tretinoin and Fever

Differentiation Syndrome (DS) has been identified in a subset of patients undergoing treatment with novel classes of differentiating therapies for acute myeloid leukemia (AML) such as IDH and FLT3 inhibitors. While DS is a well-known treatment-related complication in acute promyelocytic leukemia (APL), efforts are still ongoing to standardize diagnostic and treatment parameters for DS in AML. Though the rates of incidence vary, many of the signs and symptoms of DS are common between APL and AML. So, DS can lead to fatal complications in AML, but prompt management is usually effective and rarely necessitates interruption or discontinuation of AML therapy.

Topics: Acute Kidney Injury; Adrenal Cortex Hormones; Antineoplastic Agents; Arsenic Trioxide; Cell Differentiation; Clinical Trials as Topic; Cytokine Release Syndrome; Edema; Enzyme Inhibitors; Epigenesis, Genetic; Fever; fms-Like Tyrosine Kinase 3; Humans; Hypotension; Isocitrate Dehydrogenase; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Myelopoiesis; Neoplasm Proteins; Pleural Effusion; Respiration Disorders; Tretinoin

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

Sweet syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by tender, red inflammatory nodules or papules that occur in association with infection, malignancy, connective tissue disease, or following exposure to certain drugs. Although drug-induced Sweet syndrome is rare, granulocyte colony-stimulating factor, all-trans-retinoic acid, and miscellaneous drugs have been implicated in causing this disorder in adults. In pediatric patients, granulocyte colony-stimulating factor, all-trans-retinoic acid, trimethoprim-sulfamethoxazole, and azathioprine have been implicated as potential causes of drug-induced Sweet syndrome. To date, six cases, including the patient reported here, have been reported in children.

Topics: Adult; Azathioprine; Child; Connective Tissue Diseases; Erythema; Fever; Granulocyte Colony-Stimulating Factor; Humans; Infections; Sweet Syndrome; Tretinoin; Trimethoprim, Sulfamethoxazole Drug Combination

All trans retinoic acid is the drug of choice in the treatment of acute promyelocytic leukemia. But this drug has some side effects, some of which may be life-threatening. Retinoic acid syndrome is the most frequent and dangerous side effect of this differentiation inducing agent. Other side effects include Sweet's syndrome, vasculitis, hypercalcemia, bone marrow necrosis and fibrosis, thromboembolic events, erythema nodosum, granulomatous proliferation and some pulmonary complications. Here, we report vasculitis in a case with APL treated with ATRA and review the literature.

Topics: Adult; Anti-Inflammatory Agents; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Fever; Humans; Leukemia, Promyelocytic, Acute; Male; Methylprednisolone; Remission Induction; Tretinoin; Vasculitis

Induction therapy of promyelocytic leukemia with all-trans retinoic acid is a standard therapy despite significant side-effects. The most important, the "retinoic acid syndrome", consists of a hyperinflammatory reaction with capillary leakage (edema, pleural, and pericardial effusion), infiltration of myeloid cells into internal organs and systemic signs of inflammation. We describe here two cases of another hyperinflammatory reaction during all-trans retinoic acid therapy, the Sweet's syndrome, consisting of infiltrates of the skin and internal organs by neutrophilic granulocytes. Fever, painful erythematous cutaneous plaques, prominent musculoskeletal involvement (myositis, fasciitis), a sterile pulmonary infiltration and intercurrent proteinuria characterized the clinical course of all-trans retinoic acid-associated Sweet's syndrome. Treatment with glucocorticoids led to resolution of the syndrome within 48 h. Three other cases of all-trans retinoic acid-associated Sweet's syndrome without involvement of internal organs, prominent on our cases, were published previously. Recognition of ATRA-associated Sweet's syndrome is of practical importance.

