tretinoin and Dyspnea

Acute promyelocytic leukemia(APL) is characterized by the t(15;17) chromosomal translocation leading to the formation of the PML-RARalpha oncoprotein. This leukemia has attracted considerable interest in recent years, being the first in which therapies that specifically target the underlying molecular lesion, i.e., all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), leading to induction of differentiation and apoptosis have been successfully used in clinical practice. The advent of ATRA therapy has transformed APL from being a disease with a poor outlook to one of the most prognostically favorable subsets of acute myeloid leukemia. Further improvements in outcome may be achieved with the use of ATO, which achieves high rates of remission in the relatively small proportion of patients now relapsing following standard first-line therapy with ATRA and anthracycline-based chemotherapy. Moreover, recent studies have suggested that ATO and ATRA, or even ATO alone, used as front-line treatment of PML-RARA- associated APL can induce long-term remissions. This raises the possibility that some patients can be cured using differentiation therapies alone, without the need for chemotherapy, thereby potentially reducing treatment-related toxicity. It is clear that the success of such an approach is critically dependent upon molecular diagnostics and monitoring for minimal residual disease (MRD) to distinguish those patients who can potentially be cured with differentiation therapy from those requiring additional myelosuppressive agents. This represents an exciting new phase in the treatment of acute leukemia, highlighting the potential of molecularly targeted and MRD-directed therapies to achieve an individualized approach to patient management.

Topics: Antineoplastic Agents; Apoptosis; Arsenic Trioxide; Arsenicals; Cell Differentiation; Dyspnea; Fever; Gene Expression Regulation, Leukemic; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Models, Biological; Neoplasm, Residual; Oncogene Proteins, Fusion; Oxides; Transcription, Genetic; Treatment Outcome; Tretinoin

The evaluation of new therapies in prostate cancer requires unique end points for agents with diverse mechanisms of action. Because retinoic acid may have a confounding effect on prostate-specific antigen, we incorporated a pathological end point into the outcome assessment of two sequential clinical trials using all-trans-retinoic acid (ATRA) and the combination of 13-cis-retinoic acid and IFN-2a (cRA¿IFN). Pre- and posttherapy tumor biopsy specimens were studied for histological changes, apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling assay), and proliferation index (Ki67). Prostate-specific membrane antigen (PSMA) expression was also evaluated using two different monoclonal antibodies to its intracellular domain (Cytogen 7E11 and Hybritech PM2). Fourteen patients with androgen-independent disease were treated with ATRA (50 mg/m2 p.o. every 8 h daily) and 16 androgen-independent and 4 androgen-dependent patients were treated with cRA¿IFN (10 mg/kg/day cRA plus 3, 6, or 9 million units daily IFN). Both therapies were well tolerated, with fatigue and cheilitis being the most common adverse events. Clinical activity, assessed by radiographs and serum prostate-specific antigen, was minimal, and the majority of patients progressed within 3 months. One patient with androgen-dependent disease had prolonged stabilization for >1 year. The majority of cases (95%) showed no gross histological changes and no difference in apoptotic or proliferative indices. Increased PSMA immunoreactivity was seen in seven of nine (78%) cases using PM2 antibody and in two of nine (22%) cases using the 7E11 antibody. Although antitumor effects were modest, the results suggest a role for retinoids in modulating the expression of PSMA on prostate cancer cells.

Topics: Aged; Antigens, Surface; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bone Neoplasms; Carboxypeptidases; Cheilitis; Dyspnea; Exanthema; Fatigue; Glutamate Carboxypeptidase II; Hematologic Diseases; Humans; Interferon alpha-2; Interferon-alpha; Ki-67 Antigen; Liver; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Recombinant Proteins; Transaminases; Treatment Outcome; Tretinoin

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Diagnosis, Differential; Dyspnea; Female; Fever; Humans; Hypotension; Leukemia, Promyelocytic, Acute; Leukocytosis; Lung Diseases; Oxides; Risk Factors; Severity of Illness Index; Syndrome; Treatment Outcome; Tretinoin

Topics: Acute Lung Injury; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Catheter-Related Infections; Dexamethasone; Dyspnea; Fever; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Staphylococcal Infections; Tretinoin

