Clinical Analysis of Children with High-Risk Acute Promyelocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the treatment of children with high-risk acute promyelocytic leukemia (APL), aiming to improve the prognosis.@*METHODS@#The clinical datas of 24 children with high-risk APL in our hospital from January 2015 to June 2021 were retrospectively analyzed.@*RESULTS@#The main manifestations of 24 children (including 15 males and 9 females) were purpura, gingiva bleeding and nasal hemorrhage, with a median age of 7 years old and a median leukocyte count of 28.98 (10-232)×109/L, including 15 cases with leukocyte count between 10×109/L and 50×109/L, 2 cases between 50×109/L and 100×109/L, and 7 cases >100×109/L. The leukocyte count of 2 cases in 3 children admitted from 2015 to November 2016 was >100×109/L, in which 1 case was first treated with homoharringtonine for cytoreduction, 7 days later treated with all-trans retinoic acid (ATRA) after genetic diagnosis, then died of differentiation syndrome and pulmonary hemorrhage after 3 days. The other one was treated with reduced ATRA+daunorubicin+arsenic trioxide (ATO) for induction, then achieved complete remission. The third one with leukocyte count 12×109/L had cerebral hemorrhage before admission and died on the 7th day of treatment. The remaining 21 children were treated with chemotherapy according to the APL regimen for children in South China, including 14 cases with leukocyte count between 10×109/L and 50×109/L, 2 cases between 50×109/L and 100×109/L, and 5 cases >100×109/L. In the 5 children with leukocyte count >100×109/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines, 3 cases died of cerebral hemorrhage after the addition of anthracyclines to chemotherapy on the second day of oral ATRA, and another one developed differentiation syndrome after the addition of mitoxantrone on the second day of oral ATRA, then achieved complete remission after ATRA reduction chemotherapy and survived without disease till now. In the 2 children with leukocyte count between 50×109/L and 100×109/L, 1 case died of cerebral hemorrhage on the second day of oral ATRA before the addition of anthracyclines. All the children were followed up until 1st August, 2021, with a median follow-up time of 40 months, including 7 deaths and 1 recurrence in maintenance therapy who achieved second remission after chemotherapy, 14 cases survived in 3 years and 13 cases survived without event. The 7 dead children had a median time from treatment to death of 5 days, including 1 case with leukocyte count between 10×109/L and 50×109/L, 1 case between 50×109/L and 100×109/L, and 5 cases >100×109/L.@*CONCLUSION@#High-risk APL children with leukocyte count >100×109/L have a high mortality rate. Gradual addition of chemotherapy starting at small doses and early addition of ATO may help to improve the prognosis.

The Effects of Decitabine Combined with All-Trans Retinoic Acid on the Number of Immune Cells in Myeloid Neoplasms / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of decitabine (DEC) combined with all-trans retinoic acid (ATRA) on the number of immune cells, efficacy and adverse reactions in the treatment of myeloid neoplasms patients.@*METHODS@#Eighty-four patients with myeloid tumors, including AML, MDS-EB-1 or MDS-EB-2 treated by the regimen containing decitabine in our hospital from January 2009 to October 2019 were enrolled and retrospectively analyzed, among the patients, 21 patients treated with DEC alone, 24 patients treated with DEC combined with ATRA (DEC/ATRA) and 39 patients treated with DEC combined with G-CSF priming regimen (DEC/priming). The changes of peripheral blood immune cell levels before and after treatment of the patients between the three groups were compared, and the differences in clinical efficacy and adverse reactions of the patients between the three groups were also compared.@*RESULTS@#There was no statistical differences in the number of immune cells among the patients in the three groups before treatment (P>0.05). NK cell levels decreased significantly in the patients in DEC and DEC/ATRA group after treatment (P<0.05); After treatment, the levels of CD8+ and CD3+T cells in the patients treated by DEC /priming regimen significantly increased (P<0.05), while the levels of CD3-HLA-DR+ B cells significantly decreased (P<0.05). The overall response rate (ORR) of the patients in DEC/ATRA group (75%) and DEC/priming group (74.36%) was significantly higher than 42.86% in DEC monotherapy group, and the differences showed statistically significant (P<0.05), while the ORR between the patients in DEC/ATRA and DEC/priming group showed no statistic differences (P>0.05). There were no statistical differences in overall survival (OS) and incidence of bleeding between the patients in the three groups (P>0.05). The incidences of grade 3 to 4 bone marrow suppression and the infection rate of the patients in DEC monotherapy and DEC/ATRA group were significantly lower than that in DEC/priming regimen group after treatment (all P<0.05), however, there was no statistical difference between DEC monotherapy and the DEC/ATRA group.@*CONCLUSION@#The efficacy of DEC/ATRA on myeloid neoplasms is comparable to that of DEC/priming regimen, and the anti-myeloid tumor effect of DEC/ATRA regimen may be related to the regulation of NK cells and T cells.

