tretinoin and Hypercalcemia

Topics: Alkalosis; Benzothiadiazines; Calcinosis; Cholecalciferol; Diuretics; Humans; Hypercalcemia; Hyperparathyroidism; Isotretinoin; Lithium; Osteitis Deformans; Sarcoidosis; Sodium Chloride Symporter Inhibitors; Tamoxifen; Tretinoin; Vitamin A

All-trans retinoic acid (ATRA) inhibits human myeloma cell growth in vitro, presumably through the down-regulation of interleukin 6 receptors (IL-6R). Based on these and other studies, we initiated a phase II clinical trial using ATRA in patients with advanced refractory multiple myeloma (MM). We report that three out of six treated patients developed severe hypercalcaemia following administration of ATRA, which was accompanied by a significant rise in serum IL-6 levels. Normal calcium levels were restored after the discontinuation of the drug and the administration of standard anti-hypercalcaemic care. We suspect that down-regulation of IL-6R resulted in increased serum IL-6 levels, leading to advanced bone resorption and hypercalcaemia. We conclude that the use of ATRA in patients with advanced MM is not warranted.

Topics: Humans; Hypercalcemia; Interleukin-6; Multiple Myeloma; Tretinoin

All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A and it is used for the treatment of acute promyelocytic leukemia (APL). Hypercalcemia is a rare side effect of ATRA and it may be potentiated after interaction of ATRA with azole group antifungals. Herein, we have reported an APL case with hypercalcemia that is caused by the interaction of ATRA and posaconazole.. A 49-year-old female patient was diagnosed as APL after the examinations performed upon the detection of pancytopenia when she had presented with the complaints of widespread bruising and fever. After the initiation of posaconazole and ATRA, her serum calcium levels begin to increase (10.3 to 11.1mg/dl). Her vitamin D level was 21.9 ng/ml and PTH 17.8 pg/ml, both were in the normal ranges. The Drug Interaction Probability Scale score of our case was calculated as 6, indicating that the probable adverse drug reaction. Therefore, the high level of serum calcium was attributed to the interaction between ATRA and posaconazole.. Although hypercalcemia with ATRA and other antifungal agents have been previously reported in the literature, this is the first report of hypercalcemia with the concomitant use of ATRA and posaconazole.. This case highlights the importance of monitoring ATRA's side effects when it is used in combination with drugs inhibiting the cytochrome P450 enzymes. In conclusion, the concomitant use of posaconazole and ATRA may lead to hypercalcemia and serum calcium levels return to normal ranges with the discontinuation of these drugs.

Topics: Female; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Middle Aged; Tretinoin; Triazoles

We report a rare case of hypercalcemia and acute pancreatitis in a subject with acute promyelocytic leukemia (APL) and pulmonary tuberculosis, during all-trans-retinoic acid (ATRA) treatment. Both associated complications were potentially due to several causes. A careful monitoring and exclusion of all causative factors must be addressed. Further research is necessary to improve our understanding of risk factors for these complications in patients with (APL). Studying these patterns may help us to improve outcomes for all children and young adults with hematologic malignancies.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Causality; Febrile Neutropenia; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Models, Biological; Pancreatitis; Pleural Effusion; Prednisone; Pulmonary Aspergillosis; Risk Factors; Tretinoin; Tuberculosis, Pulmonary; Vincristine

This study aimed to evaluate the outcome and predictors of survival in hemodialysis patients of Hasheminejad Kidney Center where a comprehensive dialysis care program has been placed since 2004.. Data of 560 hemodialysis patients were used to evaluate 9-year survival rates and predictors of mortality. Cox regression models included comorbidities as well as averaged and 6-month-averaged time-dependent values of laboratory findings as independent factors.. Survival rates were 91.9%, 66.0%, 46.3%, and 28.5%,  at 1, 3, 5, and 9 years, respectively, in all patients and 90.8%, 61.6%, 42.1%, and 28.0% in 395 incident patients starting hemodialysis after 2004. Adjusted survival models demonstrated age, male sex, diabetes mellitus, cardiovascular disease, and high-risk vascular access as baseline predictors of mortality, as well as averaged low hemoglobin level (hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.36 to 2.90) and a single-pool KT/V < 1.2 (HR, 2.28; 95% CI, 1.60 to 3.26). The averaged high-density lipoprotein cholesterol (HR, 0.67; 95% CI, 0.55 to 0.81) and serum creatinine (HR, 0.71; 95% CI, 0.64 to 0.79) levels demonstrated protective effects. The adjusted time-dependent model further revealed the significant association of hypocalcemia (HR, 1.63; 95% CI, 1.13 to 2.34), hypercalcemia (HR, 1.50; 95% CI, 1.02 to 2.21), and hyperphosphatemia (HR, 1.68; 95% CI, 1.20 to 2.37) with death.. Our patients have relatively comparable survival rates with high-profile dialysis centers. Aiming to better achieve the recommended targets, especially hemoglobin and nutritional and bone metabolism factors, should be considered for optimal dialysis outcomes.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Cardiovascular Diseases; Cause of Death; Cerebrovascular Disorders; Child; Cholesterol, HDL; Creatinine; Diabetes Mellitus; Female; Humans; Hypercalcemia; Hyperphosphatemia; Hypocalcemia; Infections; Iran; Kidney Failure, Chronic; Male; Middle Aged; Mortality; Neoplasms; Proportional Hazards Models; Renal Dialysis; Retrospective Studies; Risk Factors; Sex Factors; Survival Rate; Time Factors; Tretinoin; Young Adult

