Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a rare case of pseudotumor cerebri associated with all-trans retinoic acid (ATRA) treatment of acute promyelocytic leukemia (APL). An 18-year-old male was admitted to our hospital complaining of palpitations and shortness of breath; he was found to have APL. The administration of ATRA and chemotherapy was started. After 23 days, he complained of nausea, headache and double vision. Computed tomography and magnetic resonance imaging of the head showed no intracranial abnormalities. Bilateral papilledema, a symptom of increased intracranial pressure, was noted. A diagnosis of pseudotumor cerebri was made. Symptoms were improved by administration of glycerin and the discontinuation of ATRA. After 29 days, a complete remission was achieved.
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PMID:Pseudotumor cerebri in a patient with acute promyelocytic leukemia during treatment with all-trans retinoic acid. 967 91

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.
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PMID:Clinical study of 9-cis retinoic acid (LGD1057) in acute promyelocytic leukemia. 976 93

A novel intravenous liposomal formulation of all-trans retinoic acid (ATRA) was evaluated in 69 patients with acute promyelocytic leukemia (APL): 32 new diagnoses, 35 relapses, and 2 oral ATRA failures. Liposomal ATRA (90 mg/m(2)) was administered every other day until complete remission (CR) or a maximum of 56 days. Treatment following CR was liposomal ATRA with or without chemotherapy. In an intent-to-treat (ITT) analysis of all patients, CR rates were 62%, 70%, and 20% in newly diagnosed, group 1 first relapses (ATRA naive or off oral ATRA more than or equal to 1 year), or group 2 relapses (second or subsequent relapse or first relapses off oral ATRA less than 1 year), respectively. In 56 evaluable patients (receiving 4 or more doses), CR rates for the same groups were 87% (20 of 23), 78% (14 of 18), and 23% (3 of 13). Remission failure in newly diagnosed patients was not from resistant disease. Several patients in CR became polymerase chain reaction (PCR) negative for promyelocytic leukemia/retinoic acid receptor-alpha (PML/RARalpha) after liposomal ATRA alone. Toxicity was generally mild, most commonly headaches (67. 5%). Eighteen patients (26%) had ATRA syndrome develop during induction. One-year survival of ITT patients was 62%, 56%, and 20% for newly diagnosed, group 1, and group 2, respectively. The medium duration of CR has not yet been reached and was 18 and 5.5 months in the same groups. These results demonstrate that liposomal ATRA is effective in inducing CR in newly diagnosed or group 1 APL patients. It provides a reliable dosage of ATRA for patients with APL unable to swallow or absorb medications and can induce molecular remissions without chemotherapy.
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PMID:Treatment of newly diagnosed and relapsed acute promyelocytic leukemia with intravenous liposomal all-trans retinoic acid. 1113 44

Pseudotumor cerebri is a condition characterized by increased intracranial pressure with normal cerebrospinal fluid composition. It is usually associated with many medical conditions and drugs. It has been reported that all-trans-retinoic acid can induce pseudotumor cerebri. The authors report a 35-year-old patient diagnosed with acute promyelocytic leukemia who developed pseudotumor cerebri after receiving all-trans-retinoic acid. The patient was treated with 60 mg/day of all-trans-retinoic acid. Two weeks later, she had severe headache and blurred vision. The neurological examination revealed papilledema and decreased visual acuity. Other physical examinations were unremarkable. Brain CT was normal. Additionally, lumbar puncture was performed and the CSF finding was normal except for high CSF pressure. According to modified Dandy criteria, the diagnosis was pseudotumor cerebri. The patient's symptoms disappeared after all-trans-retinoic acid was discontinued. To our knowledge, this is the first case report in Thailand.
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PMID:Pseudotumor cerebri caused by all-trans-retinoic acid: a case report. 1121 76

Emphysema results from progressive destruction of alveolar septae and was considered irreversible until all-trans-retinoic acid (ATRA) was shown to reverse anatomic and physiologic signs of emphysema in a rat model. To evaluate the feasibility of ATRA as a clinical therapy, 20 patients with severe emphysema were enrolled into a randomized, double-blind, placebo-controlled pilot study. Participants included 16 male and 4 female former smokers, two with alpha(1)-antitrypsin deficiency. Patients were treated with either 3 mo of ATRA (50 mg/m(2)/d) or 3 mo of placebo, followed by a 3-mo crossover phase. Plasma drug levels were followed and outcome measures included serial pulmonary function tests, blood gases, lung compliance, computed tomography (CT) imaging, and quality of life questionnaires. In general, treatment was well tolerated and associated with only mild side effects including skin changes, transient headache, hyperlipidemia, transaminites, and musculoskeletal pains. Plasma drug levels varied considerably between subjects and decreased significantly over time in 35% of the participants. Physiologic and CT measurements did not change appreciably in response to therapy. We conclude that ATRA is well tolerated in patients with emphysema, and trials evaluating higher doses, longer treatment, or different dosing schedules are feasible.
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PMID:A pilot study of all-trans-retinoic acid for the treatment of human emphysema. 1187 21

