Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study we assess the antitumor effect and circulating stem cells (CSC) mobilizing capacity of high-dose cyclophosphamide (5 to 7 gr/m2, HDCY). This treatment was given to 21 patients with various hematologic malignancies (8 NHL, 5 MM, 4 HD, 3 CML) excluding 1 with neuroblastoma. All were eligible for later autologous blood stem cell transplantation (ABSCT). To reduce the hematologic toxicity of HDCY, GM CSF was simultaneously administered in 5 patients. HDCY produced a response (as defined by a > 50% reduction of previous tumor mass) in 3 out of 12 HD/NHL and 1 out of 3 MM. Patients with CML were not considered to be evaluable for tumor response. Cell collection yields after HDCY varied widely with a range of 1.5 to 169.9 x 10(4)/Kg (median 13.1) CFU-GM and 1.7 to 18.4 x 10(8)/Kg (median 5.8) MNC collected per patient. Hematologic recovery was rapid and sustained with a median of 16 (12-18) days to PMN > 0.5 x 10(9)/L and 14 (11-18) days to Plt > 100.0 x 10(9)/L. Granulocyte recovery was significantly faster after GM-CSF (13 vs 16 days to PMN > 0.5, p = 0.0008). Non hematologic toxicity consisted mainly of nausea and vomiting, but fatal complications occurred in 2 patients, from pulmonary infection in one and from tumor-lysis syndrome in the other. HDCY represents a useful means of increasing collection of CSC, but toxicity is not irrelevant. Whether a similar anti-tumor effect and mobilizing capacity would be offered by single lower intermediate doses of the drug is still to be ascertained.
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PMID:High dose cyclophosphamide: stem cell mobilizing capacity in 21 patients. 792 Feb 30

Lymphoreticular neoplasms of the larynx are rare and comprise a heterogeneous group of tumors. A systematic survey of the literature and autoptic evaluation of the larynx in a relatively small number of patients with systemic lymphoreticular malignancies yielded the following findings: Primary tumors of the larynx must be clearly distinguished from laryngeal involvement by systemic or leukemic infiltrations. By far the most common primary hemopoietic tumors of the larynx are extramedullary plasmacytoma (about 90 cases published) and non-Hodgkin's lymphoma (NHL; about 65 cases published). Primary Hodgkin's disease, granulocytic sarcoma and mast cell sarcoma are extremely rare at this site. Plasmacytoma and NHL both preferentially involve the supraglottis. The subglottis is infrequently affected. Laryngeal plasmacytoma and NHL usually present clinically as localized stage IE and IIE tumors that exhibit no significant tendency to recur or generalize. The therapy of choice is local irradiation while chemotherapy should be reserved for recurrent or progressive disease. Prognosis is favourable in most cases of primary laryngeal plasmacytoma and NHL. Secondary involvement of the larynx by systemic lesions or leukemic infiltrations is usually associated with a very poor prognosis. The prognosis of patients with laryngeal involvement in acute or chronic myeloid leukemia is always poor. Although the histopathological diagnoses given in many case reports are often difficult to compare because of differences in terminology, there seems to be a marked preponderance of B-cell tumors of high-grade malignancy (centroblastic or immunoblastic lymphoma in the Kiel classification of NHL) that probably represents lymphomas originating from mucosa-associated lymphoid tissue (MALT).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The larynx in lymphoproliferative and myeloproliferative diseases. Part II: Laryngeal autopsy findings and discussion]. 792 29

The WT1 gene encoding a zinc finger polypeptide is a tumor suppressor gene that plays a key role in the carcinogenesis of Wilms' tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine relative levels of WT1 gene expression (defined in K562 cells as 1.00) in 45 patients with acute myelogenous leukemia (AML), 22 with acute lymphocytic leukemia (ALL), 6 with acute mixed lineage leukemia (AMLL), 23 with chronic myelogenous leukemia (CML), and 24 with non-Hodgkin's lymphoma. Significant levels of WT1 gene were expressed in all leukemia patients and for CML the levels increased as the clinical phase progressed. In striking contrast with acute leukemia, the levels of WT1 gene expression for NHL were significantly lower or even undetectable. Clear correlation was observed between the relative levels of WT1 gene expression (< 0.6 v > or = 0.6) and the prognosis for acute leukemia (AML, ALL, and AMLL). Patients with less than 0.6 levels had significantly higher rates of complete remission (CR), disease-free survival, and overall survival than those with > or = 0.6 levels, whereas CR could not be induced in any of the 7 patients with acute leukemia having greater than 1.0 levels of WT1 gene expression. The quantitation of the WT1 gene expression made it possible to detect minimal residual disease (MRD) in acute leukemia regardless of the presence or absence of tumor-specific DNA markers. Continuous monitoring of the WT1 mRNA was performed for 9 patients with acute leukemia. In 4 patients, MRD was detected 2 to 8 months before clinical relapse became apparent. In 2 other patients, the WT1 mRNA gradually increased after discontinuation of chemotherapy. No MRD was detected in the remaining 3 patients with AML who received intensive induction and consolidation therapy. Simultaneous monitoring of MRD by RT-PCR using primers for specific DNA markers in 3 patients (2 AML-M3 with PML/RAR alpha, and 1 AML-M2 with AML1/ETO) among these 9 patients detected MRD comparable with that obtained from quantitation of WT1 gene expression. In a patient with acute promyelocytic leukemia, the limits of leukemic cell detection by RT-PCR using either WT1 or promyelocytic leukemia/retinoic acid receptor-alpha gene primers were 10(-3) to 10(-4) and 10(-4) for bone marrow, and 10(-5) and 10(-4) for peripheral blood, respectively. Therefore, we conclude that WT1 is a new prognostic factor and a new marker for the detection of MRD in acute leukemia.
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PMID:WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. 794 79