Topics: Adult; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Tretinoin

Although all-trans retinoic acid (ATRA) is widely used in acute promyelocytic leukemia (APL), there is little data as to whether or not ATRA is useful for patients with liver and renal failure. A 63-year-old APL patient, complicated by Child-Pugh class A liver cirrhosis and chronic renal failure (creatinine 3.2 mg/dL), was successfully treated with 45 mg/m(2)/day of ATRA. With three courses of chemotherapy, complete remission has been maintained for four years in this patient. Serum trough and maximum ATRA concentration, and the area under the curve (AUC) were not elevated. These observations suggest that full-dose ATRA therapy might be safely applicable to such a complicated case with APL.

Topics: Antineoplastic Agents; Humans; Hypercalcemia; Kidney Failure, Chronic; Leukemia, Promyelocytic, Acute; Liver Cirrhosis; Liver Failure; Male; Middle Aged; Polycystic Kidney Diseases; Remission Induction; Tretinoin

Topics: Adult; Antineoplastic Agents; Diphosphonates; Drug Interactions; Drug Therapy, Combination; Humans; Hypercalcemia; Imidazoles; Itraconazole; Leukemia, Promyelocytic, Acute; Male; Treatment Outcome; Tretinoin; Zoledronic Acid

A 24-year-old man was admitted to the hospital for pancytopenia. Peripheral blood test and bone marrow aspiration demonstrated an increase in hypogranular promyelocytes. Karyotype analysis and RT-PCR showed 47, XY, t(15;17)(q22;q12), +12, and PML-RARA, respectively. The patient was diagnosed as having acute promyelocytic leukemia microgranular type (M3v) and was therefore administered all-trans retinoic acid (ATRA). Idarubicin and Ara-C were later added to the treatment regimen because of an increased number of leukemic cells. Nausea, vomiting and general fatigue associated with hypercalcemia developed on day 30. There were no findings indicating infection. The administration of ATRA was thus suspected to have induced hypercalcemia. ATRA was therefore discontinued and prednisolone and elcatonin were administered instead. Five days after this change, the serum calcium level normalized. Complete remission was thereafter confirmed on day 45. Hypercalcemia associated with ATRA therapy for APL is rare, and to date, there have been no case reports describing hypercalcemia associated with M3v in the literature. Interaction of fosfluconazole was suspected of causing hypercalcemia when used concomitantly with ATRA.

Topics: Adult; Antineoplastic Agents; Drug Interactions; Drug Therapy, Combination; Fluconazole; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Male; Organophosphates; Tretinoin

All-trans-retinoic acid (ATRA) is a new and effective treatment of acute promyelocytic leukemia. It has many side-effects, including the retinoic acid syndrome and Sweet's syndrome. There have been only nine cases of hypercalcemia associated with ATRA described in the literature. We discuss a case of hypercalcemia, which we believe was due to inhibition of cytochrome P450 function by voriconizole when used concomitantly with ATRA.

Topics: Adult; Antifungal Agents; Antineoplastic Agents; Female; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Pyrimidines; Treatment Outcome; Tretinoin; Triazoles; Voriconazole

Topics: Antineoplastic Agents; Child; Diagnosis, Differential; Diphosphonates; Headache; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Male; Nausea; Remission Induction; Time Factors; Tretinoin

Topics: Adult; Blood Cell Count; Calcium; Dose-Response Relationship, Drug; Female; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Reference Values; Tretinoin

Topics: Child, Preschool; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Male; Parathyroid Hormone-Related Protein; Proteins; Tretinoin

Topics: Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Tretinoin

Recent reports have described clinical benefits of all-trans-retinoic acid (ATRA) therapy for acute promyelocytic leukemia (APL). This paper describes severe hypercalcemia (serum calcium: 18.7 mg/dl) in association with ATRA treatment in a 14 year old girl with APL. Serum parathyroid hormone (PTH) concentrations were normal (0.21 ng/ml), which precludes the possibility of primary hyperparathyroidism or ectopic PTH secretion as a cause of the hypercalcemia. As for the factors which can accelerate mineral resorption, there were no apparent increases in the levels of PTH-related protein (PTH-rP), prostaglandins and vitamin D metabolites. In our in vitro experiment, ATRA did not stimulate the leukemic cells to produce PTH-rP. We speculate that ATRA, like PTH, may increase osteoclastic activity and induce hypercalcemia.

Topics: Adolescent; Female; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Parathyroid Hormone-Related Protein; Proteins; Tretinoin

Topics: Adult; Calcium; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Male; Tretinoin

Topics: Humans; Hypercalcemia; Isotretinoin; Risk; Tretinoin

Topics: Acne Vulgaris; Administration, Oral; Adult; Humans; Hypercalcemia; Isotretinoin; Male; Tretinoin