Topics: Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Diagnosis, Differential; Dyspnea; Female; Follow-Up Studies; Humans; Induction Chemotherapy; Leukemia, Promyelocytic, Acute; Middle Aged; Mitoxantrone; Pleural Effusion; Pulmonary Edema; Thioguanine; Tomography, X-Ray Computed; Tretinoin

Retinoic acid syndrome is a novel complication of therapy with all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APML). Primarily the syndrome consists of fever and respiratory distress. Additional features include weight gain, oedema over lower extremities, pleural or pericardial effusion and hypotension. We report electrophysiological changes in a 16 year old patient with acute promyelocytic leukemia following treatment with ATRA. Such an unusual complication is a rarity and to the best of our knowledge has not been previously reported.

Topics: Adolescent; Antineoplastic Agents; Arrhythmias, Cardiac; Dexamethasone; Dyspnea; Female; Glucocorticoids; Humans; Leukemia, Promyelocytic, Acute; Pericardial Effusion; Syndrome; Tretinoin

It is now possible to achieve complete remission in the majority of patients with acute promyelocytic leukemia (APL) if all-trans retinoic acid (ATRA) is administered as a single agent or in combination with cytotoxic chemotherapy. Despite its positive influence on recovery, ATRA is not without the potential for toxicity. It is important for clinicians participating in the care of patients undergoing treatment with this drug to be aware of ATRA syndrome and institute the appropriate therapy to reduce the likelihood of an adverse outcome.

Topics: Aged; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Dyspnea; Female; Humans; Leukemia, Promyelocytic, Acute; Respiratory Insufficiency; Tretinoin

To explore the clinical features, risk factors an d treatment of retinoic acid syndrome (RAS) in patients with acute promyelocytic leukemia (APL) treated with retinoic acid, the clinical and laboratory data of 11 APL patients with RAS were retrospectively analysed. The results showed that earlier and more common symptoms of RAS were successively dyspnea (11/11), fever (10/11) and hydrothorax (6/11). Higher WBC count (> or = 15.0 x 10(9)/L) in the course of treatment of all-trans retinoic acid susceptible to develop RAS (9/11). The RAS patients were treated with dexamethasone without discontinuing the treatment of retinoic acid, complete remission was achieved in 10 cases and one patient died from disseminated intravascular coagulation. It is concluded that the identification and dexamethasone treatment of RAS in earlier period are extremely important for obtaining better clinical curative effect, and it does not influence therapeutic effect of continuing application of retinoic acid.

Topics: Adolescent; Adult; Child; Dyspnea; Female; Fever; Humans; Hydrothorax; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Syndrome; Tretinoin

A 62-year-old woman with acute promyelocytic leukaemia was treated with all-trans retinoic acid. On day 2 she suffered with dyspnoea and general fatigue. Marked hypoxia suggested the occurrence of retinoic acid syndrome. She underwent endotracheal intubation and mechanical ventilation with the administration of dexamethasone. Her symptoms promptly abated. She was subsequently treated with conventional chemotherapy and achieved complete remission.

Topics: Antineoplastic Agents; Dyspnea; Female; Fever; Humans; Leukemia, Promyelocytic, Acute; Middle Aged; Radiography; Respiration, Artificial; Respiratory Distress Syndrome; Syndrome; Tretinoin

Arsenic trioxide, like all-trans-retinoic acid (RA), induces differentiation of acute promyelocytic leukemia (APL) cells in vivo. Treatment of APL patients with all-trans RA is commonly associated with leukocytosis, and approximately 50% of patients develop the RA syndrome. We reviewed our clinical experience with arsenic trioxide to determine the incidence of these two phenomena.. Twenty-six patients with relapsed or refractory APL were treated with arsenic trioxide for remission induction at daily doses that ranged from 0.06 to 0.17 mg/kg.. Twenty-three patients (88%) achieved complete remission. Leukocytosis was observed in 15 patients (58%). The median baseline leukocyte count for patients with leukocytosis was 3,900 cells/microL (range, 1,200 to 72,300 cells/microL), which was higher than that for patients who did not develop leukocytosis (2,100 cells/microL; range, 500 to 5,400 cells/microL; P =.01). No other cytotoxic therapy was administered, and the leukocytosis resolved in all cases. The RA syndrome was observed in eight patients (31%). Patients who developed leukocytosis were significantly more likely to develop the RA syndrome (P <.001), and no patient without a peak leukocyte count greater than 10,000 cells/microL developed the syndrome. Among the patients with leukocytosis, there was no observed relation between the leukocyte peak and the probability of developing the syndrome (P =.37).. Induction therapy of APL with all-trans RA and arsenic trioxide is associated with leukocytosis and the RA syndrome. These clinical effects seem to be intrinsically related to the biologic responsiveness and the differentiation process induced by these new agents.

