Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a family with an inherited constitutional balanced translocation t(3;6)(p14;p11) and hematologic malignancies. Of two proven translocation carriers, one had acute myeloid leukemia and the other had myelofibrosis. A third member who had died of acute leukemia was a possible translocation carrier (chromosome analysis had not been performed). Five healthy translocation carriers were detected. Neither the translocation nor additional hematologic malignancies were found outside the nuclear family. It could not be definitely clarified if this constitutional translocation predisposes to hematologic malignancies. Breakpoint 3p14 has previously been implicated in recurrent cancer-associated rearrangements but 6p11 has not. We suggest that other investigators look for involvement of these breakpoints in cancer patients.
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PMID:Constitutional translocation t(3;6)(p14;p11) in a family with hematologic malignancies. 346 36

The Seattle Marrow Transplant Team treated about 130 patients (age 4-68 yr) for hematologic cancer with supralethal chemoradiotherapy and bone marrow transplantation (BMT) from the normal genetically identical twin. The procedure was well tolerated. The principal problem was tumor resistance. Nevertheless, BMT for acute leukemia in relapse still cured about 20% of the patients. Moreover, BMT performed while in complete remission cured about 50% of patients with acute lymphocytic leukemia or acute nonlymphocytic leukemia. Sixteen patients received transplantation in the chronic phase of Ph1+ chronic granulocytic leukemia (CGL). All showed disappearance of all Ph1+ cells. Two died of pneumonitis. Of the 14 who are alive, 3 continue to have CGL 37-76 months after BMT and 11 remain in complete hematologic and cytogenetic remission without any Ph1+ metaphases at 31-108 months (median = 68) after BMT. Thus the Ph1-positive clone can be ablated and blast crisis prevented. BMT in the accelerated or blastic phase was far less effective. Syngeneic BMT also benefited or cured patients with lymphoma, hairy-cell leukemia, and multiple myeloma. Therefore, BMT should be considered for every patient who has a hematologic cancer and an identical twin.
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PMID:Identical-twin (syngeneic) marrow transplantation for hematologic cancers. 352 68

We reviewed 53 publications reporting 751 patients with hematologic malignancies treated with low doses (5 to 20 mg/m2/d) of cytosine arabinoside (LoDAC). Of 507 patients evaluable for response, complete remission (CR) rates varied from 32% for patients with primary acute non-lymphoblastic leukemia (1 degree ANLL) to 16% for patients with hematologic malignancies secondary to previous chemotherapy or following a myelodysplastic syndrome (MDS) (2 degrees ANLL), and 16% for MDS. Median duration of CR was 9.5 months for 1 degree ANLL, and 10.5 months for both 2 degrees ANLL and MDS. Based on limited available survival data, overall median survival for these groups was 9 months, 3 months, and 15 months, respectively. Only three CRs were reported of 31 evaluable patients treated for a variety of other hematologic malignancies. CR rates for patients with 1 degree ANLL greater than or equal to 50 years old was 56%, compared with 29% less than 50 years old (P = .10). While prior chemotherapy was more common in 1 degree ANLL patients less than 50 years of age (86% v 21%; P less than .001), it did not influence response rates in those greater than 50 years of age, suggesting other biases. Hematologic toxicity was mentioned in only 33 of 53 publications, affecting 254 of 289 patients (88%), with at least 15% treatment-related deaths. LoDAC hypothetically acts as a differentiating agent; however, correlative laboratory studies were rarely performed. Cytogenetic data were available for only 15%, and in vitro studies for 10% of all patients with marked discrepancies in the interpretation of results. LoDAC is clearly cytotoxic for both malignant and normal hematopoietic cells. While large numbers of patients have been reported, the lack of well-designed clinical trials prohibits definitive conclusions as to its role as a differentiating agent. Future LoDAC studies should determine optimal dose and schedule, with clinical laboratory correlates to assess differentiation. Trials in ANLL comparing LoDAC with conventional chemotherapy, and in MDS with supportive care alone, may help identify the role of LoDAC. Until appropriate indications can be identified, LoDAC should not be routinely used in clinical practice.
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PMID:A critical appraisal of low-dose cytosine arabinoside in patients with acute non-lymphocytic leukemia and myelodysplastic syndromes. 353 19

