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

Blood cell transplantation (BCT) is now common practice in the autologous setting. We performed a pilot study of allogeneic BCT, collected after the priming of an HLA-identical sibling with a glycosylated rhu-G-CSF (lenograstim) (10 microg/kg). Fifty-four patients were included (38 +/- 11; M/F = 33/21; CML (n = 17), AML (n = 14), ALL (n = 15); MDS (n = 8)). Transplant procedures were standard (TBI regimen = 47 (87%); MTX-CsA: n = 37; CsA-PDN: n = 17). No serious adverse events were reported in donors. A median of 11 (3.5-29.1) x 10(6)/kg CD34+ cells, 332 (33-820) x 10(6)/kg CD3+ cells were collected. Four patients did not engraft (early death: n = 2; graft failure: n = 2). Fifty-one patients initially recovered 0.5 x 10(9)/l ANC and 25 x 10(9)/l platelets at 15 (10-30) and 13 (9-188) days. 29/51 and 29/38 experienced grade > or =2 acute and chronic GVHD. With a median follow-up of 25 months (18-36), relapse rate is 16% +/- 8, survival and DFS probabilities are similar (50% +/- 13). A better outcome is documented for patients under 45 years and in the early phase of the disease (n = 28), with an identical survival and DFS of 71% +/- 13. In conclusion, lenograstim is a potent rhu-G-CSF for mobilisation of allogeneic hematopoietic progenitors. Two-year follow-up indicates good haematological recovery but some concerns about graft failure and chronic GVHD have arisen deserving prospective evaluation.
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PMID:Mobilisation of healthy donors with lenograstim and transplantation of HLA-genoidentical blood progenitors in 54 patients with hematological malignancies: a pilot study. 1045 58

Among 290 BMT procedures: 74 AML, 78 ALL, 34 CML, 6 SAA, 3 MDS, 42 HD, 35 NHL, 11 MM, and 7 solid tumours (breast or testis cancer) Allogeneic BMT was performed in 76 patients and ABMT/APBCT in 214 patients. Survival, DFS and relapse curves were calculated using the Kaplan-Meier product limit method. Variables potentially affecting survival and DFS were assessed in a multivariate analysis by the Cox proportional hazard model in a stepwise regression. The promising results were obtained in high risk adult ALL in the first CR. DFS in CR1 patients transplanted after full dose induction and high dose consolidation was significantly longer if compared to those who received dose/time reduced or postponed treatment. For CR> or =2 patients and with CNS involvement at diagnosis ABMT offers a salvage therapy that needs further improvement. In relapsed and refractory HD better results are obtained in patients relapsing > 1 year after first CR and in patients with entirely nodal localisation of this relapse. In NHL bone marrow and spleen infiltration at diagnosis appear to be an unfavourable prognostic factor.
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PMID:Allogeneic and autologous bone marrow transplantation in single centre experience. 991 50

The oral antitumor drugs against hematological malignancies are summarized. Sobuzoxane, a topoisomerase II inhibitor, is useful for the treatment of lymphoma, especially adult T cell leukemia/lymphoma. Sobuzoxane has an effect to protect against doxorubicin cardiotoxicity. Cytarabine ocfosfate, a derivative of cytosine arabinoside, is a useful agent against acute leukemia and MDS, especially RAEB, RAEB in T, CMMoL. The JALSG AML 92 study for APL with all-trans retinoic acid resulted in a 89% CR rate in 196 and 64% 4-year DFS in CR cases. Hydroxycarbamide is can control the WBC in CML. This agent is also effective for other myeloproliferative disorders, such as acute leukemia and MDS. Oral administration of 50 mg etoposide daily showed a good outcome in old patients with malignant lymphoma. For old patients and those with refractory hematological malignancies, oral administration of these agents can offer a new form of palliative therapy to allow them to remain at home while maintaining a high quality of life.
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PMID:[Oral antitumor drugs for hematological malignancies]. 1006 91

