cell surface antigens and molecular probes that identify immunoglobulin and T cell receptor genes. Results of these studies have been combined with markers such as surface membrane and cytoplasmic immunoglobulin on B lymphocytes, sheep erythrocyte receptors on T lymphocytes, and cytochemical stains. Using all of the above markers, it is now clear that acute lymphoblastic leukemia (ALL) is heterogeneous. Furthermore, monoclonal antibodies that identify B cells, such as the anti-B1 and anti-B4 antibodies in combination with studies of immunoglobulin gene rearrangement, have demonstrated that virtually all cases of non-T-ALL are malignancies of B cell origin. At least six distinct subgroups of non-T-ALL can now be identified. T-ALL is subdivided by the anti-Leu-9, anti-Leu-1, and antibodies that separate T lymphocyte subsets into three primary subgroups. Monoclonal antibodies are also useful in the subclassification of non-Hodgkin's lymphoma, and certain distinct markers can be correlated with morphologic classification. The cellular origin of the malignant Reed-Sternberg cell in Hodgkin's disease remains uncertain. A substantial number of investigators favor a myelocyte/macrophage origin based on cytochemical staining; however, consistent reactivity with antimonocyte reagents has not been demonstrated. Although monoclonal antibodies are useful in distinguishing acute myeloid from acute lymphoid leukemias, they have less certain utility in the subclassification of acute myelogenous leukemia (AML). Attempts to subclassify AML by differentiation-associated antigens rather than by the French-American-British (FAB) classification are underway in order to document the potential prognostic utility of surface markers. Therapeutic trials using monoclonal antibodies in leukemia and lymphoma have been reported. Intravenous (IV) infusion of unlabeled antibodies is the most widely used method; transient responses have been demonstrated. Antibodies conjugated to radionuclides have been quite successful in localizing tumors of less than 1 cm in some studies. Therapy trials with antibodies conjugated to isotopes, toxins, and drugs are currently planned. Purging of autologous bone marrow with monoclonal antibodies and complement in vitro has been used in ALL and non-Hodgkin's lymphoma; preliminary data suggest that this approach may be an effective therapy and may circumvent many of the obstacles and toxicities associated with in vivo monoclonal antibody infusion.
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PMID:Immunologic classification of leukemia and lymphoma. 294 Oct 82

A 5-yr experience of massive therapy and autologous bone marrow transplantation (ABMT) for Burkitt's lymphoma is reviewed. Thirty courses were given to 28 patients. Three patients were in resistant relapse and all three died before day 54 post ABMT. Thirteen patients were in non-resistant relapse and seven are alive with non-evidence of disease (NED). All three patients grafted in partial remission (PR) are alive NED including two with initial central nervous system (CNS) disease. Nine patients were grafted in 1st complete remission (CR) either because of long delay to achieve CR or as consolidation in those with initial CNS involvement or leukaemia. Three of these nine are alive including 2/3 with a long delay to CR and 1/5 initial CNS. The overall survival NED for the 28 patients is 46%. The median observation time post ABMT, 22 months. Clear indications for ABMT in BL are in our opinion restricted to about 20% of the patients: non-resistant relapses and PR after initial induction therapy. Massive therapy as consolidation of 1st CR after initial CNS involvement and in resistant relapses should still be considered as experimental. In 14 patients whose marrow was purged there is laboratory evidence suggesting that the purging procedures used in this study may have been incomplete. Purging techniques still require perfection at a laboratory level and their rationale should not be judged on the basis of incomplete procedures.
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PMID:Massive therapy and autologous bone marrow transplantation in pediatric and young adults Burkitt's lymphoma (30 courses on 28 patients: a 5-year experience). 353 58

