Pharmacodynamic and DNA methylation studies of high-dose 1-?-d-arabinofuranosyl cytosine before and after in vivo 5-azacytidine treatment in pediatric patients with refractory acute lymphocytic leukemia

1989 ◽  
Vol 24 (4) ◽  
Author(s):  
VassiliosI. Avramis ◽  
RobertA. Mecum ◽  
Jonathan Nyce ◽  
DavidA. Steele ◽  
JohnS. Holcenberg
Keyword(s):  
Dna Methylation ◽  
Acute Lymphocytic Leukemia ◽  
Pediatric Patients ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Before And After

New Therapeutic Approach to Reduce Methotrexate Toxicity after High-Dose Chemotherapy in a Child with Acute Lymphocytic Leukemia: Efficacy and Safety of Hemoadsorption with HA-230 Adsorber

2021 ◽  
pp. 1-5
Author(s):  
Vitaliy Sazonov ◽  
Zaure Tobylbayeva ◽  
Askhat Saparov ◽  
Bolatbek Jubaniyazov ◽  
Samat Issakov ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Pediatric Patients ◽  
High Dose Chemotherapy ◽  
The Body ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Successful Implementation ◽  
Efficacy And Safety ◽  
Related Complication ◽  
Dose Methotrexate

Background: High-dose methotrexate (HDMTX) is likely to cause a number of side effects and manifest itself as hepatotoxicity, nephrotoxicity, mucositis, and neurotoxicity. A several studies demonstrated the efficacy of extracorporeal detoxification methods such as plasma exchange, hemodialysis (HD), HD filtration, and hemoperfusion for the treatment of MTX delayed clearance. However, none of the existing methods as effective as expected and limited for general implementation due to a procedure-related complication. Case Report: Here, we report a successful implementation of HA-230 hemoadsorption procedure to remove cumulated MTX from the body and reduce its toxicity in a child with ALL after high-dose chemotherapy. Results and Conclusion: Based on our results, single-hemoadsorption procedure with the HA-230 adsorber in case of delayed methotrexate clearance was safe and well-tolerated in a pediatric patient with ALL and would significantly improve the patient’s condition. Further studies need to demonstrate its safety and efficacy in a large number of pediatric patients.

Aberrant DNA methylation in pediatric patients with acute lymphocytic leukemia

Cancer ◽  
2003 ◽  
Vol 97 (3) ◽  
pp. 695-702 ◽  
Author(s):  
Guillermo Garcia-Manero ◽  
Sima Jeha ◽  
Jerry Daniel ◽  
Jason Williamson ◽  
Maher Albitar ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Lymphocytic Leukemia ◽  
Pediatric Patients ◽  
Lymphocytic Leukemia ◽  
Aberrant Dna Methylation

scholarly journals The Effect of Honey on Granulating Tissue of The Mandibular Bone

1970 ◽  
Vol 1 (3) ◽  
Author(s):  
Anastasia Dessy Harsono ◽  
Gentur Sudjatmiko
Keyword(s):  
Granulation Tissue ◽  
Acute Lymphocytic Leukemia ◽  
Conventional Medicine ◽  
Tissue Growth ◽  
Lymphocytic Leukemia ◽  
Poor General Condition ◽  
Mandibular Bone ◽  
Surgical Wounds ◽  
Before And After ◽  
Ancient Civilizations

Background: For many years, ancient civilizations used honey to heal wounds. Rediscovery of honey by modern physicians its use in conventional medicine. Few detailed descriptions of honey in healing difficult surgical wounds have been previously published.Methods: We report patient, male, 16 years old, who suffered acute lymphocytic leukemia and extensive mandibular eschar and had presented half of mandible bone exposed after escharectomy. Given the of closing the defect due to poor general condition of the patient, we advocated to applicate honey dressing on mandible bone to promote granulation tissue, to prevent infection and to promote epithelialization.Results: Due to honey’s effect are anti inflammatory and antimicrobial activity, promotes debridement, reduces malodor, maintains moist wound environment, and stimulates healing, in a month, all mandible exposed had been covered by granulation tissue, followed by skin grafting.Conclusion: In this case, honey had been proven effectively to stimulate granulation tissue growth on mandible bone both before and after surgery.

