National Cancer Institute®
Last Modified: February 1, 2002
UI - 11593299
AU - Dorlhiac-Llacer PE; Marquezini MV; Toffoletto O; Carneiro RC; Maranhao
TI - RC; Chamone DA In vitro cytotoxicity of the LDE: daunorubicin complex in acute myelogenous leukemia blast cells.
SO - Braz J Med Biol Res 2001 Oct;34(10):1257-63
AD - Departamento de Hematologia e Hemoterapia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil. firstname.lastname@example.org
Acute myelogenous leukemia (AML) blast cells show high-affinity degradation of low-density lipoprotein (LDL), suggesting an increased expression of cellular LDL receptors. LDE is a lipid microemulsion easily synthesized in vitro which is known to mimic the metabolic pathway of LDL. We used LDE as a carrier for daunorubicin and assayed the cytotoxicity of the complex using AML blast cells since RT-PCR analysis showed that AML cells express LDL receptor mRNA. The LDE:daunorubicin complex killed 46.7% of blast cells and 20.2% of normal bone marrow cells (P<0.001; Student t-test). Moreover, this complex destroyed AML blast cells as efficiently as free daunorubicin. Thus, LDE might be a suitable carrier of chemotherapeutic agents targeting these drugs to neoplastic cells and protecting normal tissues.
UI - 11804070
AU - Wollina U; Sayer HG; Wollina K; Graefe T
TI - Very late appearance of acute graft-versus-host disease after tapering immunosuppression.
SO - J Dermatol 2001 Dec;28(12):734-6
AD - Department of Dermatology and Allergology, School of Medicine, Friedrich-Schiller-University of Jena, Germany.
Graft-versus-host disease (GVHD) is a major complication of stem cell transplantation. Here we report a 40-year-old woman who developed an acute GVHD 30 months after transplantation. Late and very late appearance of acute GVHD has only been described in rare cases.
UI - 11501968
AU - Ozpolat B; Lopez-Berestein G; Mehta K
TI - ATRA(ouble) in the treatment of acute promyelocytic leukemia.
SO - J Biol Regul Homeost Agents 2001 Apr-Jun;15(2):107-22
AD - Department of Bioimmunotherapy, The University of Texas, MD Anderson Cancer Center, Houston 77030, USA.
Acute promyelocytic leukemia (APL) is a unique disease that responds to differentiation-inducing effects of all-trans-retinoic acid (ATRA). ATRA induces complete clinical remissions (CRs) in most patients and now constitutes a standard therapy in patients with APL. However, CRs induced by ATRA are usually brief, and resistance to the therapy rapidly develops, leading to relapses in almost every patient; thus limiting the use of ATRA as a single agent. On the basis of clinical and in vitro studies, the following mechanisms have been proposed to explain ATRA resistance: 1) induction of accelerated metabolism of ATRA, 2) increased expression of cellular retinoic acid-binding proteins (CRABPs), 3) constitutive degradation of PML-RAR alpha, 4) point mutations in the ligand-binding domain of RAR alpha of PML-RAR alpha, 5) P-glycoprotein expression, 6) transcriptional repression by histone deacetylase activity, 7) isoforms of PML-RAR alpha, 8) persistent telomerase activity, and 9) expression of type II transglutaminase. In this review, we discuss the evidence provided in support of each mechanism, the mechanism's possible impact on the outcome of APL, and the newer approaches that are being employed to overcome ATRA resistance.
UI - 11737750
AU - Sakamoto O; Yoshinari M; Rikiishi T; Fujiwara I; Imaizumi M; Tsuchiya S;
TI - Iinuma K Hypercalcemia due to all-trans retinoic acid therapy for acute promyelocytic leukemia: a case report of effective treatment with bisphosphonate.
SO - Pediatr Int 2001 Dec;43(6):688-90
AD - Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. email@example.com
UI - 11743652
AU - Suwanai H; Matsushita H; Kobayashi H; Ikeda Y; Kizaki M
TI - A novel therapeutic technology of specific RNA inhibition for acute promyelocytic leukemia: improved design of maxizymes against PML/RARalpha mRNA.
SO - Int J Oncol 2002 Jan;20(1):127-30
AD - Division of Hematology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Targeting of PML/RARalpha using a loss of function strategy in acute promyelocytic leukemia (APL) is a direct therapeutic approach for patients and may be the basis of future gene therapy for this leukemia. To achieve this, we designed specific maxizymes, novel allosterically controllable ribozymes, against both short and long PML/RARalpha isoforms. The maxizyme has sensor arms that can only recognize target sequences, and it can form a cavity that captures catalytically indispensable Mg2+. We deleted 1 base nucleotide in the Mg2+-binding pocket designed MzPRT50 and MzPRK55. The distance from the PML/RARalpha junction site to the center of effectors is only 2 bases, and there are 8 and 9 complementary bases in their inactive forms, respectively. Both maxizymes specifically cleaved PML/RARalpha mRNA but not wild-type RARalpha mRNA in a cell-free system. Modification of the sequence of the Mg2+-binding pocket will be important in designing the sequence-specific maxizymes against oncogenic genes.