Effects of interferon regulatory factor 9 on the biological phenotypes in PML-RARα-induced promyelocytic leukemia / 中华血液学杂志

Objective: To investigate the prognostic significance of interferon regulatory factor 9 (IRF9) expression and identify its role as a potential therapeutic target in acute promyelocytic leukemia (APL) . Methods: The gene expression profile and survival data applied in the bioinformatic analysis were obtained from The Cancer Genome Atlas and Beat acute myeloid leukemia (AML) cohorts. A dox-induced lentiviral system was used to induce the expression of PML-RARα (PR) in U937 cells, and the expression level of IRF9 in U937 cells treated with or without ATRA was examined. We then induced the expression of IRF9 in NB4, a promyelocytic leukemia cell line. In vitro studies focused on leukemic phenotypes triggered by IRF9 expression. Results: ①Bioinformatic analysis of the public database demonstrated the lowest expression of IRF9 in APL among all subtypes of AML, with lower expression associated with worse prognosis. ②We successfully established a PR-expression-inducible U937 cell line and found that IRF9 was downregulated by the PR fusion gene in APL, with undetectable expression in NB4 promyelocytic cells. ③An IRF9-inducible NB4 cell line was successfully established. The inducible expression of IRF9 promoted the differentiation of NB4 cells and had a synergistic effect with lower doses of ATRA. In addition, the inducible expression of IRF9 significantly reduced the colony formation capacity of NB4 cells. Conclusion: In this study, we found that the inducible expression of PR downregulates IRF9 and can be reversed by ATRA, suggesting a specific regulatory relationship between IRF9 and the PR fusion gene. The induction of IRF9 expression in NB4 cells can promote cell differentiation as well as reduce the colony forming ability of leukemia cells, implying an anti-leukemia effect for IRF9, which lays a biological foundation for IRF9 as a potential target for the treatment of APL.

Cost-effectiveness of the regimen proposed by the International Consortium on Acute Promyelocytic Leukemia for the treatment of newly diagnosed patients with Acute Promyelocytic Leukemia

ABSTRACT Introduction: We performed cost-effectiveness and cost-utility analyses of the modified International Consortium on Acute Promyelocytic Leukemia protocol in Mexico for the treatment of acute promyelocytic leukemia Acute Promyelocytic Leukemia. Methods: We performed a three-state Markov analysis: stable disease (first line complete response [CR]), disease event (relapse, second line response and CR) and death. The modified IC-APL protocol is composed of three phases: induction, consolidation and maintenance. Cost and outcomes were used to calculate incremental cost-effectiveness ratios (ICERs); quality-adjusted life-years were used to calculate incremental cost-utility ratios (ICURs). Results: The CR was achieved in 18 patients (90%), treated with the IC-APL protocol as the first-line option; one patient (5%) died in induction, another one never achieved CR (5%); of the 18 patients that achieved CR, 1 relapsed (5.5%). The median treatment cost of the IC-APL protocol was $21,523 USD. The average life-year in our study was 7.8 years, while the average quality-adjusted life-year (QALY) was 6.1 years. When comparing the ICER between the IC-APL and the all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) protocols, we found the different costs of $6497, $19,133 and $17,123 USD in Italy, the USA and Canada, respectively. In relation to the ICUR, we found the different costs to be $13,955 and $11,979 USD in the USA and Canada, respectively. Conclusion: Taking into account the similar response rates, lower cost and easy access to the modified IC-APL regimen, we consider it a cost-effective and cost-utility protocol, deeming it the treatment of choice for our population.

