Identification of prognostic factors predicting outcome in Hodgkin's lymphoma patients relapsing after autologous stem cell transplantation.

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT. METHODS: Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed. RESULTS: Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure. CONCLUSION(S): Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches.

Successful tigecycline lock therapy in a Lactobacillus rhamnosus catheter-related bloodstream infection.

INTRODUCTION: Catheter-related bloodstream infections very often involve the premature removal of long-term intravascular devices (LTID). The antibiotic lock therapy (ALT) represents a conservative approach to the treatment of uncomplicated infections of tunneled LTID when catheter removal is not a feasible option. CASE REPORT: We present here the first reported case of tunneled LTID bloodstream infection due to a multidrug resistant Lactobacillus rhamnosus. The patient, who had large granular lymphocytic leukemia, was successfully treated with systemic tigecycline therapy and lock therapy. CONCLUSION: Our results confirm ALT as a valid catheter-salvage strategy for the treatment of CRBSIs in clinically stable patients when catheter removal is not a feasible option, tigecycline appear to be a good option.

The HSE indicator tool, psychological distress and work ability.

BACKGROUND: The Health and Safety Executive (HSE) indicator tool is one of the most commonly used tools for assessing the risk of work-related stress. Few studies, however, have investigated whether and how its scales are related to psychological distress or other work-related health outcomes. AIMS: To investigate the relationship between the HSE indicator tool, psychological distress, as measured by the General Health Questionnaire (GHQ)-12, and work ability, assessed by the Work Ability Index (WAI). METHODS: All the employees of a mid-sized bank in Italy were asked to fill in an anonymous cross-sectional questionnaire. The questionnaire was structured in four sections: the first one comprised socio-demographic questions and the other three corresponded, respectively, to the Italian translations of the GHQ-12, the HSE and the WAI questionnaires. RESULTS: Four hundred and thirteen employees completed the questionnaire. The response rate was 99%. Controlling for age and gender, the indicator subscales were negatively associated with the adopted measures of psychological distress and work ability. The GHQ score was also highly correlated with the WAI score and able to explain ≈ 47% of its variance. The only subscale that was still significantly associated with the WAI after removing the effect of psychological distress was 'control'. CONCLUSIONS: The study presents new evidence for the validity of the HSE indicator tool to estimate the risk of work-related stress and suggests that most but not all the effects of psychosocial conditions on work ability might be mediated by the level of psychological distress induced by these conditions.

Autologous stem cell transplantation improves microcirculation in systemic sclerosis.

BACKGROUND: In systemic sclerosis (SSc) reduced capillary density decreases blood flow and leads to tissue ischaemia and fingertip ulcers. Nail fold videocapillaroscopy (NVC) is a diagnostic and follow-up parameter useful to evaluate the severity, activity and the stage of SSc microvascular damage. Autologous haemopoietic stem cell transplantation (HSCT) is a new treatment for patients with severe diffuse cutaneous systemic sclerosis (dcSSc) refractory to conventional therapies. We aimed to evaluate the improvement of microvasculature after HSCT using NVC. METHODS: A total of 16 patients with severe dcSSc with a "late" videocapillaroscopy pattern underwent an immunesuppressive treatment: 6 were treated with HSCT and 10 with monthly pulse cyclophosphamide (CYC) 1 g for 6 months and then orally with 50 mg/day for further 6 months. NVC was performed before and after 3 months from the beginning of each treatment and then repeated every 3 months. RESULTS: In all patients, before HSCT NVC showed large avascular areas and ramified capillaries and vascular architectural disorganisation ("late" pattern). At 3 months after HSCT, the NVC pattern changed from "late" into "active", showing frequent giant capillaries (>6/mm) and haemorrhages, absence of avascular areas and angiogenesis phenomena; 1 year after HSCT, microvascular abnormalities were still in the "active" pattern. In patients treated with CYC, no NVC modifications were observed during 24 months of follow-up and the pattern always remained "late". CONCLUSIONS: These results indicate that HSCT with a high dose CYC regimen may foster vascular remodelling, while CYC at lower doses and with a chronic regimen does not influence the microvasculature.

Effect of salt addition on sous vide cooked whole beef muscles from Argentina.