Topics: Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Dyspnea; Fever; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Oxides; Pleural Effusion; Syndrome; Tretinoin

All-trans-retinoic acid (ATRA) is considered the recommended induction treatment for acute promyelocytic leukemia. In the pre-ATRA era pulmonary bleeding was a common cause of death in these patients, mostly due to disseminated intravascular coagulation which was further exacerbated by the administration of chemotherapy. Although ATRA syndrome, the most serious adverse effect of ATRA treatment, involves the lungs, pulmonary hemorrhage has only rarely been reported as a manifestation of ATRA syndrome. Here we describe 2 patients who developed diffuse alveolar hemorrhage during treatment with ATRA. The possible mechanisms of pulmonary bleeding in these cases are discussed.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Coagulation Tests; Cytarabine; Daunorubicin; Dyspnea; Fatal Outcome; Fever; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Lung Diseases; Male; Middle Aged; Pulmonary Alveoli; Remission Induction; Syndrome; Tretinoin

All-trans retinoic acid (ATRA) has been used successfully in inducing remission in patients with acute promyelocytic leukemia (APL). Its overall toxicity is considerably less compared to standard induction chemotherapy; however, it is associated with a high incidence of a potentially fatal symptom complex referred to as "retinoic acid syndrome." This report describes a patient with APL who developed the syndrome a few weeks after initiating induction therapy with ATRA despite being treated for hyperleukocytosis. The case illustrates the classic features of the syndrome and its dramatic response to corticosteroid treatment.

Topics: Antineoplastic Agents; Dexamethasone; Dyspnea; Glucocorticoids; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Male; Middle Aged; Pulmonary Edema; Syndrome; Tretinoin

All-trans-retinoic acid is an effective agent to induce remission in patients with acute promyelocytic leukemia (APL). Unlike conventional chemotherapy, this drug exerts its effect by inducing differentiation of immature leukemic cells. A distinctive clinical syndrome characterized by fever, dyspnea, effusions, weight gain, and organ failure (the "retinoic acid syndrome") can occur during treatment with this drug. Postmortem studies have shown extensive organ infiltration by leukemic cells, and the early administration of corticosteroids can result in prompt resolution of symptoms. We describe a patient with APL in whom acute renal failure developed during treatment with all-trans-retinoic acid. Transient renal enlargement during a period of leukocytosis and a beneficial response to treatment with dexamethasone suggest that renal failure in this patient was probably related to the retinoic acid syndrome.

Topics: Acute Kidney Injury; Dyspnea; Fever; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Pericardial Effusion; Pleural Effusion; Syndrome; Tretinoin

Topics: Adrenal Cortex Hormones; Adult; Antineoplastic Combined Chemotherapy Protocols; Bronchoalveolar Lavage Fluid; Dyspnea; Fever; Humans; Leukemia, Promyelocytic, Acute; Male; Syndrome; Tretinoin; Weight Gain

Topics: Adult; Dyspnea; Female; Fever; Humans; Hypotension; Leukemia, Promyelocytic, Acute; Middle Aged; Syndrome; Tretinoin

Topics: Adult; Child, Preschool; Drug Tolerance; Dyspnea; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Pseudotumor Cerebri; Tretinoin

Topics: Aged; Dyspnea; Female; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Male; Middle Aged; Pseudotumor Cerebri; Tretinoin

Topics: Adult; Dyspnea; Female; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Male; Syndrome; Tretinoin

