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)

Sixteen patients [13 acute nonlymphocytic leukemia (ANLL), 2 acute lymphocytic leukemia, 1 chronic myelogenous leukemia in a blast crisis; median age, 40 yr; range, 25-78 yr; 9 male, 7 female] received 23 courses of carboplatin given as a bolus on a daily X 5 schedule. Six patients were given 7 courses of carboplatin at 200 mg/m2/day; 3 patients received 5 courses at 250 mg/m2; 9 patients received 11 courses at 300 mg/m2; 2 patients initially treated at 200 mg/m2 were given their 2nd course at 300 mg/m2. Significant hearing loss documented by audiometry occurred in five patients, including three of nine treated at 300 mg/m2. All five had prior or recent exposure to aminoglycoside antibiotics. Three patients developed cancer and acute leukemia group B grade 3 or 4 mucositis, and 18 of 23 courses were complicated by nausea and vomiting. Marrows were hypocellular or aplastic in all patients treated at the highest dose. No complete responses occurred, although two patients with ANLL treated at 300 mg/m2 achieved partial responses lasting 71 and 138 days. The t1/2 alpha [half-life (t1/2)], t1/2 beta, and total body clearance of ultrafilterable platinum were comparable to those previously described by us in patients receiving bolus doses of carboplatin of 22-77 mg/m2/day X 5. Carboplatin has activity in ANLL.
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PMID:Phase I and pharmacokinetic trial of carboplatin in refractory adult leukemia. 327 22

The fundamental pathogenetic significance of the Ph chromosome abnormality in CML has been clarified by molecular studies. However, this balanced reciprocal t(9;22) is probably not the primary event in the pathogenesis of this disease, at least at a cytogenetic level. The cause of Ph variants in +/- 5% of patients is still unknown. Improvements in cytogenetic techniques and molecular studies in a limited number of cases indicate that simple variants do not exist: Region 9q34 appears to be involved in all types of Ph variants. There is tentative evidence that these variants may in fact represent a clonal evolution from a standard t(9;22). The types of additional secondary abnormalities found in Ph variants are the same as those commonly found in standard cases. Ph negative CML represents a heterogeneous group of myeloproliferative/myelodysplastic disorders. The various mechanisms that could lead to Ph negativity are discussed. Some karyotypically normal cases and those showing a chromosome abnormality other than the Ph during the chronic phase have shown the same molecular changes as found in Ph positive CML. The types of clonal changes accompanying transformation to an acute phase are similar to those seen in myeloid disorders as a whole. The prognostic karyotypic factors in predicting imminent metamorphosis to the acute stage and during the acute phase are discussed. The extent of clonal evolution, the type of secondary abnormalities, and their relationship to the hematopoietic lineage of blast cells should be assessed. The nonrandom clonal changes found in 80% of cases are +Ph, +8, i(17q), +19, and loss of the Y. The significance of +Ph is possibly related to amplification of the bcr/abl fusion gene product, but the reason for the other persistent nonrandom changes is still speculative. Recent cytogenetic data indicate that the specific changes observed in various types of ANLL may be seen in corresponding types of MT, such as t(15;17) in promyelocytic transformations and abnormalities of 3q21-3q26 in megakaryoblastic transformations. Patients with LT usually have an early precursor B phenotype associated with a better prognosis. They tend to have either normal or hypodiploid karyotypes. An i(17q) is never seen and +8 and +19 are absent in most series. Duplication of the Ph and loss of the Y are common to both MT and LT. Data relating 14q+ abnormalities to LT are presently ambiguous.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cytogenetics of chronic myelogenous leukemia. 327 13