Four patients with aspergillosis of the central nervous system collected in less than two years are reported. Three patients had hematologic malignancies (acute myelogenous leukemia, Hodgkin's disease) and were treated with corticosteroids and chemotherapy. One patient received antimicrobial agents fort a post operative meningitis (after acoustic neuroma surgery). Analysis of these cases and review of literature available us to point out the increased frequency of invasive and cerebral aspergillosis particularly in immunocompromised hosts treated by cytotoxic drugs or broad spectrum antibiotic therapy. Diagnosis is very difficult because: --there are non specific radiologic features for aspergillus granuloma, abscess, aneurysm or meningitis, --blood and cerebrospinal fluid cultures are invariably negative, --serologic tests have limited value in immunosuppressed patients (poor capacity to elaborate antibodies). Diagnosis can be made only by surgical biopsy who isolate fungal elements. However diagnosis in greatest cases is only made at autopsy. Treatment consist by antifungal drugs administered intravenously and surgery when it is possible. Prognosis of cerebral aspergillosis is very poor and mortality rate very high about 70%.
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PMID:[Cerebral aspergillosis. Apropos of 4 cases]. 360 Sep 44

A hematologic malignancy occurred simultaneously with a malignant mediastinal germ cell tumor in two men. In one instance the blood disorder was acute nonlymphocytic leukemia, and in the other, malignant histiocytosis. We subsequently identified nine additional patients, all male (age range 12-48 years), with a mediastinal germ cell tumor and either acute nonlymphocytic leukemia or malignant histiocytosis. Six of the 11 patients had not received either radiation or chemotherapy before development of the hematologic malignancy. One patient developed malignant histiocytosis and was found to have a malignant mediastinal germ cell tumor after having received steroid therapy for a renal allograft. The four remaining patients developed acute nonlymphocytic leukemia 5-32 months after initiation of irradiation or chemotherapy for a mediastinal germ cell tumor. In four patients with acute leukemia, karyotypic analysis established the clonal nature of the leukemic process. Although the leukemia may be therapy-related in four or possibly five patients, this explanation cannot be applied to the remaining six patients. These six patients, coupled with studies of in vitro growth characteristics of teratocarcinoma cells described previously, suggest that a previously unrecognized association between malignant mediastinal germ cell tumors and hematologic malignancies may exist in humans.
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PMID:Association between mediastinal germ cell tumors and hematologic malignancies. Report of two cases and review of the literature. 385 13

Since 1971, 8,483 women with primary breast cancer participated in seven trials evaluating adjuvant chemotherapy. Leukemia occurred in only three of 2,068 patients treated by operation alone. The cumulative risk was 0.06% after 10 years in those free of metastases or a second primary tumor, and 0.27% in those with tumor. Thus, leukemia is not an important factor in the natural history of breast cancer. Five of 646 women receiving postoperative regional radiation developed leukemia, an overall risk of 1.39 +/- .49% at 10 years. Twenty-seven cases of leukemia (0.5%) and seven of myeloproliferative syndrome (0.1%) were recorded in 5,299 patients who received L-phenylalanine mustard (L-PAM)-containing regimens. The maximum cumulative risk of leukemia in chemotherapy recipients (leukemia of any type and myeloproliferative syndrome) was 1.68 +/- .33% at 10 years following operation. The risk excluding those with myeloproliferative syndrome was 1.29 +/- .28%. The risk of leukemia in patients free of metastases or a second primary was 1.11 +/- .30% at 10 years, and when combined with myeloproliferative syndrome, it was 1.54 +/- .36%; risks not significantly greater than observed following radiation (P = .58 and .29). No cases of leukemia were observed during the 2 years of chemotherapy and none have occurred after the seventh postoperative year. Comparisons with the surveillance, epidemiology, and end results tumor registries (SEER) data indicate an increased relative risk of acute myelogenous leukemia following postoperative regional radiation (P less than .01) and adjuvant chemotherapy (P less than .001). The findings indicate that hematologic disorders are side effects of both radiation and alkylating agents used in the adjuvant treatment of primary breast cancer. The risk of such events is lower than that reported following treatment of other solid tumors and hematologic malignancies by chemotherapy. The benefit from adjuvant chemotherapy for breast cancer exceeds the risk of leukemia. Since chemotherapy is not uniformly beneficial, efforts should be directed toward identifying responders so that only those who will benefit are exposed to the risk.
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PMID:Leukemia in breast cancer patients following adjuvant chemotherapy or postoperative radiation: the NSABP experience. 390 49