Fitness landscapes, which provide a unique perspective for viewing co-evolving cell populations, were used to study the evolution of CML and MDS. This led to several conclusions: (1) accelerated phase CML and RAEB/RAEBt are not specific disease entities. They represent the time when AML cells are replacing preleukemia cells; (2) monoclonal hemopoiesis and RA/RARS represent a variety of clinical syndromes with a common appearance but with different evolutionary potential; (3) malignant cells alter the fitness landscape enhancing their proliferative advantage. These studies provide the basis for new approaches to treatment.
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PMID:Fitness landscapes and the myeloid leukemias. 1007 Nov 32

Differentiation of essential thrombocythemia (ET) from thrombocythemias occurring in various subtypes of chronic myeloproliferative disorders (MPDs) is controversial, because of the lack of uniform clinical and morphological criteria. A retrospective clinicopathologic study was performed on 375 patients presenting with a MPD and a platelet count exceeding 500 x 10(9/)l. For comparison 35 patients with reactive thrombocytosis (RT) and five patients with a myelodysplastic syndrome (MDS-5q(-) syndrome) were enrolled into this study. In addition to a complete clinicopathological work-up, procedures included histochemical and immunological staining techniques and morphometry of bone marrow biopsies for proper evaluation of megakaryocytes (CD61) and erythroid precursors (Ret40f). Because of the high patient's age on admission, relative survival rates with corresponding disease-specific loss of life expectancy were calculated. Analysis of clinical and morphological characteristics, in particular megakaryopoiesis revealed features which enabled a clear-cut distinction between thrombocythemias in MPDs and thrombocythemic states in MDS. This rationale proved to be most important for the diagnostic discrimination of the 33 patients with initial (prefibrotic) stages of idiopathic myelofibrosis (IMF) from ET (40 patients). A new set of relevant criteria for the diagnosis of IMF with special regard to early stages and its distinction from ET has been proposed. Hemorrhagic episodes were more frequently observed in ET than in thrombocythemias associated with polycythemia vera (PV). Computation of specific loss of life expectancy revealed two extremes: thrombocythemia in CML (81%) and ET (3%), whereas thrombocythemias in PV and IMF did not show a significantly different life loss (19-22%). The revised criteria for ET, PV and IMF are reliable by taking histopathological features from bone marrow biopsies into consideration, particularly for the diagnosis of ET and its differentiation from thrombocythemias as a presenting symptom accompanying the various subtypes of MPDs.
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PMID:Clinicopathological diagnosis and differential criteria of thrombocythemias in various myeloproliferative disorders by histopathology, histochemistry and immunostaining from bone marrow biopsies. 1022 1

The two matrix metalloproteinases (MMPs) Mr 72,000 type IV collagenase (MMP-2, gelatinase A) and Mr 92,000 type IV collagenase (MMP-9, gelatinase B) play key roles in tissue remodeling and tumor invasion by digestion of extracellular matrix barriers. We have investigated the production of these two enzymes as well as the membrane-type MMP (MT1-MMP) and the tissue inhibitors of metalloproteinases (TIMPs) TIMP-1 and TIMP-2 in the bone marrow mononuclear cells (BM-MNCs) of patients with acute myeloid leukemia (AML; n = 24), chronic myeloid leukemia (CML; n = 17), myelodysplastic syndromes (MDS; n = 8), and healthy donors (n = 5). Zymographic analysis of BM-MNC-conditioned medium showed that a Mr 92,000 gelatinolytic activity, identified as MMP-9 by Western blotting, was constitutively released from cells of all patients and healthy individuals examined in this study. In contrast, MMP-2 secretion was found to be absent in all samples from healthy donors but present in 8 of 11 (73%) of the samples from patients with primary AML, 7 of 8 (88%) with secondary AML, and only 1 of 5 (20%) cases with AML in remission, indicating MMP-2 to be produced by the leukemic blasts. MMP-2 release was not detected in CML cell-conditioned medium with the exception of two cases, both patients either being in or preceding blast crisis. In MDS, MMP-2 was found in three of eight (38%) of the patients, two of them undergoing progression of disease within 12 months. Quantitative Northern blot analysis in freshly isolated BM-MNCs showed a relatively low constitutive expression of TIMP-1 in all samples, whereas MMP-9 gene transcription was higher in healthy donors and CML samples, than in AML and MDS. Reverse transcriptase-PCR analysis revealed the presence of TIMP-2 mRNA in the majority of MMP-2-releasing BM-MNCs. MT1-MMP expression was present in most samples of patients with MDS or AML but absent in those with secondary AML and CML. Thus, we have shown that BM-MNCs continuously produce MMP-9 and TIMP-1 and demonstrated that leukemic blast cells additionally secrete MMP-2 representing a potential marker for dissemination in myeloproliferative malignancies.
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PMID:Matrix metalloproteinase production by bone marrow mononuclear cells from normal individuals and patients with acute and chronic myeloid leukemia or myelodysplastic syndromes. 1035 46