Sodium chloride (NaCl, 0-1.4%) and sodium tripolyphosphate (STPP, 0-0.5%) were added to Semitendinosus muscles and submitted to sous vide cooking at different temperatures (55-75°C). The effects of these three factors on pH, cooking loss, instrumental colour parameters, protein solubilization and distribution, and micro- and ultra-structure were evaluated. Quadratic surface responses equations were obtained from data (pH, cooking loss and colour parameters) as a function of the salts concentrations and cooking temperature. Both salts - alone or in combination - successfully reduced cooking loss. The best results were obtained for the combinations 0.25%STPP+1.20%NaCl and 0.25%STPP+0.70%NaCl, and temperatures between 60 and 65°C. Under these conditions, cooking loss was reduced close to 0%. pH was only dependent on STPP concentration, with a threshold concentration value of 0.25%. Temperature increment and NaCl addition produced a redness reduction. STPP incorporation recovered partially this parameter in comparison to non-added samples. Microscopy and SDS-PAGE results support the effect of the selected combinations of factors, suggesting that both salts together induced protein solubilization and gelation upon heating.

'Real-life' report on the management of chronic GvHD in the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

Several guidelines have been published about management of chronic GvHD (cGvHD), but the clinical practice still remains demanding. The Gruppo Italiano Trapianto di Midollo Osseo (GITMO) has planned a prospective observational study on cGvHD, supported by a dedicated software, including the updated recommendations. In view of this study, two surveys have been conducted, focusing the management of cGvHD and ancillary therapy in cGvHD, to address the current 'real life' situation. The two surveys were sent to all 57 GITMO centers, performing allografting in Italy; the response rate was 57% and 66% of the interviewed centers, respectively. The first survey showed a great disparity especially regarding steroid-refractory cGvHD, although extracorporeal photo-apheresis resulted as the most indicated treatment in this setting. Another challenging issue was the strategy for tapering steroid: our survey showed a great variance, and this disagreement could be a real bias in evaluating outcomes in prospective studies. As for the second survey, the results suggest that the ancillary treatments are not standardized in many centers. All responding centers reported a strong need to standardize management of cGvHD and to participate in prospective trials. Before starting observational and/or interventional studies, a detailed knowledge of current practice should be encouraged.

Decision analysis of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome stratified according to the revised International Prognostic Scoring System.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Crucial questions in clinical decision-making include the definition of optimal timing of the procedure and the benefit of cytoreduction before transplant in high-risk patients. We carried out a decision analysis on 1728 MDS who received supportive care, transplantation or hypomethylating agents (HMAs). Risk assessment was based on the revised International Prognostic Scoring System (IPSS-R). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of different treatment policies on survival. Life expectancy increased when transplantation was delayed from the initial stages to intermediate IPSS-R risk (gain-of-life expectancy 5.3, 4.7 and 2.8 years for patients aged ⩽55, 60 and 65 years, respectively), and then decreased for higher risks. Modeling decision analysis on IPSS-R versus original IPSS changed transplantation policy in 29% of patients, resulting in a 2-year gain in life expectancy. In advanced stages, HMAs given before transplant is associated with a 2-year gain-of-life expectancy, especially in older patients. These results provide a preliminary evidence to maximize the effectiveness of allo-SCT in MDS.

Sex differences in the hilar mossy cells of the guinea-pig before puberty.

Numerous sex differences have been detected in the morphology of the dentate and hippocampal neurons and hippocampus-dependent memory functions. The aim of the present study was to ascertain whether the mossy cells, an interneuron population forming a recurrent excitatory circuit with the dentate granule cells, are sexually dimorphic. The brains of juvenile (15-16 days old) and peripubescent (45-46 days old) male and female guinea-pigs were Golgi-Cox stained. Mossy cells were sampled from the hilus in the septal third of the dentate gyrus and their dendritic tree and somata were analyzed. The analysis was separately conducted on mossy cells with soma located in the portions of the hilus that face the upper blade (upper hilus) and lower blade (lower hilus), respectively. The mossy cells in the upper hilus were found to be sexually dimorphic in both juvenile and peripubescent animals. At both ages females had a larger dendritic tree than males. This difference was due to a greater mean branch length and, in peripubescent animals, also to a greater number of branches. In juvenile males, the spines on the proximal dendrites (thorny excrescences) had a greater density than in females. No differences in spine density were present in peripubescent animals. Unlike the mossy cells in the upper hilus, the mossy cells in the lower hilus showed very few sex differences in juvenile animals and no differences in peripubescent animals. The few differences favored females, that had more proximal branches and a greater spine density on the distal dendrites than males. The results show that the mossy cells of the guinea-pig are sexually dimorphic prior to puberty. Extending a previous investigation, the present data provide evidence that sex differences are mainly confined to the dentate region corresponding to the upper blade and upper hilus. The observed segregation of the sexual dimorphism in the upper blade/upper hilus suggests that this region might underlie the sexual dimorphism in hippocampus-dependent memory functions.

