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)

Low doses of endotoxin were administered to normal and acute anc chronic myeloid leukaemic subjects. Temperature, leucocyte count, blood colony stimulating activity and the number of circulating colony forming units were monitored. All subjects acquired fever while the leucocyte count remained unaltered. Blood CSA rose sharply in 6 normal individuals, but failed to increase in 4 acute leukaemic patients and in 2 patients with CML in blast crisis. 2 patients with CML in the chronic stage increased their blood CSA comparable to normal individuals. The number of circulating colony forming units rose following endotoxin with a peak at 30 min and declined subsequently. 4 patients with acute leukaemia showed no increase of circulating colony formers.
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PMID:Endotoxin-induced colony stimulating activity in normal and myeloid leukaemic subjects. 31 73

Fractionated total body irradiation (FTBI) and methotrexate-cyclosporin A(MTX-CSA) have been found useful in reducing interstitial pneumonia (IP) and acute graft-versus-host-disease (GVHD) in bone marrow transplantation patients, but an increase in relapse rate has been observed by some authors when these strategies are used. To evaluate this relapse risk, we performed a retrospective analysis in 24 consecutive first chronic phase chronic myeloid leukemia patients who received an HLA-identical non-T cell-depleted graft in a single institution. All were conditioned with cyclophosphamide plus FTBI (12 Gy in six fractions delivered twice daily for 3 days) (CY-FTBI) and received MTX-CSA as GVHD prophylaxis. Serial hematologic and cytogenetic bone marrow analysis were performed at least three times (days +30, +100, +360) and at variable intervals thereafter in long-term survivors. Actuarial probabilities of developing IP and acute GVHD greater than or equal to II were respectively 5.9% and 44.2%, with a GVHD-associated mortality of 33%. Four-year actuarial relapse and disease-free survival rates were 7.7% and 48.2% respectively. No exclusively cytogenetic relapses were observed. Our results suggest that CY-FTBI and MTX-CSA are not associated with an increase in relapse rate in 1CP-CML patients.
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PMID:Fractionated TBI and methotrexate-cyclosporin do not seem to increase relapses in BMT for first chronic phase CML patients: results of a single centre study. 142 77

Bone marrow transplantation (BMT) offers potentially curable treatment for patients with high-risk hematologic malignancies. However, relapse remains the major cause for failure of autologous BMT in these diseases and of allogeneic BMT in subsets of patients with these diseases. With our current preparative regimens, relapse rates following autologous BMT are over 30% for patients with intermediate or high-grade non-Hodgkin lymphoma and relapsed Hodgkin's disease in sensitive relapse and over 50% following autologous BMT for patients with acute non-lymphoblastic leukemia (ANLL) and acute lymphoblastic leukemia (ALL). Relapse rates exceed 80% in patients treated with autologous BMT for non-Hodgkin lymphomas and Hodgkin's disease in drug-resistant relapse. We also see a relapse rate over 50% in patients given allogeneic BMT for ANLL in second or third remission or early relapse, for ALL in third or subsequent remission or early relapse, and for chronic myelogenous leukemia (CML) in accelerated phase or blast crisis. We have explored two new approaches for improving the anti-tumor activity of our BMT preparative regimens. One involves combining etoposide, a chemotherapeutic agent that has excellent activity against leukemias and lymphomas, has shown synergistic activity with cyclophosphamide in vitro, and can be substantially dose-escalated, with busulfan and cyclophosphamide. The other approach attempts to induce graft-versus-host disease (GVHD), which appears to provide a clinical anti-tumor effect following allogeneic BMT, in recipients of autologous BMT. A syndrome similar to mild GVHD has been reported to occur spontaneously in a small number of patients receiving autologous or syngeneic transplants. GVHD can also be induced in rats undergoing syngeneic BMT by treatment with cyclosporine (CSA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New conditioning regimens for high risk marrow transplants. 262 18

Marrow and peripheral blood cells from nine children with juvenile chronic granulocytic leukemia (JCGL) demonstrated intense (94 +/- 16% maximum) spontaneous granulocyte/macrophage colony growth but cells from five children with the adult variety of CGL did not. This unusual pattern of colony growth depended upon a stimulatory protein(s) produced by mononuclear phagocytes. No GM-CSA activity was found in any chromatofocused fraction of JCGL monocyte-conditioned media but an activity that induced GM-CSA in umbilical vein endothelial cells was detected at pI 6.9-7.2. Moreover, the CSA-inducing monokine was neutralized by an anti-IL-1 antibody in vitro and, in the one case so tested, the same antibody also inhibited "spontaneous" colony growth. Therefore granulocyte/macrophage colony growth in JCGL is characteristically abnormal and distinguishes JCGL from the adult form of the disease. This abnormality depends upon the production, by mononuclear phagocytes, of IL-1 which, in turn, stimulates the release of high levels of colony stimulating activity by other cells. The high proliferative activity of CFU-GM we found in JCGL patients, and the high levels of GM-CSA found in their serum are compatible with the view that the in vitro abnormality reflects a similar abnormality in vivo.
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PMID:Interleukin 1-dependent paracrine granulopoiesis in chronic granulocytic leukemia of the juvenile type. 326 28

