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)

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

Arsenic trioxide (ATO) induces remission in 85% of adults with refractory acute promyelocytic leukemia (APL). We conducted a phase 1 trial of ATO in children (median age 13 y, range, 2-19) with refractory leukemia. ATO was administered intravenously over 2 hours, 5 d/wk for 20 doses/cycle. Patients with APL (n=13) received 0.15 mg/kg per day, and patients with other types of leukemia received 0.15 mg/kg per day (n=2) or 0.2 mg/kg per day (n=4). Nineteen of the 24 enrolled patients were fully evaluable for toxicity. At 0.15 mg/kg per day, 2 of 15 patients experienced dose-limiting corrected QT interval (QTc) prolongation, pneumonitis, or neuropathic pain. At 0.2 mg/kg per day, 2 of 4 patients had dose-limiting QTc prolongation or pancreatitis. Non-dose-limiting toxicities included elevated serum transaminases, nausea, vomiting, abdominal pain, constipation, electrolyte imbalance, hyperglycemia, dermatitis, and headache. At 0.15 mg/kg per day, the median (range) plasma arsenic maximum concentration (Cmax) was 0.28 microM (0.11-0.37 microM) and at 0.2 mg/kg per day, Cmax was 0.40 and 0.46 microM; area under the concentration times time curve (AUC0-24) was 2.50 microM-hr (1.28-3.85 microM-hr) and 4.37 microM-hr and 4.69 microM-hr, respectively. Morphologic complete response (CR) was achieved in 85% of patients with APL; no responses were observed in non-APL patients. ATO is well-tolerated in children at the recommended dose of 0.15 mg/kg per day. The response rate in children with relapsed APL is similar to the response rate in adults. This trial was registered as #NCT00020111 at www.ClinicalTrials.gov.
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PMID:Phase 1 trial and pharmacokinetic study of arsenic trioxide in children and adolescents with refractory or relapsed acute leukemia, including acute promyelocytic leukemia or lymphoma. 1795 55

A 12-year-old boy who presented with headache and papilledema was diagnosed with cerebral sinus venous thrombosis and promyelocytic leukemia. Cerebral sinus venous thrombosis is an uncommon manifestation of acute promyelocytic leukemia, and acute promyelocytic leukemia is an unusual etiology for cerebral sinus venous thrombosis. This case highlights the importance of a complete evaluation for risk factors in a child presenting with cerebral sinus venous thrombosis. Anticoagulation was initiated for treatment of cerebral sinus venous thrombosis, and new asymptomatic hemorrhage was identified in the cerebellum 1 day later. Anticoagulation was discontinued for 5 days and then reinitiated in the intensive care unit without hemorrhage expansion or other complications. We review the literature regarding anticoagulation in children with cerebral sinus venous thrombosis and issues specific to acute promyelocytic leukemia. This case suggests that in a controlled setting, anticoagulation may be safe in selected patients with cerebellar hemorrhage.
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PMID:Cerebral sinus venous thrombosis complicated by cerebellar hemorrhage in a child with acute promyelocytic leukemia. 1916 26

Use of all-transretinoic acid (ATRA) with other chemotherapeutic agents in the treatment of acute promyelocytic leukemia (APL) has been shown to cause the differentiation of abnormally granulated specific blast cells into mature granulocytes by acting on the t(15; 17) fusion gene product. The complete remission rate is increased and survival time is prolonged in APL patients who receive chemotherapy plus ATRA, whereas ATRA syndrome and other ATRA-related adverse effects including pseudo tumor cerebri, headache, severe bone pain, mucosal and skin dryness, hypercholesterolemia, and cheilitis may be observed especially during induction phase of the treatment. In this paper, we report a 9-year-old girl with APL who developed pancarditis while receiving the APL-93 treatment protocol. In our patient, endocarditis and myocarditis were initially determined after ATRA treatment during the induction part of the protocol. All findings disappeared after ATRA was discontinued. When ATRA was readministered in the maintenance part of the treatment protocol, she developed pancarditis and severe pulmonary edema. As her symptoms decreased dramatically with the discontinuation of ATRA and the initiation of steroid treatment, the clinical picture strongly suggested the ATRA treatment as the causative factor. To the best of our knowledge, this clinical picture of pancarditis secondary to ATRA treatment has not been reported earlier in the English literature.
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PMID:All-transretinoic acid (ATRA) treatment-related pancarditis and severe pulmonary edema in a child with acute promyelocytic leukemia. 2088 74

