Multicentre surveillance study on feasibility, safety and efficacy of antifungal combination therapy for proven or probable invasive fungal diseases in haematological patients: the SEIFEM real-life combo study.

UNLABELLED: This multicentre observational study evaluated the feasibility, efficacy and toxicity of antifungal combination therapy (combo) as treatment of proven or probable invasive fungal diseases (IFDs) in patients with haematological malignancies. Between January 2005 and January 2010, 84 cases of IFDs (39 proven and 45 probable) treated with combo were collected in 20 Hematological Italian Centres, in patients who underwent chemotherapy or allogeneic haematopoietic stem cell transplantation for haematological diseases. Median age of patients was 34 years (range 1-73) and 37% had less than 18 years. Acute leukaemia was the most common underlying haematological disease (68/84; 81%). The phase of treatment was as follows: first induction in 21/84 (25%), consolidation phase in 18/84 (21%) and reinduction/salvage in 45/84 (54%). The main site of infection was lung with or without other sites. The principal fungal pathogens were as follows: Aspergillus sp. 68 cases (81%), Candida sp. six cases (8%), Zygomycetes four cases (5%) and Fusarium sp. four cases (5%). The most used combo was caspofungin+voriconazole 35/84 (42%), caspofungin + liposomal amphotericin B (L-AmB) 20/84 (24%) and L-AmB+voriconazole 15/84 (18%). The median duration of combo was 19 days (range 3-180). The overall response rate (ORR) was 73% (61/84 responders) without significant differences between the combo regimens. The most important factor that significantly influenced the response was granulocyte (PMN) recovery (P 0.009). Only one patient discontinued therapy (voriconazole-related neurotoxicity) and 22% experienced mild and reversible adverse events (hypokalaemia, ALT/AST increase and creatinine increase). The IFDs-attributable mortality was 17%. This study indicates that combo was both well tolerated and effective in haematological patients. The most used combo regimens were caspofungin + voriconazole (ORR 80%) and caspofungin + L-AmB (ORR 70%). The ORR was 73% and the mortality IFD related was 17%. PMN recovery during combo predicts a favourable outcome. CLINICAL TRIALS REGISTRATION: NCT00906633.

A prospective survey of febrile events in hematological malignancies.

The Hema e-Chart prospectively collected data on febrile events (FEs) in hematological malignancy patients (HMs). The aim of the study was to assess the number, causes and outcome of HM-related FEs. Data were collected in a computerized registry that systematically approached the study and the evolution of FEs developing in a cohort of adult HMs who were admitted to 19 hematology departments in Italy from March 2007 to December 2008. A total of 869 FEs in 3,197 patients with newly diagnosed HMs were recorded. Fever of unidentified origin (FUO) was observed in 386 cases (44.4%). The other causes of FE were identified as noninfectious in 48 cases (5.5%) and infectious in 435 cases (50.1%). Bacteria were the most common cause of infectious FEs (301 cases), followed by fungi (95 cases), and viruses (7 cases). Mixed agents were isolated in 32 episodes. The attributable mortality rate was 6.7% (58 FEs). No deaths were observed in viral infection or in the noninfectious groups, while 25 deaths were due to FUO, 16 to bacterial infections, 14 to fungal infections, and three to mixed infections. The Hema e-Chart provided a complete system for the epidemiological study of infectious complications in HMs.

Electric conductivity measurements employing 3D printed electrodes and cells.

The electric conductivity is one the most routinely inspected characteristics of aqueous media, being employed in monitoring drinking water quality and determining thermodynamic properties of electrolytes. In this work, we utilize fused deposition modelling 3D printing (3DP) to manufacture a platform composed of supporting cells and sensing electrodes for electric conductivity measurements of aqueous solutions. For the first time, the electric conductivity of liquid electrolytes is sensed by 3DP electrodes, employing a direct electrode/electrolyte contact. Conductivity measurements performed in the presented 3DP platform are controlled by an electronic circuitry developed employing a programmable system on chip prototyping kit. The entire conductometric setup was validated employing commercial conductance standards as well as in-lab prepared aqueous solutions of potassium chloride and formic and acetic acid as representatives of strong and weak electrolytes. Conductivity measurements enabled the correct determination of limiting molar conductivity (for potassium chloride) and dissociation constants (for the two weak acids). Finally, the functionality of the presented platform was confirmed by measuring conductivity of various bottled water samples. Results obtained in this work pave the wave for further development and applications of conductometers based on 3DP electrodes and cells.

