FOLFIRINOX in Locally Advanced and Metastatic Pancreatic Cancer: A Single Centre Cohort Study.

Introduction: FOLFIRINOX is emerging as new standard of care for fit patients with locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC). However, some of the physicians are reluctant to use FOLFIRINOX due to high toxicity rates reported in earlier studies. We reviewed our experience with FOLFIRINOX in LAPC and MPC, focussing on dose adjustments, toxicity and efficacy. Methods: We reviewed all patients with LAPC or MPC treated with FOLFIRINOX in our institution between April 2011 and December 2015. Unresectability (stage III and IV) was determined by the institution's multidisciplinary team for pancreatic cancer. Results: Fifty patients (18 LAPC and 32 MPC) were enrolled, with a median age of 55 years (IQR 49-66) and WHO performance status of 0/1. FOLFIRINOX was given as first-line treatment in 82% of patients. Dose modifications were applied in 90% of patients. The median number of completed cycles was 8 (IQR 5-9). Grade 3-4 toxicity occurred in 52% and grade 5 toxicity in 2%. The response rate was 25% (12% in LAPC, 32% in MPC). Median overall survival and progression-free survival were 14.8 and 10.3 months in LAPC, and 9.0 and 5.9 months in MPC, respectively. Overall 1- and 2-year survival was 65% and 10% in LAPC and 40% and 5% in MPC. Within the LAPC group, 6 patients (33%) underwent local ablative therapy and 1 patient (6%) a resection, leading to a median survival of 21.8 months. Conclusion: FOLFIRINOX treatment with nearly routine dose modification was associated with acceptable toxicity rates, relatively high response rates and an encouraging overall survival.

Exon-level expression analyses identify MYCN and NTRK1 as major determinants of alternative exon usage and robustly predict primary neuroblastoma outcome.

BACKGROUND: Using mRNA expression-derived signatures as predictors of individual patient outcome has been a goal ever since the introduction of microarrays. Here, we addressed whether analyses of tumour mRNA at the exon level can improve on the predictive power and classification accuracy of gene-based expression profiles using neuroblastoma as a model. METHODS: In a patient cohort comprising 113 primary neuroblastoma specimens expression profiling using exon-level analyses was performed to define predictive signatures using various machine-learning techniques. Alternative transcript use was calculated from relative exon expression. Validation of alternative transcripts was achieved using qPCR- and cell-based approaches. RESULTS: Both predictors derived from the gene or the exon levels resulted in prediction accuracies >80% for both event-free and overall survival and proved as independent prognostic markers in multivariate analyses. Alternative transcript use was most prominently linked to the amplification status of the MYCN oncogene, expression of the TrkA/NTRK1 neurotrophin receptor and survival. CONCLUSION: As exon level-based prediction yields comparable, but not significantly better, prediction accuracy than gene expression-based predictors, gene-based assays seem to be sufficiently precise for predicting outcome of neuroblastoma patients. However, exon-level analyses provide added knowledge by identifying alternative transcript use, which should deepen the understanding of neuroblastoma biology.

Bolus-tracking MRI with a simultaneous T1- and T2*-measurement.

The aim of this study was to propose and evaluate a methodology to analyze simultaneously acquired T2*-weighted dynamic susceptibility contrast (DSC) MRI and T(1)-weighted dynamic contrast enhanced (DCE) MRI data. Two generalized models of T2*-relaxation are proposed to account for tracer leakage, and a two-compartment exchange model is used to separate tracer in intra- and extravascular spaces. The methods are evaluated using data extracted from ROIs in three mice with subcutaneously implanted human colorectal tumors. Comparing plasma flow values obtained from DCE-MRI and DSC-MRI data defines a practical experimental paradigm to measure T2*-relaxivities, and reveals a factor of 15 between values in tissue and blood. Comparing mean transit time values obtained from DCE-MRI and DSC-MRI without leakage correction, indicates a significant reduction of susceptibility weighting in DSC-MRI during tracer leakage. A one-parameter gradient correction model provides a good approximation for this susceptibility loss, but redundancy of the parameter limits the practical potential of this model for DSC-MRI. Susceptibility loss is modeled more accurately with a variable T2*-relaxivity, which allows to extract new parameters that cannot be derived from DSC-MRI or DCE-MRI alone. They reflect the cellular and vessel geometry, and thus may lead to a more complete characterization of tissue structure.