Extramedullary relapse occurs infrequently in acute promyelocytic leukaemia (APL) but has been increasingly reported after the advent of all-trans retinoic acid (ATRA) treatment, probably as a consequence of improved patient survival. We describe our single centre experience of six APL patients who had disease localization in the central nervous system (CNS). In three patients, clinical symptoms (headache and/or nausea) that presented during follow-up led to the performance of a lumbar puncture and detection of overt CNS infiltration. Two of these patients had simultaneous haematological relapse and one was in molecular remission when CNS leukaemia was documented. One patient with no local symptoms showed CNS infiltration at the time of molecular relapse. Following the introduction of routine lumbar puncture, carried out after front-line induction in all newly diagnosed patients with white blood cell count (WBC) greater than 10 x 109/l, two additional patients in molecular remission with no local symptoms were found to have initial APL localization in the CNS. Presenting features included in 6/6 patients an elevated WBC count (> 10 x 109/l) and a predominance of the PML/RAR bcr3 type (5/6 patients) and of microgranular morphology (5/6 patients). Our findings highlight the importance of carrying out lumbar puncture in APL patients presenting with high-risk features.
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PMID:Early detection of meningeal localization in acute promyelocytic leukaemia patients with high presenting leucocyte count. 1254 84

The involvement of central nervous system is rare in acute promyelocytic leukemia (APL). We report a APL patient of a 41 yr-old Korean male who presented with fever and petechia. Complete molecular remission was achieved with all-trans retinoic acid (ATRA), idarubicin, and cytarabine. Ten months later, he complained of a mild headache. The results of the physical examination and the complete blood counts were normal. The examination of cerebrospinal fluid showed the presence of promyelocyte. Bone marrow studies showed cytogenetic remission but with molecular relapse. He was treated with intrathecal and systemic chemotherapy.
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PMID:Meningeal relapse in a patient with acute promyelocytic leukemia: a case report and review of the literature. 1508 12

Induction therapy with all-trans-retinoic acid (ATRA), an oral vitamin A derivative, has been shown to improve the short and long-term outcome of patients with acute promyelocytic leukemia (APML). Common side effects include headache, fever, dry skin, and bone pain, and approximately 25% of treated patients experience ATRA syndrome, which includes fever, dyspnea, weight gain, pulmonary infiltrates, and pleural or pericardial effusions. Scrotal ulcerations due to ATRA are rare with 16 previously documented cases, most of whom were Asian. We report a Caucasian male with APML who developed scrotal ulceration during ATRA induction therapy and review the previously reported cases. Physicians and patients should be aware of this disturbing, but self-limited, dermatologic complication of ATRA.
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PMID:Scrotal ulceration as a consequence of all-trans-retinoic acid (ATRA) for the treatment of acute promyelocytic leukemia. 1577 85

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) and is rare in children (< 10% of childhood AML). It tends to bleed with disseminated intravascular coagulation (DIC) and intracranial hemorrhage complication is often fatal. We report a 12-year-old child with APL who suffered a subdural hemorrhage and initially presented with a subtle headache mistaken as the side effect of all-trans-retinoic acid (ATRA). Blood component therapy and a pediatric dosage of ATRA (25 mg/m2/day) combined with idarubicin as induction chemotherapy were administered in the first week, but the bleeding diathesis persisted and DIC profiles showed no improvement. The patient then developed photophobia, neck stiffness, and constant headache. Evidence of increased intracranial pressure (IICP) and persistent bleeding from previous venous puncture sites were also noticed clinically. DIC and life-threatening IICP were beyond control until the ATRA dosage was increased to adult levels (45 mg/m2/day). This case suggests that the ATRA dosage for pediatric APL patients must be modified according to clinical condition. Emergency brain imaging should be considered in APL patients with signs of IICP to distinguish intracranial lesions from ATRA complications.
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PMID:Subdural hemorrhage in a child with acute promyelocytic leukemia presenting as subtle headache. 1618 2

The meningeal involvement is rare in acute promyelocytic leukemia. We experienced a 39-year-old woman who achieved complete remission with all-trans retinoic acid, idarubicin and cytarabine therapy. Several months later, she complained of non-specific headache. Her complete blood cell count was normal, but magnetic resonance image of brain revealed focal meningeal enhancement and cerebrospinal fluid showed leukemic promyelocytes and PML/RARA rearrangement. Bone marrow study showed hematologic, cytogenetic and molecular remission. She was treated with intrathecal and systemic chemotherapy and whole brain radiotherapy. The patient has survived for 68 months since the last systemic chemotherapy.
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PMID:Long-term survival in a patient with acute promyelocytic leukemia with isolated meningeal relapse. 2112 Feb 12


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