We have developed a rapid and simple procedure for the elimination of mature T-cells from the donor marrow using a single incubation with the monoclonal antibody Campath-1 and donor complement. This resulted in a reduction of T-cell contamination to a mean of 1%. This regimen reduced the incidence of acute graft-versus-host disease significantly in 21 consecutive bone marrow grafts in 18 patients with leukaemia and non-Hodgkin's lymphoma. Purging was responsible for an increased incidence of graft rejection in HLA-identical transplants (13%).
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PMID:Ex vivo T-cell depletion with the monoclonal antibody Campath-1 plus human complement effectively prevents acute graft-versus-host disease in allogeneic bone marrow transplantation. 353 72

The success of autologous stem cell transplantation using bone marrow or peripheral blood stem cells depends not only on in vivo irradication of the disease by cytotoxic therapy but also on complete hematopoietic engraftment with no risk of relapse from the infused cells. Various methods are available for removing (purging) such contaminants. Purging techniques were developed by use of various in vitro models utilizing cell lines and fresh cancer cells. Once effective conditions were developed, they were advanced onto clinical trials. Various approaches for purging have been used. Subgroups of leukemia and lymphoma have now shown clinical benefit by the use of purged stem cells. Emphasis is now being placed on utilizing the information already obtained by the pre-clinical investigators on designing better clinical trials.
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PMID:Rationale for purging in autologous stem cell transplantation. 791 49

Autologous bone marrow transplantation for leukemia was developed to extend the apparent curative potential of myeloablative therapy with allogeneic bone marrow transplantation to leukemia patients without histocompatible marrow donors. The conceptual problem with this approach is obvious: if the need for the transplant is based on overt or occult contamination of the marrow by leukemia, the use of autologous marrow seems destined to failure because of reinfusion of leukemia cells along with the harvested marrow. For this reason, ex vivo antileukemic treatment ("purging") of remission marrow was developed to justify autologous transplants for leukemia. Clinical trials involving thousands of patients worldwide have demonstrated curative potential of autologous bone marrow transplants, using purged or untreated remission marrow, for selected patients with acute myelogenous leukemia and acute lymphocytic leukemia. Purging appears to contribute to increased leukemia-free survival, at least in a subset of patients who are at very high risk of relapse, but this has not been tested in a prospective randomized trial and remains controversial. In acute myelogenous leukemia, in which the greatest experience exists, procedure-related mortality is much less for autologous than for allogeneic transplants; however, since leukemia relapse is much more frequent for autologous than for allogeneic transplants, the long-term disease-free survival is similar. In general, autologous transplants are preferred for older individuals and those without matched related donors, whereas allogeneic transplants are preferred for younger patients with matched related donors. Leukemia relapse has greatly limited the success of autologous transplants for acute lymphocytic leukemia. Autologous transplants for the chronic leukemias are in a much earlier stage of investigation. Autologous transplantation for leukemia is a fertile area for research. Important topics include conditioning regimens with improved antileukemic efficacy, the value of purging and the best method(s) for leukemia stem cell purging or normal stem cell selection, the possibility of inducing an autologous graft versus leukemia reaction, the use of immunomodulatory cytokines for postgrafting immune system manipulation, and the use of hematopoietic growth factors for ex vivo stem cell expansion and postgrafting support of marrow recovery.
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PMID:Autologous bone marrow transplantation for leukemia. 821 Dec 15

