OBJECTIVETo compare the efficacy and adverse effects between arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL).

METHODSThe clinical data of 71 patients with newly diagnosed APL were retrospectively analyzed. Two groups were classified according to the induction regimens, namely ATO group (n = 41) and ATRA group (n = 30). The complete remission (CR) rate and the time to CR were compared between these two groups.

RESULTSThe CR rate was 97.5% in ATO group and 93.3% in ATRA group (P > 0.05). The median time to CR was 29 days (21-45 days) in ATO group, which was significantly shorter than 38.5 days (24-63 days) in ATRA group (P < 0.001). Retinoic acid syndrome occurred in 52.9% of patients treated with ATRA, which affected the further use of ATRA.

CONCLUSIONSBoth ATO and ATRA have high response rates for newly diagnosed patients with APL. Compared with ATRA, ATO induction therapy has shorter time to achieve CR and less adverse effects, and therefore may be the first-line therapy for APL.

Adolescent ; Adult ; Aged ; Arsenicals ; adverse effects ; therapeutic use ; Female ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Oxides ; adverse effects ; therapeutic use ; Remission Induction ; Retrospective Studies ; Treatment Outcome ; Tretinoin ; adverse effects ; therapeutic use ; Young Adult

OBJECTIVETo identify the side effect of all-trans retinoic acid (ATRA), and improve early therapeutic response in patients with acute promyelocytic leukemia (APL).

METHODThe first case of Sweet's syndrome (SS) developed in a APL patient treated with ATRA was reported in mainland of China, and reviewed correlative literature.

RESULTSOnly 14 cases of SS associated with ATRA therapy in APL have been reported in the literature, including the present case. The median age was 49.5 years (9 -84) and 10 were women and 4 men. Of them, SS was restricted to the skin in 10 case, the other 4 muscle, fascia, kidney, and lung were involved. SS appeared after a median of 18 days of ATRA therapy (6 - 34 days). The median WBC count was 7.05 (0.80 - 23.00) x 10(9)/L. Four patients continued with the ATRA therapy without interruption, 13 patients treated with steroids and 12 responded. One patient improved without any treatment. Two cases of SS developed retinoic acid syndromes after ATRA therapy.

CONCLUSIONSweet's syndrome is a rare adverse effect of ATRA, and has similar features with inflammatory or infective dermatosis. The corticosteroids treatment could improve the systemic and cutaneous symptoms. When ATRA therapy was restarted after SS subsided, no recurrence of rashes was observed.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Sweet Syndrome ; chemically induced ; Tretinoin ; adverse effects ; therapeutic use

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.
Adolescent ; Adult ; Child ; Dyspnea ; etiology ; Female ; Fever ; etiology ; Humans ; Hydrothorax ; etiology ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Syndrome ; Tretinoin ; adverse effects

The aim of this study was to explore the regulating effects of hyperoside (Hyp) on lipid metabolism in high-fat diet mice. The high-fat diet mouse model was established by high-fat diet induction. After 5 weeks of Hyp intragastric administration in high-fat diet mice, the serum lipid levels before and after Hyp administration were measured by the corresponding kits. The tissue structure of mouse liver was observed by HE staining before and after Hyp administration. The changes of intestinal flora and transcriptome were measured by Illumina platforms. Liquid chromatography-mass spectrometry (LC-MS) was used to determine non-targeted metabolites. The results showed that Hyp significantly reduced lipid levels in the high-fat diet mice and effectively restored the external morphology and internal structure of liver tissue. Hyp changed the species composition of the intestinal flora in high-fat diet mice, increased the abundance of beneficial flora such as Ruminococcus, and decreased the abundance of harmful flora such as Sutterella. Combined multi-omics analysis revealed that the effect of retinoic acid on lipid metabolism was significant in the high-fat diet mice treated with Hyp, while the increase of retinoic acid content was significantly negatively correlated with the expression of genes such as cyp1a2 and ugt1a6b, positively correlated with AF12 abundance, and significantly negatively correlated with unidentified_Desulfovibrionaceae abundance. These results suggest that Hyp may modulate the abundance of AF12, unidentified_Desulfovibrionaceae and inhibit the expression of genes such as cyp1a2 and ugt1a6b, thus increasing the content of retinoic acid and regulating lipid metabolism in the high-fat diet mice.
Animals ; Mice ; Diet, High-Fat/adverse effects* ; Lipid Metabolism ; Cytochrome P-450 CYP1A2/pharmacology* ; Multiomics ; Liver ; Lipids/pharmacology* ; Tretinoin/pharmacology* ; Mice, Inbred C57BL

OBJECTIVETo observe the efficacy and side effect of the all-trans retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) combination in acute promyelocytic leukemia (APL).

