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

A rare variant of acute promyelocytic leukemia (APL) is associated with basophilic differentiation. Such a patient presented with basophilia, headaches, and diffuse engorgement of superficial blood vessels, attributable to hyperhistaminemia. Karyotype analysis showed a clonal rearrangement of chromosome 12p13 in addition to the t(15;17). During treatment with all-trans-retinoic acid (TRA), the absolute basophil count rose steadily during the first week, then declined. By one month, the basophilia resolved, an abrupt rise occurred in both the platelet and absolute neutrophil count, and the bone core biopsy showed complete maturation of all cell lines. Abnormalities of chromosome 12p13 in acute myelogenous leukemia have been associated with basophilia. Since every cell in our patient with t(12p13;?) also had the t(15;17), we speculate that the basophilia was due to clonal evolution with acquisition of the t(12p13;?). In two out of five other reported cases, abnormalities of chromosomes known to be associated with basophilia were present in addition to t(15;17). It is possible that the basophilia in this variant is reactive; however, since TRA induces differentiation of leukemic promyelocytes into mature neutrophils, we speculate that the leukemic promyelocytes in our patient differentiated into basophils. Future studies employing either fluorescent in situ hybridization or polymerase chain reaction using a probe to the breakpoint on t(15;17) may establish whether or not the basophils derive from the leukemic clone.
Leukemia 1993 Apr
PMID:Basophilic differentiation in acute promyelocytic leukemia. 784 22

Methotrexate, a mainstay treatment for children with acute lymphoblastic leukaemia, can cause neurotoxicity, with paralysis, seizures, somnolence, anorexia, and headaches. The pathophysiology of this reaction is unknown. It has been suggested that the anti-inflammatory effect of methotrexate in patients with arthritis is due to adenosine release brought on by inhibition of purine synthesis. Since adenosine is a central nervous system depressant, we wondered whether adenosine release in the central nervous system could account for some of the neurotoxicity due to methotrexate, and whether that toxicity could be lessened by displacement of adenosine from its receptor by aminophylline. 6 patients (age 3-16 years) who had methotrexate-induced neurotoxicity unresponsive to standard treatment received 2.5 mg/kg aminophylline. In addition, the concentration of adenosine in the cerebrospinal fluid (CSF) from 11 children completing a 24-h systemic methotrexate protocol was compared with that in 8 newly diagnosed patients and 12 who had not received any treatment for at least a week. 4 of 6 patients with toxic signs and symptoms attributed to methotrexate and unrelieved by steroids, epidural blood patch, promethazine, 5-hydroytryptamine antagonists, paracetamol, and narcotics, had complete resolution of neurotoxicity after or during a 1-h infusion of aminophylline; 2 others had a pronounced improvement but persistent nausea. CSF adenosine concentrations of patients receiving methotrexate, even when there was very slight or no toxicity, were greatly increased compared with control subjects (mean values of 217 and 51 nmol/L, median 175 and 52 nmol/L). Subacute methotrexate neurotoxicity may be mediated by adenosine and relieved by aminophylline.
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PMID:Aminophylline for methotrexate-induced neurotoxicity. 777 73

