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

All-trans-retinoic acid (ATRA) is known to induce differentiation of promyelocytes in vitro and also to induce remission of acute promyelocytic leukaemia in vivo. We treated 11 patients with poor prognosis acute promyelocytic leukaemia (APL) with ATRA and obtained seven complete and one partial remission. Remissions took one to three months to achieve and were associated with adverse effects including dry skin and bone pain. In eight patients the white cell count rose above 20 x 10(9)/L within the first ten days of retinoic acid treatment and this was associated with the development of pulmonary leukostasis in three patients which was fatal in one. Another two patients died of intracranial haemorrhage also within the first ten days. ATRA is a promising new agent in the induction therapy of this particular category of acute leukaemia.
 ...
PMID:All-trans retinoic acid in the treatment of acute promyelocytic leukaemia. 144 33

The use of chemical agents that induce differentiation of malignant cells to normal cells has held great promise as an adjunct to standard chemotherapy. In vitro data has shown that 13-cis-retinoic acid can differentiate certain leukemia cell lines (e.g., HL-60) into stable granulocyte cells. In this study, oral 13-cis-retinoic acid was administered to four patients with the myelodysplastic syndrome (MDS) and to four patients with acute nonlymphocytic leukemia (ANLL). None of the MDS patients showed an hematologic response to the drug, while three of four ANLL patients responded with normalized peripheral blood counts. The side effects of the drug at 80-120 mg/d (dry skin, cheilitis, epistaxis) were self limiting.
 ...
PMID:Use of differentiation-inducing agents in the myelodysplastic syndrome and acute non-lymphocytic leukemia. 329 38

A 27-year-old Chinese woman with acute promyelocytic leukaemia in first relapse after the initial conventional induction chemotherapy 18 months earlier was treated with all-trans retinoic acid (ATRA) at an initial dose of 45 mg/m2 and subsequently increased to 65 mg/m2 on day 15. Complete remission was achieved after a total of 40 days of ATRA alone. Serial marrow examinations during induction showed progressive maturation of myelopoiesis without bone marrow hypoplasia. There was a significant reduction in number of cells with the t(15;17) translocation when complete remission was achieved. ATRA was very well-tolerated. The symptoms of dry skin and intermittent headache were self-limiting.
 ...
PMID:Treatment of acute promyelocytic leukaemia in first relapse with all-trans retinoic acid. 760 89

Chemotherapy may decrease relapses of acute promyelocytic leukemia (APL) following induction with all-trans retinoic acid (ATRA), however the optimal timing of these two modalities remains to be determined. We treated eight patients with morphologic evidence of APL with intensive induction chemotherapy followed by ATRA (45 mg/m2/d for 10 weeks). All eight patients achieved a complete remission following chemotherapy. After a median follow-up of 29.0 months, seven patients remain in complete remission; one patient relapsed at 26.9 months. RT-PCR analysis for the PML/RAR alpha rearrangement was performed to monitor patients for evidence of minimal residual disease. Both of the patients with persistence of this rearrangement after induction chemotherapy converted to negative following ATRA. Toxicity of ATRA given in the post-remission setting was mild and consisted of headache, dry skin, and elevations of triglycerides and transaminases. No patient developed evidence of the retinoic acid syndrome. The administration of ATRA after intensive induction chemotherapy is associated with durable remissions and minimal toxicity in patients with APL. Disappearance of the PML/RAR alpha rearrangement after ATRA suggests that ATRA is effective against minimal residual disease.
Leukemia 1995 Jan
PMID:Pilot study of all-trans retinoic acid as post-remission therapy in patients with acute promyelocytic leukemia. 784 10

A 44-year-old woman was diagnosed as having acute promyelocytic leukemia (APL) in April 1988. On her first admission, chromosomal translocation (15; 17), +8, and +12 was detected. When she was readmitted to our hospital with the second relapse in May 1990, t(3; 13) and +8 was detected, instead of t(15;17). Complete remission was re-achieved with VP-16, MIT, and BHAC, but the third relapse occurred in September 1990. After obtaining informed consent, she was given etretinate 40 mg per day orally for 17 days, without any effect on leukemia. She was then given all-trans retinoic acid (ATRA) 60 mg per day orally for 29 days. Although a mild granulocytic recovery was observed, no sufficient hematological recovery was obtained (minor response). Besides common side effects of ATRA, such as dry skin and hypertriglycedemia, she had a myeloblastoma in the oral cavity, but it is unknown whether the symptom was a complication of ATRA therapy or not.
 ...
PMID:[A case of acute promyelocytic leukemia (APL) with myeloblastoma in the oral cavity developing after receiving all-trans retinoic acid (ATRA)]. 807 96

