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)

The success of autologous bone marrow transplantation (ABMT) in acute leukemia (AL) in complete remission (CR) is limited by the high relapse rate. It is generally accepted that minimal residual disease (MRD) plays a major role in determining the relapse of disease. In our study we investigated in adult acute leukemia and in chronic myelogenous leukemia (CML), the efficacy of ex vivo marrow purging with mafosfamide (an in vitro derivative of cyclophosphamide). We also describe an improved purging approach ("programmed method") based on the evaluation of sensitivity to the drug measured in each individual patient prior to ABMT. The analysis of clinical data in terms of disease-free survival (DFS) shows that the "programmed method" gives significantly better results than those obtained using the standard dose of mafosfamide (80% DFS in 18 AL patients vs. 44% in 33 ANLL patients and 33% in 56 ALL patients). The evaluation of the CR to purging interval in ALL and ANLL shows that a period of greater than 6 months is necessary to obtain longer DFS. Considering pre-transplant regimens, busulfan-cyclophosphamide is more effective in ANLL, and cyclophosphamide-fractionated total body irradiation is the best treatment for ALL. The studies using mafosfamide marrow purging in CML demonstrate that the drug is able to achieve a decrease of the Ph1+ marker. Three patients who showed conversion of this cytogenetic marker have been autografted with interesting clinical results.
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PMID:Pharmacological-mediated purging with mafosfamide in acute and chronic myeloid leukemias. The Italian Study Group. 230 82

Eighty consecutive patients were transplanted with human leukocyte antigen (HLA)-identical sibling marrow for acute myelogenous leukemia (AML, N = 29), acute lymphoid leukemia (ALL, N = 23), or chronic myelogenous leukemia (CML, N = 28). Donor marrow was depleted of lymphocytes using counterflow centrifugation. Median age of the recipients was 31 years. Pretransplant conditioning consisted of cyclophosphamide and fractionated total body irradiation (TBI) with a low (4.1 +/- 0.3 cGy/min) or high (13.1 +/- 1.6 cGy/min) midline average dose rate. In 43 patients, cytosine-arabinoside or anthracyclines were added to the conditioning regimen. Immunoprophylaxis posttransplant consisted of methotrexate (MTX) alone, cyclosporine A (CsA) in combination with MTX, or CsA alone; two patients received no immunoprophylaxis at all. Graft failure occurred in 4 of 77 evaluable patients (5%). The probability of acute graft-versus-host disease (GVHD) greater than or equal to grade 2 at day 100 after transplantation was 15%. The projected 3-year estimate of extensive chronic GVHD was 12%. Only three patients died of cytomegalovirus-interstitial pneumonitis. The projected 3-year probability of relapse was 30% (95% confidence interval [CI], range 8% to 53%) in transplants for AML in first complete remission (CR1), 35% (95% CI, 1% to 69%) after transplantation for ALL in CR1, and 38% (95% CI, 2% to 74%) after transplantation for CML in first chronic phase (CP1). The projected 3-year probability of leukemia-free survival (LFS) was 56% (95% CI, 35% to 77%) after transplantation for AML-CR1, 42% (95% CI, 16% to 69%) in patients transplanted for ALL-CR1, and 49% (95% CI, 18% to 80%) after transplantation for CML-CP1. After transplantation for AML-CR1, ALL-CR1, or CML-CP1, the median follow-up time for leukemia-free survivors was 31+, 30+, and 21+ months, respectively. Probabilities of relapse, survival, and LFS in AML-CR1 and ALL-CR1 transplants were comparable with those reported in recipients of untreated grafts. In patients transplanted for CML-CP1, probability of relapse was higher and probability of LFS was lower than in recipients of untreated grafts. In transplants for leukemia in CR1 and CP1, preparative regimen and immunoprophylaxis posttransplant were not associated significantly with the probability of acute GVHD greater than or equal to grade 2, extensive chronic GVHD, relapse, survival, or LFS. In bone marrow transplantation for leukemia, counterflow centrifugation is a useful technique for the prevention of GVHD.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Allogeneic bone marrow transplantation for leukemia with marrow grafts depleted of lymphocytes by counterflow centrifugation. 231 Aug 32