Epstein-Barr virus-associated post-transplant lymphoproliferative disease with central nervous system involvement after unrelated allogeneic hematopoietic stem cell transplantation.

Post-transplant lymphoproliferative disorders (PTLD) represent an heterogeneous group of abnormal lymphoid proliferation related to Epstein-Barr virus (EBV) reactivation that arise early after allogeneic hematopoietic stem cell transplant (HSCT). PLTD with central nervous system (CNS) involvement has been reported in few cases. We describe the case of a 31-year-old-man who developed an EBV-related PTLD with CNS involvement 2 months after an allogeneic unrelated HSCT for acute myeloid leukemia in first complete remission who was successfully treated with rituximab, cidofovir and intrathecal infusion of methotrexate and methylprednisolone.

Sex differences in the stereological parameters of the hippocampal dentate gyrus of the guinea-pig before puberty.

Studies in rats and mice have shown several sex-dependent functional and structural differences in the hippocampal region, a brain structure playing a key role in learning and memory. The aim of the present study was to establish whether sex differences exist prior to puberty in the stereological parameters of the dentate gyrus in the guinea-pig, a long-gestation rodent, whose brain is at a more advanced stage of maturation at birth than the rat and mouse. The number of granule cells and volumes of the granule cell layer, molecular layer and hilus were evaluated in Nissl-stained brains of neonatal (15-16 days old) and peripubescent (45-46 days old) guinea-pigs. Based on a pilot study, the optical disector method was preferred to the optical fractionator method to estimate cell number. For volume (Vref) estimation with the Cavalieri principle, contour tracing was preferred to the point counting method, as the latter appeared to underestimate volumes. The results showed that neonatal males had more granule cells than females in both the dorsal and ventral dentate gyrus and a larger volume in all layers. Peripubescent males had a larger volume of the granule cell layer than females in both the dorsal and ventral dentate gyrus, more granule cells in the ventral dentate gyrus, a larger volume of the hilus in both the dorsal and ventral dentate gyrus and a larger volume of the molecular layer in the ventral dentate gyrus. The results show that sex differences are present in the guinea-pig dentate gyrus prior to puberty and go in the same direction at both investigated ages, with males exhibiting more granule cells and larger volumes than females. The widespread distribution of these sex differences suggests that in the guinea-pig, similarly to other rodents, hippocampus-dependent functions may be sexually dimorphic.

Stimulation of erythroid engraftment by recombinant human erythropoietin in ABO-compatible, HLA-identical, allogeneic bone marrow transplant patients.

Recombinant human erythropoietin (rhEpo) was given i.v. at a dose of 50 U/kg/tid to eight patients undergoing an HLA-matched, ABO-compatible bone marrow transplantation (BMT), from day +1 up to day +30. Compared to the data recorded in 13 similar BMT patients who had not received the hormone, the administration of rhEpo resulted in a faster erythroid engraftment: in fact, the time required to reach a stable hematocrit value greater than or equal to 35% decreased from 123.0 to 58.0 days after BMT. Moreover, the number of blood reticulocytes on day +21 was about fourfold greater in the rhEpo group than in the controls, while the number of the most immature, high RNA content reticulocytes (HFR), as determined by a flow cytometric technique, was more than sixfold greater; finally, the recovery time of both total and HFR reticulocytes was significantly reduced by rhEpo. The stimulation of erythroid progenitors also resulted in a reduction in red blood cell (RBC) transfusion requirements: the number of RBC units delivered in the first 30 days following BMT decreased from 8.1 in the controls to 4.0, while the total number of RBC units before transfusion independence was about threefold lower than in the control. Finally, the time of transfusion dependence was significantly shortened by rhEpo. No clinically significant adverse effect directly attributable to rhEpo was recorded. These data suggest that the administration of rhEpo may be beneficial in hastening erythroid engraftment, and possibly in reducing RBC transfusion requirements following BMT.

Allogeneic stem cell transplantation.