METHODSTwenty APL patients were treated with the ATRA and As(2)O(3) combination, and 18 of them could be evaluated. The treatment protocol was as following: 10 mg As(2)O(3) (0.1% solution) in 500 ml 50 g/L glucose solution for intravenous drip over 4 to 6 hours once a day, ATRA was given 25 mg/m(2) every day.

RESULTSSeventeen of the 18 patients achieved complete remission (CR), the CR rate was 94.4%. All 14 newly diagnosed patients and 3 of 4 relapsed patients achieved CR. No significant side effect was observed.

CONCLUSIONThe As(2)O(3) and ATRA in the treatment of APL can obtain a higher CR rate and a shorter duration for achieving CR.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Arsenicals ; administration & dosage ; adverse effects ; Child ; Female ; Follow-Up Studies ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Oxides ; administration & dosage ; adverse effects ; Remission Induction ; Treatment Outcome ; Tretinoin ; administration & dosage ; adverse effects

OBJECTIVETo study whether all-trans retinoic acid (ATRA) combined with arsenic trioxide (As(2)O(3)) in acute promyelocytic leukemia (APL) treatment could further improve the clinical and molecular remission rate.

METHODThirty one newly-diagnosed APL patients of whom 15 were males, 16 females and median age 35.4 years entered into the study. They were treated with ATRA 25 mg x m(-2) x d(-1) combined with As(2)O(3) 0.16 mg x kg(-1) x d(-1) until complete remission (CR). The doses were adjusted according to white blood cell (WBC) counts, occurrence of RA syndrome and the status of liver function. CR rate, time of reaching clinical and molecular remission and side effects were observed.

RESULTTwo patients died 2 approximately 3 days after the treatment due to intracranial hemorrhage, and 29 (93.5%) achieved CR. The average time for achieving CR was 25.1 +/- 3.9 days. Hyperleukocytosis emerged in 66.5% and hepatic damages in 65.5% of the patients, they were ameliorated within one week after reduction of the As(2)O(3) dose or its suspension. The PML/RAR alpha fusion gene that was positive in all 29 patients before treatment turned negative only in 3 cases (10.3%) after obtaining CR (CR1) and in 10/13 cases (77%) after consolidation treatment. Up to now (1-8 months follow-up), all 29 patients remain in CR1.

CONCLUSIONATRA combined with As(2)O(3) in de novo APL treatment can yield a high CR rate without intolerable side effects. Long term effect needs further observation.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Arsenicals ; administration & dosage ; adverse effects ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gene Expression ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics ; Male ; Middle Aged ; Oncogene Proteins, Fusion ; genetics ; Oxides ; administration & dosage ; adverse effects ; Remission Induction ; Time Factors ; Treatment Outcome ; Tretinoin ; administration & dosage ; adverse effects

OBJECTIVETo observe the prevention and therapeutic effects of tanshitone (TAN) on retinoic acid induced osteoporosis in mice.

METHODThe mice osteoporosis was induced by given retinoic acid intragastrically for two weeks. The histomorphological features of bone were observed and biochemical indexes in serum (Ca, P, ALP, TRAP, E2, BGP) were determined after the mice were given TAN at the dose of 40, 80, 160 mg x kg(-1) respectly.

RESULTTanshinone can induce high conversion of osteoporosis. The levels of P, ALP, TRAP and BGP in the TAN groups were lower than the model group, while the E2 level was higher than the model group.

CONCLUSIONTanshitone can prevent the loss bone in the experimental mice. The mechanism may be that it improves the level of estrogenic hormone and inhibits the high bone turnover.

Alkaline Phosphatase ; blood ; Animals ; Bone Density ; drug effects ; Disease Models, Animal ; Diterpenes, Abietane ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Male ; Mice ; Osteoporosis ; blood ; chemically induced ; drug therapy ; prevention & control ; Phenanthrenes ; administration & dosage ; Tretinoin ; adverse effects

OBJECTIVETo explore the characteristics and risk of etoposide-related leukemia in the treatment of hemophagocytic lymphohistiocytosis (HLH).

METHODClinical characteristics of a case with secondary acute promyelocytic leukemia (APL) were summarized and 10 cases of secondary leukemia after treatment for HLH from literature were analyzed.