Seven cases of miliary tuberculosis in patients with hematologic disease were analyzed clinicopathologically. Mean age of the patients was 65 years, and the hematologic diseases were CML, AML, ALL, MDS and malignant lymphoma. Diabetes mellitus was present as a complication in three patients. Miliary tuberculosis was found in 5 cases during the first admission to our hospital owing to hematologic problems. In 4 of 6 cases, fever had started more than two months before admission, consequently, the tuberculosis probably began about that time. After admission, chemotherapy was administered in 5 cases, and steroid in 6 cases for hematologic disease. The mean total quantity of steroid administered was 2,134 mg of prednisolone and average treatment duration was 69 days. The chest roentgenographic shadow was so atypical that miliary tuberculosis was suspected in only one case. The initial chest roentgenogram showed hilar and mediastinal lymph node swelling as well as the shadow of pulmonary tuberculosis in two cases. It was thought that the hilar and mediastinal lymph node swelling could be explained by primary complex, although the patients were of advanced age, or by "secondary complex" reported by Terplan, K in 1940. The diagnosis of tuberculosis was made in two patients before their death by smear of aspirated fluid of cervical lymph node and by bone marrow cell block in one patients, and by pathological examination of mediastinal lymph node biopsy in the other patients. Tubercles were found from bone marrow cell block in 2 out of 5 patients and from bone marrow biopsy in 1 out of 3 patients, but the positive results were reported in 2 patients following death. Smears of sputum, gastric juice, urine, spinal fluid and pleural effusion were negative in all cases. One patient diagnosed as miliary tuberculosis also had pneumocystis carinii pneumonia. This case was treated with antituberculosis drugs for 20 days without improvement. Another patient diagnosed as miliary tuberculosis improved under treatment with antituberculosis drugs, but died of cytomegalovirus pneumonia. Autopsy in 5 cases revealed non-reactive miliary tuberculosis, and pulmonary hemorrhage probably due to DIC was present as a complication in two cases. In these cases, severe immunosuppression, which is a major precipitating factor of miliary tuberculosis, is thought to be induced by hematologic disease itself, chemotherapy, steroid or other underlying disease such as diabetes mellitus. Miliary tuberculosis in such compromised host is cryptic and progresses rapidly. Consequently, early diagnosis is very important. Retrospectively, the unexplained pyrexia was most important to suspect tuberculosis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Clinicopathological study of miliary tuberculosis in patients with hematologic disease]. 237 32

A recombinant plasmid library representing the more abundant polyadenylated RNA of a relapsed acute myelomonocytic leukaemic (FAB class M4) has been constructed. One recombinant, designated pAM6, contains a DNA sequence complementary to an RNA of about 1100 nucleotides in length. The relative concentrations of pAM6 RNA in the RNAs from cloned human haematopoietic cell lines and from fractionated leukaemic leukocytes and normal bone marrow cells, measured by an RNA dot hybridization method, indicated that pAM6 RNA occurs in myeloid cells, probably those of the monocyte lineage at the earlier stages in differentiation. Similar assays showed that pAM6 RNA could not be detected in the peripheral blood leukocytes of normal individuals, or of ALL and CLL patients, but that the relative abundance of pAM6 RNA varied widely in leukocytes from CGL chronic phase, CGL acute phase, and ANLL. No correlation between pAM6 RNA occurrence and FAB classification of ANLL could be made; thus it would appear that the relative abundance of pAM6 RNA in ANLL leukocytes can be used to subdivide the ANLLs in a novel manner. It is suggested that this criterion, in conjunction with existing diagnostic markers, may provide a subclassification of the ANLLs that could be of some prognostic and therapeutic value.
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PMID:Subdivision of the acute non-lymphoblastic leukaemias by measurement of the relative abundance of a specific RNA sequence. 241 18