UI - 11779431
AU - Guo W; Wang H; Zhao W; Zhu J; Ju B; Wang X
TI - Effect of all-trans retinoic acid and arsenic trioxide on tissue factor expression in acute promyelocytic leukemia cells.
SO - Chin Med J (Engl) 2001 Jan;114(1):30-4
AD - Shanghai Institute of Hematology, Ruijin Hospital Affiliated Shanghai Second Medical University, Shanghai 200025, China.
OBJECTIVE: To study the effect of all-trans retinoic acid (ATRA) and arsenic troxide (As2O3) on tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia (APL) cells in vivo and in vitro. METHODS: PCA from freshly isolated APL blasts from APL patients treated with ATRA or As2O3 was detected using a one-stage clotting assay. TF antigen was detected by ELISA and TF mRNA by RT-PCR. The maturation sensitive (NB4) or resistant subclones (NB4-R1) of the promyelocytic NB4 cell line, as well as U937 cells infected with pMSCV-PML-RARa treated with or without ATRA or As2O3, were also examined. RESULTS: Both ATRA and As2O3 can down-regulate the TF antigen, its mRNA transcription and membrane PCA of APL cells in vivo and in vitro, in a time-dependent manner. The TF antigen level in PML-RARa + U937 cells was significantly higher than that in U937 cells infected with retrovirus vector. Both ATRA and As2O3 can also down-regulate the TF antigen in U937 cells transfected with or without PML-RARa. CONCLUSION: Tissue factor expression and PCA in APL cells may be down-regulated by ATRA and As2O3. By down-regulating TF expression, As2O3 might also be used to improve the DIC-related hemorrhage in APL. Our data indicate that elevated TF antigen in PML-RARa + U937 may be related to the fusion protein PML-RARa. The down-regulating effect of ATRA and As2O3 on TF expression in U937 cells might not involve this fusion protein.
UI - 11697629
AU - Ritchie DS; Wirth A; Grigg AP
TI - Successful transplant outcome in a morbidly obese patient with acute myeloblastic leukemia.
SO - Leuk Lymphoma 2001 Sep-Oct;42(5):1111-4
AD - Department of Clinical Haematology and Medical Oncology, Royal Melbourne Hospital, Australia.
We report a case of matched unrelated bone marrow transplant (BMT) in a morbidly obese patient with acute myeloblastic leukaemia. The challenges presented in the management of this case included the calculation of chemotherapy and radiotherapy doses and the acute presentation of obstructive sleep apnea. Despite these difficulties, an ultimately successful outcome was obtained, indicating that although associated with increased risk of peri-transplant morbidity, obesity need not represent a contraindication to BMT.
UI - 11697646
AU - Stein RS; Wolff SN; Greer JP; Flexner JM; Goodman S; Jagasia M; Brandt
TI - SJ; Morgan DS; Arrowsmith E; McCurley TL Age and cytogenetics as predictors of event free survival in patients with acute non-lymphocytic leukemia receiving high dose cytosine arabinoside and daunorubicin as consolidation chemotherapy.
SO - Leuk Lymphoma 2001 Sep-Oct;42(5):913-22
AD - Department of Medicine, Vanderbilt University School of Medicine, and VA Medical Center, Nashville, TN, USA. firstname.lastname@example.org
Between 1991 and 1999, 67 patients with acute non-lymphocytic leukemia (ANLL) in complete remission received high dose cytarabine (HiDAC) 3 gm/m2 q12h x 12 doses followed by daunorubicin 45 mg/m2/day x 3 days as consolidation therapy. Five year actuarial event free survival (EFS) was 34% +/- 6%. Age was significantly associated with EFS. EFS was 60% +/- 15% in patients age 20 to 29, 48% +/- 16% in patients age 30 to 39, 23% +/- 10% in patients age 40 to 49, 31% +/- 11% in patients age 50 to 59, and 0% in patients age > or = 60. Contrary to other reports which have used different HiDAC regimens, we found no relationship between cytogenetics and EFS. Cytogenetics were defined as favorable risk: t(8;21), inv (16), and del (16); neutral risk: normal or t(15;17); and unfavorable risk: any abnormality not included in favorable risk or neutral risk. EFS was 29% +/- 17% in patients with favorable cytogenetics, 37% +/- 14% in patients with neutral cytogenetics, and 31% +/- 12% in patients with unfavorable cytogenetics. These differences were not statistically significant. Because of the successful use of allogeneic transplantation at relapse in patients with matched related donors, five year actuarial survival (S) in this series was 40% +/- 6%. Five year actuarial survival was 57% +/- 9% for patients age < or = 44 and 25% +/- 8% for patients age > or = 45. This difference is statistically significant, p < .025. Clinicians should be cautious about making clinical decisions regarding consolidation therapy of ANLL on the basis of the presence or absence of cytogenetic abnormalities as the importance of cytogenetics may depend on the specific therapy which is employed.
