Maternal and fetal outcomes in pregnant women with acute promyelocytic leukemia.

The management of pregnant women with acute promyelocytic leukemia (APL) is a challenge with limited evidence-based information available. We are reporting a series of 14 consecutive pregnant women with APL who were registered in the PETHEMA Data Centre between 1996 and 2012. APL was diagnosed during early pregnancy in five women, late pregnancy in seven, and two additional patients after delivery in an extremely poor clinical condition (pulmonary and cerebral hemorrhage). Eleven of the 12 patients eligible for induction therapy with all-trans retinoic acid and idarubicin achieved complete remission (CR 92 %) and are still in the first CR. All early pregnancies ended in abortion (four induced and one spontaneous), with four of them achieving CR. Eight of nine women in late pregnancy delivered a healthy infant (six cesarean section and two vaginal delivery). All eight babies developed normally. Our results confirm a high cure rate for pregnant women with APL who received all-trans retinoic acid and idarubicin for induction therapy, and an excellent outcome for babies when the disease is diagnosed during late pregnancy.

All-trans retinoic acid with daunorubicin or idarubicin for risk-adapted treatment of acute promyelocytic leukaemia: a matched-pair analysis of the PETHEMA LPA-2005 and IC-APL studies.

Front-line treatment of acute promyelocytic leukaemia (APL) consists of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. In this setting, a comparison of idarubicin and daunorubicin has never been carried out. Two similar clinical trials using ATRA and chemotherapy for newly diagnosed APL were compared using matched-pair analysis. One was conducted by the PETHEMA/HOVON group with idarubicin and the other by the International Consortium on APL (IC-APL) using daunorubicin. Three hundred and fifty patients from the PETHEMA/HOVON cohort were matched with 175 patients in the IC-APL cohort, adjusting for the significantly unbalanced presenting features of the two entire cohorts. Complete remission (CR) rate was significantly higher in the PETHEMA/HOVON (94 %) than in the IC-APL cohort (85 %) (P = 0.002). The distribution of causes of induction failure and the time to achieve CR were similar in both cohorts. Patients who achieved CR had comparable cumulative incidence of relapse and disease-free survival rates, but lower overall and event-free survivals were observed in the IC-APL cohort, which was mainly due to a higher death rate during induction therapy. A higher death rate during consolidation therapy was also observed in the IC-APL. These results show that daunorubicin and idarubicin have similar antileukaemic efficacy in terms of primary resistance, molecular persistence, as well as molecular and haematological relapse rates when combined with ATRA in treatment of APL. However, a higher toxic death rate during induction and consolidation therapy was observed in the IC-APL cohort. This trial was registered at www.clinicaltrials.gov as #NCT00408278 [ClinicalTrials.gov].

Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome.

A risk-adapted strategy based on all-trans retinoic acid (ATRA) and anthracycline monochemotherapy (PETHEMA LPA99 trial) has demonstrated a high antileukemic efficacy in acute promyelocytic leukemia. We designed a new trial (LPA2005) with the objective of achieving stepwise improvements in outcome. Between July 2005 and April 2009, low- and intermediate-risk patients (leukocytes < 10 x 10(9)/L) received a reduced dose of mitoxantrone for the second consolidation course, whereas high- risk patients younger than 60 years of age received cytarabine combined with ATRA and idarubicin in the first and third consolidation courses. Of 372 patients attaining complete remission after ATRA plus idarubicin (92.5%), 368 proceeded to consolidation therapy. For low- and intermediate-risk patients, duration of neutropenia and thrombocytopenia and hospital stay were significantly reduced without sacrificing antileukemic efficacy, compared with the previous LPA99 trial. For high-risk patients, the 3-year relapse rate was significantly lower in the LPA2005 trial (11%) than in the LPA99 (26%; P = .03). Overall disease-free survival was also better in the LPA2005 trial (P = .04). In conclusion, the lower dose of mitoxantrone resulted in a significant reduction of toxicity and hospital stay while maintaining the antileukemic activity, and the combination of ATRA, idarubicin, and cytarabine for high-risk acute promyelocytic leukemia significantly reduced the relapse rate in this setting. Registered at http://www.clinicaltrials.gov as NCT00408278.

Therapy-related myeloid neoplasms in patients with acute promyelocytic leukemia treated with all-trans-retinoic Acid and anthracycline-based chemotherapy.