A 46-year-old woman with acute promyelocytic leukemia (APL) was treated with all-trans retinoic acid (ATRA) and chemotherapy according to the AML-92, M3 regimen of the Japan Adult Leukemia Study Group (JALSG). Between days 7 and 18 of therapy, she suffered chest discomfort, fever, cough, dyspnea and general fatigue. A chest roentogenogram showed bilateral interstitial infiltrates. Her leukocyte count began to increase rapidly to 6,400/microliters on day 14. Marked hypoxia (PO2 35.9 mmHg) suggested occurrence of retinoic acid (RA) syndrome. She underwent endotracheal intubation and mechanical ventilation with administration of methyl-prednisolone (m-PSL) pulse therapy. Her symptoms promptly abated. Therapy with ATRA was continued and her leukocyte count reached 44,800/microliters on day 19 of therapy. She achieved complete remission on day 48.

Topics: Dyspnea; Female; Fever; Humans; Leukemia, Promyelocytic, Acute; Methylprednisolone; Middle Aged; Remission Induction; Syndrome; Tretinoin

Two cases of acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) developed fever, dyspnea and chest pain. A chest roentgenogram showed bilateral pleural effusion (case 1) and bilateral interstitial infiltration (case 2). The first case was a 50-year-old female in her first relapse, who was initially diagnosed as having pleuritis tuberculosa and was treated with anti-tuberculotic agents. Her symptoms continued for 44 days and complete remission was achieved 53 days after commencing ATRA therapy. The second case was a previously untreated 46-year-old male. His case had been diagnosed as adult respiratory distress syndrome and he had been treated with prednisolone. His symptoms rapidly improved and complete remission was achieved 38 days after the ATRA therapy. This was the first report of patients in Japan considered to have developed "retinoic acid syndrome (RAS)". In our five APL cases treated with ATRA, the syndrome was not always accompanied by peripheral blood leukocytosis even though the two cases with RAS showed higher leukocyte counts than the other two cases without RAS and also had DIC. We should pay attention to the severe respiratory symptoms that develop in APL patients after ATRA treatment and immediate steroid therapy is required for such patients.

Topics: Adult; Chest Pain; Dyspnea; Female; Fever; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Syndrome; Tretinoin

To describe a novel complication of therapy with all-trans retinoic acid in patients with acute promyelocytic leukemia.. Case series.. Comprehensive cancer center.. Consecutive patients with a morphologic diagnosis of acute promyelocytic leukemia who underwent remission induction treatment with all-trans retinoic acid, 45 mg/m2 body surface area per day.. Nine of 35 patients (26%; 95% CI, 9% to 52%) with acute promyelocytic leukemia who were treated with all-trans retinoic acid developed a syndrome consisting primarily of fever and respiratory distress. Additional prominent signs and symptoms included weight gain, lower-extremity edema, pleural or pericardial effusions, and episodic hypotension. The onset of this symptom complex occurred from 2 to 21 days after starting treatment. Three deaths occurred; post-mortem examinations in two patients showed pulmonary interstitial infiltration with maturing myeloid cells. Six other patients survived, each achieving complete remission (five patients with all-trans retinoic acid only; 1 patient with chemotherapy). In six of the nine cases, the onset of the syndrome was preceded by an increase in peripheral blood leukocytes to a level of at least 20 x 10(9) cells/L. Certain therapeutic interventions, including leukapheresis, temporary cessation of therapy with all-trans retinoic acid, and cytotoxic chemotherapy in moderate doses were not useful after respiratory distress was established. However, the administration of high-dose corticosteroid therapy (dexamethasone, 10 mg IV intravenously every 12 hours for 3 or more days) early in the course of the syndrome resulted in prompt symptomatic improvement and full recovery in three of four patients.. The use of all-trans retinoic acid to induce hematologic remission in patients with acute promyelocytic leukemia is associated in some patients with the development of a potentially lethal syndrome that is not uniformly accompanied by peripheral blood leukocytosis. Early recognition of the symptom complex of fever and dyspnea, combined with prompt corticosteroid treatment, may decrease morbidity and mortality associated with this syndrome.

Topics: Adult; Aged; Autopsy; Dyspnea; Edema; Female; Fever; Humans; Hypotension; Leukemia, Promyelocytic, Acute; Leukocytosis; Male; Middle Aged; Remission Induction; Syndrome; Tretinoin