The relative abundances of c-myc-related RNA in the total cellular RNA of peripheral blood leukocytes from 36 patients with leukaemia have been compared with those in normal peripheral blood leukocytes and in HL60 cells. Varying amounts of c-myc-related RNA were found in RNAs from leukocytes from patients with ANLL, CGL and ALL. High concentrations (comparable with that in HL60 cells) were found in 13 (36%) of the leukaemias and lower, but still significant, concentrations in a further 15 (42%). Low concentrations of c-myc-related RNA, comparable to that in normal leukocytes, were found in 2 of 8 CGLs, 1 of 12 ANLLs, and 5 of 5 CLLs. DNAs from 11 leukaemia patients' leukocytes, in which c-myc-related RNA concentrations ranged from very high to very low, were examined for rearrangements and/or amplification of the c-myc gene. No rearrangements were detected, and the small degree of amplification (2- to 4-fold at most) found was not correlated with increased levels of c-myc RNA. There was, however, a noteworthy (though incomplete) correlation between elevated levels of c-myc-related RNA and the occurrence of higher proportions of blast cells in leukocyte populations from leukaemic patients. It is suggested that high levels of c-myc-related RNA in a population of peripheral blood leukocytes indicate the presence of a high proportion of leukaemic leukocytes that are maturation-arrested at early stages of development.
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PMID:Expression of the myc gene locus in populations of leukocytes from leukaemia patients and normal individuals. 242 11

A panel of 14 monoclonal antibodies (McAb) against hematopoietic cell surface antigens was applied on mononuclear blood or bone marrow cells from 40 cases of acute leukemia in order to compare immunoenzymatic staining (IE) (alkaline phosphatase) of fixed cells with immunofluorescence staining (IF) of unfixed suspended cells. According to the immunological results, 25 cases were phenotyped as ALL and 15 cases as AML. Cases with blast crisis secondary to chronic myelogenous leukemia (CML-BC) were not represented in this series. In all ALL cases the two methods gave an identical antigenic distribution. In 20 our of 21 cases of non-T-cell ALL, a B-cell progenitor origin was demonstrated by a positive staining reaction with the anti-CD19 McAb AB1 or HD37, and in 10 cases additionally with the anti-CD20 McAb B1 or 1F5. In contrast to the results obtained with IF, IE revealed a poor preservation of the AB1 epitope on CD19, whereas the HD37 epitope was equally well demonstrated by both methods. In 15 cases of AML the distribution of positive versus negative cells with IE or IF was identical for all McAb except J5 (anti-CALLA) (CD10) and B1 (CD20). Thus, 10/15 AML cases expressed CALLA with IE compared to 2/15 with IF. The corresponding figures for B1 were 5/15 and 0/15, respectively. Accordingly, normal myeloid precursor cells were CALLA-positive with IE but negative with IF. The discrepancy probably reflects the fact that, whereas both intracytoplasmatic and membrane-bound antigens are exposed in IE, only the latter are in IF. If the alteration of antigenic accessibility after fixation is considered, IE can safely be used for immunophenotyping of acute leukemia.
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PMID:Immunological typing of acute leukemias: immunoenzymatic staining of fixed cells compared with immunofluorescence staining of unfixed cells in suspension. 245 10