Results of Treatment With Hyper-CVAD, a Dose-Intensive Regimen, in Adult Acute Lymphocytic Leukemia

2000 ◽  
Vol 18 (3) ◽  
pp. 547-547 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Susan O’Brien ◽  
Terry L. Smith ◽  
Jorge Cortes ◽  
Francis J. Giles ◽  
...  
Keyword(s):  
B Cell ◽  
Acute Lymphocytic Leukemia ◽  
Philadelphia Chromosome ◽  
Lymphocytic Leukemia ◽  
Prognostic Models ◽  
Poor Performance Status ◽  
High Dose ◽  
Cell Disease ◽  
Adult Acute Lymphocytic Leukemia ◽  
Intensive Regimen

PURPOSE: To evaluate the efficacy and toxicity of Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), a dose-intensive regimen, in adult acute lymphocytic leukemia (ALL). PATIENTS AND METHODS: Adults with newly diagnosed ALL referred since 1992 were entered onto the study; treatment was initiated in 204 patients between 1992 and January 1998. No exclusions were made because of older age, poor performance status, organ dysfunction, or active infection. Median age was 39.5 years; 37% were at least 50 years old. Mature B-cell disease (Burkitt type) was present in 9%, T-cell disease in 17%. Leukocytosis of more than 30 × 109/L was found in 26%, Philadelphia chromosome–positive disease in 16% (20% of patients with assessable metaphases), CNS leukemia at the time of diagnosis in 7%, and a mediastinal mass in 7%. Treatment consisted of four cycles of Hyper-CVAD alternating with four cycles of high-dose methotrexate (MTX) and cytarabine therapy, together with intrathecal CNS prophylaxis and supportive care with antibiotic prophylaxis and granulocyte colony-stimulating factor therapy. Maintenance in patients with nonmature B-cell ALL included 2 years of treatment with mercaptopurine, MTX, vincristine, and prednisone (POMP). RESULTS: Overall, 185 patients (91%) achieved complete remission (CR) and 12 (6%) died during induction therapy. Estimated 5-year survival and 5-year CR rates were 39% and 38%, respectively. The incidence of CNS relapse was low (4%). Compared with 222 patients treated with vincristine, doxorubicin, and dexamethasone (VAD) regimens, our patients had a better CR rate (91% v 75%, P < .01) and CR rate after one course (74% v 55%, P < .01) and better survival (P < .01), and a smaller percentage had more than 5% day 14 blasts (34% v 48%, P = .01). Previous prognostic models remained predictive for outcome with Hyper-CVAD therapy. CONCLUSION: Hyper-CVAD therapy is superior to our previous regimens and should be compared with established regimens in adult ALL.

scholarly journals Efficacy of high-dose methotrexate in childhood acute lymphocytic leukemia: analysis by contemporary risk classifications

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 866-869 ◽  
Author(s):  
M Abromowitch ◽  
J Ochs ◽  
CH Pui ◽  
D Fairclough ◽  
SB Murphy ◽  
...  
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Leukemic Cell ◽  
Risk Groups ◽  
Cranial Irradiation ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Average Risk ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Table Analysis

Abstract High-dose methotrexate (HDMTX) added to a basic regimen of chemotherapy proved superior to cranial irradiation and sequentially administered drug pairs (RTSC) in prolonging complete remissions in children with “standard-risk” acute lymphocytic leukemia. To extend this result to more contemporary risk groups, we reclassified the patients according to methods of the Pediatric Oncology Group (POG), the Childrens Cancer Study Group (CCG), the Rome workshop, and St Jude Total Therapy Study XI. By life table analysis, 70% to 78% of patients with a favorable prognosis would remain in continuous complete remission (CCR) at 4 years if treated with HDMTX. Uniformly lower CCR rates could be expected with RTSC, especially in St Jude better-risk patients. HDMTX also would show greater efficacy than RTSC in the CCG average-risk and POG poor-risk groups, but the results appear inferior to those being achieved with intensified regimens for high-risk leukemia. Although both therapies would provide adequate CNS prophylaxis in favorable-risk groups, RTSC would offer greater protection in patients classified as being in a worse-risk group by St Jude criteria. We conclude that HDMTX- based therapy, as described in this report, would be most effective in patients with a presenting leukocyte count of less than 25 x 10(9)/L, of the white race, aged 2 to 10 years, and having leukemic cell hyperdiploidy without translocations.

scholarly journals Effect of a thymic factor on T lymphocytes in B cell chronic lymphocytic leukemia: in vitro and in vivo studies

