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A pixel-segmented ionization chamber has been designed and built by Torino University and INFN. The detector features a 24 x 24 cm2 active area divided in 1024 independent cylindrical ionization chambers and can be read out in 500 micros without introducing dead time; the digital charge quantum can be adjusted between 100 fC and 800 fC. The sensitive volume of each single ionization chamber is 0.07 cm3. The purpose of the detector is to ease the two-dimensional (2D) verifications of fields with complex shapes and large gradients. The detector was characterized in a PMMA phantom using 60Co and 6 MV x-ray photon beams. It has shown good signal linearity with respect to dose and dose rate to water. The average sensitivity of a single ionization chamber was 2.1 nC/Gy, constant within 0.5% over one month of daily measurements. Charge collection efficiency was 0.985 at the operating polarization voltage of 400 V and 3.5 Gy/min dose rate. Tissue maximum ratio and output factor have been compared with a Farmer ionization chamber and were found in good agreement. The dose profiles have been compared with the ones obtained with an ionization chamber in water phantom for the field sizes supplied by a 3D-Line dynamic multileaf collimator. These results show that this detector can be used for 2D dosimetry of x-ray photon beams, supplying a good spatial resolution and sensibly reducing the time spent in dosimetric verification of complex radiation fields.

Tumor therapy takes advantage of the energy deposition of radiation to concentrate high doses in the target while sparing healthy tissue. Elective pathologies for highly conformal radiotherapies such as photon Intensity Modulated Radiotherapy (IMRT) and radiotherapy with hadrons are head and neck, eye, prostate and in general all tumors that are either deep or located close to critical organs. In the world there are several centers that are using such techniques and a common problem that is being experienced is the verification of treatment plans and monitoring of the beam. We have designed and built two detectors that allow 2D and 3D measurements of dose and fluence of such beams. The detectors allow measurements on big surfaces, up to 25∗25 cm2. The active media are parallel plate, strip and pixel segmented ionization chambers with front-end Very Large Scale Integration (VLSI) readout and PC based data acquistion. The description of dosimeter, chamber and electronics will be given with results from beam tests and therapy plan verification.

The precise application of proteins and other biomolecules to create patterned surfaces is an important step in many processes, including the creation of biosensors and directed cell growth for tissue engineering [1, 2]. While traditional poly-dimethylsiloxane (PDMS) elastomeric stamps have been used to successfully transfer proteins with sub-micron resolution, the resulting patterns are limited to a single, uniform protein concentration. The technique presented here utilizes varied-topography hydrophilic stamps as a diffusion medium, allowing protein gradients to be easily applied and accurately reproduced. Specifically, stamps of a 2% agarose hydrogel are used to demonstrate variable-concentration patterning of a fluorescently-labeled protein.Copyright © 2009 by ASME

The new radiotherapy techniques require new detectors to monitor and measure the clinical field. The Intensity Modulated Radiation Therapy (IMRT) techniques like step and shoot, sliding window, dynamic wedge or scanning beam add the time variable to the treatment field. In this case the water phantom with a single ionization chamber moving inside the field needs very long measurement time. Linear arrays of ionization chambers or diodes measure the field only along a line. 2D detectors like radiographic or gafchromic film are not suitable to be used as on line detectors. We have developed, built and tested an ionization chamber segmented in pixels that measure the dose in a plane at several points. Every channel has a dedicated electronic chain that digitizes the collected charge and data from all the channels are sent to the computer that performs the data acquisition. One read out cycle is very fast allowing to measure in real time the fluency and the shape of the field. The chamber can be used in two different ways, as monitor chamber and as relative dosemeter. A description of the detector, the electronics, and test results with both photon and hadron beams will be reported.

