Search

cited By 1; International audience; Sustained activation of JAK/STAT3 signaling pathway is classically described in Multiple Myeloma (MM). One explanation could be the silencing of the JAK/STAT suppressor genes, through the hypermethylation of SHP-1 and SOCS-1, previously demonstrated in MM cell lines or in whole bone marrow aspirates. The link between such suppressor gene silencing and the degree of bone marrow invasion or the treatment response has not been evaluated in depth. Using real-time RT-PCR, we studied the expression profile of three JAK/STAT suppressor genes: SHP-1, SHP-2 and SOCS-1 in plasma cells freshly isolated from the bone marrows of MM patients and healthy controls. Our data demonstrated an abnormal repression of such genes in malignant plasma cells and revealed a significant correlation between such defects and the sustained activation of the JAK/STAT3 pathway during MM. The repressed expression of SHP-1 and SHP-2 correlated significantly with a high initial degree of bone marrow infiltration but was, unexpectedly, associated with a better response to the induction therapy. Collectively, our data provide new evidences that substantiate the contribution of JAK/STAT suppressor genes in the pathogenesis of MM. They also highlight the possibility that the decreased gene expression of SHP-1 and SHP-2 could be of interest as a new predictive factor of a favorable treatment response, and suggest new potential mechanisms of action of the therapeutic molecules. Whether such defect helps the progression of the disease from monoclonal gammopathy of unknown significance to MM remains, however, to be determined.

The aim of this prospective observational study was to evaluate the incidence of hemophagocytic syndrome (HPS) after hematopoietic stem cell transplantation (HSCT). Between July 2006 and December 2007, all patients who received a HSCT in our institution were included in this study. All the following criteria were needed for the diagnosis of HPS: sustained fever over 7 days; cytopenia (neutropenia and/or thrombocytopenia); presence of more than 3% mature macrophages in bone marrow; hyperferritinaemia (>1,000 ng/mL). During this study, 171 patients received a HSCT (68 allogeneic and 103 autologous). The median age was 32 years (3-62). We observed six cases of HPS (6/68; 8.8%) after allogeneic stem cell transplantation (ASCT): one case of EBV-related HPS, two cases of CMV-related HPS, and three cases with no evidence of bacterial, fungal or viral infections. We observed only one case of CMV-related HPS (1/103; 0.9%) after autologous stem cell transplantation. Four patients died despite aggressive supportive care. To our knowledge, this is the first prospective observational study conducted with the aim to evaluate the incidence of HPS after HSCT. This study provides a relatively high incidence of HPS after ASCT. When sustained fever with progressive cytopenia and hyperferritinaemia are observed, HPS should be suspected, and bone marrow aspirate considered. The rapid diagnosis of HPS and the early initiation of an appropriate treatment are essential for patient management.

T1D after BMT constitutes a human model of autoimmune disease transmission. This case report refers to T1D onset after allogeneic HLA-matched BMT in a six-yr-old recipient affected by aplastic anemia. The donor was his sister who had T1D. The recipient had a complication free course apart from grade 1 acute GVHD, which was resolved spontaneously. With the predictive value and significance of T1D-associated autoantibodies, we tried to consolidate the T1D transfer possibility based on our patient characteristics and a literature review.

The aim of this study was to assess the impact of fractionated total body irradiation (F-TBI) on treatment-related mortality (TRM) and relapse in patients who received a non-T-cell-depleted allogeneic stem cell transplantation (ASCT) for hematological malignancies. Between March 2003 and December 2004, a total of 24 patients with HLA-identical sibling donors entered this study and received three doses of 3.33 Gy F-TBI separated by 24 h and cyclophosphamide or etoposide. At a median follow-up of 37 months (range 29–47 months), 4 of the 24 patients (16.6%) died of TRM. Relapse occurred in 10 patients at a median of 9 months (range 2–18 months). Overall, 13 of 24 patients (54%) died. Relapse was the most common cause of death (9/13). The 2-year actuarial survival rate was 46% (±11%). In our experience, ASCT conditioned with F-TBI was associated with low TRM but a high early relapse rate in patients with hematological malignancies.

We report an unusual case of a woman with acute myeloid leukemia who showed an isolated extramedullary relapse (IEMR) in the breast following allogeneic stem cell transplantation and review the related literature. Eighty cases of IEMR following allogeneic stem cell transplantation, including our case, were identified. The review suggests that an M2 or M4 phenotype in the French-American-British classification and a favorable cytogenetic risk group are more frequently associated with the occurrence of IEMR. Combined treatment with radiation and high-dose chemotherapy may be effective.