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

Seventy-six patients with acute promyelocytic leukemia (APL) in first complete remission after induction and consolidation by daunorubicin and cytosine arabinoside received oral arsenic trioxide (As(2)O(3))-based maintenance. Three regimens were used: oral As(2)O(3) (10 mg/day, regimen A, n = 20), oral As(2)O(3) plus all-trans retinoic acid (ATRA, 45 mg/m(2) per day, regimen AA, n = 19), and oral As(2)O(3) plus ATRA plus ascorbic acid (1000 mg/day, regimen AAA, n = 37), each given for 2 weeks every 2 months for 2 years. Patients receiving A, AA, and AAA maintenance did not differ significantly in clinicopathologic features and risk factors. Headache, dyspepsia, reversible liver function derangement, and herpes zoster reactivation were adverse effects observed during maintenance. QTc prolongation and arrhythmias were not encountered. At a median follow-up of 24 months (range, 1-115 months), there were 8 relapses. The 3-year leukemia-free-survival, event-free-survival, and overall-survival were 87.7%, 83.7%, and 90.6%, respectively. Adverse prognostic factors included male gender for leukemia-free-survival, and unrelated cancers for overall survival. Age, presentation WBC count and platelet count, and the type of oral As(2)O(3) maintenance regimens had no impact on survivals. Prolonged oral As(2)O(3) maintenance was feasible and safe and resulted in favorable outcomes when used with a simple induction and consolidation regimen compared with other protocols composed of multiple chemotherapeutic agents.
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PMID:Oral arsenic trioxide-based maintenance regimens for first complete remission of acute promyelocytic leukemia: a 10-year follow-up study. 2217 3

All-trans retinoic acid (ATRA) induces complete remission in most cases of acute promyelocytic leukemia. Toxicity of ATRA has been shown to be mild, consisting of headache, dry skin, dermatitis, and gastrointestinal disorders. We describe a case of scrotal ulceration with ATRA use in a Moroccan patient, an occurrence that has been rarely reported in the medical literature. The pathogenesis of scrotal ulceration remains unknown. Our experience indicates the importance of recognizing genital ulcers associated with ATRA in order that appropriate countermeasures can be taken.
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PMID:Scrotal ulceration following all-trans retinoic Acid therapy for acute promyelocytic leukemia. 2212 Dec 79

Acute promyelocytic leukemia (APL) is a biologically and clinically separate type of acute myeloid leukemia characterized by a translocation involving the retinoic acid receptor-alpha (RARa) locus on chromosome 17, the great majority of which is t(15; 17)(q24.1; q21.1) (Collins (1998), Melnick and Licht (1999), and Grimwade (1999)). Retinoic acid is a critical ligand in the differentiation pathway of multiple tissues, mediated through binding to an RAR. All-trans retinoic acid (ATRA) is a subgroup of the retinoid family, which induces complete remission (CR) in APL by causing differentiation and apoptosis in immature malignant promyelocytes rather than inducing cell death by cytotoxicity (Warrell et al. (1993), Liu et al. (2000), and Cassinat et al. (2001)). ATRA-associated toxicity consisting of headache, fever, weakness, fatigue, dry skin, dermatitis, gastrointestinal disorders, and hypertriglyceridemia has been shown to be mild (Kurzrock et al. (1993)). Herein, we describe a patient with APL that developed an erythematous reaction of the whole body followed by desquamation and exfoliation during ATRA therapy.
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PMID:Disseminated exfoliative dermatitis associated with all-transretinoic Acid in the treatment of acute promyelocytic leukemia. 2284 26


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