Effects of ATRA on diabetic rats with renal ischemia-reperfusion injury

Abstract Purpose To explore the role of all-trans retinoic acid (ATRA) in renal ischemia/reperfusion injury of diabetic rats. Methods Sixty adult male rats were randomly divided into 6 groups, including sham group (S group), ischemia-reperfusion group (I/R group), ischemia-reperfusion+ATRA group (A group), diabetic group (D group), diabetic ischemia-reperfusion group (DI/R group), diabetic ischemia-reperfusion +ATRA group (DA group). The levels of creatinine (Cr), cystatin C (Cys-C) and β2-microglobulin (β2-MG) were measured. Morphology of renal tissue was observed under light microscope. Results DJ-1, Nrf2, HO-1 and caspase-3 were detected by western blot. DJ-1, Nrf2, HO-1 and caspase-3 in I/R group, D group and DI/R group was higher than that in S group. Compared with I/R group, Nrf2 and HO-1 in A group was decreased, but caspase-3 was increased. However, Nrf2 in DA group was higher than that in DI/R group, HO-1 and caspase-3 in DA group were lower than that in DI/R group. Compared with group S, Cr, Cys-C and β2-MG in I/R group, A group, D group, and DI/R group were higher. Whereas the levels of Cr, Cys-C, β2-MG and renal injury score in DA group were lower than those in DI/R group. Conclusion ATRA has a protective effect on renal ischemia-reperfusion injury in diabetic rats, maybe relating to DJ/Nrf2 pathway.

Poroqueratosis de Mibelli en la edad pediátrica / Porokeratosis of Mibelli in pediatric age

Las poroqueratosis son un grupo heterogéneo de trastornos de la queratinización epidérmica, de presentación infrecuente. Se caracterizan clínicamente por pápulas hiperqueratósicas que confluyen y forman placas anulares con un centro atrófico y bordes sobreelevados. Hay seis variantes clínicas. El examen histopatológico evidencia la característica laminilla cornoide. Se presenta el caso de una niña de 2 años con diagnóstico de poroqueratosis de Mibelli y respuesta parcial al tratamiento tópico con tretinoína al 0,025%, que actualmente continúa en seguimiento clínico (AU)

Porokeratosis is a heterogeneous group of disorders in epidermal keratinization. It is an infrequent entity characterized clinically by hyperkeratotic papules that converge forming annular plaques with an atrophic center and raised borders. There are six clinical variants. The histopathological examination evidences the typical cornoid lamella. We present a 2-year-old girl diagnosed with porokeratosis of Mibelli and partial response to topical treatment of tretinoin 0,025%, still under clinical control (AU)

Effects of isotretinoin on the olfactory function in patients with acne

Abstract: Background: Isotretinoin is a synthetic analog of vitamin A. Recent studies support a role for retinoic acid in the recovery of olfactory function following injury in mice. Objective: This study aimed at determining the effect of isotretinoin on olfactory function in patients who have acne and are otherwise healthy. Methods: Forty-five patients (aged 25-40 years) with acne were included in the study. All patients underwent a rhinological examination. Olfactory function was assessed by the Sniffin' Sticks Test. The test was assessed at baseline and in the third month of isotretinoin treatment. Results: Isotretinoin improved the performance of patients in the olfactory test. The SST score increased from 8.7±1.09 to 9.5±1.19 (p<0.001), prevalence of hyposmia decreased from 40% to 24% and normosmia increased from 60% to 75% (p=0.059). The percentage of patients whose olfactory function was categorized as "good" increased from 6% to 21.3%. This increase was statistically significant (p<0.05). Study limitations: Absence of a control group is one of the limitations of this study. Also, we did not evaluate patients with smell test after stopping isotretinoin treatment. Conclusion: We examined the effect of systemic isotretinoin on olfactory function. It can be concluded from the present investigation that isotretinoin therapy improves the sense of smell.

Tratamiento de la leucemia promielocítica con trióxido de arsenico y acido trans-retinoico / Treatment of acute promielocytic leukemia with arsenic trioxide and trans-retinoic acid