Image-guided and passively tumour-targeted polymeric nanomedicines for radiochemotherapy.

Drug targeting systems are nanometer-sized carrier materials designed for improving the biodistribution of systemically applied (chemo-) therapeutics. Reasoning that (I) the temporal and spatial interaction between systemically applied chemotherapy and clinically relevant fractionated radiotherapy is suboptimal, and that (II) drug targeting systems are able to improve the temporal and spatial parameters of this interaction, we have here set out to evaluate the potential of 'carrier-based radiochemotherapy'. N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers were used as a model drug targeting system, doxorubicin and gemcitabine as model drugs, and the syngeneic and radio- and chemoresistant Dunning AT1 rat prostate carcinoma as a model tumour model. Using magnetic resonance imaging and gamma-scintigraphy, the polymeric drug carriers were first shown to circulate for prolonged periods of time, to localise to tumours both effectively and selectively, and to improve the tumour-directed delivery of low molecular weight agents. Subsequently, they were then shown to interact synergistically with radiotherapy, with radiotherapy increasing the tumour accumulation of the copolymers, and with the copolymers increasing the therapeutic index of radiochemotherapy (both for doxorubicin and for gemcitabine). Based on these findings, and on the fact that its principles are likely broadly applicable, we propose carrier-based radiochemotherapy as a novel concept for treating advanced solid malignancies.

[100 years Heidehaus--from sanatorium for tuberculosis to a modern chest hospital]. / 100 Jahre Heidehaus--vom Tuberkuloseheim zum modernen Lungenzentrum.

When the sanatorium "Heidehaus" was founded on June 1, 1907 in the northern countryside of Hannover with Dr. Otto Ziegler as head about 120 beds for patients with tuberculosis were available. By 1914 about 200 patients were being treated by 4 physicians and 10 nurses. An operating theatre and a modern radiology unit were added in 1927. Shortly after the 2nd World War 400 patients with tuberculosis were hospitalised simultaneously. With the introduction of antituberculous triple drug treatment the number of patients dropped significantly. During this period many traditional facilities, used to care for patients with tuberculosis lost their financial basis and closed. However in the 1960s Prof. Schindler, the head of Heidehaus, widened the spectrum of the hospital into a modern chest hospital, focused on lung and airway diseases. In particular in the 1980s and 1990s this trend continued and 2 independent departments, i. e., pneumology and thoracic surgery were founded. In 2005 due to restructuring by the community of Hannover the "Heidehaus" moved completely and merged with another traditional hospital to become the new "Oststadt-Heidehaus". In its new surroundings both departments for pulmonary medicine and thoracic surgery offer a broad spectrum of modern thoracic medicine in cooperation with other disciplines.

Any clinical benefit from the use of oncofoetal markers in the management of chemotherapy for patients with metastatic colorectal carcinomas?

AIMS: Computed tomography (CT) is the reference technique for evaluating response to chemotherapy. The potential helpfulness of tumour markers is debated. MATERIALS AND METHODS: From March 1997 to January 1999, 91 consecutive patients receiving chemotherapy for metastatic colorectal carcinoma underwent whole-body spiral CT, estimates of anti-carcinoembryonic antigen (CEA) and CA19-9 every 8 weeks. RESULTS: CEA and CA19-9 levels were above normal in 78 (85.7%) and 61 (67.5%) patients, respectively. Tumour response evaluation according to the RECIST criteria was obtained at 8-week evaluation in 83 (91%) patients. The positive predictive values (PPV) for response of a decrease of the marker levels were 53.8 for CEA and 41.7 for CA19-9 using a 30% decrease threshold, and 60/52.2, respectively, using a 50% decrease threshold. Meaningful PPV values (> 90%) for progression of an increase of the marker levels were only obtained using the 200% increase threshold for CEA alone or a combination of CEA and CA 19-9. A 100% CEA increase between baseline and the 8-week evaluation was correlated to overall survival (P = 0.0023). The need for a radiological confirmation of tumour progression could be avoided by the systematic dosage of tumour markers at baseline and after 8 weeks of treatment only in a sub-population of 13% of the patients with a 200% increase of CEA or CA 19-9 at 8 weeks. CONCLUSIONS: CEA, CA 19-9, or both should be used with caution for tumour response evaluation to chemotherapy in addition to CT in metastatic colorectal carcinoma.