Lymphoreticular neoplasms of the larynx are rare and comprise a heterogeneous group of tumors. A systematic survey of the literature and autoptic evaluation of the larynx in a relatively small number of patients with systemic lymphoreticular malignancies yielded the following findings: Primary tumors of the larynx must be clearly distinguished from laryngeal involvement by systemic or leukemic infiltrations. By far the most common primary hemopoietic tumors of the larynx are extramedullary plasmacytoma (about 90 cases published) and non-Hodgkin's lymphoma (NHL; about 65 cases published). Primary Hodgkin's disease, granulocytic sarcoma and mast cell sarcoma are extremely rare at this site. Plasmacytoma and NHL both preferentially involve the supraglottis. The subglottis is infrequently affected. Laryngeal plasmacytoma and NHL usually present clinically as localized stage IE and IIE tumors that exhibit no significant tendency to recur or generalize. The therapy of choice is local irradiation while chemotherapy should be reserved for recurrent or progressive disease. Prognosis is favorable in most cases of primary laryngeal plasmacytoma and NHL. Secondary involvement of the larynx by systemic lesions or leukemic infiltrations is usually associated with a very poor prognosis. The prognosis of patients with laryngeal involvement in acute or chronic myeloid leukemia is always poor. Although the histopathological diagnoses given in many case reports are often difficult to compare because of differences in terminology, there seems to be a marked preponderance of B-cell tumors of high-grade malignancy (centroblastic or immunoblastic lymphoma in the Kiel classification of NHL) that probably represents lymphomas originating from mucosa-associated lymphoid tissue (MALT).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The larynx in lymphoproliferative and myeloproliferative diseases. I: An overview with special reference to primary laryngeal malignant lymphomas and plasmacytomas]. 807 Oct 93

In a variety of human tumors, including high grade Non-Hodgkin's lymphoma (hgNHL), a linkage between expression of CD44 variant isoforms (CD44v) and tumor progression has been described. In search of an easily accessible diagnostic parameter, expression of CD44 standard (CD44s) and CD44 variant isoforms (exons v5, v6, v7 and v10) in peripheral blood lymphocytes (PBLs) of patients with hematological malignancies was evaluated by fluorescence activated cell scanning. The analysis of 30 blood samples of healthy donors and patients with non-malignant diseases and of 183 blood samples of patients with malignant hematological disorders revealed that only in patients with malignant disorders did a measurable proportion of PBLs express CD44 variant isoforms, mostly exons v5, v6, v7 and, less frequently, exon v10. Elevated levels of CD44v expression were noted in PBLs of patients with acute and chronic myeloid leukemia (AML: 16%, CML: 25%), Hodgkin's disease (HD: 17%), multiple myeloma (MM: 22%), polycythemia vera (PV: 33%), acute lymphoid leukemia (ALL: 23%) and, most frequently, in PBLs of patients with non-Hodgkin's lymphoma (NHL:54%). CD44v expression was not restricted to the malignant phenotype, but instead was also noted in T cells, B cells and monocytes, preferentially in a subpopulation of large cells. Furthermore, expression of CD44v in PBLs was not linked to the histological grading or clinical staging. There was, however, an inverse correlation with tumor progression, whereas response to therapy was frequently accompanied by upregulation of CD44v. Thus, expression of CD44v in the PBLs of patients with NHL mainly reflected immune responsiveness. Since NHL manifests itself primarily in lymphoid organs, its progression is difficult to follow. Monitoring of CD44v in PBLs could be used as an additional and convenient parameter for surveying the course of disease.
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PMID:Expression of CD44 variant isoforms in peripheral blood leukocytes in malignant lymphoma and leukemia: inverse correlation between expression and tumor progression. 896 Jan 9