Introducción: en los últimos 25 - 30 años se ha propuesto el tratamiento de la leucemia promielocítica mediante métodos de inducción de la diferenciación celular. Método : se compararon algunos de los resultados de dos protocolos para el tratamiento de la leucemia promielocítica, el LPM-TOA en el que la droga de primera línea fue el trióxido de arsénico y el LPM-03 con el que se usó el ácido transretinoico y rubidomicina en la inducción a la remisión. Resultados : con el LPM-TOA la remisión hematológica se logró en el 83,3 por ciento de los pacientes a los 43,22 días como promedio, el síndrome de diferenciación celular se presentó en 6 casos (9,1 por ciento), la sobrevida libre de eventos a los 60 meses fue de 89,26 por ciento al igual que la sobrevida global, debido a que no se presentaron recaídas en el período estudiado; mientras que con el protocolo LPM-03 la remisión hematológica se logró en el 96 por ciento de los pacientes a los 44,35 días; 5 enfermos (10 por ciento) presentaron el síndrome de diferenciación celular, la sobrevida libre de eventos a los 60 meses fue del 75 por ciento y la sobrevida global del 83,3 por ciento. En la comparación de los parámetros no hubo significación estadística, excepto en la sobrevida libre de enfermedad a los 60 meses en que con el LPM-TOA fue del 100 por ciento mientras que con el LPM-03 fue del 78 por ciento (p=0,001). Conclusiones: se comprobó que el arsénico es una opción más para manejar la enfermedad, tanto en la recaída como en los casos de reciente diagnóstico. Con estos resultados, nuestro país muestra cifras de sobrevida libre de eventos a los 5 años del diagnóstico y de curación comparable con los de los países más desarrollados a nivel mundia(AU)

Introduction . In the last 25-30 years the treatment of acute promyelocytic leukemia has been proposed by methods of induction of cell differentiation. Method . We compared some of the results of two protocols for the treatment of acute promyelocytic leukemia, LPM-TOA in which the first line drug was arsenic trioxide and LPM-03 in which transretinoic acid was used with Rubidomycin in induction to remission. Results: With LPM-TOA hematologic remission was achieved in 83.3 percent of patients at 43.22 days on average, the cell differentiation syndrome was present in 6 cases (9.1 percent), the event free survival at 60 months was 89.26 percent, as was overall survival, due to the fact that there were no relapses during the study period, whereas with the LPM-03 protocol hematologic remission was achieved in 96 percent of the patients at 44.35 days; 5 patients (10 percent) presented the cell differentiation syndrome, the events free survival at 60 months was 75 percent and the overall survival was 83.3 percent. In the comparison there was no statistical significance, but not in the disease-free survival at 60 months in which the LPM-TOA was 100 percent while in the LPM-03 it was 78 percent (p = 0.001). Conclusions: Arsenic was found to be one more option to manage the disease, both in relapse and in cases of recent diagnosis. With these results, our country shows figures of event-free survival at 5 years of diagnosis and cure comparable to those of the most developed countries worldwide(AU)

TeleCondutas: acne / TeleGuides: acne

Acne é a dermatose mais comum, acometendo cerca de 80% dos adolescentes e adultos jovens. É caracterizada por lesões não-inflamatórias (comedões abertos e/ou fechados) e por lesões inflamatórias (pápulas, pústulas, cistos ou nódulos) tipicamente localizados na face, pescoço, dorso, tórax e braços. A etiologia da acne vulgar resulta da associação dos seguintes fatores: hiperqueratinização e obstrução do infundíulo folicular, devido à descamação anormal do epitélio folicular; aumento da produção de sebo estimulada pelos andrógenos; colonização do folículo pelo Propionibacterium acnes, gerando inflamação. Esta guia apresenta informação que orienta a conduta para casos de acne no contexto da Atenção Primária à Saúde, incluindo: classificação da acne vulgar, Características da acne vulgar, Erupção acneiforme, Diagnóstico da acne vulgar, Tratamento - Orientações gerais, Tratamento - Medicamentos, Terapia tópica, Antibióticos sistêmicos, Terapia antiandrogênica, Acne na Gestante, Acompanhamento, Encaminhamento para serviço especializado.

Reporte de seis casos de úlceras genitales durante la inducción en leucemia aguda promielocítica con ácido all-transretinoico y revisión bibliográfic / Report of six cases of Genital Ulcers during induction therapy of Acute Promyelocytic Leukemia with ATRA and review of literature

El ácido all-transretinoico (ATRA) es uno de los mayores avan-ces en el tratamiento de las leucemias promielocíticas agudas (LPA). Con el uso asociado de quimioterapia y corticoides hacen de ésta leu-cemia las de mejor pronóstico hematológico con altas tasas de cu-ración. El ATRA es generalmente bien tolerado pero puede presen-tar efectos adversos sistémicos, englobados dentro del denominado sindrome ATRA (SATRA), o efectos directos gastrointestinales y mu-cocutáneos tales como las úlceras escrotales, transitorias y de buena respuesta clínica, tratándose de una entidad diferente al SATRA con presencia de vasculitis en el estudio anatomopatológico. En la revisión que realizáramos, hemos detectado 44 casos reportados en la literatu-ra a los que hemos agregado, en el siguiente documento, seis pacientes evaluados en nuestra institución con úlceras genitales asociadas al uso de ATRA, cuatro de ellos con presencia de vasculitis como lesión histo-lógica y un paciente con diagnóstico de síndrome Sweet