Sweat analysis with a wearable sensing platform based on laser-induced graphene.

The scientific community has shown increasing interest in laser scribing for the direct fabrication of conductive graphene-based tracks on different substrates. This can enable novel routes for the noninvasive analysis of biofluids (such as sweat or other noninvasive matrices), whose results can provide the rapid evaluation of a person's health status. Here, we present a wearable sensing platform based on laser induced graphene (LIG) porous electrodes scribed on a flexible polyimide sheet, which samples sweat through a paper sampler. The device is fully laser manufactured and features a two layer design with LIG-based vertical interconnect accesses. A detailed characterization of the LIG electrodes including pore size, surface groups, surface area in comparison to electroactive surface area, and the reduction behavior of different LIG types was performed. The bare LIG electrodes can detect the electrochemical oxidation of both uric acid and tyrosine. Further modification of the surface of the LIG working electrode with an indoaniline derivative [4-((4-aminophenyl)imino)-2,6-dimethoxycyclohexa-2,5-dien-1-one] enables the voltammetric measurement of pH with an almost ideal sensitivity and without interference from other analytes. Finally, electrochemical impedance spectroscopy was used to measure the concentrations of ions through the analysis of the sweat impedance. The device was successfully tested in a real case scenario, worn on the skin during a sports session. In vitro tests proved the non-cytotoxic effect of the device on the A549 cell line.

Gastric fundus tension before and after division of the short gastric vessels in a cadaveric model of fundoplication.

Short gastric vessels (SGV) division is a controversial topic in antireflux surgery. Some surgeons do not divide the SGV routinely to perform a fundoplication; however, excessive tension of the gastric fundus (GF) forces this procedure necessary in some cases. This study aims to evaluate in a cadaveric model of Nissen fundoplication: (i) the correlation of GF tension with anatomic parameters; and (ii) the effect of SGV division on GF tension. In total, 23 fresh cadavers (18 men, mean age 62 years) were studied. The abdominal esophagus was dissected, and the GF transposed to a limit of 3 cm to the right border of the esophagus. A dynamometer was attached to the GF and the tension recorded. Cadavers were grouped according to the presence or absence of tension. SGV were divided and GF tension measured again. The presence or absence of initial GF tension was correlated to: (i) number of SGV; (ii) length of the GF; (iii) distance between His angle and the first SGV; and (iv) size of the spleen. The mean GF pressure was 0.5 N +/- 1.0 (0-2.5) before SGV division and 0.1 N +/- 0.3 (0-1.5) after SGV division (P= 0.002). Initial tension was absent in 12 (52.2%) cases. GF tension did not correlate with any of the anatomic parameters. Our results show that: (i) GF tension does not correlate with anatomic parameters; and (ii) SGV division affects GF tension significantly.

A Biosensor for the Detection of Acetylcholine and Diazinon.

Acetylcholine is a neurotransmitter and a neuromodulator found in the autonomic, peripheral and central nervous systems. Diazinon is a pesticide with toxic effects on humans, such as the inhibition of acetylcholine. In this paper, a biosensor is proposed for the detection of acetylcholine (range 70 - 1000 µM) and diazinon (range 0.3 - 20000 ppb). This biosensor combines a pH-sensitive layer of reduced graphene oxide functionalized with 4-aminobenzoic acid and acetylcholinesterase. This enzyme was immobilized on reduced graphene oxide and it catalyzed the conversion of acetylcholine into choline and acetic acid, locally decreasing the pH value and triggering the sensor response. The limit of detection for the acetylcholine and diazinon were 70 µM and 0.3 ppb, respectively.

A graphene-based pH sensor on paper for human plasma and seawater.

The relevance of pH assessment in clinical analysis, environmental and industrial control, has raised the demand for the development of portable, low cost and easy-to-use monitoring systems. This paper proposes a pH sensor printed on a paper support passivated with a solid-ink coating. The sensor exploits the pH sensitivity of a reduced graphene oxide functionalized with 3-(4-aminophenil)propionic acid. The sensor responded in the pH range [4], [10] and had a sensitivity of 46 mV/pH. Tests on human plasma and seawater proved this pH sensor to have similar performances than those of a commercial pH-meter with an uncertainty of 0.1 and 0.2 pH unit in plasma and seawater, respectively.

Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study--Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne.

BACKGROUND: The purpose of our study was to evaluate the incidence and outcome of invasive fungal infection (IFI) among patients who underwent autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at 11 Italian transplantation centers. METHODS: This cohort-retrospective study, conducted during 1999-2003, involved HSCT patients admitted to 11 tertiary care centers or university hospitals in Italy, who developed IFIs (proven or probable). RESULTS: Among 3228 patients who underwent HSCT (1249 allogeneic HSCT recipients and 1979 autologous HSCT recipients), IFI occurred in 121 patients (overall incidence, 3.7%). Ninety-one episodes (2.8% of all patients) were due to molds, and 30 (0.9%) were due to yeasts. Ninety-eight episodes (7.8%) occurred among the 1249 allogeneic HSCT recipients, and 23 (1.2%) occurred among the 1979 autologous HSCT recipients. The most frequent etiological agents were Aspergillus species (86 episodes) and Candida species (30 episodes). The overall mortality rate was 5.7% among allogeneic HSCT recipients and 0.4% among autologous HSCT recipients, whereas the attributable mortality rate registered in our population was 65.3% (72.4% for allogeneic HSCT recipients and 34.7% for autologous HSCT recipients). Etiology influenced the patients' outcomes: the attributable mortality rate for aspergillosis was 72.1% (77.2% and 14.3% for allogeneic and autologous HSCT recipients, respectively), and the rate for Candida IFI was 50% (57.1% and 43.8% for allogeneic and autologous HSCT recipients, respectively). CONCLUSIONS: IFI represents a common complication for allogeneic HSCT recipients. Aspergillus species is the most frequently detected agent in these patients, and aspergillosis is characterized by a high mortality rate. Conversely, autologous HSCT recipients rarely develop aspergillosis, and the attributable mortality rate is markedly lower. Candidemia was observed less often than aspergillosis among both allogeneic and autologous HSCT recipients; furthermore, there was no difference in either the incidence of or the attributable mortality rate for candidemia among recipients of the 2 transplant types.

Efficacy of caspofungin as secondary prophylaxis in patients undergoing allogeneic stem cell transplantation with prior pulmonary and/or systemic fungal infection.

Transplanted patients with a history of invasive fungal infection (IFI) are at high risk of developing relapse and fatal complications. Eighteen patients affected by hematological malignancies and a previous IFI were submitted to allogeneic stem cell transplantation, using Caspofungin as a secondary prophylaxis. Patients had a probable or proven fungal infection and 16 had a pulmonary localization. No side effects were recorded during treatment with Caspofungin. Compared to pre-transplant evaluation, stability or improvement of the previous IFI was observed in 16 of the 18 patients at day 30, in 13 of the 15 evaluable patients at day 180 and in 11 of the 11 evaluable patients at day 360 post transplant. In particular, all the six patients with a proven fungal infection were alive, with a stable or improved IFI after 1 year from transplant. At a maximum follow-up of 31 months, eight patients died for disease progression or transplant-related complications, but only two had evidence of fungal progression. Secondary prophylaxis with Caspofungin may represent a suitable approach to limit IFI relapse or progression, allowing patients with hematological malignancies to adhere to the planned therapeutic program.

Field Assessments to Control the Lesser Mealworm (Coleoptera: Tenebrionidae) Using Diatomaceous Earth in Poultry Houses.

Control of the lesser mealworm (Alphitobius diaperinus Panzer, 1797 [Coleoptera: Tenebrionidae]) is usually conducted with chemical insecticides, which have limited efficacy as well as environmental and health risks. Diatomaceous earth (DE) is safe and effective in controlling many insects including lesser mealworm. However, little is known of DE efficacy against this pest. Thus, an assessment of DE was conducted for the first time in commercial broiler houses in Brazil, with the aim of developing a strategy for the use of DE in the control of this insect. The efficacy of DE was determinate to a minimum concentration, and the application was directed to the most infested sites. The DE applied to the entire poultry house (280 g/m2) was verified to control the insects. DE was also comparable to chemical treatments, with a reduction of 80% in the insect population. DE controlled the lesser mealworm and is recommended for application at a concentration of 280 g/m2 when applied to the surface of new poultry litter, before the first lot of birds is housed. Thereafter, DE should be reapplied before the housing of each lot of birds, in the same concentration, only in the housing area and under the feeders and near the walls and pillars. In addition to being a control strategy, DE can be an important tool in the management of lesser mealworm insecticide resistance.

