Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The linear growth of 26 children with progressive and advanced neuroblastoma treated with high-dose chemotherapy, total body irradiation, and bone marrow transplantation between 1978 and 1988 at the Children's Hospital of Philadelphia was compared with the growth of 33 children who had transplants for leukemia and of 12 who had transplants for aplastic anemia. The mean growth velocity, expressed as a standard deviation score, for the children who underwent bone marrow transplantation for neuroblastoma was -2.83. This was significantly (p less than 0.005) less than the standard deviation scores for children with transplants for acute lymphoblastic leukemia, acute nonlymphocytic leukemia, and aplastic anemia, which were -0.98, -0.07, and -1.05, respectively. A 6-year follow-up study of 32 long-term survivors of cancer revealed that the 11 patients with neuroblastoma continued to grow poorly, whereas a comparison group of 21 survivors of bone marrow transplantation for leukemia had essentially normal growth 2 years after the procedure. Major therapeutic differences between the two groups included the doses of local radiotherapy and the type and number of cytotoxic agents used. In comparison with the relatively mild growth-inhibiting effects of preparative regimens for leukemia and aplastic anemia, the very intensive preparative regimens used in patients with neuroblastoma have significant negative effects on growth.
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PMID:Growth in children after bone marrow transplantation for advanced neuroblastoma compared with growth after transplantation for leukemia or aplastic anemia. 157 7

Since January 1988, 91 children with ANLL have been treated with a polychemotherapy regimen containing Mitoxantrone (MTZ), excluding other anthracyclines. Induction consisted of Ara-C, MTZ, and VP 16. Consolidation lasted 6 weeks with Vincristine, MTZ, Ara-C and 6-thioguanine (6TG), and was followed by 2 intensification courses combining High-dose Ara-C with respectively MTZ or VP 16. Maintenance therapy associated 6TG, Ara-C and MTZ up to a cumulative dose of 150 mg/m2. 91 patients are evaluable: 70 (76.9%) achieved complete remission, 59 (64.8%) after induction alone. There were 7 early deaths, 5 deaths in complete remission, and 17 relapses. Major toxic side effects were observed during the consolidation phase, mainly infectious complications, and the median duration of neutropenia was 82 days in this phase, leading to decrease the MTZ dose from 10 to 8 mg/m2. The event-free survival at three years is 38%. Cardiac toxicity is presently absent in children without previous cardiopathy.
Leukemia 1992
PMID:Mitoxantrone and high dose Ara-C for the treatment of ANLL in childhood: a pilot study of the EORTC CLCG (EORTC 58 872). 157 44

The results of four consecutive trials designed by the GIMEMA group for the treatment of ANLL in elderly patients are reviewed. Complete remission (CR) has been achieved in 20.8% of patients older than 60 years treated with 5-day courses of ARA-C plus thioguanine, in 22.7% of patients treated with high dose ARA-C (HDARAC) plus Asparaginase, in 39.5% of patients aged 55 to 80 receiving either Idarubicin or Daunorubicin in combination with Cytarabine in a standard 3+7 protocol and in 51% of patients older than 60 years treated with intermediate dose ARA-A (IDARAC) plus Mitoxantrone. From 1988, patients ineligible for aggressive chemotherapy entered a study of palliative treatment with Thioguanine and ARA-C. This 18 year GIMEMA experience showed that: CR can be obtained only with regimens producing marrow aplasia, the inclusion of anthracyclines or Mitoxantrone improves the CR rate, without prohibitive toxicity, haematological toxicity is very high in elderly patients and account for the most frequent cause of treatment failure namely death in aplasia, palliative treatment does not improve the quality of life and prolongs median survival only slightly. When comparing the results of these trials, it appears that in the GIMEMA group the capability of offering effective treatment to elderly patients with ANLL has continuously improved and that IDARAC plus Mitoxantrone is so far the most active and best tolerated regimen. Death in aplasia remains a major problem and future trials will be aimed at exploiting the possibility of reducing the haematological toxicity by using recombinant colony stimulating factors.
Leukemia 1992
PMID:Treatment of acute non lymphoid leukemia (ANLL) in elderly patients. The GIMEMA experience. 157 48

