YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==LEUKEMIA, PROMYELOCYTIC - ACUTE== 2 AUTHOR Schechter GP TITLE All-Trans Retinoic Acid vs. Cytosine Arabinoside and Duaorubicin for Patients with Previously Untreated Acute Promyelocytic Leukemia SOURCE FEDRIP DATABASE, NATIONAL TECHNICAL INFORMATION SERVICE (NTIS) ABSTRACT RPROJ/FEDRIP REMISSION INDUCTION; LEUKOCYTOSIS; LEUKEMIA This protocol is a multicenter randomized prospective trial sponsored by CALGB of the use of a differentiating agent, all-trans retinoic acid (ATRA) for the treatment of acute promyelocytic leukemia, an uncommon form of acute myelogenous leukemia (M3 AML). Patients with M3 AML will be randomized to receive either ATRA or standard cytosine arabinoside + daunorubicin therapy. Both drugs produce a high rate of complete remission in M3AML, however in the case of ATRA, the less toxic agent, the duration of remission may be quite short. Therefore this study employs intensive consolidation chemotherapy in both arms. If a complete response is achieved the patients will be treated with 2 consolidation courses (one of standard and one of high dose cytosine arabinoside, both courses including daunorubicin.). Patients randomized to ATRA will be treated only if the white blood cell count is reduced below 10,000/ul (hydroxyurea will be used to lower the count if necessary). Patients who do not achieve a CR with ATRA will be crossed over to standard anti-leukemic therapy. Patients not achieving a complete response to the standard therapy arm after 2 cycles will be off study. Patients who complete the consolidation therapy will be randomized to receive maintenance therapy (or not) with ATRA for one year. The side effects of standard therapy are mainly due to life-threatening myelosuppression and the exacerbation of coagulation abnormalities causing severe bleeding due to disseminated intravascular coagulation, a common complication of M3AML which may be potentiated by intensive chemotherapy. ATRA causes relatively little myelosuppression and coagulation abnormalities in pilot studies. However severe leukocytosis and a capillary leak syndrome may occur which may require the addition of corticosteroids and has been fatal in a few patients. Since this is an uncommon form of acute leukemia (5-15% of adults) we believe that only 1 or 2 patients might be eligible for this protocol. (Only 2 patients with M3AML have been seen in this hospital in the last 5 years.) However without this protocol ATRA will not be available to patients on a compassionate plea basis. The study has been closed because its accrual goal was reached. 3 AUTHOR ROWLEY JD AUTHOR ALIMENA G AUTHOR GARSON OM AUTHOR HAGENMEIJER A AUTHOR MITELMAN F AUTHOR PRIGOGINA EL TITLE A collaborative study of the relationship of the morphological type of acute nonlymphocytic leukemia with patient age and karyotype. SOURCE BLOOD; 59 (5). 1982. 1013-1022. ABSTRACT HEEP COPYRIGHT: BIOL ABS. Chromosome analysis was performed on cells from nonlymphocytic leukemia patients. The karyotypic pattern was correlated with the patient's age and the FAB (French American British) classification. Of the 503 patients in the study, 260 had acute myeloblastic leukemia (AML, M1 and M2), 142 had acute myelomonocytic leukemia (AMMoL, M4), 43 had acute monocytic leukemia (AMoL, M5), 30 had erythroleukemia (EL, M6), and 28 had acute promyelocytic leukemia (APL, M3). The percentage of patients with an abnormal karyotype was higher in EL (63%) and AML (59%) than in AMMoL (40%) and AMoL (42%). In AML, the chromosome pattern showed a clear correlation with age. The consistent translocation involving (chromosomes) no. 8 and 21, which is specifically associated with AML M2, occurred with the greatest frequency in younger patients, particularly those under the age of 45 yr. Other abnormalities, notably loss of no. 5 or part of its long arm, were not seen in children and showed a progressive increase in frequency with increasing age. Still other abnormalities, such as -7 or +8, were present in all age groups, but were more