Potential Side Effects of the Entomopathogenic Fungus Metarhizium anisopliae on the Egg Parasitoid Trichogramma pretiosum (Hymenoptera: Trichogrammatidae) Under Controlled Conditions.

The purpose was to evaluate the side effects of strains Metarhizium anisopliae (Metsch.) Sorokin sensu lato Unioeste 43 and M. anisopliae sensu stricto ESALQ 1641 on Trichogramma pretiosum Riley (Hymenoptera: Trichogrammatidae) under controlled conditions. A free-choice test for parasitism was performed, with the confinement of T. pretiosum females mated with cards (1 × 5 cm) containing age-standardized Anagasta kuehniella Zeller eggs, either sprayed with a fungal strain (109 conidia/ml) or 0.01% v/v Tween 80 (control). For the no-choice tests, T. pretiosum females mated were confined with cards sprayed with fungal strains before or after parasitism, and cards with fungal applications at different times. The number of parasitized eggs, percentage of emergence, longevity, egg-to-adult period, sex ratio, total and confirmed mortality by the fungus, and longevity of females that parasitized previously sprayed eggs, were assessed. Histological analysis of immature phases was also performed. The fungus was repellent to T. pretiosum in the free-choice test, while in the no-choice test, fungal applications before and after parasitism did not affect the number of eggs parasitized by T. pretiosum or the sex ratio of emerging adults. However, both strains affected adult emergence rates, the egg-to-adult period, and longevity. Overall, both M. anisopliae strains had minor effects on these biological parameters of T. pretiosum under controlled conditions. Hyphae were not detected in histological observations of immature stages of the parasitoid.

The ambiguous role of healthcare providers: a new perspective in Human Resources Management.

BACKGROUND AND AIM: A strategic Human Resources Management approach, that overcomes anadministrative Personnel Management, is becoming crucial for hospital organizations. In this sense, the aimof this work was to examine the figure of healthcare provider using the concept of role, as expected behaviourin term of integration in the organizational culture. METHOD: The instrument used to analyse the healthcareprovider figure was "role mapping". Particularly, semistructured interviews were conducted and involved to36 health professionals of four units in order to examine the behaviour expectations system towards thehealthcare providers. RESULTS: The analysis revealed that the expectations of different professionals relatedto the healthcare provider were dissimilar. Physicians' expectations referred to technical preparation and efficiency,while nurses and nurse coordinators required collaboration in equip work and emotional support forpatients. In all Operating Units, directors were perceived as missing persons with vague expectations of efficiency.Differences concerned also the four Units. For example, in intensive care Unit, the role of healthcareprovider was clearer and this figure was perceived as essential for patients' care and for the equip teamwork.On the contrary, in Recovery Unit the healthcare provider was underestimated, the role was ambiguous andnot integrated in the equip even if there was a clear division of tasks between nurses and healthcare providers. CONCLUSION: The "role mapping" instrument allows to identify healthcare provider profile and find possible roleambiguity and conflicts in order to plan adequate human resources management interventions.

A graphene oxide pH sensor for wound monitoring.

This article describes the fabrication and characterization of a pH sensor for monitoring the wound status. The pH sensitive layer consists of a graphene oxide (GO) layer obtained by drop-casting 5 µÎ of GO dispersion onto the working electrode of a screen-printed substrate. Sensitivity was 31.8 mV/pH with an accuracy of 0.3 unit of pH. Open-circuit potentiometry was carried out to measure pH in an exudate sample. The GO pH sensor proved to be reliable as the comparison with results obtained from a standard glass electrode pH-meter showed negligible differences (<; 0.09 pH units in the worst case) for measurements performed over a period of 4 days.