One hundred and nine consecutive patients with de novo acute nonlymphocytic leukemia aged over 56 years were admitted with the intention of administering high-dose cytosine arabinoside (HD Ara-C) intensification. After remission induction, the patients were consolidated with a course of daunorubicin (30 mg/m2/day, days 1-3) and Ara-C (100 mg/m2/day, days 1-7), followed by the intensification (Ara-C, 2 g/m2/12 h, days 1-4). The planned induction course was not started in 13 patients because of cardiac failure or unsatisfactory general status. Remission was achieved in 55% (53/96) of the patients. Twenty-seven patients (28%) had refractory disease, seven died early during induction therapy, five died of hemorrhage and three of infection during the hypoplasia that followed induction treatment. Thirty-nine patients started consolidation and 32 had the planned intensification. In these last patients the 3-year leukemia-free survival (LFS) probability was 29% (SE, 8%). No patient died as a consequence of intensification. The relapse rate of the intensified patients did not differ from the relapse rate of those patients who did not receive the planned intensification (p = 0.12). The only pretreatment variables significantly associated with a better LFS were younger age (p = 0.02) and a low WBC at diagnosis (p = 0.04). For the whole patient group, the 3-year survival probability was 15% (SE, 4%). This study shows that elderly patients can tolerate HD Ara-C. The patients completing consolidation-intensification have a currently acceptable LFS. To what extent HD Ara-C contributed to the length of the remissions remains unclear.
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PMID:High-dose cytosine arabinoside intensification for acute nonlymphocytic leukemia in patients over 56 years of age. 158 6

The lamins are intermediate filament proteins that form a fibrous layer at the periphery of the nucleus. Experiments in cell-free systems have suggested that mammalian lamins A and C mediate an interaction between chromatin and the inner nuclear membrane that is essential for the reformation of the nucleus after mitosis. Other investigations, however, have suggested that lamins A and C are absent from myeloid cells and myeloid leukemia cell lines. To further investigate this apparent paradox, highly sensitive Western blotting techniques were utilized in the present study to examine the expression of lamins A and C in a series of human myeloid leukemia cell lines and in bone marrow samples from patients with acute nonlymphocytic leukemia (ANLL) and chronic myelogenous leukemia. Western blotting revealed that HL-60 progranulocytic leukemia cells contained an average of 0.1 x 10(6) copies of lamins A and C per cell compared to 0.5 x 10(6) copies of lamin B1 (the quantitatively prominent human B-type lamin) per cell. During the process of phorbol ester-induced maturation to macrophages, the mRNA for lamins A and C increased in abundance, with a concomitant 4-fold increase in the average cellular content of these polypeptides. To rule out the possibility that the low but detectable levels of lamins A and C observed in untreated HL-60 cells reflected incipient maturation, the content of lamins A and C was analyzed in ANLL cell lines that do not mature toward granulocytes or monocytes. Lamins A and C were readily detected in cell lines (KG1a, HEL, Mo-7e) derived from patients with a variety of subtypes of ANLL. Expression of lamins A and C was not limited to myeloid cell lines. These polypeptides were also detectable in marrow samples from 9 of 26 patients with ANLL including at least 1 patient from each of the 5 subtypes of ANLL examined. In contrast, only 1 of 12 marrow samples from patients with aggressive phase chronic myelogenous leukemia and chronic myelogenous leukemia in blast crisis contained readily detectable lamins A and C. The implications of these findings for current hypotheses regarding the functions of the lamin polypeptides are discussed.
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PMID:Expression of nuclear envelope lamins A and C in human myeloid leukemias. 158 98

In a retrospective study of 352 patients with primary myelodysplastic syndromes, 61 (17.3%) revealed myelofibrosis in bone marrow biopsies. The fibrosis was observed to occur mostly focally (41/61 cases), and collagen deposits were found very rarely (4/61). The histopathology of bone marrow biopsies revealed hyperplasia and disturbed differentiation in megakaryopoiesis; the frequency and grade of dysplasia in megakaryopoiesis increased with advancing myelofibrosis. Reticulin fibrosis occurred in all subtypes of MDS; however, there was a higher incidence in chronic myelo-monocytic leukaemia (CMMoL). The frequency of cytogenetic aberrations was significantly higher in the MDS cases with myelofibrosis, compared to the cases without fibrosis. Clinical data showed significantly lower values of haemoglobin and lower platelet counts in MDS with myelofibrosis. Life expectancy was reduced to 9.6 months, compared with 17.4 months in MDS without fibrosis. In refractory anaemia, the survival times were 10.0 months in MDS with myelofibrosis, compared to 28.9 months in MDS without myelofibrosis. 36.6% of the patients with MDS and myelofibrosis developed a transformation into ANLL during the course of the disease. Myelofibrosis therefore seems to herald a poor prognosis.
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PMID:Myelofibrosis in primary myelodysplastic syndromes: a retrospective study of 352 patients. 159 1