Combination chemotherapy consisting of etoposide and cytosine arabinoside (Ara-C) was given to 38 children with hematological malignancy. They included 18 patients with acute lymphocytic leukemia (ALL), two with non-Hodgkin's lymphoma (NHL), one with myeloproliferative disorder (MPD), and one with histiocytic medullary reticulosis (HMR), all of whom had relapsed or not responded to initial treatment. Sixteen patients with nonlymphocytic leukemia (ANLL), 13 in remission, two in relapse, and one in induction failure, were also studied. The drug combination was administered by intravenous infusion twice a week for two consecutive weeks at a dosage of 150 mg/m2 for each drug. Among the 18 patients with ALL, seven complete responses and three partial responses were achieved. Six of the seven complete responders relapsed at 0.5-3 months, and the remainder has been in remission for 2.5+ months. None of the patients with refractory ANLL, NHL, MPD or HMR achieved complete remission; however, two of three ANLL patients and one HMR patient demonstrated partial response. Among the 13 ANLL patients in remission, 9 patients have continued remission for more than 4 months with a median of 26+ months, ranging from 6+ months to 40+ months, while 4 relapsed within 4 months after the administration of this regimen. The toxic effects were tolerable. Results indicate that an etoposide and Ara-C combination is effective especially in refractory ALL in childhood.
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PMID:[Etoposide (VP 16/NK 171) and cytosine arabinoside combination chemotherapy in refractory childhood leukemia]. 396 59

Ten women with breast cancer and hematological malignancy (nine with double malignancy and one with triple malignancy) were analyzed. Mastectomy was performed on all patients in our hospital between July 1959 and June 1982 (23 years). Diagnoses of hematological malignancy were seven acute leukemias (five AML, two AMMoL), one CML, two lymphomas and one myeloma. Irradiation and chemotherapy were postoperative treatments in eight and three patients, respectively. The median interval between the first diagnosis and the second was four years and 10 months (one year and five months to 21 years and seven months). The median survival time from the first diagnosis was five years and eight months, while that from the second was six and a half months. In a clinical setting, it is difficult to ascertain the causative factors of multiple malignancy. Accumulation of additional patients is needed for further analysis.
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PMID:[Breast cancer and hematological malignancy in the same patients]. 399 89

Bone marrow collected from patients with hematologic malignancies were cryopreserved using DMSO as a cryoprotective agent. The growth kinetics of hemopoietic stem cells frozen to -196 degrees C were monitored immediately after thawing by the semisolid agar CFU-C assay and 2 different methods of cell reconstitution were compared. In the first way, thawed cells were plated after the removal of DMSO by washing the cell suspension, in the second, cell suspensions were cultured after a simple 1:1 dilution of DMSO with medium. The number of CFU-C per 2 X 10(5) cells plated was higher washing out the DMSO in all the groups studied. However, the absolute numbers of CFU-C contained in the whole ampoules after the freezing procedures was approximately the same with both methods. It is concluded that washing the cells only apparently yielded a better cloning efficiency, suggesting that such a procedure led to a higher mature nucleated cell loss with the consequence of a CFU-C concentration. This trend seems particularly evident in the AML and CML patients.
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PMID:[The use of autologous bone marrow transplants in malignant hemopathies and solid tumors]. 646 Apr 3

We have analyzed G-banded metaphase chromosomes from 20 patients with treatment-associated acute nonlymphocytic leukemia (t-ANLL). Nine patients were previously treated for hematologic malignancies and 11 for solid tumors. The interval from initial therapy to t-ANLL ranged from 35 to 182 mo (median 75.5 mo). Medial age at diagnosis of t-ANLL was 58.5 years. Clonal chromosome abnormalities were found in 19 patients (95%). Loss or partial deletion of the long arm of chromosomes #5 and/or #7 were most common, occurring in nine patients. These abnormalities were associated with hypodiploid complex karyotypes. Other nonrandom abnormalities recurring among karyotypes with abnormalities of chromosome #5 included loss of one #18, partial deletion of the long arm of chromosome #2, ring chromosomes, and a Philadelphia (Ph1) chromosome. We also identified a group of five patients whose only karyotypic abnormality was addition of whole chromosomes. The remaining five patients had other karyotypic abnormalities, the most common of which were structural rearrangements in a pseudodiploid clone. Combined data from our study and the three previously published large series of patients with t-ANLL studied with banding suggest a relationship between karyotype and intensity of prior therapy, with abnormalities of chromosomes #5 and #7 occurring more often in the intensively treated patients.
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PMID:Banded chromosome analysis in patients with treatment-associated acute nonlymphocytic leukemia. 672 61


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