Set-up error in supine-positioned patients immobilized with two different modalities during conformal radiotherapy of prostate cancer.

BACKGROUND: Conformal radiotherapy requires reduced margins around the clinical target volume (CTV) with respect to traditional radiotherapy techniques. Therefore, high set-up accuracy and reproducibility are mandatory. PURPOSE: To investigate the effectiveness of two different immobilization techniques during conformal radiotherapy of prostate cancer with small fields. MATERIALS AND METHODS: 52 patients with prostate cancer were treated by conformal three- or four-field techniques with radical or adjuvant intent between November 1996 and March 1998. In total, 539 portal images were collected on a weekly basis for at least the first 4 weeks of the treatment on lateral and anterior 18 MV X-ray fields. The average number of sessions monitored per patient was 5.7 (range 4-10). All patients were immobilized with an alpha-cradle system; 25 of them were immobilized at the pelvis level (group A) and the remaining 27 patients were immobilized in the legs (group B). The shifts with respect to the simulation condition were assessed by measuring the distances between the same bony landmarks and the field edges. The global distributions of cranio-caudal (CC), posterior-anterior (PA) and left-right (LR) shifts were considered; for each patient random and systematic error components were assessed by following the procedure suggested by Bijhold et al. (Bijhold J, Lebesque JV, Hart AAM, Vijlbrief RE. Maximising set-up accuracy using portal images as applied to a conformal boost technique for prostatic cancer. Radiother. Oncol. 1992;24:261-271). For each patient the average isocentre (3D) shift was assessed as the quadratic sum of the average shifts in the three directions. RESULTS: Group B showed a better accuracy and reproducibility than group A for PA shifts (2.6 versus 4.4 mm, 1 SD), LR shifts (2.4 versus 3.6 mm, 1 SD) and CC shifts (2.7 versus 3.3 mm, 1 SD). Furthermore, group B showed a rate of large PA shifts (>5 mm) equal to 4.4% with respect to the 21.6% of group A (P<0.0001). This value was also better than the corresponding value found in a previously investigated group of 21 non-immobilized patients (Italia C, Fiorino C, Ciocca M, et al. Quality control by portal film analysis of the conformal radiotherapy of prostate cancer: comparison between two different institutions and treatment techniques (abstract). Radiother. Oncol. 1997;43(Suppl. 2):S16, 16.8%, P = 0.001). For both groups there was no clear prevalence of one component (systematic or random) with respect to the other. The average isocentre shifts (averaged on all patients) were 3.0 mm (+/-1.4 mm, 1 SD) for group B and 5.0 mm (+/-2.8 mm, 1 SD) for group A against a value of 4.4 mm (+/-2.4 mm, 1 SD) for the previously investigated non-immobilized patient group. CONCLUSIONS: Immobilization of the legs with an alpha-cradle system seems to improve both the accuracy and reproducibility of the positioning of patients treated for prostate cancer with respect to alpha-cradle pelvic-abdomen immobilization. Based on these data, we decided to use the legs immobilization system and to reduce the margin around the CTV (from 10 to 8 mm) in the PA direction.

Quality assurance by systematic in vivo dosimetry: results on a large cohort of patients.