Allogeneic stem cell transplantation (HSCT) requires the harvest of an adequate number of stem cells (SC) from a histocompatible donor and their infusion into a patient following a conditioning regimen. During the past 35 years, the role of HSCT has changed from an experimental procedure for terminally ill patients to a curative treatment. In 2003, 1170 procedures were registered in Italy (Italian Group for Blood and Marrow Transplantation). The main reported indications were as follows: leukemia, lymphoproliferative diseases, myelodysplasia, and nonmalignant diseases such as thalassemia and severe aplastic anemia. Important changes have been observed in the last 5 years: the shift from bone marrow to peripheral blood as the SC source, the increasing number of alternative donors such as unrelated, partially matched family donors and cord blood SC, and the new extra-hematological indications including solid tumors. Moreover, the development of nonmyeloablative conditioning regimens have allowed physicians to perform HSCT in patients with advanced age or important comorbidities. In contrast, the availability of the Tyrosine kinase inhibitor (STI-571) for treatment of patients affected by chronic myelogenous leukemia, which was formerly the main indication for HSCT, has produced a dramatic decrease in the number of transplantations in this setting. HSCT performed in the early phases of disease and in young patients offers more than a 50% cure rate. The transplant-related mortality still represents the greatest obstacle, ranging from 20%-30%, despite the less toxic conditioning regimens, high-resolution HLA typing, and better supportive care. GvHD and infections remain the main causes of morbidity. As regards relapses, they correlate with disease status at the time of transplantation. Promising results have been recently obtained with haploidentical and with cord blood SC transplantation also in adult patients.

[The treatment of diffuse cutaneous systemic sclerosis with autologous hemopoietic stem cells transplantation (HSCT): our experience on 2 cases]. / Trattamento della forma diffusa di sclerosi sistemica con trapianto autologo di cellule staminali emopoietiche: esperienza su due casi.

OBJECTIVES: Autologous hematopoietic stem cell transplantation (HSCT) is a treatment option which may be considered for severe diffuse cutaneous systemic sclerosis (dcSSc) patients not responding to cyclophophamide (CY). We present two cases of dcSSc not responding to CY >10 g who were successfully treated with HSCT. PATIENTS AND METHODS: Two dcSSc patients were unresponsive to monthly i.v. pulse of CYC (0.75 g m²). Both patients had significant reduction of DLCO and mild-moderate pulmonary hypertension and HSCT was considered due to the rapid progression of the disease. Following informed consent and ethics committee approval, HSCT was performed. Mobilisation was performed with CY 4 g/m² and recombinant human granulocyte colony stimulating factor (rHu GCSF) followed by a successful apheresis (CD34+ cells, >7X106). Conditioning regimens were: CY 100mg/kg body weight plus thiotepa 10 mg/ kg in the first patient and CY 200 mg/kg in the second. Both graft products were CD34 selected. No arrhythmias occurred during the procedure and no other severe side effects were observed during hospitalisation. RESULTS: Follow up: Patients underwent a monthly follow up with physical examination, pulmonary function tests and echocardiography every 3 months. Chest CT has been performed 6 months post transplantation. The following was observed: skin score (from 40 to 10 for the first patient and from 38 to 12 for the second one), LVEF and pulmonary function remained stable, PAP decreased from 45 mmHg to 35 mmHg and from 40 to 32 mmHg. No late complications or cardiac toxicity was observed. CONCLUSION: These two dcSSc cases demonstrate that HSCT may be successfully performed without serious side effects in cases in whom despite a cumulative CY dose was ineffective. This suggests an "immunological threshold" effect which may be exploited in other severe, therapy refractory autoimmune cases.

Circulating CFU-E during hematopoietic recovery after allogeneic bone marrow transplantation: relationship to erythroid engraftment.