Twenty-nine patients were conditioned for allogeneic marrow transplant with cytarabine (ara-C) (3 g/m2 every 12 hours for 12 doses) and total body irradiation (TBI) (200 cGy daily for six days) with or without cyclophosphamide (CY) (60 mg/kg) to determine toxicity and efficacy. Four patients had chronic myelogenous leukemia (CML) in accelerated phase or blast crisis, and 25 patients had acute leukemia, 24 at stages later than first remission. Three patients (10%) had fatal regimen-related toxicity and another 10% experienced severe toxicity in at least one organ system. The addition of CY to the ara-C and TBI regimen was not associated with an increase in the frequency of severe toxicity. Twenty-five of 29 patients engrafted eight to 33 days posttransplant: three died early before engraftment, and one patient failed to engraft. Ten of 29 patients are alive without disease, and the actuarial probability of disease-free survival for the entire group at 3 years is 33%. Three of ten patients with acute nonlymphocytic leukemia (ANL), six of 15 with acute lymphocytic leukemia (ALL), and one of four with CML are alive and disease free 25 to 42 months (median, 30 months) after transplant. High-dose ara-C (HDara-C) and TBI with or without CY can be administered with approximately the same toxicity as CY plus TBI. Phase III studies appear warranted to determine if these newer regimens provide improved results compared with currently used regimens.
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PMID:High-dose cytarabine and total body irradiation with or without cyclophosphamide as a preparative regimen for marrow transplantation for acute leukemia. 328 31

Two cases of Philadelphia chromosome positive chronic myelogenous leukemia (CML) demonstrated ring chromosomes. The appearance of the ring coincided with evolution from the stable to the aggressive phase. A literature search yielded six other cases of ring chromosomes in CML; all were in or were entering the aggressive phase of the disease. Thus, as is the case with acute nonlymphocytic leukemia, in CML the finding of an acquired ring chromosome is associated with a poor prognosis.
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PMID:Ring chromosomes in chronic myelogenous leukemia: an ominous finding. 328 14

Busulfan 16 mg/kg and cyclophosphamide 120 mg/kg were used as conditioning prior to allogeneic marrow transplantation in 50 adult patients with acute nonlymphocytic leukemia (ANLL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML). A standard risk group of 20 patients included those with acute leukemia in remission and CML in chronic phase. A high-risk group of 30 patients included individuals with refractory acute leukemia, acute leukemia in relapse, acute leukemia following preleukemia, and CML in accelerated and blastic phase. Complete remission and sustained complete engraftment were achieved in all evaluable patients. The duration of aplasia was remarkably short (median of 8 days), resulting in a low infection rate during the period of neutropenia, a reduced need for blood product support, and a short length of hospital stay. Three-year actuarial relapse-free survival in both standard-risk (88.9% +/- 10.5%) and high-risk (50.5% +/- 9.6%) groups compares favorably with that reported with total body irradiation (TBI) containing regimens.
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PMID:Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. 331 Dec 3

Six patients with Philadelphia-positive (Ph1+) acute nonlymphocytic leukemia (ANLL) were studied by morphological, immunological, cytogenetic, and molecular techniques. Seven Ph1+ acute lymphocytic leukemia (ALL) cases were also studied for comparison. Three of ANLL cases were classified in M1, M2, and M4 groups of the FAB nomenclature, while the three other cases do not fit with any FAB subgroup and are described as M0. Immunophenotypical marker studies, double immunolabeling, and combined immunological and cytogenetic studies of metaphases showed that these ANLL expressed several lineage differentiation antigens. Rearrangements of immunoglobulin heavy chain gene (C mu) were detected in the six ANLL cases and in the seven ALL cases studied, as well as, in most cases, rearrangement of T cell receptor beta chain genes and/or T cell rearranging gamma genes. The results favored the assumption that the Ph1 translocation originated from a multipotent stem cell in Ph1+ ANLL. A common t(9;22) translocation was found in all cases, and additional chromosomal abnormalities were present in the six ANLL cases and in five of the seven ALL cases. Molecular studies of bcr gene configuration and c-abl transcription allowed two groups of Ph1+ ANLL to be distinguished. Three cases had bcr rearrangement and c-abl mRNA expression comparable to those reported in Ph1+ chronic myeloid leukemia, while three others had not detectable bcr rearrangement and a 7.2-7.5 kb c-abl mRNA. The existence of Ph1+ ALL with and without classical bcr rearrangement was confirmed.
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PMID:Philadelphia-positive acute leukemia: lineage promiscuity and inconsistently rearranged breakpoint cluster region. 337 67