[Isolation measurements for cystic fibrosis patients]. / Hygienemassnahmen für Patienten mit Cystischer Fibrose.

BACKGROUND: Respiratory tract infections significantly contribute to morbidity and mortality of cystic fibrosis patients. METHODS: We conducted a systematic literature review (Pubmed 01/1966 up to 09/2003) in order to present recommendations for the isolation of CF patients colonized with Burkholderia cepacia spp., Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Alcaligenes spp. Evidence and quality of 64 publications dealing with pathogen transmission or isolation measurements of colonized patients were evaluated. RESULTS: B. cepacia spp. was dealt most often with and 35 of 36 authors recommended the isolation of patients colonized with this pathogen. Isolation of patients colonized with P. aeruginosa was proposed by 21 of 25 authors. Only 5 studies concerned S. maltophilia or Alcaligenes spp. CONCLUSIONS: A) B. cepacia spp. colonized patients need to get a single room for their own. B) P. aeruginosa colonized CF patients should be separated from non-colonized CF patients. C) Patients harbouring even multi drug resistant P. aeruginosa, S. maltophilia or Alcaligenes spp. may not share their room with immunocompromised patients and should also be isolated when treated in intensive care units.

[Detection of prostate carcinomas with T1-weighted dynamic contrast-enhanced MRI. Value of two-compartment model]. / Detektion von Prostatakarzinomen mit T1-gewichteter Kontrastmittel-unterstützter dynamischer MRT. Wertigkeit des Zweikompartimentemodells.

AIM: The suitability of dynamic parameters of the two-compartment model for detecting prostate carcinomas and its correlation with tumor microvascular density were evaluated. METHODS: The study included 43 patients with biopsy-proven prostate carcinoma: 28 were examined by 1.0-T MRI (Turbo-FLASH) and 15 by 1.5-T MRI (FLASH) with infusion of 0.1 mmol/kg Gd-DTPA. Signal time curves were parametrized with an open two-compartment model in amplitude and exchange rate constants (k(ep)). The microvascular density of resected prostate carcinomas was determined. RESULTS: The microvascular density in the tumors was significantly higher than in the adjacent healthy prostate tissue and correlated in both sequences with k(ep). Prostate carcinomas of the peripheral zone were demarcated by amplitude and k(ep). In the Turbo-FLASH sequence there was a significant difference between the tumor tissue and healthy peripheral zone in terms of k(ep) and in the FLASH sequence in terms of amplitude. CONCLUSION: Prostate carcinomas can be visualized with dynamic T1-weighted MR sequences using a two-compartment model. Moreover, the parameter k(ep) reveals the microvascular density in the tumor and can thus provide valuable clinical information for characterizing the tumors.

[Hemodynamic and metabolic characterization of orthotopic rat prostate carcinomas using dynamic MRI and proton magnetic resonance spectroscopy]. / Hämodynamische und metabolische Charakterisierung orthotoper Prostatakarzinome der Ratte mittels dynamischer MRT und Protonen-MR-Spektroskopie.

AIM: The aim of this study was the noninvasive characterization of prostate carcinoma orthotopically implanted in rats using Gd-DTPA-assisted dynamic MRI (dMRI) and proton magnetic resonance spectroscopy ((1)H-MRS). MATERIAL AND METHODS: After surgical exposure of the prostate, Dunning R3327 orthotopic prostate carcinoma was induced by injecting cells of the MAT-LyLu subline. Six rats were examined 5 and 14 days after tumor induction with dMRI and (1)H-MRS at 1.5 T. Six tumor-free rats served as controls. Using an open two-compartment model, the parameters A (amplitude) and k(ep) (exchange rate constants) were calculated from the signal time curves of the dMRI. The relative signal intensities (Cho/Cr) of the resonances of choline (Cho) and the creatine-phosphocreatine complex (Cr) were computed from the MR spectra. RESULTS: Already after 5 days, the tumors in the prostate could be clearly identified based on the decrease in signal intensity to T2w and increase of A and k(ep). High Cho/Cr levels and resonances of two lipid fractions (Lip(1) at 0.8-1.5 ppm and Lip(2) at 2.0-2.2 ppm) were observed by MRS in the highly necrotic tumors. CONCLUSIONS: The orthotopic rat prostate carcinoma model resembles human prostate carcinoma in regard to MR morphology, dMRI, and (1)H-MRS. The noninvasive characterization of perfusion and metabolism makes a comparative examination of different treatment modalities possible.