Twenty-seven consecutive Italian patients with Fanconi's anaemia (FA) underwent stem cell transplantation (SCT) from an HLA-matched related donor in 10 Italian centres of the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP), Gruppo Italiano di Trapianto di Midollo Osseo (GITMO). Twenty-two patients (81.5%) were conditioned with low-dose (median 20 mg/kg) cyclophosphamide (Cy) and thoraco-abdominal or total body irradiation (median dose 500 cGy), five patients (18.5%) with high-dose Cy (median 120 mg/kg). Graft-vs.-host disease (GVHD) prophylaxis was carried out with cyclosporin A in 26 cases; methotrexate (MTX) was added in eight cases. One patient received MTX alone. The median follow-up was 36 months. Ninety-two percent of patients (25 out of 27) engrafted, grade II and III acute GVHD occurred in 28% and 8% of patients, respectively, with chronic GVHD in 12.5%. Conditioning-related toxicity was mild: 4% of patients had grade III mucositis, 7.4% had grade II haemorrhagic cystitis, 14.8% had grade III liver toxicity and 11.1% had grade III renal toxicity. Transplant-related mortality at 12 months was 19.2%, survival at 36 months was 81.5%, with a median Karnofsky score of 100%. No late tumours occurred after a mean follow-up of the survivors of 5 years. None of the studied variables significantly affected the survival, including conditioning regimen, acute GVHD and clinical non-haematological phenotype. Among the studied variables, only conditioning regimens containing high-dose Cy and the presence of genital abnormalities were significantly (P0.05) associated with an increased rate of acute GVHD. Our study demonstrates that the Italian FA patients undergoing SCT from an HLA-matched related donor have a very good outcome. These patients, when compared with others of different ethnic origin who underwent allogeneic bone marrow transplantation, showed a less severe non-haematological phenotype, raising the possibility that this milder phenotype may have, at least in part, contributed to the outcome. Our data may provide a useful tool for further studies aiming to correlate genotype with phenotype.

The prevalence of seizures in children with acute lymphoblastic leukemia (ALL) varies between 3 and 13% depending on the various studies, whereas it is 1% in the general population aged under 15 years etiopathogenesis and outcome of seizures in children during treatment for ALL.A retrospective study was carried out in 204 children with a consecutive diagnosis of ALL, 89 females and 115 males, aged between 5 months and 17 years and 11 months, diagnosed between 15-4-1988 and 15-4-1998, and treated at the Division of Pediatric Oncology and Pediatric Hematology of Turin University using three successive generations of AIEOP protocols 88 (48 cases), 91 (86 cases) and 95 (70 cases). Observation of the patients in the study ended on 30-9-1998. The criteria for eligibility were those stated in the respective protocols. Seizures were classified using the international classification; the diagnosis was made if a doctor, a nurse or a reliable relative witnessed the event with confirmation by the consultant neurologist.Twelve out of 204 (5.8%) patients in this series presented seizures: 2 out of 48 cases using protocol 88 (4.1%), 6 out of 86 cases using protocol 91 (6.9%) and 4 out of 70 cases using protocol 95 (5.7%). None of the patients had critical episodes or other significant neurological pathologies prior to the onset of ALL, nor had they been affected by leukemic meningosis or undergone cranial radiotherapy. When evaluating the possible etiology, the authors noted that, except for one case of febrile convulsion, the seizures in the remaining patients could be attributed to the toxicity of chemotherapy. With regard to the evolution of seizures, only one patient died, whereas the others showed no neurologic sequelae.The frequency of seizures in children receiving treatment for ALL in the series analysed here is in line with that reported in the literature. Neurotoxicity caused by chemotherapy appears to be the main etiopathogenetic factor.