We report on the characterization of four monoclonal antibodies which were prepared against membrane markers of human myeloid lineage. Fusion, isolation of hybridoma cells and their cloning and testing of the monoclonal antibodies by indirect immunofluorescence and FACS 440 analysis were performed by means of standard procedures. The results indicate that the monoclonal antibodies have a specificity against membrane markers of human myeloid lineage (exactly promyelo-granulocytes). These monoclonal antibodies do not react with human T and B lymphocytes, monocytes, erythrocytes and thrombocytes of peripheral blood. In normal bone marrow reactivity to matured myeloid cells was found to occur in promyelocytes and expressed on all granulocytes. These monoclonal antibodies also react with cells of myeloid cell lines and with other precursor cell lines represented by NALM-1, NALM-16, HEL, K-562, REH no reactivity was detected. The produced antibodies react with some leukaemic cells from patients with more mature myeloid cells (AML with promyelocytes, myelocytes and CML) they do not react with pathological cells from patients with CLL, AML (with myeloblasts), ALL, hairy cell leukaemia, erythroleukaemia and several types lymphoma. All antibodies have a IgM class and express granulocytotoxic and granuloagglutination activity. Using flow cytometry comparative analysis with other monoclonal antibodies was performed to detect the membrane structure (X-haptene) included in standard International classification as CD 15 group.
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PMID:Human leukocyte markers defined by monoclonal antibodies. I. Expression of X-hapten structure on cells of myeloid lineage. 246 63

With increasing survival rates of children grafted for different malignancies concerns about the longterm side effects of this treatment are growing. Therefore, investigations on the function of endocrine systems were conducted in a total 28 patients grafted for various reasons: ALL (N = 18), AML (N = 1), SAA (N = 3), CML(N = 4), neuroblastoma (N = 2). The results can be summarized as follows: 1. The extent of hormonal derangements is primarily dependent on the extent of irradiation prior to BMT. Integrity of hormonal systems was found in cases without irradiation (SAA) or if TBI did not exceed 3 Gy. 2. Primary hypogonadism was present in 18 patients. 3. Primary hypothyroidism was present in 2 patients. 4. Growth impairment was observed in 8 patients. In four of these cases growth hormone deficiency was the cause. In four other cases with graft-versus-host-disease and hepatic involvement SmC/IGF I levels were severely diminished. The data suggest that in most cases BMT itself has relatively few negative effects on the endocrine regulatory system. However, more detailed investigations before and after BMT will be needed to further validate these observations.
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PMID:Influence of allogeneic bone marrow transplantation on the endocrine system in children. 248 Mar 5

In the present study plasma fibronectin levels were determined in patients with hematopoietic malignancy, particularly leukemias, in an effort to clarify their clinical implications. Among leukemia patients, those with AML, ALL, ATL or CLL had various plasma fibronectin levels that were higher in some cases, while lower in others, as compared to normal control values. An elevation of the fibronectin level was noted often in APL, while lower fibronectin values were observed in many instances of CML. In these types of leukemia, acute exacerbation as well as supervention of infection tended to be associated with lower than normal levels of fibronectin. An especially marked depression of fibronectin occurred, when leukemia was complicated by sepsis or DIC, in which a good parallel was noted between the progress of disease and the fibronectin level. In lymphoproliferative diseases, the fibronectin value varied widely, but low fibronectin levels were frequently associated with intercurrent infection or an extreme deterioration of the general physical conditions.
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PMID:Variation of plasma fibronectin levels in leukemia patients. 248 45

The indications and results of allogeneic bone marrow transplantation are well known by the analyses of European and International registries. In acute nonlymphoblastic leukemia in first CR, the disease-free survival (DFS) is 45% with a risk of relapse (RR) of 15%, in ALL in first CR the DFS is 60% with a RR of 15%, in ALL in second CR the DFS is 40% with a RR of 30%, and in CML in the chronic phase the DFS is 60%, with a RR of 20%. These results must be adjusted with other risk factors such as age, sex mismatch, disease status, CMV serology, and GvHD. The use of donors who differ from genotypically matched related donors is currently under investigation. Mismatched related transplants give disappointing results except in the case of 1 HLA mismatch. Unrelated HLA-matched donor panels have recently been established in various countries with 200 transplants performed with a DFS of approximately 40%. Researchers are currently trying to reduce the RR by intensifying the conditioning regimen or using the graft-versus-leukemia effect of allogeneic T cells, reducing GvHD by the use of monoclonal antibodies, and improving the engraftment by the use of growth factors. The recent use of cryopreserved cord blood cells for transplantation may improve the results of partially mismatched transplants in children.
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PMID:Recent trends in allogeneic bone marrow transplantation. 248 57


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