A considerable proportion of cases of myeloproliferative and lymphoproliferative disorders exhibit renal involvement. However, it is unclear whether the cytologic features, immunophenotype or grade of malignancy of the cells infiltrating the kidney differ from those of the primary tumor. This study was performed on 120 autopsy cases with the following diagnoses: acute myelogenous leukemia (AML, n = 22; subtypes M1 + M2, n = 12, subtype M4, n = 10), chronic myelogenous leukemia (CML, n = 7), agnogenic myeloid metaplasia/myelofibrosis (AMM/MF, n = 6), acute lymphocytic leukemia (ALL, n = 6), chronic lymphocytic leukemia (CLL, n = 9), other low-grade non-Hodgkin's lymphomas (low-grade NHL, n = 24), high-grade NHL (n = 21) and multiple myeloma (MM, n = 25). Renal involvement was investigated by light microscopy and immunohistochemistry. It was found in 34% of the cases, and was most common in ALL (83%) and low-grade NHL (50%) and least common in high-grade NHL (10%) and MM (12%). Dense infiltration of almost the entire kidney was most commonly seen in AML, low-grade NHL and ALL. Infiltration was bilateral and involved both the cortex and medulla in the majority of cases. When involvement of other organs was compared with that of the kidney, the lung was found to be involved in approximately the same number of cases, but liver involvement was more common and heart involvement less common. Reactive lymphocytic infiltration of the kidney was found in 18 of the 120 cases (15%), and was distinguished from scanty tumorous infiltration by immunohistochemical staining. No major phenotypical differences were found between the tumor cells infiltrating the kidney and those of the primary tumors in the bone marrow or lymph nodes. However, in one case of CML, the cells infiltrating the kidney were negative for KP1 and chloroacetate esterase, but could be identified by reactivity for CD34. The grade of malignancy in NHL was similar in both the nodal and renal manifestations.
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PMID:Renal involvement in myeloproliferative and lymphoproliferative disorders. A study of autopsy cases. 906 78

IL-10 plays an important role in the control of immune reactions during systemic infection. Here, IL-10 serum levels were investigated in patients after BMT. The IL-10 levels correlated with the clinical course of the patients and with serum levels of C-reactive protein (CRP) and neopterin (NP). A total of 26 patients with AML (7), ALL (12), CML (2), NHL (3) and multifocal Ewing's sarcoma (2) had received autologous (10) or allogeneic (16) BMT from related (9) or unrelated donors (7). Routine serum samples were obtained prior to BMT and at days 46 and 100 after BMT. However, in patients with severe complications additional samples were drawn at individual points in time. Prior to BMT, IL-10 serum levels were not detectable in 24/24 patients. Post-BMT, 11 patients developed elevated IL-10 levels, of these eight died of complications (DOC), whereas only one of 15 patients with undetectable IL-10 died of complications, indicating that high IL-10 levels were significantly correlated with severe life-threatening complications (chi2, P < 0.01). To determine the pathomechanism and role of the increased IL-10 levels, they were correlated to the respective NP and CRP serum concentrations. CRP and NP concentrations were found significantly elevated in patients with detectable IL-10, indicating a severe acute phase reaction associated with macrophage activation. In conclusion, high IL-10 serum levels in patients after BMT were significantly associated with fatal outcome. Since IL-10 is a strong suppressor of T cell immunity, high IL-10 production in patients with severe complications such as septic shock or GVHD > grade II after BMT might lead to functional immunodeficiency contributing to the poor prognosis of these patients.
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PMID:High interleukin-10 serum levels are associated with fatal outcome in patients after bone marrow transplantation. 933 50