Topics: Adult; Aged; Aged, 80 and over; Female; Fever; Humans; Leukemia, Promyelocytic, Acute; Middle Aged; Remission Induction; Sweet Syndrome; Tretinoin

All-trans retinoic acid (ATRA) has recently been recognized as the first line therapeutic agent in the treatment of patients with acute promyelocytic leukemia (APL). The extraordinary high remission rate achieved by ATRA in comparison with other chemotherapeutic agents suggested that ATRA differentiation induction therapy seemed superior to conventional chemotherapy for APL patients. However, after the great excitement aroused after the initial successes, we have to take stock and examine in detail several problems which have emerged preventing us from improving the clinical outcome in APL. Maintenance in order to prolong remission and prevention of or retreatment for the relapse are the major subjects of concern at present. Efforts should be made either to keep ATRA effective for APL patients or to resensitize the relapsing patients for repeated ATRA therapy. The administration of ATRA should be carefully adapted in accordance with the individual patient's condition. From both conceptual and practical points of view, ATRA differentiation therapy should be combined with chemotherapy, bone marrow transplantation and biomodifier treatment. Thus, a more comprehensive strategy must be planned and developed in the near future. Using molecular biological techniques, the diagnosis of APL can be more precisely made and the course of the disease more closely monitored. The central dogma, still to be revealed, is the relationship between APL pathogenesis, the chromosome translocation present with the relevant molecular alterations and the response to ATRA treatment. Current studies in all these above fields have provided us with a deeper understanding of the pathogenesis of APL and the physiological function and curative action of ATRA.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Edema; Fever; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Lung Diseases; Remission Induction; Syndrome; Treatment Outcome; Tretinoin

This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of an oral tetra-arsenic tetra-sulfide (As4S4) -containing formula named the Realgar-Indigo naturalis formula (RIF) compared with intravenous arsenic trioxide (ATO) as both induction and maintenance therapies for newly diagnosed acute promyelocytic leukemia (APL).. In all, 242 patients with APL were randomly assigned (1:1) to oral RIF (60 mg/kg) or ATO (0.16 mg/kg) combined with all-trans retinoic acid (ATRA; 25 mg/m(2)) during induction therapy. After achieving complete remission (CR), all patients received three courses of consolidation chemotherapy and maintenance treatment with sequential ATRA followed by either RIF or ATO for 2 years. The primary end point was the rate of disease-free survival (DFS) at 2 years, which was assessed for noninferiority with a 10% noninferiority margin.. The median follow-up time was 39 months. DFS at 2 years was 98.1% (106 of 108) in the RIF group and 95.5% (107 of 112) in the ATO group. The DFS difference was 2.6% (95% CI, -3.0% to 8.0%). The lower limit of the 95% CI of DFS difference was greater than the -10% noninferiority margin, confirming noninferiority (P < .001). No significant differences were noted between the RIF and ATO groups with regard to the CR rate (99.1% v 97.2%; P = .62) or the overall survival at 3 years (99.1% v 96.6%; P = .18). The rates of adverse events were similar in the two groups.. Oral RIF plus ATRA is not inferior to intravenous ATO plus ATRA as first-line treatment of APL and may be considered as a routine treatment option for appropriate patients.

Topics: Administration, Intravenous; Administration, Oral; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Disease-Free Survival; Drugs, Chinese Herbal; Female; Fever; Follow-Up Studies; Humans; Induction Chemotherapy; Leukemia, Promyelocytic, Acute; Liver; Maintenance Chemotherapy; Male; Middle Aged; Oxides; Remission Induction; Sulfides; Treatment Outcome; Tretinoin; Young Adult

We examined the incidence, clinical course, and outcome of patients with newly diagnosed acute promyelocytic leukemia (APL) who developed the retinoic acid syndrome (RAS) treated on the Intergroup Protocol 0129, which prospectively evaluated the role of alltrans retinoic acid (ATRA) alone during induction and as maintenance therapy. Forty-four of 167 (26%) patients receiving ATRA for induction developed the syndrome at a median of 11 days of ATRA (range, 2-47). The median white blood cell (WBC) count was 1,450/microL at diagnosis and was 31,000/microL (range, 6,800-72,000/microL) at the time the syndrome developed. ATRA was discontinued in 36 of the 44 patients (82%) and continued in 8 patients (18%), with subsequent resolution of the syndrome in 7 of the 8. ATRA was resumed in 19 of the 36 patients (53%) in whom ATRA was stopped and not in 17 (47%). The syndrome recurred in 3 of those 19 patients, with 1 death attributable to resumption of the drug. Ten of these 36 patients received chemotherapy without further ATRA, and 8 achieved complete remission (CR). Among 7 patients in whom ATRA was not restarted and were not treated with chemotherapy, 5 achieved CR and 2 died. Two deaths were definitely attributable to the syndrome. No patient receiving ATRA as maintenance developed the syndrome. (Blood. 2000;95:90-95)