RESULTThe child was diagnosed with Epstein-Barr virus associated HLH and received HLH-2004 protocol. The cumulative dose of etoposide (VP16) was 3520 mg/m(2). The patient was diagnosed with APL after 28 months of HLH.He achieved complete remission after induction chemotherapy of all-trans-retinoic acid and darubicin. Consolidated chemotherapy was continued. There were 10 reports of etoposide-related leukemia after treatment for HLH in the literature.Review of 11 cases treated with VP16, of which cumulative doses were 900-20 500 mg/m(2). The interval period between HLH and secondary leukemia was 24 months. The types of secondary leukemia included 1 case with acute lymphoblastic leukemia, 1 case with myelodysplastic syndrome and 9 cases of acute myeloid leukemia. The abnormalities of chromosome included 3 patients with 11q23, 3 APL patients with t (15, 17).Seven patients survived and 4 died.

CONCLUSIONThe latency period of etoposide-related leukemia is short. Acute myeloid leukemia and balanced chromosomal abnormality are common in etoposide-related leukemia. The risk factors for development of secondary leukemia are related to cumulative drug doses of etoposide, treatment schedules and co-administration of other antineoplastic agents.It is appropriate to keep suitable range of the cumulative dose of etoposide in HLH therapy in order to reduce the risk of therapy related leukemia.

Acute Disease ; Antineoplastic Agents ; administration & dosage ; adverse effects ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Child, Preschool ; Daunorubicin ; administration & dosage ; Epstein-Barr Virus Infections ; complications ; drug therapy ; virology ; Etoposide ; administration & dosage ; adverse effects ; Humans ; Leukemia, Promyelocytic, Acute ; chemically induced ; drug therapy ; Lymphohistiocytosis, Hemophagocytic ; complications ; drug therapy ; virology ; Male ; Neoplasms, Second Primary ; chemically induced ; Risk Assessment ; Treatment Outcome ; Tretinoin ; administration & dosage

To explore therapeutic efficacy of androgens and low dose all-trans retinoic acid (ATRA) for myelodysplastic syndrome (MDS) patients, 55 patients of MDS were observed, including 41 cases of refractory anemia (RA), 11 cases of refractory anemia with excess of blasts (RAEB), 2 cases of refractory anemia with excess of blasts in transformation (RAEB-t) and 1 case of chronic myeloic-monocytic leukemia (CMML). These patients received danazol (600 mg/day) or stanazol (6 mg/day) and ATRA (10 mg/day) for at least 3 months. The results showed that according to MDS international working group response criteria, at the end of three months,complete remission (CR) was seen in 1 patient, partial remission (PR) was found in 2 patients. Hematologic improvement: major response (MaR) were seen in 15 patients, minor response (MiR) were seen in 4 patients. The total response rate was 35.8%. In conclusion, danazol or stanazol in combination with low dose ATRA are partialy effective in therapy for patients with low-risk myelodysplastic syndrome.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Androgens ; adverse effects ; therapeutic use ; Anemia, Refractory ; drug therapy ; Anemia, Refractory, with Excess of Blasts ; drug therapy ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Chemical and Drug Induced Liver Injury ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; drug therapy ; Treatment Outcome ; Tretinoin ; administration & dosage ; adverse effects ; therapeutic use

All-trans retinoic acid (ATRA) is the standard induction treatment for acute promyelocytic leukemia (APL). Quite many ATRA-related side effects, including retinoic acid syndrome, were reported. So far, it has rarely been reported that Sweet's syndrome, characterized by fever, neutrophilia, painful erythematous cutaneous plaques, dense dermal infiltrates of mature neutrophils and rapid response to steroid therapy, is associated with ATRA. In the case that Sweet's syndrome associated with ATRA is found, physicians will have to face a great challenge over the possibility of infectious conditions. We present here a case of Sweet's syndrome associated with ATRA. A 35-year-old female with APL developed fever, painful erythematous cutaneous plaques on both cheeks, right wrist and both shins during induction chemotherapy with ATRA. A skin biopsy revealed a dense dermal infiltrate, consisting of mature neutrophils without vasculitis or cutaneous immunoglobulin deposits, which is compatible with Sweet's syndrome. Oral prednisone was administered and the lesions started to improve within 48 hours
Adult ; Biopsy, Needle ; Case Report ; Female ; Follow-Up Studies ; Human ; Leukemia, Promyelocytic, Acute/diagnosis/*drug therapy ; Prednisone/administration & dosage ; Risk Assessment ; Sweet's Syndrome/*chemically induced/drug therapy/*pathology ; Tretinoin/*adverse effects/therapeutic use