PURPOSE: We analyzed the incidence, risk factors, and outcome of therapy-related myeloid neoplasms (t-MNs) in patients with acute promyelocytic leukemia (APL) in first complete remission (CR). PATIENTS AND METHODS: From 1996 to 2008, 1,025 patients with APL were enrolled onto three sequential trials (LPA96, LPA99, and LPA2005) of the Programa Español para el Tratamiento de Enfermedades Hematológicas and received induction and consolidation therapy with all-trans-retinoic acid (ATRA) and anthracycline-based chemotherapy. RESULTS: Seventeen of 918 patients who achieved CR developed t-MN (10 with < 20% and seven with > or = 20% of bone marrow blasts) after a median of 43 months from CR. Partial and complete deletions of chromosomes 5 and 7 (nine patients) and 11q23 rearrangements (three patients) were the most common cytogenetic abnormalities. Overall, the 6-year cumulative incidence of t-MN was 2.2%, whereas in low-, intermediate-, and high-risk patients, the 6-year incidence was 5.2%, 2.1%, and 0%, respectively. Multivariate analysis identified age more than 35 years and lower relapse risk score as independent prognostic factors for t-MN. The median overall survival time after t-MN was 10 months. CONCLUSION: t-MN is a relatively infrequent, long-term, and severe complication after first-line treatment for APL with ATRA and anthracycline-based regimens. Therapeutic strategies to reduce the incidence of t-MN are warranted.

Dificultades y controversias en el diagnóstico biológico de los síndromes antifosfolipídicos de embarazo / Difficulties and controversies in biological diagnosis of antiphospholipidic syndromes of pregnancy

Aún existen dificultades y controversias para el diagnóstico biológico de los síndromes antifosfolipídicos. La importancia del diagnóstico en mujeres con historia obstétrica sospechosa de un síndrome antifosfolipídico es de enorme trascendencia por las implicancias que tiene un tratamiento adecuado. Este estudio tiene dos objetivos: 1. Comparar los resultados de diferentes técnicas de laboratorio en una población de mujeres enviadas para confirmar o descartar un síndrome antifosfolipídico del embarazo. 2. Establecer si la determinación de m s de una técnica en una misma paciente aumenta las posibilidades de llegar al diagnóstico. Material y método: en 607 pacientes enviadas al Centro Especializado en Afecciones de la Hemostasis y Trombosis (CEAHT) por diferentes complicaciones obstétricas se realizó la determinación de anticuerpos antifosfolipídicos por dos técnicas inmunológicas empleando reactivos comerciales disponibles en el medio (ACA y APA). En 407 de estas pacientes se determinó, adem s, el anticoagulante lúpico (AL). Resultados: 102 (16 por ciento) presentaron por lo menos un test positivo confirmado en m s de dos oportunidades. Los ACA (anticuerpos anticardiolipinas) fueron positivos en 78,4 por ciento seguidos por los APA, 29,4 por ciento (anticuerpos contra una mezcla de fosfolípidos) y con mucho menor frecuencia el AL, 8 por ciento. Sólo en 18,4 por ciento de los casos se observó la concomitancia de dos o m s técnicas positivas. Conclusión: es recomendable, de acuerdo con estos datos, realizar por lo menos dos técnicas inmunológicas adem s del AL antes de descartar un síndrome antifosfolipídico del embarazo.

Trombofilia y pérdida recurrente de embarazo / Thrombophilia and recurrent pregnancy loss

La búsqueda de factores pro trombóticos que incidan en la pérdida recurrente de embarazo, ha adquirido en los últimos años un especial interés para hematólogos y obstetras. La identificación progresiva de las diferentes enfermedades trombofílicas constituye un desafío en el diagnóstico de nuevas causas que puedan ser responsables de la pérdida recurrente de la gestación. Se estudió una población de 115 mujeres con pérdida recurrente de embarazo en quienes se descartaron previamente causas hormonales, anatómicas, infecciosas o genéticas. En ellas se buscaron diferentes causas trrombofílicas y se comparó con una población control. Dentro de los factores pro trombóticos estudiados se encontró una prevalencia significativamente mayor en los anticuerpos antifosfolípidos/anticoagulante lúpico, (p<0,0001, OR=8,85, IC95 por ciento 3,8-20,8), la lipoproteína (a) (p<0,0001, OR=6,05, IC95 por ciento 5,5-14,3), el factor V leiden (p<0,005, OR=5, IC95 or ciento 1,5-21), el factor II G20210A (p<0,005, OR=4, IC95 por ciento 1,4-11,5) y l avariante homocigota de la MTHFR C677T (p=0,0002, OR=2,4, IC95 por ciento 1,1-5,1). La asociación de 2 o más factores de riesgo trrombótico se observa en 65 por ciento de las pacientes por lo cual el estudio trombofílico de las mismas debe ser completo.