UI - 11734299
AU - Kishino K; Muroi K; Kawano C; Obata T; Sugano N; Nakagi Y; Nagashima T;
TI - Watari K; Iwamoto S; Ozawa K Evaluation of engraftment by ABO genotypic analysis of erythroid burst-forming units after bone marrow transplantation.
SO - Leuk Res 2002 Jan;26(1):13-7
AD - Division of Cell Transplantation and Transfusion, Jichi Medical School, Minamikawachi, 329-0498, Tochigi, Japan.
Six patients received an allogeneic bone marrow transplant from HLA-identical ABO-mismatched donors. ABO genotype of erythroid burst-forming units (BFU-E) from peripheral blood was analyzed using polymerase chain reaction with sequence specific primers (PCR-SSP). After bone marrow transplantation (BMT), engraftment of donor cells by ABO genotypic analysis of BFU-E was compared with ABO phenotypic analysis of red blood cells (RBCs). During the early stage after BMT, ABO genotype of BFU-E in the recipients converted to that of the donors. In contrast, mixed ABO phenotype of RBCs persisted for about 3 months. In one patient, autologous hemopoietic cell recovery was detected by the ABO genotypic analysis before clinical manifestation. ABO genotypic analysis of BFU-E is relevant for enagraftment after ABO-mismatched BMT.
UI - 11587228
AU - Fadilah SA; Hatta AZ; Keng CS; Jamil MA; Singh S
TI - Successful treatment of acute promyelocytic leukemia in pregnancy with all-trans retinoic acid.
SO - Leukemia 2001 Oct;15(10):1665-6
UI - 11086179
AU - Thomas X; Cambier N; Taksin AL; Reman O; Vekhoff A; Pautas C; Leblond V;
TI - Soler-Michel P; Ecstein-Fraisse E; Archimbaud E Dose-escalation study of single dose mitoxantrone in combination with timed sequential chemotherapy in patients with refractory or relapsing acute myelogenous leukemia.
SO - Leuk Res 2000 Nov;24(11):957-63
AD - Service d'Hematologie, Hopital Edouard Herriot, Lyon, France. email@example.com
A dose-escalation study was realized in order to assess the maximally tolerated dose (MTD) of high-dose mitoxantrone in a single injection combined with cytarabine and etoposide (EMA regimen) in refractory or 1998, 24 patients with relapsed or refractory AML entered the study. All but one patient had normal left ventricular ejection fraction (LVEF) at baseline. Performance status according to World Health Organization (WHO) criteria was less than two in all cases. All patients have been previously treated by mitoxantrone or anthracyclines. Four cohort of ten patients were scheduled with the following doses: (1) mitoxantrone 36 mg/m2 on day 1; (2) mitoxantrone 45 mg/m2 on day 1; (3) mitoxantrone 60 mg/m2 on day 1; (4) mitoxantrone 75 mg/m2 on day 1 in combination with cytarabine 500 mg/m2 per day (days 1-3, and days 8-10), and etoposide 200 mg/m2 per day (days 8-10). All patients received the full doses of the three drugs. The limiting toxicity was defined as WHO grade 4 nonhematologic toxicity and for impairment of cardiac function by Alexander's criteria (moderate or severe toxicity). The occurrence of limiting toxicity in at least three patients from the same dose level determined the MDT. No limiting toxicity was observed in mitoxantrone dose level 1. Two limiting toxicities were observed in mitoxantrone dose level 2 (one mucositis, one moderate cardiac toxicity), and three limiting toxicities in mitoxantrone dose level 3 (1 high transaminase levels, two moderate cardiac toxicities) ending the assay. Overall, 16 patients (67%) achieved complete remission (CR). One drug-addict patient died from cerebral hemorrhage due to severe aspergillosis and was not considered as a limiting toxicity. After EMA chemotherapy, 13 patients received subsequent chemotherapy courses involving anthracyclines or their derivatives. Six patients underwent allogeneic bone marrow transplantation. No late toxicity occurred. The median survival of the entire cohort was 41.4 weeks. We conclude that (i) EMA chemotherapy using a single injection of mitoxantrone is effective in the treatment of refractory or relapsing AML; (ii) the recommended phase II dose of mitoxantrone is 45 mg/m2 administered over 30 min as a single dose in combination with cytarabine and etoposide.
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