Retinoids have anti-tumor activity in several malignant and premalignant conditions. Since Kaposi's sarcoma is regulated by steroid hormones both in vivo and in vitro, we hypothesized that retinoids may have anti-tumor effects in AIDS-related Kaposi's sarcoma. Thus, 27 patients with mucocutaneous, non-visceral AIDS-related Kaposi's sarcoma were treated with all-trans retinoic acid (tRA). Poor tolerance was observed at the initial starting dose of 150 mg/m2, and thus subsequent patients were treated using a weekly dose escalation, starting with 45 mg/m2 (given daily, in subdivided doses), to the target dose of 150 mg/m2 (given daily in three subdivided doses). Nearly half (46%) of the patients had extensive mucocutaneous disease with over 25 lesions. No patient had received prior cytotoxic chemotherapy. Ten patients had CD4 lymphocytes of 200/mm3 or greater (strata I); and 17 had under 200/mm3 CD4 lymphocytes (strata II). The median of the average daily tRA dose administered was 150 mg (90 mg/m2; there was no significant difference in the dose tolerance between the two strata). Adverse effects consisted of transient mild to moderate headaches in 65% of patients, mild to moderate skin dryness and cheilitis in 61%, and nausea and vomiting in 31%. Hematologic toxicities included hypertriglyceridemia in 62%, anemia in 23%, and neutropenia in 23%. Partial response to therapy was observed in 4/24 (17%) evaluable patients, occurring after 12, 20, 24, and 28 weeks of therapy, and lasting 4-24 weeks. Three responders had baseline CD4 lymphocyte counts < 200/mm3. Three additional patients experienced reduction in measured indicator lesions of greater than 25% but less than 50%, and seven patients experienced disease stabilization of 16 weeks or greater. In evaluable patients, the median time to disease progression was 22 weeks and the overall median survival in all patients was 27.3 months. No significant changes in CD4 lymphocyte counts, p24 antigen, and beta 2 microglobulin were observed over time. However, a statistically significant increase was observed in soluble IL-2 receptor levels while on tRA (p = 0.037). We conclude that tRA has activity in patients with mucocutaneous AIDS-related Kaposi's sarcoma with acceptable toxicity. tRA has immunological effects without upregulation of HIV parameters. Additional studies in combinations or with more active retinoids are warranted.
Leukemia 1994
PMID:All-trans retinoic acid for the treatment of AIDS-related Kaposi's sarcoma: results of a pilot phase II study. 780 21

All-trans retinoic acid was evaluated in metastatic measurable non-small cell lung cancer. All-trans retinoic acid was given at 175 mg/m2 orally on a daily basis. Twenty-eight patients (median age 58, 16 males, 12 women) had an ECOG performance status of 0 (26 patients) and 1 (two patients). Sixteen of the 28 had no weight loss. Eleven had between 5 and 10% and only one had greater than 10% weight loss at time of entry. Toxicities included cutaneous (cheletis 25/28), fatigue (10/28), myalgias/anthralgias (9/28), and headache (17/28). Alterations in triglycerides and hepatic transaminases were noted in a majority of patients. Two partial responses occurred in patients with adenocarcinoma. Both responses were 7 months in duration. Activity of all-trans retinoic acid in metastatic non-small cell lung cancer is minimal, but due to its low toxicity profile it should be tested in setting with other agents.
Leukemia 1994
PMID:First hints in non-small cell lung cancer (NSCLC). 780 26

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

An association between primary mediastinal germ cell tumors and hematologic malignancies has been recognized since 1985. We present a patient with a suprasellar germ cell tumor and an associated leukemia. A 20-year-old black female presented in December 1987 with a 6-month history of headaches and weight loss, confusion, polyuria, and polydipsia. Evaluation revealed hypernatremia, normal neurologic examination except poor recall, and an enhancing inhomogeneous suprasellar mass on cranial computed tomography. Biopsy of the mass diagnosed a dysgerminoma, which was treated with craniospinal radiation. In February 1988, the patient developed pancytopenia, which resolved with discontinuation of cimetidine and phenytoin. She did well until June 1988 when she presented with skin lesions over the trunk and extremities. Skin biopsy revealed a leukemic infiltration. She was admitted with a WBC 1,500/microliter (without blasts), Hb 11.6 g/dl, PLT 210,000 microliter. Bone marrow biopsy revealed hypercellularity with 50% blasts, demonstrating mixed-lineage acute myeloblastic leukemia (myelomonocytic-M4; megakaryoblastic-M7). The patient was induced with a standard Ara-C/daunorubicin regimen. Two weeks postinduction, she became septic and expired. An autopsy demonstrated leukemic involvement of the spleen, liver, bone marrow, and skin, without residual dysgerminoma. This represents the first reported case of suprasellar dysgerminoma associated with a mixed-lineage leukemia not related to chemotherapy.
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PMID:Mixed-lineage acute myeloid leukemia associated with a suprasellar dysgerminoma. 784 66