BACKGROUND: In vivo dosimetry is widely considered to be an important tool for quality assurance in external radiotherapy. INTRODUCTION: In this study we report on our experience over more than 4 years in systematic in vivo dosimetry with diodes. MATERIALS AND METHODS: From November '94 an in vivo entrance dosimetry check was performed for every new patient irradiated at one of our treatment units (Linac 6/100, 6 MV X-rays). Diodes were calibrated in terms of entrance dose; appropriate correction factors had been previously assessed (taking SSDs, field width, wedge, oblique incidence and blocking tray into account) and were individually applied to in vivo diode readings. The in vivo measured entrance dose was compared with the expected one, with a 5% action level; if a larger deviation was found, all treatment parameters were verified, and the in vivo dosimetry check was repeated. During the period November '94-May '99, 2824 measurements on 1433 patients were collected. RESULTS: Nine out of 1433 (0.63%) serious systematic errors (leading to a 5% or more on the delivered dose to the PTV) were detected by in vivo dosimetry; four out of nine would produce a 10% or more error if not detected. The rate of serious systematic errors detected by an independent check of treatment chart and MU calculation was found to be 1.5%, showing that less than 1/3 of the errors escapes this check. One hundred and twelve out of 1433 (7.8%) patients had more than one check: the rate of second checks was significantly higher for breast patients (31/250, 12.4%) against non-breast patients (81/1183, 6.8%, P=0.003). A number of patients demonstrated a persistent relatively large error even after two or more checks. For almost all patients the cause of the deviation was assessed; the most frequent cause was the difficulty in correctly positioning the patient and/or the diode. When analyzing the distribution of the deviations between measured and expected entrance doses (excluding first checks in the case of repetition of the in vivo dosimetry control) the mean deviation was 0.4% with a standard deviation equal to 3.0%. The rates of deviations larger than 5 and 7% were 9.9 and 2.6%, respectively. When considering the same data taking the average deviation in the case of opposed beams, the SD became 2.6% and the rates of deviations larger than 5 and 7%, respectively, 5.2 and 0.8%. When dividing the beams according to their orientation, significantly higher rates of large deviations (>5 and 7%) were found for oblique and posterior-anterior (PA) fields against lateral and anterior-posterior (AP) fields (P<0.05). Similarly, higher rates of large deviations were found for wedged fields against unwedged fields (P<0.03) and for blocked fields against unblocked fields (P<0.01). When dividing the data according to the anatomical district, accuracy was worse for breast (mean deviation 0.1%, 1 SD: 3.5%) and neck AP-PA fields (mean deviation 1%, 1 SD: 3,4%). Better accuracy was found for vertebrae (0.1%, 1 SD 2. 1%) and brain patients (-0.7%, 1 SD: 2.6%). During the considered period, in vivo dosimetry was also able to promptly detect a systematic error caused by a wrong resetting of the simulator height couch indicator, with a consequent error in the estimate of patient thickness of about 4 cm. CONCLUSIONS: In our experience, systematic in vivo dosimetry demonstrated to be a valid tool for quality assurance, both in detecting systematic errors which may escape the data transfer/MU calculation check and in giving an effective way of estimating the accuracy of treatment delivery.

Autoimmune neutropenia after unrelated bone marrow transplantation.

A 26-year-old male with Ph+ chronic myeloid leukemia, recipient of an HLA-compatible marrow from a matched unrelated donor, showed good platelet engraftment coupled with poor neutrophil recovery. On day +33 the presence of surface-bound anti-neutrophil antibodies was detected by immunofluorescence. At variance with previously reported cases, the WBC count improved without any specific treatment, and the test became negative on day +42.

Big BU/CY is associated with a favorable long-term outcome in patients allotransplanted for chronic myelogenous leukemia in chronic phase.

Twenty-six adult patients, median age 36 years (range 21-53) with chronic myeloid leukemia in first chronic phase were allotransplanted between October 1989 and May 1995. The preparative regimen consisted of busulphan 16 mg/kg and cyclophosphamide 200 mg/kg (big BU/CY). Cyclosporin A and methotrexate were used for GVHD prophylaxis. Twenty-two donors were HLA-identical siblings and four donors were mismatched for one antigen of class I. The global incidence of acute GVHD was 50%, that of severe aGVHD (grades 3-4) was 11%; the global incidence of chronic GVHD was 30%. No patients developed veno-occlusive disease of the liver or interstitial pneumonia. Five patients died, one of relapse, four of transplant-related causes, mostly related to aGVHD; thus, the transplant-related mortality was 16%. Twenty-one patients are alive, in remission, with a median follow-up of 55 months (range 24-90); actuarial probability of survival is 78% (CI 64-96). Our study shows that this conditioning regimen is relatively easy to administer and seems to be as effective as, if not superior to, regimens containing TBI, in patients with chronic myeloid leukemia in chronic phase and the transplant-related mortality is not excessive even in older patients.

Double reinforcement with fludarabine/high-dose cytarabine enhances the impact of autologous stem cell transplantation in acute myeloid leukemia patients.