Residual leukemia was evaluated in autologous bone marrow grafts harvested in first (n = 11) or second (n = 3) complete remission from 14 patients with BCR-ABL-positive acute lymphoblastic leukemia after treatment according to the German multicenter ALL protocols. The intervals from diagnosis to BM harvest were median 159 (range 78-463) and from preceding chemotherapy to BM harvest median 39 (range 26-69) days, respectively. A limiting log(10)-dilution RT-PCR was used to semiquantify BCR-ABL-positive cells. All autografts appeared to be significantly contaminated with residual leukemic cells. The BCR-ABL-specific titers ranged from 1:10(3) to 1:10(6) (median 1:10(4)) above the limit of detection. This was the rationale to purge the grafts using two cycles of IgM anti-CD10, CD19, and AB4 MoAbs-coated immunomagnetic beads (IMB). Purging depleted median 3 (range 2-4) logs of residual leukemia, resulting in a median 1:10(1) (range 1:10(0) to 1:10(3)) postpurge BCR-ABL-specific titer. The second purging cycle accounted for 1 log of depletion. The mean +/- s.e.m. post-purge recoveries of MNC and CFU-GM were 59 +/- 4%, and 61 +/- 9%, respectively. We conclude that all BCR-ABL-positive ALL patients achieving CR by cytological criteria have critically high levels of residual leukemia in their bone marrow, which can be reduced by median 3 log using immunomagnetic bead purging.
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PMID:Residual leukemia and immunomagnetic bead purging in patients with BCR-ABL-positive acute lymphoblastic leukemia. 887 15

Purging of autologous bone marrow (BM) grafts of children in second remission after a relapse of precursor B acute lymphoblastic leukaemia (ALL) in the BM has been carried out in our laboratory since 1987, initially by complement mediated cell lysis. This protocol was extended by performing an immunorosette depletion before lysis with complement. The aim of the present study was to assess by polymerase chain reaction the presence of residual leukaemic cells in the BM grafts before and after purging. The results were then correlated to clinical outcome. In 24/28 patients a PCR product was obtained by amplification of IgH and/or TcR junctional regions. BM before purging was available for analysis in 13 patients. We found that leukaemic cells could be detected in 8/13 (62%) of these grafts before purging . All these eight patients experienced a relapse, regardless of whether the purging procedure had been successful (defined as achievement of PCR-negativity) or not. In contrast, none of the five patients with PCR-negative grafts before purging relapsed (P = 0.0008). One patient died due to transplant-related toxicity. Of the remaining 23 patients, nine patients received a PCR-positive BM graft after purging. All these nine patients experienced a relapse as compared to 6/14 whose BM was PCR-negative after purging (P = 0.0072). Two of eight PCR-positive BM grafts could be purged to PCR-negativity. Thus, improvements both in treatment of leukaemia and in purging efficacy are still needed.
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PMID:PCR-positivity in harvested bone marrow predicts relapse after transplantation with autologous purged bone marrow in children in second remission of precursor B-cell acute leukaemia. 902 32

Autologous bone marrow transplantation (ABMT) offers a therapeutic alternative for children with poor prognosis acute lymphoblastic leukemia (ALL) who lack an HLA-matched sibling donor. The most common cause of treatment failure after ABMT in these patients is leukemia relapse. We have developed an ex vivo autologous marrow purging program for children with ALL using an immunomagnetic method. BM purging has been performed in 37 children with ALL (31 B-lineage ALL and 6 T-lineage ALL) following an indirect method, using panels of mouse monoclonal antibodies (MAbs) directed against B or T cell antigens, Dynabeads M-450 (Dynal) coated with sheep antimouse (SAM) antibodies, and the MaxSep Magnetic Cell Separator (Baxter). Purging efficiency has been assessed by flow cytometry. Considering the limit of detection of target cells 0.1%, the median depletion was 2.0 log (range 0.8- > 2.8 log) for the B-lineage ALL and 2.7 (range 2.2- > 2, 9 log) for the T-lineage ALL patients. Twenty-seven patients have been autografted (6 in first complete remission, CR, 13 in second CR, and 8 in third or subsequent CR). Engraftment has been satisfactory in all of them, reaching levels of 500 neutrophils/mm3 and 20,000 platelets/mm3 after a median of 17 (range 12-39) and 30 (range 13-96) days post-ABMT, respectively. In summary, our results show that this immunomagnetic procedure achieves high levels of target cell depletion and can be safely applied to bone marrow purging in childhood ALL patients.
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PMID:Immunomagnetic bone marrow purging in children with acute lymphoblastic leukemia. 923 81


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