common in older groups. In AMMoL, loss of no. 5 was rare, loss of no. 7 was less frequent in older than in younger patients, and gain of no. 8 showed some increase with age. Young patients with AMoL had a +8 or a translocation involving the long arm of no. 11 (11q23); older patients had +8 or other changes, with no loss of no. 7 rare and loss of no. 5. In EL, the percentage of aneuploid patients was highest particularly in older patients, of whom 75% had an abnormal karyotype. Although loss of no. 5 or no. 7 was not seen in any patient under age 50, loss of one or both was seen in 47% of all EL patients over age 50. A +8 was almost twice as common in younger than in older patients. In APL, 39% had the t(15;17) that is specifically associated with this type of leukemia; other abnormalities were seen in a few older patients. Loss of no. 5 and/or no. 7 occurred in 30% of all EL patients, in 19% of all AML patients, and in only 7% of AMMoL, in 5% of AMoL, and in 4% of APL patients. These observations are significant because patients with ANLL secondary to aggressive therapy for a primary malignant disease tend to have AML or EL, and the majority have -5 and/or -7. These same morphological types of leukemia and the same abnormalities, -5 and/or -7, are also increased in patients with ANLL de novo who have a history of occupational exposure to potentially mutagenic substances. The type of leukemia and the particular karyotypic pattern may be useful in identifying a subset of patients with ANLL de novo whose leukemia may be mutagen-induced. 1 AUTHOR MELE A AUTHOR STAZI MA AUTHOR PULSONI A AUTHOR VISANI G AUTHOR MONARCA B AUTHOR CASTELLI G AUTHOR ROCCHI L AUTHOR AVVISATI G AUTHOR MANDELLI F TITLE Epidemiology of acute promyelocytic leukemia. SOURCE HAEMATOLOGICA; 80 (5). 1995. 405-408. ABSTRACT BIOSIS COPYRIGHT: BIOL ABS. Background. The estimated incidence of acute promyelocytic leukemia (APL) is approximately 6 cases per 10 million people per year with no apparent differences between sexes. The age of APL cases is younger than that of other acute myeloid leukemias (AML). Spatial and temporal clusters of APL have been reported. These observations suggest a possible selective role for environmental and/or occupational factors in APL development. Methods. A multicenter case-control study was carried out on risk factors for acute leukemias and preleukemias. In this report data related to APL are selectively analyzed from the larger study to identify specific risk factors. Results. The case-control study on 38 cases of APL showed a strong association with shoemaking (odds ratio 6.3, 95% confidence interval 1.3-31.1). A moderate leukemogenic effect from living in houses built with tuff, a porous building material containing gamma-emitting radionuclides and having a high radon concentration, and from using hair dyes was also suggested. Conclusions. These data, together with the reported spatial and temporal clustering of APL, support the hypothesis of specific environmental and/or occupational risk factors for APL among other AML subtypes and indicate the need for additional ad hoc multicenter studies. 2 AUTHOR Fenaux P AUTHOR Chomienne C TITLE Biology and treatment of acute promyelocytic leukemia [see comments] SOURCE Curr Opin Oncol; VOL 8, ISS 1, 1996, P3-12 (REF: 89) ABSTRACT Recent progresses made in the biology of acute promyelocytic leukemia and therapeutic improvements obtained in acute promyelocytic leukemia since the advent of all-trans retinoic acid have continued to generate a large number of publications on this disease in the past 12 months, which concern both its biological and therapeutic aspects. 