Sex steroids and body composition in men with cystic fibrosis.

OBJECTIVE: Delayed sexual maturation and low body weight is common in cystic fibrosis (CF). Concomitant data on sex hormones and concomitant body composition are lacking in men with CF. DESIGN: Cross-sectional study. SUBJECTS AND METHODS: Serum levels of testosterone, 17beta-oestradiol (E(2)), 25-hydroxyvitamin D (25(OH)D), sex hormone-binding globulin (SHBG) and LH were measured by RIA and total and regional lean body mass (LBM), fat body mass (FBM), bone mineral content and bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry, in men with CF (n=40; age 24.7+/-5.4 years) and age-matched healthy controls (n=28; age 25.7+/-3.7). Only men without acute disease exacerbation or systemic glucocorticoid treatment were included. RESULTS: Mean levels of hormonal serum parameters differed significantly between healthy controls (testosterone=20.2+/-5.5 nmol/l; E(2)=95.0+/-20.2 pmol/l; 25(OH)D=62.8+/-28.3 nmol/l) and patients (testosterone=15.9+/-4.1 nmol/l; E(2)=60.7+/-19.4 pmol/l; 25(OH)D=39.5+/-17.8 nmol/l; P<0.001) while no difference was found for SHBG or LH. Eleven (for E(2), 19 of 40, for 25(OH)D, 20 of 40) out of 40 patients had serum testosterone levels 2 s.d. below the mean of normal. Men with CF showed a relative shift from FBM to LBM and a different body fat distribution compared with healthy controls (P<0.01). Testosterone was not correlated with weight, total or regional LBM or FBM, but significantly with BMD (r=0.32; P<0.05) independently from body height and 25(OH)D levels. E(2) was correlated with regional and total FBM (r=0.48; P<0.05). In a multiple regression analysis of the joint effect of testosterone and body components on E(2), a testosterone-independent effect was found for FBM. CONCLUSIONS: CF patients with stable disease have moderately reduced serum testosterone levels. This might already imply detrimental effects on bone. The change in LBM of patients appears to have no direct association with sex hormone levels while low FBM might cause reduced net conversion of serum testosterone to E(2) with possible effects on FBM distribution.

Assessment of tumour response to chemotherapy for metastatic colorectal cancer: accuracy of the RECIST criteria.

Evaluation of tumour size modifications in response to treatment is a critical issue in the management of advanced malignancies. In 1981, the World Health Organization (WHO) established guidelines for tumour response assessment. These WHO1981 criteria were recently simplified in a revised version, named RECIST (Response Evaluation Criteria in Solid Tumours), which uses unidimensional instead of bidimensional measurements, a reduced number of measured lesions, withdrawal of the progression criteria based on isolated increase of a single lesion, and different shrinkage threshold for definitions of tumour response and progression. In order to validate these new guidelines, we have compared results obtained with both classifications in a prospective series of 91 patients receiving chemotherapy for metastatic colorectal cancer. Data from iterative tomographic measurements were fully recorded and reviewed by an expert panel. The overall response and progression rates according to the WHO1981 criteria were 19% and 58%, respectively. Using RECIST criteria, 16 patients were reclassified in a more favourable subgroup, the overall response rate being 28% and the progression rate 45% (non-weighted kappa concordance test 0.72). When isolated increase of a single measurable lesion is not taken into account for progression with the WHO1981 criteria, only 7 patients were reclassified and the kappa test was satisfying, i.e. > or =0.75, for the whole population as well as for each of the responding and progressive subgroups. Since it provides concordant results with a simplified method, the use of RECIST criteria is recommended for evaluation of treatment efficacy in clinical trials and routine practice.

Tibial plateau fracture as a measure of early estrogen-dependent bone fragility in rats.