Human leukocyte antigen-DP (HLA-DP) typing was performed on patients with chronic myelogenous leukemia (CML, n = 44), acute nonlymphoblastic leukemia (ANLL, n = 34), or acute lymphoblastic leukemia (ALL, n = 41). Frequencies of DPw alleles in CML and ANLL patients were not significantly different from 254 controls, except that in ANNL DPw1 was absent. This was most likely due to the concurrent absence of DR3 with which DPw1 is in linkage. In contrast, in ALL, frequencies of DPw2 and DPw5 were significantly increased (corrected P less than 0.05, relative risk (RR) = 2.19 and corrected P less than 0.01, RR = 6.92, respectively). This was not due to linkage with DR. The frequency of DPw1 also tended to be reduced, but this was not caused by a similar decrease of DR3 in ALL. These results, therefore, demonstrate both positive and negative associations between major histocompatibility complex (MHC) gene products which are in only very weak linkage with the rest of HLA, and acute lymphocytic, but neither acute nor chronic myelogenous, leukemias. The HLA-DP region could thus contain long sought-after genes influencing susceptibility and resistance to leukemogenesis.
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PMID:Human leukocyte antigen-DP in leukemia. 342 71

Recombinant plasmid cDNA libraries representing the polyadenylated RNAs in the myeloid cell lines KG1 and ML1 have been constructed. The screening protocol has identified several clones which contain sequences homologous to RNAs expressed at high abundance in one or more of the myeloid cell lines KG1, ML1 and HL60. The relative abundances of RNAs homologous to three recombinants, pML15, pKG21 and pKGA/F5 were measured by an RNA dot hybridisation method in total RNAs isolated from peripheral blood leukocytes from leukaemic patients and normal individuals. High levels of these RNAs were observed mainly in ANLL and acute phase CML samples. The data suggest that these probes have the potential to sub-divide the ANLLs and to extend a molecular classification of the myeloid leukaemias.
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PMID:Isolation of molecular hybridisation probes for early myeloid lineage RNAs. 343 16

The incidence of characteristic nonrandom chromosome aberrations in malignant cells of unselected, consecutively studied, and previously untreated patients from various geographic regions has been surveyed. The results demonstrate significant geographic heterogeneity in the distribution of the specific aberrations considered among the four malignant disorders studied in a sufficient number to permit conclusions, viz., acute nonlymphocytic leukemia, chronic myeloid leukemia, polycythemia vera, and myelodysplastic syndrome.
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PMID:Geographic heterogeneity of chromosome aberrations in hematologic disorders. 345 65

Twelve pediatric patients with nonlymphocytic leukemia were treated for 10 days with high-dose (15, 20, or 30 million U/m2/day) human lymphoblastoid interferon (Wellferon) administered by continuous iv infusion. Nine children had acute nonlymphocytic leukemia (ANLL) in relapse, two had Philadelphia chromosome-positive chronic myelocytic leukemia in myeloblastic crisis, and one had juvenile chronic myelocytic leukemia. Blast cell counts in the peripheral blood decreased in five patients with ANLL treated with the higher interferon doses; however, there was no evidence of an antileukemic effect in the marrow. Dose-limiting toxicity, which included malaise, hepatotoxicity, and coagulation abnormalities, was observed in patients given 20 or 30 million U/m2/day. Studies of the growth of leukemic progenitor cells in vitro in the presence of interferon disclosed a concentration-related inhibition of colony formation. Patients who had a decrease in peripheral blast cell counts demonstrated greater in vitro inhibition of clonogenic leukemic progenitors than patients whose blast cell counts did not decrease. However, the serum interferon concentrations in patients given clinically tolerable doses were lower than those concentrations which inhibited leukemic cell growth in vitro by a median of 42% (1000 U/ml). This study failed to demonstrate clinically significant antileukemic activity against nonlymphocytic leukemia in patients given high-dose constant-infusion interferon, and the toxicity of this approach was prohibitive.
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PMID:Phase I-II study of continuous-infusion high-dose human lymphoblastoid interferon and the in vitro sensitivity of leukemic progenitors in nonlymphocytic leukemia. 345 33


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