In patients with central venous catheters (CVCs), catheter-related bloodstream infections (CRBI) are a prominent cause of morbidity, excess hospital costs, and in some cases mortality. The aim of this prospective study was to assess the validity of the Gram stain-acridine orange leukocyte cytospin (AOLC) test for the diagnosis of CRBI in hematopoietic stem cell transplant (HSCT) recipients with nontunnelled CVCs, using the differential-time-to-positivity (DTP)/clinical criteria as the criterion standard to define CRBIs. CVCs were externalized, nontunnelled, polyurethane double lumen catheters (Arrows, Readings, USA). All CVCs were placed in the subclavian vein by the infraclavicular approach, in the operating room. Catheters were inserted percutaneously, using the Seldinger technique. Study catheters were not exchanged over guidewires. Between May 2002 and December 2004, a total of 245 consecutive patients were included. Twenty-six of the 245 patients (10.6%) had CRBI as determined by the DTP method. The Gram stain-AOLC was positive in only two patients (7.6%) with a CRBI. Our results suggest that the Gram stain-AOLC test is not useful for the diagnosis of catheter-related bloodstream infection in HSCT recipients.2006.

Seventeen patients with Fanconi anemia (FA) underwent allogeneic bone marrow transplantation (BMT) from matched related donors (MRD) between January 1999 and June 2003. Median age at BMT was 11 years. Conditioning regimen consisted of low-dose cyclophosphamide (CY; 40 mg/kg) and busulfan (BU; 6 mg/kg) with the addition of lymphoglobulin (20 mg/kg) in two patients. Graft-versus-host disease (GVHD) prophylaxis included cyclosporine A (CsA) and methotrexate (MTX; 5 mg/m(2) at day 1, 3, 6). All patients engrafted (for an absolute neutrophil count >0.5 x 10(9)/L) after a median time of 12 days (range 10-16 days). Fourteen patients (82%) had sustained grafts, whereas three others (18%) rejected grafts between day +39 and +80 after transplantation. Two of them are still alive after successful second PBSC transplantation and one died. Acute and chronic GVHD occurred in 23% and 13% of patients, respectively. With a median follow-up of 16 months (range 3-53 months), survival rate was 72% and Karnofsky score was at least 90%. The low-dose BU/CY regimen, in FA patients allografted from an HLA-matched related donor, allowed engraftment with relative low toxicity. Early graft failure (GF) remains a problem and may require modification of this regimen.

Purpose Infection is a serious complication of central venous catheters in immunocompromised patients. Catheter-related infection may be caused by fibrin deposition associated with catheters. Interventions designed to decrease fibrin deposition have the potential to reduce catheter-related infections. The purpose of this study was to evaluate the role of low-dose unfractionated heparin in preventing catheter-related bloodstream infection in patients with hemato-oncological disease. Patients and Methods This study was a randomized, controlled trial in which patients with nontunneled catheters were randomly assigned to receive either intravenous unfractionated heparin (continuous infusion of 100 U/kg per day) or 50 mL/day of normal saline solution as a continuous infusion (control group). Heparin was continued until the day of discharge. Catheter-related bloodstream infection was defined according to Infectious Disease Society of America guidelines. Results Two hundred and eight patients were randomly assigned. Four patients were excluded after assignment. Ultimately, 204 patients were analyzed. Catheter-related bloodstream infection occurred in 6.8% (7 of 102 catheters) of those in the heparin group (2.5 events per 1,000 days) and in 16.6% (17 of 102 catheters) of those in the control group (6.4 events per 1,000 days) (P = .03). No other risk factors were found for the development of catheter-related bloodstream infection. Four and five patients experienced severe bleeding in the heparin and control groups, respectively (P = .2). We did not observe heparin-induced thrombocytopenia. Conclusion The use of continuous infusion of low-dose unfractionated heparin (100 U/kg per day) can be a practical and economical approach to the prevention of catheter-related bloodstream infection in patients with hemato-oncological disease.

