Linked Life Data

7949141

Source:http://linkedlifedata.com/resource/pubmed/id/7949141

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1994-12-29
pubmed:abstractText
All-trans retinoic acid (RA) has proven a major advance in the treatment of acute promyelocytic leukemia (APL). However, the proper management of patients who present with or develop leukocytosis during remission induction with all-trans RA is not established, nor is there a clear relation between leukocytosis and the development of the retinoic acid syndrome. We reviewed the course of our patients who underwent induction with all-trans RA to identify potential factors that might predict for the development of this syndrome and to identify which patients, if any, might specifically benefit from additional treatment with cytotoxic chemotherapy. Seventy-eight courses of all-trans RA therapy were administered to patients with a molecular diagnosis of APL. Initial and peak leukocyte counts, their rate of rise, leukocyte count criteria developed in Europe, and cell surface marker expression were all analyzed relative to subsequent development of both the RA syndrome as well as all causes of early mortality. The outcome of patients who received specific treatment for retinoid-induced leukocytosis was also examined. No factor was found to consistently predict for the development of the RA syndrome. Although the occurrence of the syndrome was positively associated with the peak value of the peripheral blood leukocyte count (P = .001), neither the initial leukocyte count nor the rate of rise in leukocyte counts on days preceding onset of the syndrome were sufficiently well-correlated to be clinically useful (P = .21). The leukocyte count criteria developed in Europe had a sensitivity of 62%, a specificity of 69%, and a positive predictive value that ranged from only 44% to 72%. However, we unexpectedly found that basal expression of CD13 (aminopeptidase N), a cell surface enzyme previously linked to tumor cell invasion and an inferior outcome in patients with acute myeloid leukemia, was highly associated with both development of the syndrome (P < .05) as well as an elevated leukocyte count (P = .006). Neither low-dose chemotherapy nor leukapheresis prevented development of the syndrome nor ameliorated its effects. In fact, 9 of 11 patients who received these interventions sustained fatal or near-fatal events, most of which were due to hemorrhage. However, early treatment with a short-course of high-dose corticosteroids halted progression of the syndrome in most cases. Finally, we found that expression of the type "A" isoform of PML/RAR-alpha (also known as bcr3 or "short") was associated with a significantly shorter duration of relapse-free and overall survival (P = .005).(ABSTRACT TRUNCATED AT 400 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3843-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:7949141-Adrenal Cortex Hormones, pubmed-meshheading:7949141-Antigens, CD13, pubmed-meshheading:7949141-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:7949141-Cause of Death, pubmed-meshheading:7949141-Cerebral Hemorrhage, pubmed-meshheading:7949141-Combined Modality Therapy, pubmed-meshheading:7949141-Gene Expression Regulation, Leukemic, pubmed-meshheading:7949141-Humans, pubmed-meshheading:7949141-Leukapheresis, pubmed-meshheading:7949141-Leukemia, Promyelocytic, Acute, pubmed-meshheading:7949141-Leukocytosis, pubmed-meshheading:7949141-Neoplasm Proteins, pubmed-meshheading:7949141-Pulmonary Edema, pubmed-meshheading:7949141-Receptors, Retinoic Acid, pubmed-meshheading:7949141-Remission Induction, pubmed-meshheading:7949141-Retrospective Studies, pubmed-meshheading:7949141-Survival Analysis, pubmed-meshheading:7949141-Syndrome, pubmed-meshheading:7949141-Treatment Outcome, pubmed-meshheading:7949141-Tretinoin, pubmed-meshheading:7949141-Tumor Markers, Biological
pubmed:year
1994
pubmed:articleTitle
Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, low-dose chemotherapy, PMN/RAR-alpha isoform, and CD13 expression in patients treated with all-trans retinoic acid.
pubmed:affiliation
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, Non-U.S. Gov't