Sporting activities and periods of convalescence call for an added intake of nutrients in children. This study aimed to evaluate the effect of a natural vitamin supplement on diet, food intake, body composition and muscular strength in children during convalescence and in children practising sports.A comparative study was performed in two different groups of subjects: 20 children aged between 6 and 12 years old during convalescence following infections of upper airways, and 20 9-year-old children forming part of a football team. All subjects were randomly subdivided into two groups who were respectively given a vitamin supplement (Vitality Roeder 2000 Junior) or a placebo for 4 weeks. Weight, body composition using and muscolar strength using dynamometer measured before and after the study and a food diary was kept for 3 days before each visit.No significant differences in body mass and strength emerged from the data collected in the athletic group, whereas an increase was observed in appetite, calorie intake, weight and muscular strength in the convalescent group (p0.05). A significant increase in vitamin B12, B3, B5 and D levels was observed in both groups.The supplement to provides an adequate intake for those categories at risk of vitamin deficiency or in conditions of increased requirements.

Recurrences of malignant tumours in the chest wall are proposed as a valuable model of tissue mainly perfused by small size vessels (the so-called 'phase III' vessels). Invasive thermal measurements have been performed on two patients affected by cutaneous metastasis of malignant tumours during hyperthermic sessions. Thermal probes were inserted into catheters implanted into the tissue at different depths. In one of the catheters a probe connected with laser-Doppler equipment was inserted to assess blood perfusion in the tumour periphery. The perfusion was monitored throughout the sessions, and a noticeable temporal variability was observed. The effect of the perfusion on the thermal map in the tissue was evaluated locally and the 'effective conductivity' of the perfused tissue was estimated by means of the numerical integration of the 'bio-heat' equation. The tumour temperature, at the site where the perfusion probe is located, can be predicted by the numerical model provided two free parameters, alpha and beta, are evaluated with a fitting procedure. Alpha is related to the effective conductivity and beta to the SAR term of the bio-heat equation. The model aimed at estimating the 'effective conductivity' K(eff) of the perfused tissue, and average values of K(eff) of 0.27 +/- 0.03 W m(-1) degrees C(-1) in Patient 1 and of 0.665 +/- 0.005 W m(-1) degrees C(-1) in Patient 2 were obtained throughout the treatment. However, when the average temperature in a larger tumour volume is to be predicted but only a single, 'local' measurement of the perfusion is available and is assumed to be representative for the whole region, the model results are far less satisfactory. This is probably due to the fact that changes of blood perfusion throughout hyperthermic sessions occur to different extents within the tumour volume, and the differences in perfusion cannot be ignored. The above result suggests that, in addition to the 'temperature map', also a 'perfusion map' within the heated volume should be monitored routinely throughout hyperthermic sessions.

Purpose: The comparison of stereotactic treatments for small spherical and ellipsoidal intracranial lesions using three different collimators with single isocenter: the standard circular collimators and two dynamic multileaf collimators (DMLC) with 3 mm and 5 mm leaf thickness, micro and mini DMLC respectively. Method and Materials: Spherical and ellipsoidal lesions of different sizes were designed to evaluate treatments with collimators under consideration. For spherical lesions with diameter from 15 mm up to 35 mm a treatment with 9 arcs of 140 degrees was performed. For ellipsoidal lesions treated with circular collimators, different combinations of treatment variables were studied to achieve 80% isodose surface conformation: number of arcs, gantry start/stop angles, couch angles and arc spacing. This treatment was matched up to 9 arcs with the two DMLCs. For the comparison geometrical (penumbra, difference between the target volume and 80% isodose volume and conformal indexes) and radiobiological (EUD, TCP and NTCP) parameters were used. Results: Circular collimators and micro DMLC behave similarly with spherical targets in terms of conformal indexes and TCP/NTCP, but EUD and 20% isodose volume are greater for micro DMLC. In the case of ellipsoidal target TCP/NTCP are comparable, EUD is greater for micro DMLC but conformal indexes are higher for circular collimators. The 20% isodose volume is less with micro DMLC; the difference, however, is entirely due to the wider penumbra along the deformation axis with circular collimators. The same considerations are valid for targets with diameters ⩾ 35 mm, where mini DMLC becomes competitive versus circular collimator.Conclusion: The analysis shows that micro and mini DMLC are more functional for non spherical lesions. Circular collimators however are widely used and yield sharper dose fall off along directions perpendicular to the deformation axis and thus are preferable in the case of neighbourhood of organs at risk.