To explore the feasibility and potential advantages of PBSC in allogeneic transplantation, we grafted 24 patients (age 16-57, median 37) with different hematologic diseases (ALL = 10, AML = 5, MM = 4, NHL = 2, CML = 1, MDS = 1, AA = 1), 23 HLA-identical to their siblings and 1 partially matched. Cells were collected from donors by apheresis after G-CSF 10 to 16 mg/kg/day for 4 to 5 days, and stored at 4 degrees C until infusion. The patients were conditioned with chemotherapy regimens including busulfan and cyclophosphamide in the majority of cases and received GVHD prophylaxis with CSA-MTX in all but two. The graft consisted of PBSC alone, with a median of 143.5 (range 18.1-358.9) x 10(4)/kg CFU-GM, 9.0 (range 3.3-18.0) x 10(6)/kg CD34+ cells and 2.8 (range 1.2 to 8.6) x 10(8)/kg CD3+ and cells. An ANC >0.0.5 x 10(9)/L was recovered on (median) day 13 (range 11-17), and a platelet count >50 x 10(9)/L on (median) day 13 (range 12-55) post graft. There was no correlation between CD34+ cells or CFU-GM number in the inoculum and time to hematologic reconstitution. Acute GVHD (grade II-IV) occurred in 10 out of 22 (45%), chronic GVHD in 10 out of 18 evaluable (55%) patients. We found no relationship between occurrence of acute or chronic GVHD and number of CD3+ cells in the graft. Four patients relapsed and 7 died after transplantation. Fifteen patients are currently alive and disease-free 67 to 710 (median 286) days from the graft. Allogeneic transplantation with unmanipulated PBSC ensures a fast and stable engraftment. Acute GVHD incidence and severity seems comparable to that of bone marrow transplantation, but there may be an increase in chronic GVHD, mainly of the extensive form.
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PMID:Transplantation of unmanipulated allogeneic PBSC: preliminary report on 24 patients. 957 Jun 80

We investigated the expression-percentage as well as MESF values ("molecules of equivalent soluble fluorochrom" that represent approximately the density of marker expression) of HLA-DR, CD71 and CD38 markers in some human leukemias (ALL, AML, CLL, CML) and lymphomas. They are non-lineage restricted and are supposed to be activation markers except for cases where they represent pathological phenotype like HLA-DR in pre B-ALL, CD38 in some M0 AML or in plasmocytoma or CD38 and CD71 in less mature T-ALL. We used flow cytometry, immunofluorescent staining, DNA staining by propidium iodide and quantification by calibration particles. We demonstrated increased MESF values of HLA-DR compared with controls in all investigated disorders, what could have a prognostic value. We demonstrated significantly higher MESF values of HLA-DR in cALL (37,300-46,000) in comparison with AML (9400-12,400), what could represent another important parameter when distinguishing between these two groups of leukemia. In cells of CML patients with lower CD38% and CD71% increased MESF values (5100 for CD38 and 7900 for CD71), were found while in some T-ALL, AML and cALL patients with high percentages of CD71 and CD38 there were lower MESF values what could indicate a possible connection of higher stage of cell maturation with increased density of CD38 and CD71 markers. We investigated possible relationship between percentage of expression of HLA-DR, CD38 and CD71 and proliferation rate by DNA analysis of the cell cycle. In a group of non-Hodgkin's lymphoma patients, there was no significant increase of proliferation index of malignant cells compared with control. The correlation between percentage of expression of mentioned parameters and proliferation index was not significant. In one patient with Burkitt's lymphoma we demonstrated significant increase of proliferation index of CD71+ subpopulation compared with CD71- one, what indicates that in aggressive form of NHL CD71 can be evaluated not only as activation but also as proliferation marker.
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PMID:The relationship of HLA-DR, CD38 and CD71 markers to activation, proliferation and differentiation of some human leukemia and lymphoma cells. 968 89

From September 1982 to August 1997, 767 bone marrow or peripheral blood stem cell transplants have been performed at the Health Sciences Center in Oklahoma. Five hundred and two (502) autologous transplants (AutoTX) preceded by high-dose myeloablative therapy were performed for breast cancer (BC, 36%), non-Hodgkin's lymphomas (NHL, 24%), Hodgkin's disease (HD, 10%), acute myeloid leukemia (AML, 8%), testicular cancer (TC, 4%), multiple myeloma (MM, 2%) and other malignancies (16%). Two hundred and sixty-five (265) allogeneic marrow transplants (AlloTX) (related, unrelated) were carried out in chronic myeloid leukemia (CML, 30%), AML (23%), acute lymphoid leukemia (ALL, 14%), myelodysplastic syndrome (MDS, 9%), severe aplastic anemia (SAA, 8%), and other diseases (14%). Compared between 1980s to 1990s, 100-day mortality rates have decreased from 28% to 5% for AutoTX and from 40% to 25% for AlloTX. In the AutoTX setting, major changes included the routine use of growth factors post-transplant and the switch from bone marrow to growth factor-mobilized peripheral blood as a source of stem cells over the last five years. In the AlloTX setting, improvements in recognition and control of cytomegalovirus and Candida organisms, the selective use of growth factors and screened blood products, and better selection of unrelated donors using DNA-based techniques of HLA-matching have contributed to reduce early mortality from infection and primary graft failure. The five-year survival outcomes are comparable to those reported in registry data from the International Bone Marrow Transplant Registry (IBMTR) and the National Marrow Donor Program (NMDP).
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PMID:Marrow and stem cell transplantation in Oklahoma: fifteen years of experience and results. 976 68


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