We present the nonrandom occurrence, frequency, and degree of immunophenotype association of the t(1;22)(p13;q13) in children with acute nonlymphocytic leukemia (ANLL). This karyotype anomaly occurred in leukemia cells from five of 445 (1.1%) children with newly diagnosed ANLL who were successfully studied by cytogenetic analysis at four European centers between January 1987 and January 1992. The occurrence of the t(1;22) was restricted to the French-American-British classification (FAB) subtype M7. The overall incidence in children with acute megakaryocytic leukemia (AMKL) was 27.8% (5/18 cases); in infants with AMKL, the frequency of the t(1;22) was 66.7% (4/6 cases). Three of the patients carrying this anomaly had a diploid karyotype, whereas in two cases a hyperdiploid karyotype was found. However, in all five patients, the t(1;22) was the only translocation event present at diagnosis. All patients received aggressive chemotherapy for acute myelogenous leukemia (AML). Two patients died within 15 months of diagnosis without entering remission. One of three patients who entered remission died 7 months after diagnosis, most likely from intramedullar hemorrhage. Only two of the five children with the t(1;22) who received autologous bone marrow transplantation (BMT) are alive and in complete remission (CR) 23 and 40 months after diagnosis, respectively. At the time of diagnosis, the age of the oldest child carrying the t(1;22) was 18 months. The cases with this chromosome anomaly were compared with an age-matched group of five children with AMKL lacking this translocation. The patients with the t(1;22) had a lower median value of the peripheral white blood cell (WBC) count and a higher median hemoglobin level than the patients from the matched group. In the latter cases, normocellular or hypercellular bone marrow (BM) was detected at diagnosis. In contrast, all children with the t(1;22) in our series had a hypocellular BM. Histological BM analyses were available in three of these patients and showed marked fibrosis. Other clinical and laboratory parameters showed no obvious differences between the matched groups. Despite intensive chemotherapy, AMKL in children appears to be associated with a poor prognosis. The clinical courses of the children with AMKL and the t(1;22) presented may be indicative of a beneficial effect of autologous BMT in this subset of patients.
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PMID:The translocation t(1;22)(p13;q13) is a nonrandom marker specifically associated with acute megakaryocytic leukemia in young children. 159 73

A phase II pediatric trial of a continuous intravenous infusion of 6-mercaptopurine (6MP) in patients with refractory leukemia was performed. The dosing schedule, 50 mg m-2 h-1 for 48 h, was based on the results of a previous phase I trial of this approach. Among the 40 children treated for acute lymphoblastic leukemia (ALL), all of whom had received prior therapy with oral 6MP, 1 complete and 1 partial response were achieved. No response was observed in 17 patients with refractory acute nonlymphocytic leukemia (ANLL). Reversible hepatotoxicity, the primary dose-limiting toxicity, was observed in approximately 50% of cases. Mucositis was encountered infrequently and was usually not severe. 6MP given on the present continuous intravenous infusion schedule overcomes the limited and variable bioavailability of oral 6MP but shows limited activity as induction agent in children with recurrent ALL.
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PMID:A phase II trial of continuous-infusion 6-mercaptopurine for childhood leukemia. 160 May 97

Among 50 cases of acute nonlymphocytic leukemia (ANLL) with available cytogenetic data seen in our section since May 1988, two were found to carry a monosomy 21 abnormality which has been rarely reported in hematologic malignancies. The first case is a 58-year-old male with a diagnosis of AML, FAB M2, who died of refractory leukemia 9 months later. The other case is a 59-year-old female with AML, FAB M2. Complete remission was achieved initially but she died of sepsis 3 months later with no evidence of leukemic relapse. Monosomy 21 is not yet recognized as a nonrandom cytogenetic abnormality in ANLL, whereas its unusual predilection in AML, especially the FAB M2 or M4 categories, as noted in our study and others' reports, have raised this possibility. Further studies and the accumulation of new cases are needed in the hope of defining it as a subtype of ANLL.
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PMID:Monosomy 21 in two patients with acute nonlymphocytic leukemia. 163 89

Thirty-seven children and adults who developed acute nonlymphocytic leukemia after the administration of chemotherapy that included etoposide or teniposide for a variety of hematologic and solid malignancies were identified. The secondary leukemia that occurred in these patients could be distinguished from the secondary leukemia that occurs after treatment with alkylating agents by the following: a shorter latency period; a predominance of monocytic or myelomonocytic features; and frequent cytogenetic abnormalities involving 11q23. Patients receiving an epipodophyllotoxin are at risk for developing secondary leukemia that has features distinct from the syndrome of secondary leukemia associated with alkylating agents.
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PMID:Epipodophyllotoxin-related leukemia. Identification of a new subset of secondary leukemia. 164 35


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