In this prospective study, we assessed the incidence of central venous catheter (CVC)-related thrombosis in haematopoietic stem cell transplant (HSCT) recipients. We determined the contribution of inherited prothrombotic abnormalities in blood coagulation to CVC-related thrombosis in these patients. The study was conducted between May 2002 and September 2004. CVCs were externalized, nontunneled, polyurethane double lumen catheters. Before catheter insertion, laboratory prothrombotic markers included factor V Leiden, the prothrombin gene Gly20210A mutation, plasma antithrombin levels, and protein C and S activity. All patients were systematically examined by ultrasonography just before, or

SummaryWe have conducted a prospective randomized controlled trial to evaluate the role of low-dose unfractionated heparin prophylaxis in preventing central venous line-related thrombosis in patients with haemato-oncological disease. Patients were randomly assigned to receive either prophylactic intravenous unfractionated heparin (continuous infusion of 100 IU/kg/daily) or 50 ml/daily of normal saline solution as a continuous infusion. CVLs were externalized, non tunneled, double lumen catheters. All CVLs were placed percutaneously by the same physician in the subclavian vein. Upper limb veins were systematically examined by ultrasonography just before, or < 24 hours after, catheter removal, and in case of clinical signs of thrombosis. One hundred and twenty-eight CVLs were inserted. Catheterrelated thrombosis occurred in 1.5% of the catheters inserted in patients of the heparin group, and in 12.6% in the control group (p = 0.03). No other risk factors were found for the development of catheter-related thrombosis. Two and three patients experienced severe bleeding in the heparin group, and in the control group, respectively (p = 0.18). There were no other side-effects clearly ascribable to the use of unfractionated heparin. This is the first prospective, randomized study, which shows that low-dose of unfractionated heparin is safe and effective to prevent catheter-related thrombosis in patients with haemato-oncological disease.

Resume Objectif. – Evaluer les infections liees aux voies veineuses centrales exteriorisees, non tunnelisees chez des patients immunodeprimes, dans un centre de greffe de moelle osseuse. Patients et methodes. – Entre juillet 1999 et avril 2002, au niveau de la veine sous-claviere, 210 catheters exteriorises, non tunnelises, chez 139 patients atteints d’hemopathies (52F/87H) ont ete implantes. L’âge moyen des patients etait de 26 ans (extremes : 3–56 ans). Au total, 33 enfants âges de 3 a 15 ans ont beneficie de la pose de 46 catheters. Les indications de pose des 210 catheters etaient les greffes de cellules souches hematopoietiques ou la prise en charge de leurs complications (n = 145), la chimiotherapie pour des leucemies aigues (n = 58), le traitement immunosuppresseur pour des aplasies medullaires (n = 7). Resultats. – La duree moyenne du catheterisme etait de 33 jours (extremes : 7–114 j). L’incidence globale des infections liees aux catheters etait de 3,1 pour 1000 journees–catheter. Les micro-organismes incrimines etaient des staphylocoques a coagulase negative dans 64 % des cas. Deux cas de pneumothorax (0,9 %) et une ponction de l’artere sous-claviere (0,4 %) ont ete enregistres. Deux thromboses veineuses (0,9 %) liees aux catheters ont ete documentees. Conclusion. – L’utilisation de catheters exteriorises, non tunnelises chez des patients immunodeprimes (adultes et enfants) est une technique sure, et represente une alternative aux catheters de type Hickman, largement utilises dans les unites de greffe de moelle osseuse.

Between 1998 and 2001, 31 (24 male, 7 female) patients with severe aplastic anemia (SAA) and a median age of 19 years (range, 4-39 years) received an allogeneic bone marrow transplantation. Marrow donors were genotypically HLA-identical siblings in 30 cases and a monozygous twin in one case. The median time from diagnosis to bone marrow transplantation was 1 month (range, 0.5-5 months). Conditioning regimen consisted of cyclophosphamide (CY) combined with antithymocyte globulin (ATG), in all patients. For graft-versus-host disease (GvHD) prophylaxis, all patients received methotrexate and cyclosporin. A total of 84% of patients had sustained grafts, whereas 16% rejected grafts between 3 and 20 months after transplantation. Of the five rejecting patients, three are alive with successful second engraftments and two died from infections. Acute grade II-IV GvHD was seen in only 11% of patients. A limited chronic GvHD was seen in one patient. With a median follow-up of 18 months (range, 5-42 months), survival rate was 86% and Karnofsky score was at least 90%. This study confirms the high success rate of the CY/ATG regimen in SAA allografted from an HLA-identical sibling. Early and late graft failure remains a problem and may require modification of this regimen.