Sera of patients with primary myelofibrosis (PMF), primary thrombocythemia (PT), polycythaemia vera (PV) and chronic myeloid leukemia (CML) contained a significantly increased F-CSA (or F-CSAs) compared to those of normal subjects and patients with secondary thrombocytosis (ST). This F-CSA was heat sensitive and had the capacity to promote both proliferation and maturation of normal marrow fibroblast colony-forming cells (CFU-F). This F-CSA seemed to be different from human platelet derived growth factor (PDGF), tumor necrosis factor (TNF) and fibroblast growth factor (FGF) from bovine brain. This F-CSA might be of importance in the pathogenesis of bone marrow fibrosis in myeloproliferative disorders.
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PMID:Increased fibroblast colony stimulating activity (F-CSA) in serum of myeloproliferative disorders. 326 2

A new Ph1-chromosome positive cell line, KOPM-28. was established from a patient with chronic myelogenous leukemia (CML) in blast crisis. KOPM-28 cells were phenotypically immature: without azurophilic granules; negative for myeloperoxidase and positive for specific and nonspecific esterases. The nonspecific esterase reaction was intensified by TPA, and retinoic acid reinforced the specific esterase reaction without inducing morphological changes. KOPM-28 cells were not phagocytic. The cells expressed complement receptors, myeloid-monocytoid antigens, an Ia-like antigen and T4 antigen. CALLA, T-lymphocyte specific antigens, B-lymphocyte related antigen and platelet-megakaryocyte-megakaryoblast specific antigen were not detected. KOPM-28 cells formed colonies in semi-solid medium; this ability was augmented by GM-CSA. The addition of culture medium conditioned by KOPM-28 cells to normal bone marrow cells resulted in the increase of the CFU-C colonies. These findings indicate that KOPM-28 cells have features of myeloid and monocytoid precursor cells and that they are producing substance(s) which stimulates normal CFU-C.
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PMID:Ph1-positive CML-derived myeloid-monocytoid precursor cell line producing substance(s) that stimulates normal CFU-C. 349 66

The capacity of fetal bone marrow to form stromal cell colonies, granulocyte-macrophage colonies, stromal cell monolayers and to produce granulocyte-macrophage colony stimulating activity from these monolayers was evaluated in comparison to adult bone marrow. Granulocyte-macrophage colony formation on routine feeder layers was approximately equal in both cases. The fetal bone marrow colonies were larger in size than those from adult precursors. There were at least ten times more stromal cell precursors in fetal bone marrow than in adult bone marrow. The fetal bone marrow stromal cell monolayer formed within 7-12 days whereas adult stromal monolayer formation required 3-4 weeks. Fetal bone marrow stromal cell monolayer produced granulocyte-macrophage colony-stimulating activity (GM-CSA) effective only for fetal GM precursors, whereas adult bone marrow produces GM-CSA effective for fetal and adult normal and CML bone marrow.
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PMID:The properties of human fetal bone marrow stromal and hemopoietic cells. 666 7

It is apparent from the accompanying Table 9 and Figure 5, that transplantation offers an improved survival in AML. The use of CSA has made possible the technique of a mis-matched transplant, but as yet an unrelated donor has not been used. It may be that tolerance is more easily established with a one haplotype mis-match than with a completely unrelated person who may, nevertheless, be HLA identical. Clearly this would be an exciting project for the future, provided that all problems concerning relapse of disease and GvHD are overcome, and will also probably depend upon improvements in tissue typing techniques. (table; see text) Certainly we would now recommend this form of treatment to all patients under 40 years of age, in first remission from AML. Patients above this age, have responded less well and have been prone to more complications. We do not as yet know whether a complete remission is essential prior to embarking on a graft; certainly a few patients have been in early relapse, and this does not seem to have necessarily produced a poor outcome. Florid relapse at the present time is a definite contra-indication and no patients have been grafted in this situation. It will be noted that results for acute lymphoblastic leukaemia and chronic granulocytic leukaemia are bad. The first group were grafted early in the programme, but the number of relapses was extremely high and was accompanied in many circumstances by interstitial pneumonitis. Transplantation in chronic granulocytic leukaemia, a disease in which the prognosis has not improved for the past 20 years, has also not been successful except in one syngeneic graft. Two of the three deaths were in previously treated patients, one in blast transformation, but the third was virtually untreated and GvHD was a very serious problem indeed. Other reports of grafting for CGL have been discouraging except in twins. All these deaths occurred early. Whether this therapeutic approach will remain a treatment of choice remains to be seen, but we are very encouraged by our progress so far, although much work remains to be done.
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PMID:Bone marrow transplantation in acute myeloid leukaemia. 676 73