The more mature erythroid progenitor assayable in vitro, the colony-forming unit-erythroid (CFU-E), is normally found in the bone marrow (BM) but is virtually absent from peripheral blood (PB), unlike the more immature progenitor, the burst-forming unit-erythroid (BFU-E). We report on the detection of CFU-E in the PB of six of 18 patients during hematopoietic recovery following allogeneic bone marrow transplantation (BMT); three of six patients with PB CFU-E were under treatment with recombinant human erythropoietin (rhEpo) as well as six of 12 who did not present with PB CFU-E. PB CFU-E were found as early as day 14 following BMT, reached a peak on day 28, and were still detectable on day 60. The presence of PB CFU-E was associated with signs of stimulated erythroid engraftment--an accelerated reticulocyte recovery, an increased number of reticulocytes, higher levels of serum transferrin receptor, and a reduction in transfusional requirements were found in these patients compared to those without PB CFU-E. The numbers of PB and BM BFU-E were similar in the two groups, as well as the numbers of PB and BM CFU-granulocyte/macrophage (CFU-GM) and multipotential CFU (CFU-GEMM); on the other hand, the percentage of BM BFU-E in S phase of the cell cycle was higher in the group of patients with PB CFU-E. While there was no difference between the two groups in serum Epo levels assayed on days 14 and 28 after BMT, patients with PB CFU-E had higher Epo levels in serum samples collected before starting the BMT procedure. These data suggest that the appearance of circulating CFU-E early after BMT is characteristic of a group of patients with an accelerated erythroid engraftment, although the mechanisms leading to the circulation of CFU-E after BMT remain unclear.

Retinal pigment epithelium function in alopecia areata.

Electroretinography (ERG) and electro-oculography (EOG) were performed in 98 patients affected by alopecia areata (AA) free from ophthalmologic disorders, and in 40 healthy subjects, in order to evaluate whether or not the retinal pigment epithelium of AA patients shows bioelectrical changes. ERG was normal. EOG, on the contrary, showed a significantly depressed mean value in the AA patient group. Furthermore, depressed EOG occurred more frequently in patients affected by alopecia totalis or universalis as compared with multiple patchy alopecia. These findings prompt the authors to believe that the melanocytes may play a prominent part in the pathogenesis of AA.

Effects of early environment on pyramidal neuron morphology in field CA1 of the guinea-pig.

We previously demonstrated that early isolation has profound effects on the morphology of the dentate granule cells and field CA3 pyramidal neurons. Aim of the present study was to analyze the effects of early environment on the morphology of field CA1 pyramidal neurons, the third element of the hippocampal trisynaptic circuit. The dendritic trees and the soma of field CA1 pyramidal neurons were quantified in Golgi-stained brains of guinea-pigs of both sexes raised in either a social or an isolated environment. Based on the different pattern of the apical dendritic tree two major classes of CA1 pyramidal neurons were recognized (monotufted neurons and bitufted neurons). In males isolation induced in both neuron types a decrease in the number of low order apical branches but in the apical tree of the monotufted neurons isolation induced an increase in the number of intermediate order branches and dendritic length. In isolated females the apical tree of the monotufted neurons showed a very scarce atrophy. In contrast, the apical tree of the bitufted neurons from isolated females showed a decrease in the number of low and intermediate order branches and dendritic length. In isolated males the basal tree of the bitufted neurons had a large decrease in the total number of branches and dendritic length. In contrast, in isolated females the basal tree of both neuron types showed an increase in the number of low order branches. In males but not in females isolation caused a reduction in the soma dimensions of both neuron types. No isolation-induced changes were observed in dendritic spine density in either the apical or basal dendrites. The results demonstrate remarkable structural changes in CA1 pyramidal neurons following early isolation and a different reactivity to environment of the two CA1 pyramidal neuron types, their apical and basal trees and the two sexes. The neuroanatomical changes caused by isolation in field CA1 and in the two other elements of the trisynaptic circuit are likely to be associated with changes in the physiology of the hippocampal formation and in cognitive processes such as learning and memory in which the hippocampal formation plays a pivotal role.

Sex differences in the hippocampal dentate gyrus of the guinea-pig before puberty.

The aim of the present research was to ascertain the presence of sex differences in the hippocampal dentate gyrus of the guinea-pig, a long-gestation rodent which gives birth to mature young and whose brain is at a more advanced stage of maturation at birth than that of the rat and mouse. The brains of neonatal (15-16 days old) and prepubescent (45-46 days old) male and female guinea pigs were Golgi-Cox stained. Granule cells were sampled from the upper (suprapyramidal) and lower (infrapyramidal) blade of the septal dentate gyrus and their dendritic tree and soma were measured. The analysis was conducted separately on granule cells with soma in the superficial (superficial granule cells) and deep (deep granule cells) half of the granule cell layer. Numerous sex differences were found in the upper blade of the dentate gyrus. Neonatal males had more dendritic branches than females in the innermost dendritic tree of both superficial and deep granule cells, but females had more branches over the middle/outer dendritic tree and a longer dendritic length. In prepubescent animals, the sex difference in the middle dendritic tree of the superficial granule cells changed direction, with males having more branches than females. In the deep granule cells, the sex differences were similar to those in neonatal animals. In both granule cell types, the dendritic length was similar in the two sexes. While no sex differences were found in dendritic spine density in neonatal animals, in prepubescent animals spine density was greater in females. In the lower blade the granule cells showed very few sex differences in both neonatal and prepubescent animals. This study shows wide dynamically changing sex differences in the granule cells located in the upper blade of the septal dentate gyrus, but almost no differences in the lower blade. These results demonstrate that sex differences are not ubiquitous in the dentate gyrus and suggest that the lower blade, unlike the upper blade, might be involved in non-sexually dimorphic behaviors.