All-trans retinoic acid (ATRA) is one of the greatest advances in the treatment of Acute Promyelocytic Leukemia. The combination of all-trans-retinoic acid (ATRA), chemotherapy and corticoids has made acute promyelocytic leukemia (APL) a highly curable leukemia. The ATRA is generally well tolerated. Adverse effects, include ATRA syndrome (SATRA), and the gastrointestinal and mucocutaneous side effects, such us scrotal ulcers, wich are transitory and with a good clinical response. They are a different entity to SATRA, and presents vasculitis in the histological study. Of our knowledge, 44 cases were reported in the literature, we present the following document with six patients evaluated at our institution with genital ulcers associated with ATRA, four of them present vasculitis in pathological study, and one patient Sweet ́s Syndrome

Lengua negra vellosa / Beautiful black tongue

La lengua negra vellosa es una patología benigna relativamente frecuente, caracterizada por una coloración pardo-negruzca de la superficie lingual asociada a hipertrofia de papilas filiformes dando aspecto de vellosidades. Los factores de riesgo son amplios y de exposición cotidiana (antibióticos, alcohol, tabaco, higiene dental deficiente). Entre sus diagnósticos diferenciales es útil recordar aquellos asociados con neoplasias o inmunocompromiso (acantosis nigricans oral, leucoplasia vellosa, etc.). Su diagnóstico es clínico; sin embargo, cuando las causas o historia no son claras, la exploración clínica es atípica o hay refractariedad sistemática a los tratamientos habituales, se debe plantear un estudio ampliado (AU)

Black hairy tongue is a relatively common benign disease, characterized by brown-black discoloration and hypertrophic tongue surface, giving aspect of villi. Risk factors are broad and from daily exposure (antibiotics, alcohol, tobacco, poor dental hygiene). Among its differential diagnoses it is useful to recall those associated with malignancies or immunocompromise (oral acanthosis nigricans, hairy leukoplakia, etc.). Diagnosis is clinical, but when the causes are unclear, history or clinical examination is atypical, or treatment is refractory, it should be considered an extended study (AU)

A Case of Therapy-Related Acute Myeloid Leukemia With a Normal Karyotype After Sustained Molecular Complete Remission of Acute Promyelocytic Leukemia

No abstract available.

Triple nanoemulsion potentiates the effects of topical treatments with microencapsulated retinol and modulates biological processes related to skin aging / Tripla nanoemulsao potencializa os efeitos do tratamento topico com retinol microencapsulado e modula processos biologicos relacionados ao envelhecimento da pele

BACKGROUND: The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. OBJECTIVES: To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. METHODS: Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). RESULTS: A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. CONCLUSION: This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly. .

FUNDAMENTOS: A soma de fatores genéticos e ambientais afeta a aparência e a funcionalidade da pele ao longo do envelhecimento. O conhecimento a respeito das mudanças moleculares durante o envelhecimento fornece biomarcadores e possíveis alvos para intervenções terapêuticas. O ácido retinoico em diferentes formulações surgiu como uma alternativa para prevenir e reparar os danos da pele associados ao envelhecimento. OBJETIVOS: Avaliar comparativamente os efeitos de diferentes formulações contendo retinoides na expressão de genes associados a processos biológicos que são alterados com o envelhecimento da pele. MÉTODOS: Peles ex vivo foram topicamente tratadas com diferentes retinoides, micro e nanoencapsulados. A modulação dos processos biológicos associados ao envelhecimento da pele foi medida por PCR quantitativa, precedida de transcrição reversa (RT-qPCR). RESULTADOS: A formulação contendo uma mistura de princípios ativos incorporados em uma tripla nanoemulsão e retinol microencapsulado apresentou os melhores resultados de modulação de genes relacionados a processos biológicos que são normalmente alterados durante o envelhecimento da pele. CONCLUSÃO: Essa associação demonstrou uma maior eficácia terapêutica quando comparada ao uso isolado de tretinoína ou retinol microencapsulado. .