Age is an important prognostic factor in acute childhood lymphoblastic leukemia (ALL): intermediate age children (1-9 years) show a better outcome than infants (0-1 year) and adolescents (10-15 years). However recent literature data do not agree about adolescents worse prognosis. We tried to contribute to this issue with a retrospective analysis about presenting features and survival of 302 pediatric patients (65 adolescents and 237 children) with non B ALL enrolled on AIEOP protocols at the Departments of Pediatric Haematology-Oncology (University of Turin) from 1976 to 1992. The last follow up was 30.11.94. We found in adolescents, in spite of higher frequency of unfavourable prognostic factors (Hb8 g/dl, mediastinal mass, T cell immunophenotype, L2 morphology), an event free survival similar to children (EFS 52% vs 51%). In conclusion in our population we found that age at diagnosis greater than 10 years does not represent an unfavorable prognostic factor.

Multidrug resistance represents one of the most important factors that may lead to a therapeutic failure in some patients affected by malignancies. One of the best known mechanisms is linked to the genic amplification or the overproduction of a membrane glycoprotein, GP170, that is the product of the gene MDR1. The existence of drugs (calcium blockers, cyclosporine, tamoxifen, reserpine, quinidine) able to bind themselves to gp170 and to paralyze its activity in vitro is well known. We studied 20 pediatric patients (median age 9 years) affected by acute lymphoblastic leukemia (ALL), osteosarcoma, neuroblastoma and medulloblastoma, in advanced stage of disease. We employed in all cases the association of cytostatics with verapamil (50-70 mg/m2 i.v.) and cyclosporine (5-8 mg/kg i.v.) with different infusion schedules. In leukemias we administered vincristine (1.5 mg/m2), and daunomycin (40 mg/m2), in solid tumors VP16 (150 mg/m2) and adriamycin (60 mg/m2). Seventy-two therapeutic courses were performed: 39 in ALL, 16 in osteosarcoma, 16 in neuroblastoma and 1 in medulloblastoma. On the whole 5 complete remissions were achieved in ALL patients and 1 in an osteosarcoma patient. We did not observe a significant myelosuppression during treatment, therefore few infectious complications occurred; furthermore electrocardiographic changes have been mild and promptly resolved after temporary discontinuation of verapamil infusion. Our data suggest a synergy of verapamil and cyclosporine in the inhibition of multidrug resistance induced by gp170, without the occurrence of heavy toxicity. The results obtained in ALL patients are encouraging., especially in view of a possible subsequent bone marrow transplantation, while in solid tumors they are not as satisfying.

The case of a child treated for Acute Lymphoblastic Leukemia (LLA) with high-dose L-asparaginase, (HD L-ase) presented alteration who of lipidemic values (rise of total cholesterol and triglyceride values) without toxicity is described. This finding has previously been reported in only a few patients. Parameters normalized with dietetic regimen. The authors underline the importance of the control, in patient during HD L-ase treatment of lipidic values too, especially when parents also have similar alterations.