Graft-versus-host disease (GVHD) is a major obstacle to successful bone marrow transplantation (BMT) from matched unrelated donor (MUD). Currently available HLA-A, -B, and -DR serologic testing may not be sensitive enough to detect clinically relevant donor/recipient (D/R) nonidentity. Better HLA matching of D/R pairs using molecular typing for class II antigens in combination with intensive GVHD prophylaxis may potentially reduce the incidence of GVHD and lead to an improved outcome of MUD transplantation. Between July 1991 and August 1993, thirty consecutive patients with hematologic malignancies underwent MUD transplantation from donors who were identical for HLA -A, -B, and -DR by serologic typing. Twenty-five D/R pairs were matched for DRB and DQB by molecular typing (restriction fragment-length polymorphism and sequence-specific oligonucleotide probe hybridization analyses), whereas five were allele mismatched at either DRB or DQB. All patients also received GVHD prophylaxis with the combination of cyclosporine (CSA), methotrexate (MTX), and prednisone (PSE). The median age was 35 years (range, 15 to 50). The diagnoses were: chronic myelogenous leukemia (CML) in chronic phase (CP) (16), CML in more than CP (3), acute leukemia in more than first complete remission (CR) (8), acute leukemia in first CR (1), and advanced high-grade lymphoma (2). The preparative regimen consisted of 1,320 cGy fractionated total body irradiation (FTBI) and 60 mg/kg cyclophosphamide (CY) daily for 2 days in 17 good-risk patients (CML/CP and acute leukemia first CR); and 1,320 cGy FTBI in combination with 60 mg/kg etoposide and 20 to 60 mg/kg CY in 13 patients with advanced leukemia and lymphoma. All patients received CSA, PSE, and MTX on days 1, 3, 6 for GVHD prophylaxis, and 10 patients also received day +11 MTX. All patients engrafted except one who died early of regimen-related toxicity. The incidence of grade III or IV acute GVHD was 24% (95% confidence interval [CI], 10% to 44%) and that of extensive chronic GVHD was 65% (95% CI, 43% to 84%). At a median follow-up of 13.6 months, 57% of the patients are alive in remission with a median Karnofsky performance status of 90%. The cumulative probability of 2-year disease-free survival for all patients was 53% (95%) CI, 33% to 71%); for good-risk patients, 71% (95% CI, 46% to 87%) and for the poor-risk group, 34% (95% CI, 13% to 64%).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The outcome of matched unrelated donor bone marrow transplantation in patients with hematologic malignancies using molecular typing for donor selection and graft-versus-host disease prophylaxis regimen of cyclosporine, methotrexate, and prednisone. 762 Jan 76

Fifty-two patients with chronic myelogenous leukemia (CML) who underwent bone marrow transplantation (BMT) at Huddinge Hospital were analyzed retrospectively regarding type of graft-versus-host disease (GvHD) prophylaxis. With T-cell depletion (TCD) (n = 13) the incidence of grade II-IV acute GvHD was 8% compared to 27% among patients given short course methotrexate (MTX) + cyclosporin (CSA) (n = 23) (ns) and 60% in patients who received MTX or CSA alone (n = 16) (p = 0.006 vs TCD and 0.03 vs MTX + CSA). The incidence of chronic GvHD was 56%, 31% and 75%, in the three groups, respectively (p = 0.02 combination vs monotherapy). Probability of relapse differed significantly, with most relapses in the TCD group, 62% compared to 20% in the MTX + CSA group (p = 0.02) and no relapse in the monotherapy group (p = 0.01 TCD vs monotherapy). Patient survival at 6 years was 54%, 59% and 38%, in the three groups, respectively (ns). Relapse-free survival was 23% in the TCD group, 55% in the combination group (p = 0.06) and 38% in the monotherapy group (ns). We conclude that TCD in patients with CML is correlated with an increased risk of relapse and a tendency towards a decreased long-term relapse-free survival compared to patients receiving other kind of GvHD prophylaxis.
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PMID:Increased risk of relapse in patients with chronic myelogenous leukemia given T-cell depleted marrow compared to methotrexate combined with cyclosporin or monotherapy for the prevention of graft-versus-host disease. 831 89


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