An isochromosome of the long arm of chromosome 17, i(17q), is the most frequent genetic abnormality observed during the disease progression of Philadelphia chromosome-positive chronic myeloid leukemia (CML), and has been described as the sole anomaly in various other hematologic malignancies. The i(17q) hence plays a presumably important pathogenetic role both in leukemia development and progression. This notwithstanding, the molecular consequences of this abnormality have not been investigated in detail. We have analyzed 21 hematologic malignancies (8 CML in blast crisis, 8 myelodysplastic syndromes [MDS], 2 acute myeloid leukemias, 2 chronic lymphocytic leukemias, and 1 acute lymphoblastic leukemia) with i(17q) by fluorescence in situ hybridization (FISH). Using a yeast artificial chromosome (YAC) contig, derived from the short arm of chromosome 17, all cases were shown to have a breakpoint in 17p. In 12 cases, the breaks occurred within the Smith-Magenis Syndrome (SMS) common deletion region in 17p11, a gene-rich region which is genetically unstable. In 10 of these 12 cases, we were able to further map the breakpoints to specific markers localized within a single YAC clone. Six other cases showed breakpoints located proximally to the SMS common deletion region, but still within 17p11, and yet another case had a breakpoint distal to this region. Furthermore, using chromosome 17 centromere-specific probes, it could be shown that the majority of the i(17q) chromosomes (11 of 15 investigated cases) were dicentric, ie, they contained two centromeres, strongly suggesting that i(17q) is formed through an intrachromosomal recombination event, and also implicating that the i(17q), in a formal sense, should be designated idic(17)(p11). Because i(17q) formation results in loss of 17p material, potentially uncovering the effect of a tumor suppressor on the remaining 17p, the occurrence of TP53 mutations was studied in 17 cases by sequencing the entire coding region. In 16 cases, no TP53 mutations were found, whereas one MDS displayed a homozygous deletion of TP53. Thus, our data suggest that there is no association between i(17q) and coding TP53 mutations, and that another tumor suppressor gene(s), located in proximity of the SMS common deletion region, or in a more distal location, is of pathogenetic importance in i(17q)-associated leukemia.
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PMID:Isochromosome 17q in blast crisis of chronic myeloid leukemia and in other hematologic malignancies is the result of clustered breakpoints in 17p11 and is not associated with coding TP53 mutations. 1038 17

Treatment-related (Tr) AML and MDS after chemotherapy, radiotherapy, or the combination of both have been well characterized. However, tr-CML seems to differ from these better-known entities in frequency, clinical course, and prognosis. Tr-CML cannot be distinguished from de novo CML cytogenetically, and, in contrast to tr-AML and tr-MDS, typical chromosomal aberrations related to tr-CML have not been described. Treatment-related CML is a late effect of cytotoxic or immunosuppressive therapy which might be increasingly recognized due to a higher number of patients treated with intensive therapy regimens. We review here the available data on incidence of tr-CML as well as the affected individual's characteristics with regard to different treatment options in malignant and nonmalignant diseases.
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PMID:Treatment-related chronic myelogenous leukemia. 1046 Mar 47