Effect of all-trans-retinoic acid on the structure of thyroid gland and pituitary tyrotrophs in streptozotocin-diabetic male rats

Background: Diabetes mellitus, a chronic disease with increasing prevalence worldwide, is known to be associated with thyroid disorders. Retinoic acid, a metabolite of vitamin A, is currently used for the treatment of diabetes and obesity

Aim of the work: The present study aimed to evaluate the possibility of using all-trans-retinoic acid [atRA] in reducing the structural changes of the thyroid gland and pituitary thyrotrophs in streptozotocin-induced diabetic rats

Materials and methods: Thirty adult male albino rats were divided into three equal groups: group I, control; group II, which included rats in which diabetes was induced by a single intraperitoneal injection of streptozotocin [100 mg/kg]; and group III, which included rats in which diabetes was induced as in group II, followed by an intraperitoneal injection of atRA [2.5 mg/kg/day] from the third day. After 4 weeks, thyroid and pituitary specimens were processed for light and electron microscopic study

Results: Most thyroid follicles of diabetic rats were distended with colloid and lined with flattened thyrocytes with hyperchromatic nuclei and vacuolated cytoplasm that contained dilated rough endoplasmic reticulum, few colloid droplets, and few lysosomes. Some exfoliated cells were observed in the lumen. C cells had rarefied cytoplasm containing a few secretory granules. The number of mast cells showed a nonsignificant change. Thyrotrophs showed dilated rough endoplasmic reticulum, destroyed mitochondria, and decreased secretory granules. The atRA-treated diabetic group showed almost the same structural alterations in the thyroid gland, with even more changes in thyrotrophs

Conclusion: Despite its current use as a novel therapy for diabetes, atRA exerted no ameliorating effect on diabetes-induced histological changes in the thyroid gland and, moreover, exacerbated the changes of pituitary thyrotrophs

Acute promyelocytic leukemia: An experience from a tertiary care centre in north India.

Background: There are very limited data reported about acute promyelocytic leukemia (APL) from developing countries. We reviewed the clinical course and treatment outcome of APL patients treated at our center. Materials and Methods: Between January 1997 and December 2007, 33 patients with APL received induction therapy using ATRA + daunorubicin (n = 26), As = 26), As2O3 (n = 4) or daunorubicin + cytosar ( n = 3). Results: Median age was 30 years with a male to female ratio of 1.68. Twenty seven patients (82%) achieved CR. Complications during induction therapy were febrile neutropenia (33%), ATRA syndrome (30%), bleeding (58%), and diarrhea in (6%) patients. During induction and follow up, 8 (24.24%) patients died, 6 (18.18%) during induction, 1 (3%) during maintenance, and 1 (3%) after relapse. Median OS is 128 months while median EFS is 61 months. Four patients relapsed at a median time of 61 months. At the time of censoring, 25 patients were alive at a median follow up of 13 months (range 0.6 -127 months); 21 in CR1, 3 in CR2, 1 in CR3. Comparisons among the risk groups (CR and relapse rate and survival statistics) were not statistically significant. Conclusions: APL is a highly curable malignancy. Our results confirm the findings of the published literature from larger cooperative studies from the West. We may further improve outcome with quicker diagnosis and more efficient supportive care system.

Insuficiência renal aguda em paciente tratada com ATRA e anfotericina B: relato de caso / Acute renal failure in patient treated with ATRA and amphotericin B: case report

O presente relato apresenta o caso clínico de uma paciente com leucemia promie-locítica aguda tratada com ácido todo-transretinoico (ATRA), que apresentou suspeita de síndrome do ácido transreti-noico (síndrome de ATRA). Com a ocor-rência de leucopenia febril inespecífica, foram associados ao tratamento antimi-crobianos e antifúngicos. A diminuição da função renal, observada inicialmente, contribuiu para a suspeita de síndrome de ATRA, que foi agravada pelos antifúngi-cos. Assim, o uso de ATRA foi suspenso, mas somente 8 dias depois foi caracteriza-da pneumonia e descartada a hipótese de síndrome de ATRA. Nesse contexto, foi discutida a nefrotoxicidade do ATRA e a potencialização desse efeito adverso pelo uso de antifúngicos nefrotóxicos, em par-ticular da anfotericina B, assim como a im-portância do diagnóstico diferencial entre síndrome de ATRA e doença infecciosa.