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Daunorubicin; Dexamethasone; Female; Fever; Glucocorticoids; Humans; Incidence; Infant; Leukemia, Promyelocytic, Acute; Lung; Male; Middle Aged; Pericardial Effusion; Pleural Effusion; Remission Induction; Respiratory Distress Syndrome; Syndrome; Tretinoin; Weight Gain

Although advanced renal-cell carcinoma (RCC) responds poorly to standard therapies, phase I-II trials have shown activity for combinations of interferon-alpha2b (IFN) with a retinoid. Alitretinoin (9-cis RA) is an endogenous retinoid with high binding affinity for both RAR and RXR receptor families. This phase I-II study enrolled 38 patients with RCC in a dose-escalation study of tolerability, pharmacokinetics (PK), and efficacy of twice daily oral 9-cis RA with subcutaneous IFN. In contrast to studies with similar doses of daily 9-cis RA, PK studies found a consistent reduction in 9-cis RA concentrations of about 50% after multiple b.i.d. doses of 30 or 50 mg/m2, independent of cotreatment with IFN. In the phase I portion, toxicities included systemic symptoms typical of IFN and biochemical abnormalities previously associated with retinoids. Two patients experienced dose-limiting toxicity at 50 mg/m2 b.i.d. of 9-cis RA, thus the recommended phase II dose was 30 mg/m2 b.i.d. One of twenty-six evaluable patients achieved a durable objective partial remission, and repeated dosing with this regimen was poorly tolerated. This combination of retinoid and interferon is not recommended for further study in RCC.

Topics: Adult; Aged; Alitretinoin; Antineoplastic Agents; Carcinoma, Renal Cell; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Synergism; Fatigue; Female; Fever; Humans; Immunologic Factors; Interferon alpha-2; Interferon-alpha; Kidney Neoplasms; Male; Middle Aged; Nephrectomy; Pain; Recombinant Proteins; Remission Induction; Treatment Failure; Tretinoin

This study was conducted to compare the results of treatment of acute promyelocytic leukemia (APL) with all-trans retinoic acid alone (ATRA) or a combination therapy of ATRA followed by chemotherapy. Forty-three patients treated between February 1992 and February 1996 were included in this study. Eighteen patients were treated with ATRA alone and 25 patients were treated with ATRA followed by chemotherapy. The cytogenetic analysis was done in 41 patients at presentation, following treatment, and at follow-up. A complete response (CR) was achieved in 13 (72%) patients on ATRA and 19 (76%) on ATRA followed by chemotherapy. Eleven of 13 patients with response to ATRA alone relapsed with median survival of eight months (range, 1 to 28). One patient died of hepatitis in CR and one patient is alive 2 years after diagnosis. In the combination therapy arm, 10 patients are in CR with a median follow-up of 22 months (range, 6 to 56 months). After achieving a CR, four patients died due to infections during chemotherapy therapy, and only 5 of 19 patients have relapsed. Major cytogenetic response was seen in 8 of the 10 patients in whom cytogenetic data was available after treatment with ATRA at the time of remission. Similarly, 13 of 15 for whom data was available showed a major cytogenetic response after treatment with ATRA plus chemotherapy. Prior to relapse, 80% of the patients had an increase in the percentage of t(15;17) cells in the marrow. Patients with a complete hematological response but no cytogenetic response relapsed within six months. Ten patients died prior to response evaluation. Two patients who received ATRA died of retinoic acid syndrome, one of pneumonia, and one of intracranial hemorrhage. Of the six patients on ATRA and chemotherapy, four died of retinoic acid syndrome (RAS), one of intracranial hemorrhage, and one of left ventricular failure. Only one patient is alive at 24 months following treatment with ATRA alone. The relapse-free survival is 42% at four years for patients treated with ATRA followed by chemotherapy. This trial is a historical comparison of ATRA alone and ATRA with subsequent combination chemotherapy. Nonetheless, the trial shows a significant improvement in the event free survival of patients receiving chemotherapy as consolidation following ATRA.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Cause of Death; Child; Cytarabine; Daunorubicin; Female; Fever; Humans; Leukemia, Promyelocytic, Acute; Lung; Male; Middle Aged; Prospective Studies; Recurrence; Remission Induction; Survival Rate; Tretinoin; Weight Gain