In 1982, the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) started its third-generation study, aiming to improve previous results obtained by AIEOP '79 study and to deliver a standardized treatment to most Italian children with acute lymphoblastic leukemia (ALL).We treated 902 children (older than 1 year and younger than 15 years of age) with newly diagnosed ALL in multicenter studies of risk-directed therapy (111 low risk [LR] from Study 8201; 570 average risk [AR] from Study 8202; and 117 and 104 high risk [HR] from Studies 8303 and 8503, respectively). Induction therapy was composed of vincristine, prednisone, and asparaginase for LR or AR patients and these agents plus daunorubicin, (Study 8503) or vincristine, prednisone, cytarabine, and intermediate-dose methotrexate (Study 8303) for HR patients. Central nervous system (CNS) preventive therapy consisted of intrathecal methotrexate only (LR), intrathecal methotrexate plus 18 Gy cranial irradiation (AR and HR Study 8503), or high-dose (HD) cytarabine (HR Study 8303). Reinduction therapy was vincristine/prednisone/daunorubicin for AR patients with cyclophosphamide added for HR patients in Study 8303 and HD asparaginase in Study 8503. LR patients did not receive intensification therapy. Continuation therapy comprised 6-mercaptopurine plus methotrexate and monthly pulses with vincristine plus prednisone for all patients, except for HR patients in Study 8303 who also received teniposide plus cytarabine. Weekly HD asparaginase was also given in Study 8503. Duration of treatment was 24 months for Studies 8201 and 8202, 15 months for Study 8303, and 22 months for Study 8503. The overall complete remission (CR) rate was 94.7% (97.3% for LR, 94.9% for AR, and 93.2% for HR).Overall 7-year event-free survival (EFS) was 53.6% (standard error [SE], 1.8). EFS was 60.8% in LR (SE, 4.7), 60.6% in AR at 7 years (SE, 4.7), and 18.5% in Study 8303 (HR) at 5 years (SE, 3.8). Because of the poor result in HR patients, a successor study (8503) was developed that yielded a 5-year EFS of 46.1% (SE, 5.1). Site-specific relapse rates were 18.5% (LR), 13.4% (AR), 35.1% (HR on 8303), and 18.3% (HR in Study 8503) for bone marrow and 9.2%, 7.9%, 17.5%, and 19.3%, respectively, for the CNS (isolated). Isolated testicular relapse was observed in 3.9% of male patients.This risk-directed therapy cured at least 50% of patients with ALL with relatively nonintensive therapy. The 80% overall survival rate for LR and AR patients at 7 years suggested that the total cure rate may be higher than 50% because of the significant salvage rate for patients who received antimetabolite-based therapy initially.

PURPOSE This study was conducted to assess the comparative values of allogeneic bone marrow transplantation (BMT) and autologous bone marrow transplantation (ABMT) with sequential postremission chemotherapy (SPC) in children with acute myelogenous leukemia (AML) in first remission. PATIENTS AND METHODS From March 1987 to March 1990, 161 assessable patients younger than 15 years of age with newly diagnosed AML were treated uniformly with two courses of daunorubicin and standard-dose cytarabine. After initial consolidation with a course of daunorubicin, cytarabine, and thioguanine (DAT), patients in complete remission (CR) were randomized to receive either ABMT or SPC, except for those with an HLA-matched sibling who were assigned to undergo BMT. SPC consisted of three additional courses of DAT, followed by three pairs of drugs administered sequentially for a total of six cycles. RESULTS Overall, 127 of 161 patients attained CR (79%). The estimated probabilities of survival and event-free survival (EFS) at 5 years for all patients were 42% and 25%, respectively (median follow-up, 28 months). For the 127 complete responders, the 5-year probability of disease-free survival (DFS) was 31%, with a cumulative risk of relapse of 64%. For the purpose of this study, all complete responders were evaluated for analysis of disease outcome according to the intent-to-treat principle, regardless of whether they actually received the intended therapy. The 5-year DFS was 51% for the BMT group (n = 24), significantly higher (P = .03) than that observed for the other cohorts: 21% for ABMT (n = 35), 27% for SPC (n = 37), and 34% for a group of 31 nonrandomized (NR) patients. Bone marrow relapse was the most frequent cause of postremission failure in all therapeutic subgroups, including the BMT cohort, in which no deaths attributable to the toxicity of the procedure were recorded. CONCLUSION The results of this study show that BMT is more effective than ABMT or SPC in preventing leukemia relapse and extending DFS duration in children with AML in first remission.