Taxol (paclitaxel, Bristol-Myers Squibb Company, Princeton, NJ), a drug extracted from the stem bark of the western yew, shows great promise as an antineoplastic agent for ovarian, breast, nonsmall cell lung, and head and neck cancers; melanoma; and leukemia. Although Taxol first was isolated in 1971, completion of many phase I studies was delayed until 1988, primarily because the drug caused severe hypersensitivity reactions. Other side effects of Taxol include cardiotoxicity, nausea and vomiting, diarrhea, mucositis, myelosuppression, tingling and numbness of the hands and feet, myalgia and arthralgia, alopecia, fatigue, headache, irritation at the injection site, and taste changes. Nursing care includes measures for preventing or minimizing side effects, close assessment and monitoring of potential side effects, patient education, and support. Because of the environmental impact of harvesting the western yew for Taxol, semisynthetic preparations such as taxotere are being explored.
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PMID:Taxol: a promising new drug of the '90s. 790 60

In a population based register of stroke (n = 536) compiled in Perth, Western Australia during an 18 month period in 1989-90, 60 cases (11%) of primary intracerebral haemorrhage were identified among 56 persons (52% men). The mean age of these patients was 68 (range 23-93) and 46 (77%) events were first ever strokes. The crude annual incidence was 35 per 100,000, with a peak in the eighth decade, and a male predominance. Deep and lobar haemorrhages each accounted for almost one third of all cases. The clinical presentations included sudden coma (12%), headache (8%), seizures (8%), and pure sensory-motor stroke (3%). Primary intracerebral haemorrhage was the first presentation of leukaemia in two cases (both fatal) and it followed an alcoholic binge in four cases. 55% had a history of hypertension. 16 (27%) patients, half of whom had a history of hypertension, were taking antiplatelet agents, and one patient was taking warfarin. There were only two confirmed cases of amyloid angiopathy. The overall 28 day case fatality was 35%, but this varied from 100% for haemorrhages in the brainstem to 22% for those in the basal ganglionic or thalamic region. Other predictors of early death were intraventricular extension of blood, volume of haematoma, mass effect, and coma and severe paresis at onset. Although based on small numbers, these data confirm the heterogeneous nature of primary intracerebral haemorrhage, but they also suggest a different clinical spectrum of this type of stroke in the community compared with the experience of specialist neurological units.
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PMID:Spectrum of primary intracerebral haemorrhage in Perth, Western Australia, 1989-90: incidence and outcome. 805 17

Eleven cases of rhinocerebral mucormycosis (RM) encountered over a 13-year period were reviewed. Predisposing factors included leukemia (36%), diabetes mellitus (27%), aplastic anemia (9%), myelodysplastic syndrome (9%), and treatment with immunosuppressive medications necessary to maintain solid organ or bone marrow graft viability (64%). Two patients had no predisposing factors. Clinical findings included headache (73%), fever (55%), black nasal eschar (45%), orbitofacial cellulitis (36%), cranial nerve palsy (36%), altered sensorium (36%), and hemiparesis (27%). Seven patients presented with destruction of the paranasal sinuses and local invasion; three with direct extension to the frontal or temporal lobes. Four patients displayed hematogenous dissemination to the cerebrum, brain stem, and cerebellum from a primary pulmonary focus. The seven patients with sinus involvement were treated with aggressive surgical debridement. Two patients with focal intracerebral lesions underwent either open craniotomy or stereotactic biopsy. Amphotericin B was administered intravenously to all patients. Local irrigation via a percutaneous catheter was performed in the seven patients with sinus disease and in one case of intracranial abscess. All seven patients with intracranial infection died, in contrast to four patients that survived with infection localized to the sinuses and orbits. All survivors had been treated with a combination of surgery and amphotericin B therapy. This review demonstrates that RM is increasingly affecting patients with sources of immunosuppression other than diabetes mellitus. Early aggressive therapy to prevent cerebral involvement by this severe infection provides the best chance for a good outcome.
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PMID:Rhinocerebral mucormycosis: changing patterns of disease. 811 54

We report the original case of a patient with acute myelogenous leukemia who presented with a painless, complete bilateral oculomotor palsy during induction chemotherapy. Headache, signs of meningeal irritation or further neurological symptoms were absent throughout the course of illness. The CT revealed a subarachnoid hemorrhage (SAH). Within a day of the onset of symptoms, the oculomotor palsy subsided completely with no residual damage. To our knowledge, this is the first described case of SAH in leukemia with complete bilateral oculomotor palsy being the only clinical symptom. Furthermore, the spontaneous remission of this pathological condition is an extremely rare event.
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PMID:Complete bilateral oculomotor palsy: the only clinical sign of subarachnoid hemorrhage in leukemia. 821 61


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