This is a case report of a 68-year-old female referred to the SARS-CoV-2 ward with one week of intermittent fever and three days of progressive loss of vision. Laboratory work-up revealed severe coagulopathy, thrombocytopenia and hyperleukocytosis. MRI showed multiple ischaemic cortical lesions. Acute treatment with all-trans retinoic acid and cytoreduction was started and coagulation parameters corrected. Patients referred to pandemic wards must undergo stringent examination and be referred for further evaluation irrespective of suspected severe acute respiratory syndrome coronavirus-2 infection.

Topics: Aged; Betacoronavirus; Blindness; Coronavirus Infections; COVID-19; Cytoreduction Surgical Procedures; Female; Fever; Humans; Leukemia, Promyelocytic, Acute; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tretinoin

Topics: Adult; Antineoplastic Agents; Biopsy; Diagnosis, Differential; Fever; Genital Diseases, Male; Humans; Induction Chemotherapy; Leukemia, Promyelocytic, Acute; Male; Scrotum; Skin; Skin Ulcer; 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

Reports about patients with acute promyelocytic leukemia from the Middle East are few; in this study we are reporting our single center experience of treating 29 patients over 6years. Acute promyelocytic leukemia treatment response is markedly improved after the introduction of ATRA. Treatment related complication is still an important issue particularly Differentiation Syndrome. Prediction to its occurrence has been tried by other groups. We aimed to study all the possible predictive factors of acute promyelocytic leukemia. Our chemotherapy induction protocol is AIDA protocol which includes ATRA 45mg/m(2)/d in divided doses every12h, and Idarubicin 12mg/m(2)/d IV on days 3, 5, 7, and 9. Differentiation Syndrome occurred in 48.3% of patients and was mainly presented by pulmonary symptoms in 55.2%, 6 cases died during induction. None of the predictive factors studied showed a statistically significant difference between patients who developed Differentiation Syndrome and those who did not. Differentiation Syndrome did not affect overall survival. Cox regression showed an inverse yet a non significant association between PETHEMA and overall survival probability (P=0.168). In conclusion, Differentiation Syndrome has no clear predictive factor to date. The best approach is to hold ATRA and give dexamethasone which is quite effective as reported in the literature. PETHEMA risk model has a moderately significant prognostic value.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Fever; Hemorrhage; Humans; Kaplan-Meier Estimate; Leukemia, Promyelocytic, Acute; Lung Diseases; Male; Middle Aged; Proportional Hazards Models; Risk Factors; Syndrome; Tretinoin; Young Adult

Topics: Anthracyclines; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Fever; Humans; Leukemia, Promyelocytic, Acute; Maintenance Chemotherapy; Male; Mercaptopurine; Methotrexate; Middle Aged; Recurrence; Tretinoin

Most known human teratogens are associated with a unique or characteristic pattern of major and minor malformations and this pattern helps to establish the causal link between the teratogenic exposure and the outcome. Although traditional case-control and cohort study designs can help identify potential teratogens, there is an important role for small cohort studies that include a dysmorphological examination of exposed and unexposed infants for minor structural defects. In combination with other study design approaches, the small cohort study with a specialized physical examination fulfills a necessary function in screening for new potential teratogens and can help to better delineate the spectrum and magnitude of risk for known teratogens.

Topics: Abnormalities, Drug-Induced; Anticonvulsants; Antidepressive Agents; Arthritis, Rheumatoid; Carbamazepine; Case-Control Studies; Cohort Studies; Female; Fever; Fluoxetine; Humans; Isoxazoles; Leflunomide; Maternal Exposure; Neural Tube Defects; Physical Examination; Pregnancy; Prospective Studies; Research Design; Teratogens; Tretinoin

The use of all-trans retinoic acid (ATRA) is now standard therapy for the treatment of acute promyelocytic leukaemia (APML). There have been increasing reports of ATRA-induced myositis, with its frequent association with retinoic acid syndrome and Sweet's syndrome. We report a case of a young man with APML who developed ATRA-induced myositis characterized by unexplained fevers, bilateral leg swelling and a non-painful purpuric, petechial rash, with prompt resolution of symptoms and signs with high-dose steroids and cessation of ATRA. Rapid recognition of this adverse reaction and prompt institution of steroids is of prime importance given its potentially fatal course.