The high number of cord blood (CB) hematopoietic progenitors made possible CB transplantation in children with hematologic diseases. We collected and cryopreserved CB from siblings of 11 hematologic pediatric patients for possible transplant. The number of BFU-E+CFU-GEMM and CFU-GM was adequate for engraftment. However the possibility of CB transplantation in adolescents and adults is limited by the amount of CB that can be collected. We studied the possibility of expanding the pool of CB hematopoietic progenitors by preincubation of CB CD 34+ cells with several cytokines. After pre-exposition to rhIL-3, IL-1 beta, rIL-6, GM-CSF and stem cell factor (SCF) and cloning with SCF the number of hematopoietic progenitors increased 14-18 fold compared to basal values.

A fast and precise detector to monitor on-line the dose delivered by an active scanning therapeutical beam has been built and tested.

Only in these latest years has been possible to consider Hodgkin disease (HD) as a neoplastic syndrome, thank of immunohistochemistry and cytogenetic techniques which have confirmed the monoclonal origin of typical cellular marker of disease: the Reed-Sternberg cell (R-S cell). Interesting associations have been observed between children suffering from HD and the positivity of EBV antigen above all in the socio-economically developed countries. The histopathologic classification of HD is divided in four sub-types, with different incidence in the pediatric age: the nodular sclerosis and the mixed cellularity are more rap-presented than the lymphocyte predominance and mostly the lymphocyte depletion. Histopathologic classification is essential for the prognosis and a correct therapeutic approach to disease. The management of HD is based on chemotherapy and radiotherapy associated; the results of treatment are more and more encouraging with a global survival over 95%. Sequelae of treatment are reduced in modern therapeutic trials: in particularly injury to somatic growth, cardiopulmonary system, gonadal and thyroid functionality is reduced by using low dose and involved fields for the early stage patients. The most important sequela in children treated for HD is the risk to developed a second malignant neoplasm; in particularly acute nonlymphocytic leukemia and non Hodgkin's lymphoma. In patients treated with radiotherapy alone increase the risk to develop solid tumors like sarcomas and carcinomas, which can appears several years after diagnosis.

The development of Hyperthermia as a therapeutic method is closely related to the possibilty to control and quantify hyperthermic treatment in the portion of a biological body heated. For this purpose, the thermometer would have resolution and precision between 0.1°C and 0.2°C, because of the great dependence of the biological response to the temperature increase; suitable spatial resolution, between 5 and 10 mm, cause of the necessity to work in large temperature gradients; ability to follow the temporal variations of temperature with a temporal resolution of 1 second and a dimensions below 16 gauge to minimize trauma for patients. Actually the thermometry system used in the routine consist of thermistors, thermocouples and optical fibers. All these system are invasive: they give punctual temperature measurements in the whole tissue area and are traumatic for the patient.To avoid these disadvantages in our institute two non invasive methods have been tested: they’re a microwave radiometer, which measures the emitted intensity of bodies, that is directly related to their temperature and a simulation program, which calculates the temperature behavior of an heated tissue by the solution of the bio-heat equation. The results of our tests show that the thermometric technique, based on radiometer, gives temperature measurements that are to be considered as a mean among the ones obtained in the whole tissue area and not global at all; on the other hand the calculation of the heat produced by metabolism and over all of the heat taken away by the blood flow. With the intent to verify the goodness of the program we have simulated 22 hyperthermic treatments comparing the real temperature, obtained by optical fibers inserted in the tissue area during heating, with the simulated one. In parallel it was made a comparison between invasive measurements, with optical fibers, and non invasive ones, revealed by radiometer.

The study pf physical and geometrical factors influencing dose distribution is necessary in performing the Total Skin Electron Therapy. The authors examined some aspects. Photographic emulsions in humanoid phantom were used for dosimetry. The techniques uses 6 dual fields at 320 cm treatment distance, with a degrading lucite filter 100 x 200 x 0.6 cm3 at 20 cm from the patient. Absorbed dose and energy were determined according TG 30 and 21 AAPM. The position of degrading filter was recognized to be the main factor influencing dose rate, penetration depth and dose homogeneity.