The goals of this study were to develop a protocol to induce a compressive fracture at the tibial plateau of the rat knee in vitro and to determine if the biomechanical parameters provided a sensitive assessment of the early skeletal changes induced by estrogen deficiency. Sixty-one rats underwent an ovariectomy (n = 36) or sham operation (n = 25) and were maintained for 50 days after the procedure. Just before death, the proximal tibia of each animal was scanned with high-resolution x-ray tomography. From the three-dimensional images, the mean trabecular bone volume, thickness, and separation and the number of trabeculae were calculated. The knees were then harvested and mounted into a servohydraulic materials testing system so that the distal femoral condyle could be forced into the proximal tibial plateau until fracture. The fracture load of the ovariectomized rats was 24% less than that of the rats that had the sham operation. Similarly, the structural stiffness of the ovariectomized knees was decreased by 22%. Both of these differences were statistically significant (p < 0.01) and were explained by differences in trabecular bone volume (r = 0.56, p < 0.0001 and r = 0.42, p < 0.005, respectively). The other measures of trabecular bone structure were correlated with the volume and did not improve the prediction by the biomechanical parameters. These data demonstrate that biomechanical testing of the tibial plateau in rats can quantify the structural consequences of estrogen deficiency at an early time point before they become apparent at other bone sites, such as the lumbar spine.

Inhibitor against coagulation factor V after liver transplantation.

A new case of anti-factor V inhibitor is described in a 46-year-old man, who received a liver transplantation for hepatocellular carcinoma, without exposure to bovine thrombin or fibrin glue during the operative course. The inhibition occurred on the 14th postoperative day, while the patient was being treated with oxacillin, azathioprine, and a new immunosuppressive drug, FK506. The inhibition was of short duration (3 days), and no bleeding complication occurred despite a very low plasmatic level of factor V activity and antigen (<5%). Plasma samples drawn after cessation of FK506 disclosed a dose-dependent inhibitory activity when alcoholic solutions of FK506 were exogeneously added; this suggests a possible role of the FK506 drug in the occurrence of this anti-factor V inhibitor.

Comparison of bone-patellar tendon-bone interference screw fixation and hamstring transfemoral screw fixation in anterior cruciate ligament reconstruction.

While bone-patellar tendon-bone (BPTB) interference screw anterior cruciate ligament (ACL) reconstruction is a biomechanically sound construct, alternative techniques have been developed secondary to potential donor site morbidity. This study evaluates a system designed to address this problem that involves a transfemoral screw fixation device and stapling of hamstring tendons. Seven pairs of cadaveric knees underwent ACL reconstruction using either BPTB interference screw technique or semitendinosus gracilis (STG) transfemoral screw fixation and stapling. Tensile testing was performed. There was no significant difference between the two fixation types with regard to stiffness, maximum load to failure, elongation, energy to failure and yield load, displacement, and energy.

Use of electromagnetic fields in a spinal fusion. A rabbit model.

STUDY DESIGN: The biomechanical and histologic characteristics of posterolateral spinal fusion in a rabbit model with and without the application of a pulsed electromagnetic field were analyzed in a prospective, randomized trial. In addition, fusion rate with and without a pulsed electromagnetic field in this model was assessed by biomechanical testing, radiographs, and manual palpation. OBJECTIVES: To evaluate the influence of a pulsed electromagnetic field on the spinal fusion rate and biomechanical characteristics in a rabbit model. SUMMARY OF BACKGROUND DATA: Previous studies performed to assess the benefits of a pulsed electromagnetic field in spinal fusion have been complicated by the use of instrumentation, and the animal models used do not have a pseudarthrosis rate comparable to that seen in humans. In contrast, the posterolateral intertransverse process fusion in the rabbit is uncomplicated by the use of instrumentation and has been shown to have a pseudarthrosis rate similar to that found in humans (5-35%). METHODS: Ten New Zealand white rabbits each were randomly assigned to undergo spinal fusion using either 1) autologous bone with electromagnetic fields, or 2) autologous bone without electromagnetic fields. A specially designed plastic constraint was used to focus the pulsed electromagnetic field over the rabbits' lumbar spine 4 hours per day. Animals were killed at 6 weeks for biomechanical and histologic testing. RESULTS: The rate of pseudarthrosis, as evaluated radiographically and manually in a blinded fashion, decreased from 40% to 20% with the pulsed electromagnetic field, but this decrease in the nonunion rate was not statistically significant given the number of animals per group. Biomechanical analysis of the fusion mass showed that a pulsed electromagnetic field resulted in statistically significant increases in stiffness (35%), area under the load-displacement curve (37%), and load to failure of the fusion mass (42%). Qualitative histologic assessment showed increased bone formation in those fusions exposed to a pulsed electromagnetic field. CONCLUSIONS: This study demonstrates the reproducibility of a rabbit fusion model, and the ability of a pulsed electromagnetic field to induce a statistically significant increase in stiffness, area under the load-displacement curve, and load to failure of the fusion mass. This investigation provides a basis for continued evaluation of biologic enhancement of spinal arthrodesis with the use of a pulsed electromagnetic field.