Topics: Adult; Exanthema; Fever; Humans; Leukemia, Promyelocytic, Acute; Male; Myositis; Steroids; Tretinoin

A 24-year-old woman with acute promyelocytic leukemia was treated with all-trans retinoic acid (ATRA) as a remission induction therapy. After pneumonia in the neutropenic period was successfully treated with antibiotic treatment, there was recurrence of high fever alone, followed by the appearance of erythema nodosum with pain in her upper limbs on day 25 of ATRA therapy. Skin biopsy neither revealed infiltration of leukemic cells nor suggested Sweet's syndrome. We considered the eruptions to be associated with ATRA, and prednisolone (30 mg/day for 5 days) was administered. Although the administration of ATRA was continued until complete remission of the leukemia, the erythema nodosum rapidly disappeared following short-term steroid therapy and no recurrence was observed. ATRA-induced erythema nodosum is rare, however it should be recognized as a possible adverse effect in ATRA therapy.

Topics: Adult; Antineoplastic Agents; Erythema Nodosum; Female; Fever; Humans; Leukemia, Promyelocytic, Acute; Prednisolone; Recurrence; Remission Induction; Treatment Outcome; Tretinoin

Infections represent a frequent complication of chemotherapy used for acute myeloid leukaemia (AML) and are associated with important toxicity frequently leading to treatment discontinuation. Acute promyelocytic leukaemia (APL) is a unique AML subset requiring tailored therapy including all-trans retinoic acid and anthracycline-based chemotherapy. We analysed in this study the incidence and type of infections complicating the clinical course of 89 consecutive APL patients receiving the AIDA protocol at a single institution. A total of 179 febrile episodes were registered during induction and consolidation, 52% of which were of unknown origin. Infections were clinically and microbiologically documented in 10.6 and 37.4% of cases, respectively. Coagulase-negative staphylococci represented the major cause of septicaemia (28%) and were more frequently isolated during induction, whereas viridans group streptococci, the second pathogen most frequently isolated from blood (27%), represented the principal pathogen detected during consolidation and were significantly associated with mucositis. Gram-negative bacteria accounted for 33.3% of all blood isolates. Fungal infections were only occasionally observed. Bloodstream infections in APL patients were compared with those documented in 271 consecutive patients affected by other subtypes of AML. The incidence of total septicaemia episodes, of staphylococcal bacteraemias and of fungaemias was significantly higher in patients with other AMLs. Empirical antibiotic therapy with ceftriaxone plus amikacin was effective in 73% of APL cases, most of the remaining cases being successfully managed by the addition of teicoplanin. One single death apparently related to infectious complication was recorded. Overall, infections led to antileukaemic treatment withdrawal in six patients, five of whom currently remain in haematologic remission for 13-106 months. These results indicate that a particular pattern of infections is observed in APL patients receiving ATRA plus anthracycline-based chemotherapy and that these appear to be effectively counteracted by standard management.

Topics: Adolescent; Adult; Aged; Amikacin; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Bacteremia; Ceftazidime; Child; Child, Preschool; Drug Therapy, Combination; Female; Fever; Gram-Positive Bacteria; Humans; Idarubicin; Infant; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Remission Induction; Staphylococcal Infections; Streptococcal Infections; 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

Scrotal ulcer is a unique adverse effect of all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL). The pathogenesis of scrotal ulceration remains unknown. We describe genital ulcers that developed in four patients with APL who were undergoing ATRA therapy (45 mg/m2 per day p.o.). Two of the patients were female, in whom this condition is quite rare. Genital ulcers with concomitant fever appeared between 17 and 32 days of therapy in all four patients. Genital ulcers healed in three of the patients while another patient developed Fournier's gangrene and underwent left testectomy. Ulcer healing was brought by either local or intravenous corticosteroids. Intravenous dexamethasone actually enabled continued ATRA administration in one patient, while ATRA was discontinued in other two patients. If corticosteroids cannot control progression of genital ulcers nor concomitant fever, ATRA administration should be discontinued so as not to induce Fournier's gangrene nor retionic acid syndrome. Our experience indicates the importance of recognizing genital ulcers associated with ATRA in order that appropriate countermeasures can be taken.