Reinforced chemotherapy based on a double high-dose consolidation regimen could be a different way to enhance in vivo purging prior to autologous stem cell transplantation (auto-SCT) in acute myeloid leukemia (AML). We investigated the impact on outcome of auto-SCT after two different strategies of early intensification performed after an identical induction regimen in adult patients with AML. Between January 1993 and December 1998, 140 consecutive AML patients were enrolled in a program consisting of an identical anthracycline-based induction (ICE) and two different consolidation regimens: one cycle, cytarabine-based (single-NOVIA: 91 patients); two cycles, fludarabine-based (double-FLAN: 49 patients). Seventy out of 91 patients received single-NOVIA consolidation: 60 underwent a transplantation procedure (allogeneic bone marrow transplantation (allo-BMT):16 patients; auto-SCT: 44). Thirty-five out of 49 patients received double-FLAN consolidation: 31 underwent a transplantation procedure (allo-BMT: 10; auto-SCT: 21). The double consolidation regimen was well-tolerated with only minor side-effects. Median follow-up observation time for surviving patients was 38 months (range, 17-71) for the double-FLAN consolidation group and 70 months (range: 48-93) for the single-NOVIA consolidation group. Among the patients who received auto-SCT, the double consolidation strategy produced a superior disease-free survival curve at 36 months (78.6% (95%CI: 59.4-97.8) vs 47.7% (95%CI: 33-62.4)) compared with the single-NOVIA group. This difference was confirmed when the patients were analyzed for intention to treat (P = 0.04). In addition, the double-FLAN consolidation group showed a superior overall survival and lower relapse rate (P = 0.02). We conclude that the double-FLAN reinforcement strategy is safe and enhances the clinical impact of auto-SCT for AML patients in first complete remission. It may provide specific clinical benefit for patients undergoing auto-SCT.

Effective autologous peripheral blood stem cell transplantation in plasma cell leukemia followed by T-large granular lymphocyte expansion: a case report.

We report a case of de novo plasma cell leukemia, resistant to standard VMD (vincristine, mitoxantrone, dexamethasone) and CVP (cyclophosphamide, vincristine and prednisone) protocols, treated with a chemotherapy intensification regimen (high-dose cyclophosphamide, modified EDAP, Dexa-BEAM) and peripheral blood stem cell transplantation, performed using fractionated total body irradiation and high dose melphalan. The patient is currently alive and well, in very good partial remission 12 months after transplant and 22 months after diagnosis, disclosing a significant proportion of bone marrow and peripheral blood CD3+, CD8+, CD57+, HLA-Dr+ large granular lymphocytes with cytotoxic activity against neoplastic plasma cells.

High-dose busulfan and cyclophosphamide are an effective conditioning regimen for allogeneic bone marrow transplantation in chemosensitive multiple myeloma.

The present clinical trial was undertaken to investigate the toxicity and antimyeloma activity of busulfan (BU) and cyclophosphamide (CY) at the maximum tolerated doses of, respectively, 16 mg/kg and 200 mg/kg (BU-CY 4) as conditioning therapy for allogeneic bone marrow transplantation (BMT) in 19 consecutive patients with multiple myeloma (MM). Twelve (63%) had failed to respond to prior chemotherapy, while the remaining 37% had chemosensitive disease. No life-threatening or fatal regimen-related complications were observed. The incidence of veno-occlusive disease of the liver was zero according to Jones' criteria and 21% according to McDonald's system. Transplant-related mortality was 37%. Using stringent criteria, the frequency of complete remission (CR) was 42% among all patients and 53% among those who could be evaluated. With a median follow-up of 21 months for all patients and 66 months for survivors, the actuarial probability of survival and event-free survival at 4 years from BMT was 26% (95% CI: 7-46) and 21% (95% CI: 3-39), respectively. A more favorable outcome of transplantation was observed in the subgroup of patients with chemosensitive disease who had a transplant-related mortality of 14%, an overall CR rate of 86% (95% CI: 49-97) and a 4-year projected probability of event-free survival of 57% (95% CI: 20-93). Four of these patients are currently alive in continuous CR after 54, 66, 80 and 94 months, respectively. It is concluded that BU-CY 4 as conditioning for allogeneic transplantation for MM is associated with acceptable morbidity and relatively low mortality. This regimen exerts substantial antimyeloma activity, resulting in a high CR rate and durable responses, especially in patients with chemosensitive disease. Long-lasting remission and probable cure is possible following allogeneic stem cell transplantation for MM.