Over the past decade there have been significant advances in the treatment of acute myelogenous leukemia (AML). The introduction of intensive induction and post-remission chemotherapy programs, together with the improvement in supportive care, have resulted in a probability of long-term survival in 30%–50% of children with AML [1–4]. In 1982 the AIEOP (Italian Pediatric Hematology-Oncology Association) cooperative group began a multicenter prospective trial for pediatric AML in order to establish the value of a polychemotherapeutic regimen consisting of intensive induction followed by intensive consolidation and continuation chemotherapy.

Individuals with constitutional trisomy 21 (Down syndrome) are at increased risk of developing acute leukaemias, both of myeloid and lymphoid lineage. Although the cause of leukaemia in Down syndrome (DS) remains unknown, potential candidate genes include the ones on chromosome 21, and in particular AML1, the rearrangement of which in the t(8,21) is associated with the French-American-British (FAB) classification M2 subtype of acute myeloid leukaemia (AML) in the general population and has been described in Down patients with AML-M2. Recently, a new rearrangement involving AML1, the t(12;21), producing the TEL/AML1 hybrid transcript, has been described by molecular analysis as the most recurrent genetic lesion in childhood acute lymphoblastic leukemia (ALL). In order to investigate whether the t(12;21) could give a molecular clue as to the precise basis of the etiologic association between DS and acute lymphoblastic leukemia, we tested a series of 11 consecutive cases of ALL in DS children for the presence of the TEL/AML1 transcript, by RT-PCR analysis. We report absence of the TEL/AML1 rearrangement among the 11 cases tested. This data may be suggestive of alternative pathways involved in the pathogenesis of ALL in children with constitutional trisomy 21.

Hemostatic changes in 20 children with acute lymphoblastic leukemia (ALL) who were induced with L-asparaginase (L-asp), vincristine (VCR), and prednisone (PDN) (Group A) were prospectively evaluated. These data were compared with those of a previous group of ALL patients who received L-asp as a single agent during consolidation (Group B). In Group A patients, mean plasma antithrombin activity decreased in the first 2 weeks, though not significantly. Relative to pretreatment values, mean fibrinogen concentration diminished particularly by week 3 (p less than 0.001). Activated partial thromboplastin time (APTT) decreased in the last week as well as after cessation of therapy with L-asp (p less than 0.05). Mean platelet count increased significantly by week 3 (p less than 0.05). Thromboelastograms performed in seven patients confirmed the tendency for thrombosis evidenced by a decreased APTT. Patients in Group B (L-asp alone during consolidation) had decreased concentrations of fibrinogen, AT, and Factors IX and X after L-asp therapy. APTT was prolonged. Our data demonstrate that the tendency for thrombosis is the predominant manifestation of L-asp induced coagulopathy, when the drug is associated with VCR and PDN. Thus the risk/benefit ratio for the use of L-asp early in induction in children with low risk ALL needs to be further evaluated.

Clinical experience demonstrates that a number of human tumors show a high response rate to aggressive chemotherapy regimens (1–2).

Haemostatic changes induced with vincristine (VCR), prednisone (PDN) and L-asparaginase (L-ase) in 53 children with ALL were prospectively evaluated. Relative to pretreatment values, mean FG concentration diminished significantly in the first week with a minimal level in the third week and PT was prolonged during the first weeks of induction. APTT decreased significantly in the last week and after cessation of L-ase therapy. Mean concentration of factor VIII remained elevated during the entire period of L-ase therapy. Three children (5.6%) developed a cerebral thrombo/haemorrhagic complication. These data demonstrate that the tendency for thrombosis is the predominant clinical manifestation of L-ase-induced coagulopathy, when the drug is associated with VCR and PDN.

A total of 17 pediatric patients with pretreated acute lymphoblastic leukemia were included in a phase II study of idarubicin. Four of 16 complete remissions were obtained, confirming the activity of the drug in this indication. Toxicity was acceptable, though caution is needed in patients who have already received high cumulative doses of anthracyclines.