Topics: Adrenal Cortex Hormones; Adult; Anti-Inflammatory Agents; Antineoplastic Agents; Female; Fever; Fournier Gangrene; Genital Diseases, Female; Genital Diseases, Male; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Tretinoin; Ulcer

The treatment of acute promyelocytic leukemia with all-trans-retinoic acid (ATRA) sometimes results in a syndrome characterized by fever, respiratory distress, weight gain, pleural and pericardial effusion, and pulmonary infiltrates. We report the radiologic features of ATRA syndrome.. During the past 5 years, 69 patients with acute promyelocytic leukemia were treated with ATRA. Of this group, 15 patients developed ATRA syndrome. Serial chest radiographs of the 15 patients with ATRA syndrome were evaluated retrospectively for the presence of pleural effusion, pulmonary nodules, consolidation, ground-glass opacity, septal lines, increased pulmonary blood volume, peribronchial cuffing, and air bronchogram. Also, we measured the cardiothoracic ratio and the vascular pedicle width.. Chest radiographs showed increased cardiothoracic ratio in 13 of the 15 patients, increased vascular pedicle width in 13, increased pulmonary blood volume in 13, septal lines in nine, peribronchial cuffing in nine, ground-glass opacity in nine, consolidation in seven, and nodules in seven. Pleural effusion was noted in 11 of the 15 patients, and air bronchogram was noted in five of the 15 patients. Pulmonary hemorrhage developed in three patients who were being treated with ATRA; they showed bilateral, diffuse, poorly defined nodules and ground-glass opacity on radiography.. Most patients with ATRA syndrome have abnormal findings on chest radiographs, and the abnormalities are similar to those of pulmonary edema.

Topics: Adult; Antineoplastic Agents; Female; Fever; Humans; Lung Diseases; Male; Middle Aged; Pericardial Effusion; Pleural Effusion; Radiography; Syndrome; Tretinoin; Weight Gain

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Fever; Humans; Hypotension; Idarubicin; Leukemia, Promyelocytic, Acute; Leukocytosis; Lung; Male; Respiratory Distress Syndrome; Syndrome; Tretinoin

We report a case of Sweet's syndrome associated with retinoic acid syndrome in a patient with acute promyelocytic leukemia treated with all- trans retinoic acid (ATRA). Sweet's syndrome appeared on day 6 of ATRA therapy for promyelocytic leukemia. It was associated with a mild retinoic acid syndrome, an inflammatory syndrome occurring in 25% of patients treated with ATRA and characterized by features of capillary leakage with systemic inflammatory signs. The ATRA therapy was discontinued for 11 days and treatment with corticosteroids improved the systemic and cutaneous signs. Only 11 cases of Sweet's syndrome associated with ATRA have been previously reported in the literature, involving only the skin in eight cases, the skin and muscles in two cases, and the lung, kidney, fascia, and muscles in one case. Sweet's syndrome was followed by retinoic acid syndrome in one of these cases. The previously reported cases are reviewed, and the mechanisms of Sweet's and retinoic acid syndromes and the link between them are discussed.

Topics: Antineoplastic Agents; Fever; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Sweet Syndrome; Syndrome; Tretinoin; Weight Gain

All-trans-retinoic acid (ATRA) induces complete clinical remissions in a high proportion of patients with acute promyelocytic leukemia and has become the standard induction therapy. Its use as a single agent results in short-lived remissions; thus, cytotoxic drugs are used for "consolidation" therapy. Side effects reported during treatment with ATRA include retinoic acid syndrome and Sweet's syndrome. Sweet's syndrome has been associated with acute myelogenous leukemia at presentation, but only two cases of Sweet's syndrome involving the musculoskeletal system in patients treated with ATRA have been described. We describe two additional patients with acute promyelocytic leukemia who had unexplained fever and myalgias (cutaneous lesions in one patient) during induction therapy with ATRA. Radiologic findings were similar to those in previously reported ATRA-associated Sweet's syndrome of the musculoskeletal system. The clinical course was characterized by a rapid resolution of the symptoms during treatment with dexamethasone. Recognition of the syndrome is important, especially considering the rapid resolution of symptoms after early institution of therapy with corticosteroids.