Retinoids have significant antiproliferative effect against chronic myelogenous leukemia (CML) cells in vitro. We conducted a pilot study to investigate the clinical effect of all-trans retinoic acid (ATRA) in patients with CML. Thirteen patients with Philadelphia chromosome (Ph)-positive CML in late chronic phase (n=7), accelerated phase (n=5), or blastic phase (n=1) were treated. All had been previously treated and 12 (92%) had disease refractory to interferon-alpha therapy. They received ATRA 175 mg/m2 orally in two divided doses daily until disease progression. The median duration of therapy was 56 days (range 11 to 190). Only one patient in late chronic phase had a transient decrease in WBC counts; all other patients in late chronic phase showed no response to therapy. Four of the five patients in accelerated phase showed evidence of antileukemia effect manifested by a decrease in bone marrow and/or peripheral blood blasts, promyelocyte and/or basophil percentages. In all cases the response was transient. The patient in blastic phase had no evidence of antileukemic effect. The treatment was well tolerated with the major side-effects being headache, nausea, dry skin, and dry mucosal membranes. One patient required dose reductions due to toxicity. We conclude that in this population of patients with extensively treated, advanced stage, Ph-positive CML, ATRA alone is ineffective for long-term therapy. The antileukemia effect seen in some patients warrants further investigation of retinoids in other schedules and in combinations in patients with CML.
Leukemia 1997 Jul
PMID:A pilot study of all-trans retinoic acid in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. 920 70

The use of all-trans retinoic acid (RA) for remission induction markedly increases survival of patients with acute promyelocytic leukemia (APL) compared to patients treated solely with cytotoxic chemotherapy. However, clinical resistance to this agent develops rapidly, which has been associated with a progressive decline in plasma drug concentrations. Previous studies suggested that 9-cis RA, a retinoid receptor 'pan agonist' did not induce its own catabolism to the same extent as all-trans RA. Therefore, we conducted a dose-ranging study of this compound in patients with both relapsed and newly diagnosed APL. We treated 18 patients with morphologically diagnosed APL (13 relapsed, five newly diagnosed). The daily dose of 9-cis RA ranged from 30 to 230 mg/m2/day given as a single oral dose. Four of 12 (33%) relapsed patients (three of whom were previously treated with all-trans RA) and four of five (80%) newly diagnosed patients achieved complete remission. The sole failure in the newly diagnosed group died early from an intracranial hemorrhage. One other patient with t(9;12) translocation had substantial hematologic improvement. The drug was generally well tolerated; headache and dry skin were the most common adverse reactions. Three patients were treated with corticosteroids for signs of incipient 'RA syndrome.' These preliminary data suggest that 9-cis RA is an effective agent for remission induction and deserves further investigation in patients with retinoid-sensitive APL.
Leukemia 1998 Oct
PMID:Clinical study of 9-cis retinoic acid (LGD1057) in acute promyelocytic leukemia. 976 93

A multicenter phase II study was initiated to investigate the efficacy, toxicity and tolerability of an oral regimen of 9-cis retinoic acid (9CRA) as a differentiation-inducing agent stimulating both retinoic acid receptor (RAR) and retinoic X receptor (RXR). Thirty patients with myelodysplastic syndromes (MDS) were enrolled into the study. The MDS subtypes were distributed as follows: 14 refractory anaemia (RA), four refractory anaemia with ringed sideroblasts (RARS), and 12 refractory anaemia with excess blasts (RAEB). The age ranged from 40 to 81 years (median 70). None of these had previously received treatment for MDS other than supportive therapy. 9CRA (Alitretinoin capsules, kindly provided by Allergan-Ligand Retinoid Therapeutics) was given daily at 60 mg/m2 p.o. for 1 week, followed by an intra-patient escalation to 100 mg/m2 during the second week, up to a maximum of 140 mg/m2. The planned treatment duration was 48 weeks. Twenty-five were available for assessment. One patient (4%) with RA achieved complete hematological remission. Four (16%), two with RA, two with RAEB, had minor responses resulting in decreased transfusion requirements or increased neutrophils. Thus, the overall response rate was 20% in evaluable patients with MDS and 17% in the study group on an intention-to-treat basis. The most frequent side-effects included headache (77%), dry skin (57%), arthralgias (30%), and rash (23%). In conclusion, although modest responses were noted in this study, the treatment tolerability was suboptimal. It is conceivable that a lower dosage schedule may be efficacious and better tolerated so enabling prolonged exposure which may be required to induce a differentiation effect.
Leukemia 2000 Sep
PMID:Oral 9-cis retinoic acid (Alitretinoin) in the treatment of myelodysplastic syndromes: results from a pilot study. 1099 4