Between October 1995 and October 1998, 24 children aged 9 months to 17 years (median 11 years) underwent cytokine-mobilized allogeneic peripheral blood stem cell (PBSC) transplantation for treatment of hematological disorders. All of the transplants were the first allogeneic transplant for the recipient. Twenty patients were transplanted for hematological malignancies (ALL = 8, AML = 6, CML = 4, MDS = 2) and four patients were transplanted for non-malignant disease (thalassemia major = 2, Wiskott-Aldrich syndrome = 1, Kostmann's syndrome = 1). Nineteen donors were HLA-identical siblings, four were HLA-matched or single antigen mismatched parents, and one was a syngeneic transplant. Donors aged 8 to 38 years (median 15 years, 14 donors <18 years) received G-CSF 10 microg/kg/day subcutaneously beginning 4 days before PBSC collection and were submitted to one to three leukapheresis collections. The median CD34+ cell yield was 7.8 x 106 cells/kg recipient body weight. All patients achieved an ANC >0.5 x 109/l after a median of 13 days (range 10-21). Twenty-three patients eventually achieved platelet transfusion independence. One patient died on day 63 without ever achieving platelet transfusion independence. Four patients received platelet transfusions to maintain a platelet count well above 20 x 109/l due to bleeding complications. Of the 19 evaluable patients, the median time to a non-transfused platelet count of 20 x 109/l was 12 days (range 0-44). Ten of 23 at-risk patients developed acute GVHD grades II to IV, with grades III to IV in four patients. Twelve of 19 patients followed for at least 100 days have developed chronic GVHD (extensive = 2, limited = 10) with an actuarial risk of chronic GVHD of 75% at 1 year. The Kaplan-Meier estimate of event-free survival is 65% at 2 years. Four patients died (GVHD = 3, VOD = 1), three patients relapsed, and one patient with thalassemia major had a late graft failure with autologous recovery. Based upon our experience, allogeneic PBSCT is safe for both pediatric donors and recipients and engraftment of neutrophils and platelets is rapid. Bone Marrow Transplantation (2000) 25, 13-18.
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PMID:Cytokine-mobilized allogeneic peripheral blood stem cell transplants in children result in rapid engraftment and a high incidence of chronic GVHD. 1065 8

Differentiation of an elevated, repeatedly determined platelet count (> or =500x10(9)/l) includes the discrimination between reactive causes generated by a variety of underlying conditions and a neoplastic myeloproliferative disorder (CMPD). In addition to clinical findings, the evolution of laboratory data during follow-up and histology of the bone marrow exerts a significant diagnostic impact. Characteristic features are not only expressed by hematopoiesis, but also by the myeloid stromal compartment. While the megakaryocyte-rich subtype of chronic myeloid leukemia (CML) and the 5q(-) syndrome (MDS) are dominated by abnormal micromegakaryocytes, in polycythemia vera (PV) this cell lineage reveals a pleomorphous appearance. In essential thrombocythemia (ET), a prevalence of giant megakaryocytes with deeply lobulated (staghorn-like) nuclei may be encountered. A clear-cut discrimination of ET from early (hypercellular) stages of idiopathic (primary) myelofibrosis (IMF) presenting with thrombocythemia becomes possible, provided the conspicuous atypical features of megakaryopoiesis characterizing the latter entity are taken into account. Moreover, CML displays a predominance of the granulocytic lineage whereas PV shows a panmyelosis or trilineage proliferation, involving erythropoiesis, in particular. In contrast, erythropoiesis is markedly reduced in CML and to a lesser degree also in IMF. In CMPDs extreme values of iron deposits may be found, ranging from a total lack (PV) to minor amounts (CML) and a normal staining reaction (ET). Similar results are exhibited regarding reticulin fibrosis, which is usually not present in ET, rarely observed in PV and detectable to a variable degree in CML and IMF.
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PMID:[Thrombocytosis versus thrombocythemia--differential diagnosis of elevated platelet count]. 1066 67


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