Monitoring of polyomavirus BK viruria in bone marrow transplantation patients by DNA hybridization assay and by polymerase chain reaction: an approach to assess the relationship between BK viruria and hemorrhagic cystitis.

An association between long-lasting hemorrhagic cystitis (HC) in bone marrow transplantation (BMT) patients and viral infections, mostly with reactivation of the human polyomavirus BK (BKV), is suggested by several previous reports. We have carried out a prospective study in 55 (30 allogeneic, 24 autologous, 1 syngeneic) BMT recipients with the aim of evaluating the role of BKV in this frequent complication after BMT. To overcome the well known difficulties in BK virus isolation in cell cultures, a DNA hybridization assay and the polymerase chain reaction (PCR) were used for the detection and monitoring of viral urinary shedding, respectively. The presence of human polyomavirus JC and adenovirus DNA was also sought in urine specimens. BK viruria was demonstrated in 52.7% of patients (in 53.3% allogeneic and in 54.1% autologous BMT), whereas JCV and adenovirus were seldom present. Seven cases of HC (20% in allogeneic and 4% in autologous BMT) occurred and in all cases the clinical event was associated with BKV urinary shedding. This study suggests that BKV infection alone does not invariably lead to HC in BMT patients; for HC to occur the presence of other, at present unidentified, factors seems to be necessary.

Serum erythropoietin levels in patients undergoing autologous bone marrow transplantation.

Serum erythropoietin (sEpo) levels were serially measured with a radioimmunoassay in 14 patients undergoing autologous bone marrow transplantation (BMT), starting before the institution of the conditioning regimen up to day +45. An increase in sEpo levels was observed soon after starting the chemotherapy regimen, and before an evident fall in hemoglobin (Hb) levels took place. The peak in sEPo levels (221 +/- 181 mU/ml) was reached at day 0 in 9/14 patients, and was delayed up to day + 10 in the remaining five. There was a negative correlation between loge sEpo and Hb values (r = -0.730; p less than 0.01); the regression line of this correlation was comparable to the one obtained in a group of 15 iron-deficiency anemic subjects. Therefore, patients undergoing autologous BMT appear to be able to develop adequately increased sEpo levels in response to the severity of anemia. No correlation was found between sEpo and white blood cell or platelet count. On the other hand, sEpo value at day 0 was significantly related to the day of neutrophil recovery (r = -0.806; p less than 0.001): patients with the highest sEpo levels at day 0 showed significantly faster (p less than 0.001) neutrophil recovery.

Early haemostatic modifications following cryopreserved graft infusion.

The nature of the graft used for the rescue of patients undergoing autologous bone marrow transplantation is that of a complex mixture of pharmacological agents and cellular debris known to have a number of effects on the haemostatic system. The present study was undertaken to evaluate the occurrence and the degree of haemostatic alterations during and immediately following graft infusion in 24 patients suffering from haematological malignancies. On day 0, before graft infusion, the majority of patients appeared with laboratory signs of enhanced thrombin generation, platelet activation, and endothelial damage, most likely due to the conditioning regimen. However, the graft infusion per se was accompanied in the short term by a further increment of some parameters indicating a thrombotic risk (as thrombin-antithrombin complex, beta-thrombo globulin, platelet factor four, and von Willebrand factor antigen, together with a concomitant prolongation of partial thromboplastin time and a reduction of prothrombin time. In contrast there was no further modification of antithrombin III or protein C levels nor an increase in fibrinopeptide A levels. We hypothesize that complex interactions between agents contained in the graft mixture and host haemostatic system are involved in the pathogenesis of the haemostatic alterations which followed cryopreserved graft infusion; however, in our series, these were not accompanied by clinical signs of thrombotic or haemorrhagic events.