Topics: Adult; Dexamethasone; Female; Fever; Humans; Leukemia, Promyelocytic, Acute; Magnetic Resonance Imaging; Male; Muscle, Skeletal; Myositis; Sweet Syndrome; Tretinoin

Topics: Acute Disease; Aged; Antineoplastic Agents; Female; Fever; Humans; Leukemia, Myeloid; Respiratory Distress 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

The feasibility and safety of outpatient management of acute promyelocytic leukemia (APL) during the aplastic phase after intensive consolidation chemotherapy, the incidence and types of complications requiring readmission to hospital, and the number of hospital days spared by this policy have been prospectively evaluated. After chemotherapy administration, patients were evaluated on an ambulatory basis. In the event of any complication they referred to the Emergency Unit (EU) of our Department dedicated to outpatients with hematologic diseases. Forty patients with APL observed over a 4 year period were eligible for intensive chemotherapy. After the achievement of complete remission they received a total of 104 consolidation courses and in 98 instances they were followed on an ambulatory basis. There were 41 cases (42%) of rehospitalization for fever (40 cases) or severe anemia (one case). Only one patient died due to a brain hemorrhage. Streptococcus viridans was the organism most frequently isolated from blood. Empiric once-a-day antibacterial therapy with ceftriaxone and amikacin was effective in 87% of the cases and made possible early discharge in 28% of the cases to continue the antibiotic therapy on an outpatient setting. Patients were managed out of the hospital for 76% of the post-consolidation neutropenia period. Thanks to the availability of an EU specifically dedicated to outpatients with hematologic diseases, out-hospital management of APL patients after consolidation therapy appeared to be safe, well accepted, potentially cost-saving, and contributed to saving the risk of developing severe nosocomial infections.

Topics: Adult; Aged; Ambulatory Care; Amikacin; Anemia; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Ceftriaxone; Cerebral Hemorrhage; Cross Infection; Drug Therapy, Combination; Emergency Service, Hospital; Female; Fever; Hospitalization; Humans; Idarubicin; Incidence; Length of Stay; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Neutropenia; Remission Induction; Tretinoin

All-trans-retinoic acid (ATRA) can induce a clinical remission in patients with acute promyelocytic leukemia. An adverse condition called "retinoic acid syndrome" limits this therapy. It is characterized by fever and respiratory distress, along with weight gain, pleural or pericardial effusions, peripheral edema, thromboembolic events, and intermittent hypotension. The lung disease has been previously ascribed to an infiltration of leukemic or maturing myeloid cells into lung parenchyma, which is sometimes associated with pleural effusions and diffuse alveolar hemorrhage. We report a case of retinoic acid syndrome in an 18-yr-old woman who developed diffuse alveolar hemorrhage while being treated with ATRA for acute promyelocytic leukemia. An open lung biopsy revealed pulmonary capillaritis.

Topics: Adolescent; Antineoplastic Agents; Capillaries; Edema; Female; Fever; Hemoptysis; Humans; Hypotension; Leukemia, Promyelocytic, Acute; Lung; Pericardial Effusion; Pleural Effusion; Pulmonary Alveoli; Respiratory Insufficiency; Syndrome; Thromboembolism; Tretinoin; Vasculitis; Weight Gain

A 56-year-old woman was admitted for evaluation of petechiae and acute promyelocytic leukemia was diagnosed. Administration of all-trans retinoic acid (ATRA) at 60 mg per day was begun. On the same day, high fever was recognized. There was no evidence of infection nor other organ dysfunction. Administration of steroid caused a resolution of the fever. The same phenomenon was observed three times subsequently. High fever was the adverse reaction in this patient during the treatment of ATRA, and steroid was dramatically effective.

Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Female; Fever; Humans; Leukemia, Promyelocytic, Acute; Methylprednisolone; Middle Aged; 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: Antineoplastic Combined Chemotherapy Protocols; Colonic Pseudo-Obstruction; Cytarabine; Daunorubicin; Female; Fever; Humans; Leukemia, Promyelocytic, Acute; Leukocyte Count; Middle Aged; Remission Induction; Tretinoin

Topics: Acute Disease; Adult; Fever; Humans; Leukemia, Promyelocytic, Acute; Male; Pleural Effusion; Respiratory Insufficiency; 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