19 AUTHOR de Lacerda JF AUTHOR do Carmo JA AUTHOR de Lacerda JM TITLE [Acute promyelocytic leukemia. The therapeutic advances] SOURCE Acta Med Port; VOL 6, ISS 10, 1993, P473-80 (REF: 78) ABSTRACT Acute promyelocytic leukemia (APL) is a rare subtype of acute myelogenous leukemia. It is frequently associated with a life-threatening hemorrhagic diathesis, often aggravated by induction cytotoxic chemotherapy. Patients with APL have bone marrow infiltration by abnormal promyelocytes, usually with prominent cytoplasmic granulation. These patients have a unique cytogenetic abnormality, a balanced reciprocal translocation between the long arms of chromosomes 15 and 17. The nuclear retinoic acid receptor alpha gene, on chromosome 17, is translocated to the PML gene region, on chromosome 15, resulting in the synthesis of two fusion messenger ribonucleic acids, PML/RAR-alpha and RAR-alpha/PML, easily detected by the reverse transcriptase polymerase chain reaction. This assay is extremely useful in the diagnosis and detection of minimal residual disease in APL patients. All trans-retinoic acid (ATR) differentiates the malignant cell clone and corrects the coagulopathy associated with this disease. The most important adverse effect is a respiratory distress syndrome, treatable with steroids, if detected at its onset. ATR yields durable remissions in patients with APL, after consolidation with cytotoxic chemotherapy. 23 AUTHOR Dulaney AM AUTHOR Murgatroyd RJ TITLE Use of trans-retinoic acid in the treatment of acute promyelocytic leukemia. SOURCE Ann Pharmacother; VOL 27, ISS 2, 1993, P211-4 (REF: 8) ABSTRACT OBJECTIVE: To discuss acute promyelocytic leukemia (APL) and review the literature concerning differentiation treatment of APL with trans-retinoic acid (t-RA). DATA SOURCES: English-language articles concerning APL or its treatment with t-RA were identified with a MEDLINE search. STUDY SELECTION: All studies available at the time of article preparation, which addressed t-RA treatment in APL, were selected. DATA EXTRACTION: Data extraction and assessment were performed subjectively by the authors. An extensive discussion of specific study details is included in the article. DATA SYNTHESIS: APL is a unique subset of acute myelogenous leukemia and is typified by an accumulation of malignant promyelocytes in the bone marrow. Within the granulocyte cell cycle of a patient with APL, differentiation has been halted at the level of the promyelocyte, preventing formation of mature granulocytes. Upon treatment with traditional cytotoxic chemotherapy, complete remission rates of approximately 70 percent, with a five-year survival ranging from 25 to 40 percent have been achieved. In most patients with APL, a characteristic chromosomal t(15q+;17q-) translocation has been found, which may be responsible for the production of an aberrant retinoic acid receptor-alpha. Therefore, t-RA induction therapy has been investigated and has produced promising results. Administration of t-RA in dosages of 45-100 mg/m2/d has induced complete remissions. The apparent mechanism of t-RA is the induction of promyelocyte differentiation and maturation. The most common adverse effects noted have been dry skin, cheilitis, and headaches. CONCLUSIONS: Upon consideration of the initial trials, t-RA appears to be a promising and unique treatment for APL. 1 AUTHOR Ban A TITLE [Retinoids in the therapy of diseases of the hematopoietic system and malignant tumors] SOURCE Orv Hetil 1994 Jul 10;135(28):1527-30 ABSTRACT The antitumor effect of different retinoids focused attention in the treatment of malignant disorders on different pathways. The therapeutic effect was proved in acute promyelocytic leukaemia, but was limited in juvenile form of chronic myeloid leukaemia and in acute myelomonocytic and monoblastic leukaemia. Combined with different leukostatics, long remission could be achieved. The most important therapeutic pathway is direct growth inhibition with and without cell differentiation. Clinically, retinoids are effective in tumours, like: cutan T-cell lymphoma, mycosis fungoides, Sezary syndrome, oral leukoplakia (prevention of head and neck cancer metastases), variant form of small lung cell carcinoma, oestrogen dependent breast-carcinoma and cervix-carcinoma. The most serious complication of the retinoids' administration is the retinoic acid syndrome which is followed sometimes with thromboembolic events. Retinoids are teratogenic and hepatotoxic.