Decreased expression of the cystic fibrosis transmembrane conductance regulator protein in remodeled airway epithelium from lung transplanted patients.

The absence or mislocalization of cystic fibrosis transmembrane conductance regulator (CFTR) is regarded as being specific for cystic fibrosis (CF). In principle, the supply of a non-CF lung transplant to a CF patient should bring up normal CFTR expression in the lower airways. Immunolocalization of CFTR and of epithelial differentiation markers (ie, cytokeratins 13, 14, and 18, and desmoplakins 1 and 2) was carried out on 21 mucosal biopsies from the upper lobe of grafts in non-CF (n = 12) and CF patients (n = 9) retrieved between days 23 and 1,608 after lung transplantation. Biopsy specimens from seven non-CF and four CF patients presented either a pseudostratified respiratory epithelium or slight basal cell hyperplasia. CFTR was distributed at the apical membrane of the ciliated cells. In remodeled epithelia with basal cell hyperplasia or squamous metaplasia, CFTR was either weakly expressed in the cytoplasm of the superficial epithelial cells or was undetectable. The extent of epithelium remodeling was significantly correlated with an impairment of lung function. The results suggest that posttransplant airway epithelium dedifferentiation of the graft leads to the loss of properly targeted CFTR irrespective of the underlying disease of the recipient.

Influence of conditions of blood sampling on coagulation activation markers (prothrombin fragment 1 + 2, thrombin-antithrombin complexes and D-dimers) measurements.

In this study, we evaluated the effects of anticoagulants used in blood sampling on the measurements of coagulation activation markers F1 + 2, TAT, D-Dimers by Elisa methods. The study was carried out on normal subjects and patients with inherited deficiency of coagulation inhibitors, antithrombin III (ATIII) protein C (PC) and protein S (PS). Three different anticoagulant solutions were compared: 1) ACD/EDTA/adenosine/heparin, 2) EDTA/aprotinin/a synthetic thrombin inhibitor and 3) sodium citrate. The results showed that sodium citrate, commonly used in coagulation laboratories, is a suitable anticoagulant for the study of coagulation activation markers. In addition, the type of tubes (plastic tubes vs glass Vacutainer R tubes) used for blood sampling as well as the order of sampling (early or late after the phlebotomy procedure) did not influence the results. We concluded that assays of coagulation activation markers F1 + 2 and D-Dimers can be performed in samples collected routinely by haemostasis laboratory staff using Vacutainer R tubes with sodium citrate. Further investigations are needed to understand why TAT measurements gave a pattern of results quite different from F1 + 2 or D-Di measurements.

Acute promyelocytic leukemia in 57 previously untreated patients.

Fifty-seven patients in initial phase of acute promyelocytic leukemia (APL) were treated in the same department with heparin infusion, platelet transfusions, and two related induction regimens both including cytosine arabinoside and daunorubicin. Clinical and biological findings at presentation were studied. The complete remission (CR) rate was 53%. Twenty-seven patients (47%) died during the initial course of the disease, either before day 5 (early death [ED], n = 7) or after day 5 (death in aplasia [DA], n = 20). Most ED was due to intracerebral hemorrhage (6/7), especially when large hemorrhages had been seen on fundus oculi examination. Most DA was due to multivisceral failure (9/20). No correlation was found between initial disseminated intravascular coagulation (DIC) and death. However, the worsening of coagulation parameters during induction therapy, with or without initial DIC, significantly increased the occurrence of renal and respiratory failure which were particularly frequent during the first month. The median duration of survival was short (3.5 months) and the median duration of CR (11 months) was similar to that of other acute myeloid leukemias treated with the same regimens. The possible causes of the high mortality observed during the initial courses of APL and the possible benefit of a more graduate induction chemotherapy are discussed.