This is a report of the case of a patient with acute promyelocytic leukemia treated with all trans-retinoic acid (ATRA), who had suspected all-trans retinoic acid syndrome (ATRA syndrome). The nonspecific febrile leukopenia observed justified the association with antimicrobial and antifungal therapy. Signs and symptoms contributed to the sus-picion of ATRA syndrome, and renal func-tion was impaired by the combination with antifungal agents. The decrease in renal function observed initially contributed to the suspicion of ATRA syndrome and was aggravated by antifungals. Thus, the use of ATRA was discontinued. Eight days after the pneumonia characterization, the possibil-ity of ATRA syndrome was dismissed. In this context, ATRA's nephrotoxicity and the syn-ergic adverse effect by the use of nephrotoxic antifungal agents were discussed, particularly amphotericin B, as well as the importance of differential diagnosis between ATRA syn-drome and infectious diseases.

Efeito de diferentes doses de ácido retinoico sobre a resistência óssea de ratos jovens / Effect of varied doses of retinoic acid on young rats' bone resistance

OBJETIVO: Avaliar os efeitos da suplementação de diferentes doses de todo-trans ácido retinóico sobre a resistência óssea, por meio de ensaio biomecânico de flexão, em tíbia de ratos jovens. MÉTODOS: Foram estudados 58 ratos jovens, com quatro diferentes doses de vitamina A em suas dietas, sendo divididos em 4 grupos: grupo-controle (n=15), sem acréscimo de todo-trans ácido retinoico; grupo com acréscimo de 0,3mg de todo-trans ácido retinoico por kg de ração (n=13); grupo com 10mg de todo-trans ácido retinoico por kg de ração (n=15); e grupo com 50mg de todo-trans ácido retinoico por kg de ração (n=15). O estudo durou 30 dias. Após o sacrifício dos animais, suas patas esquerdas foram congeladas, dissecadas e as tíbias submetidas ao ensaio de flexão. Foram avaliados a carga máxima e o coeficiente de rigidez. Foi aplicada análise de variância one-way. O nível de significância estatístico adotado foi p<0,05. RESULTADOS: Os valores médios de carga máxima (em Newton) foram: grupo-controle =37,94, DP=4,76; grupo todo-trans ácido retinoico 0,3=36,49, DP= 4,38; grupo todo-trans ácido retinoico 10=40,12, DP=6,03; grupo todo-trans ácido retinoico 50=35,68, DP=5,22 (p=0,107). Os valores médios de coeficiente de rigidez (em Newton/milímetros) foram: grupo-controle =31,84 DP=6,75; grupo todo-trans ácido retinoico 0,3=29,18, DP=4,35; grupo todo-trans ácido retinoico 10=35,48, DP=8,14; grupo todo-trans ácido retinoico 50=30,31, DP=7,14 (p=0,85). CONCLUSÃO: Conclui-se que a exposição a diferentes doses de todo-trans ácido retinoico, em ratos, durante 30 dias, não exerce efeito sobre a resistência óssea, quando avaliada por ensaios biomecânicos.

OBJECTIVE: This study assessed the effects of different doses of all-trans retinoic acid on bone resistance by conducting a biomechanical flexion study on young rats' tibias. METHODS: Fifty-eight young rats were divided into four groups according to the all-trans retinoic acid content of their diets: control group (n=15), chow not enriched with all-trans retinoic acid; chow enriched with 0.3mg of all-trans retinoic acid per kilogram (n=13); chow enriched with 10mg of all-trans retinoic acid per kilogram (n=15); and chow enriched with 50mg of all-trans retinoic acid per kilogram (n-15). After 30 days of this diet, the animals were killed, their left paws were frozen and dissected and the tibias were submitted to the flexion study which assessed maximum force and shear modulus. One-way analysis of variance was used with significance set at p<0.05. RESULTS: The mean maximum force values in newtons (SD) were: control group =37.94, SD=4.76; 0.3mg group = 36.49, SD= 4.38; 10mg group = 40.12, SD=6.03; 50mg group =35.68, SD=5.22 (p=0.107). The mean shear modulus values (SD) in newtons/millimeter were: control group =31.84, SD=6.75; 0.3mg group =29.18, SD=4.35; 10mg group =35.48, SD=8.14; 50mg group =30.31, SD=7.14 (p=0.85). CONCLUSION: Biomechanical studies showed that different doses of all-trans retinoic acid for 30 days had no effect on young rats' bone resistance.