Blood ◽  
1984 ◽  
Vol 64 (3) ◽  
pp. 667-671 ◽  
Author(s):  
F Lauria ◽  
D Raspadori ◽  
S Tura
Keyword(s):  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
T Lymphocytes ◽  
B Cell ◽  
Proliferative Response ◽  
Lymphocytic Leukemia ◽  
Before And After ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Abnormalities of T lymphocytes in B cell chronic lymphocytic leukemia (B-CLL) have been extensively documented by several immunologic investigations. Following recent studies pointing to the favorable effect of TP-1, a partially purified extract of calf thymus, on the T cell-mediated immunity of several diseases, including Hodgkin's disease, we have used monoclonal antibodies and the enriched T lymphocytes of 16 untreated B-CLL patients to evaluate the proportion of T cell subsets before and after the administration of TP-1. In addition, the proliferative response to phytohemagglutinin (PHA) and the helper function in a pokeweed mitogen (PWM) system were assessed. In ten cases, the effect of TP-1 was also studied in vitro by evaluating the same parameters before and after incubation of B-CLL T cells with the drug. The study demonstrated that in vivo administration of TP-1 increases significantly (P less than .001) the proportion of the defective helper/inducer T cell population (OKT4-positive cells) in B-CLL, leading to a near normal OKT4/OKT8 ratio. Furthermore, the improved phenotypic profile was accompanied by an increased proliferative response to PHA and, in particular, by a significant increase (P less than .01) of T helper capacity; this increase was, however, insufficient to enable the normalization of the serum immunoglobulin levels. The in vitro incubation of B-CLL T lymphocytes did not succeed in producing significant modifications in distribution and function.

De novo purine synthesis inhibition and antileukemic effects of mercaptopurine alone or in combination with methotrexate in vivo

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1240-1247 ◽  
Author(s):  
Thierry Dervieux ◽  
Timothy L. Brenner ◽  
Yuen Y. Hon ◽  
Yinmei Zhou ◽  
Michael L. Hancock ◽  
...  
Keyword(s):  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Initial Therapy ◽  
High Dose ◽  
Purine Synthesis ◽  
Percentage Decrease ◽  
Before And After ◽  
Leukocyte Counts ◽  
B Lineage

Methotrexate (MTX) and mercaptopurine (MP) are widely used antileukemic agents that inhibit de novo purine synthesis (DNPS) as a mechanism of their antileukemic effects. To elucidate pharmacodynamic differences among children with acute lymphoblastic leukemia (ALL), DNPS was measured in leukemic blasts from newly diagnosed patients before and after therapy with these agents. Patients were randomized to receive low-dose MTX (LDMTX: 6 oral doses of 30 mg/m2) or high-dose MTX (HDMTX: intravenous 1 g/m2) followed by intravenous MP; or intravenous MP alone (1 g/m2), as initial therapy. At diagnosis, the rate of DNPS in bone marrow leukemia cells was 3-fold higher in patients with T-lineage ALL compared with those with B-lineage ALL (769 ± 189 vs 250 ± 38 fmol/nmol/h;P = .001). DNPS was not consistently inhibited following MP alone but was markedly inhibited following MTX plus MP (median decrease 3% vs 94%; P &lt; .001). LDMTX plus MP and HDMTX plus MP produced greater antileukemic effects (percentage decrease in circulating leukocyte counts) compared with MP alone (−50% ± 4%, −56% ± 3%, and − 20% ± 4%, respectively;P &lt; .0001). Full DNPS inhibition was associated with greater antileukemic effects compared with partial or no inhibition (−63% ± 4% vs −37% ± 4%; P &lt; .0001) in patients with nonhyperdiploid B-lineage and T-lineage ALL. HDMTX plus MP yielded 2-fold higher MTX polyglutamate concentrations than LDMTX plus MP (2148 ± 298 vs 1075 ± 114 pmol/109 cells;P &lt; .01) and a higher percentage of patients with full DNPS inhibition (78% vs 53%; P &lt; .001). Thus, the extent of DNPS inhibition was related to in vivo antileukemic effects, and a single dose of intravenous MP produced minimal DNPS inhibition and antileukemic effects, whereas MTX plus MP produced greater antileukemic effects and DNPS inhibition, with full inhibition more frequent after HDMTX.

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