Background Although the equimolecular mixture of oxygen and nitrous oxide (EMONO) seems a good choice to relieve procedure-related pain in children, it has not been evaluated for insertion of central venous catheters in children. To assess the safety and the effectiveness of this gas mixture for insertion of central venous catheters, we conducted a prospective observational study. Procedure This study was performed by the “Centre National de Greffe de Moelle Osseuse.” Procedure and inhalation characteristics, as well as pain evaluations and side effects, were reported. Results Fifty central venous catheters were inserted in 50 consecutive children. Median age was 7 (range, 4–13) years. An anesthesiologist was responsible for delivering EMONO, and provided constant surveillance throughout the procedure. EMLA cream was applied 2 hr before EMONO inhalation. No associated drugs were used. All catheters were inserted by the same experienced physician in the operating theater. Median inhalation length was 5 min (range, 3–6) before starting catheter's insertion and 12 min (range, 9–25) for the total inhalation. Median procedural pain evaluations were 10 (range, 0–30) for children on a 0–100 visual analog scale (VAS). Minor side effects were observed during eight (16%) inhalations. These side effects were euphoria (14%), deep sedation (4%), nausea and vomiting (2%), hallucinations (2%). All side effects were transient and resolved within 5 min after removing the inhalation device. Conclusions This study which shows that EMONO is effective for insertion of central venous catheters in children and represents a simple and safe alternative to general anesthesia. Pediatr Blood Cancer 2004;43:777–779. © 2004 Wiley-Liss, Inc.

In this article, we report a switch of beta-thalassemia major to intermedia beta-thalassemia after allogeneic bone marrow transplant of a 6-year-old girl from her HLA-matched brother. After stable mixed chimerism, the patient had a secondary graft rejection and returned to total recipient chimerism as assessed by real-time polymerase chain reaction assay. Nonetheless, with a medium hemoglobin rate of 89 g/L, she did not need further transfusions for 60 months after rejection. We conclude that complete loss of donor cells after bone marrow transplant for beta-thalassemia major is compatible with a stable clinical state, probably due to a gamma-globin gene demethylation that enhances gamma-globin chain production and further allows constitution of a fetal hemoglobin rate compatible with free transfusion survival.

Between February 1998 and October 2007, 97 (69 male, 28 female) patients with acquired aplastic anemia and a median age of 18 years (range, 2-39) received related allogeneic hematopoietic stem cell transplantation. Ninety-five patients received bone marrow grafts and two patients G-CSF primed peripheral blood stem cell transplantation. The donors were genotypically HLA-identical siblings in 94 cases, HLA-matched parents in 2 cases and a syngeneic twin in 1 case. Median time from diagnosis to transplantation was 2 months (range, 1-15). Conditioning regimen consisted of cyclophosphamide combined with antithymocyte globulin in all patients. For graft versus host disease (GVHD) prophylaxis, all patients received methotrexate and cyclosporine. Eighty-six patients showed evidence of hematopoietic engraftment. Eight patients died before engraftment. Rejection rate was 14.8% with three primary graft failures and eight secondary graft rejections occurring between 2 and 27 months post transplantation. Of the 11 rejecting patients, 3 died from infection and 8 proceeded to a second transplantation. Among the eight patients re-transplanted, seven are alive with successful second engraftments and one died from acute grade III GVHD. Acute GVHD occurred in 15.5% and extensive chronic GVHD in only 5.3% of patients. The 4-year overall probability of survival was 76.8%. Infection was the cause of 81.1% of deaths. The major factor affecting survival was onset of infection before transplantation. Major ABO donor-recipient incompatibility, disease severity and acute GVHD had also negative impact on survival. These results could be improved by reducing the time to transplant and by a more efficient supportive care policy.Bone Marrow Transplantation advance online publication, 27 July 2009; doi:10.1038/bmt.2009.175.

Among the cases yet published of development of vitiligo after BMT, only two can claim as possible adoptive transfer of such disease. We report a case of a patient with sickle cell disease in whom vitiligo developed after allogeneic BMT from his HLA identical father affected by vitiligo. We reviewed and searched for some particularities in the reported cases of post-BMT vitiligo.

In 1998, the Tunisian team of the ‘Centre National de Greffe de Moelle Osseuse’ initiated allogeneic hematopoietic SCT (AHSCT) in Tunisia. As of June 2007, information was collected about 299 patients with a first AHSCT and 12 additional retransplants. The median age was 19 years (range 2–49 years). The main indications were aplastic anemia (n=106, 36%), leukemia and nonmalignant disorders (n=153, 51%), Fanconi anemia (n=26, 9%) and other nonmalignant disorders (n=14, 4%). Preparative regimens depended on indication. All donors were HLA geno-identical. The stem cell sources were BM (87%) and PBSCs (13%). At the time of analysis, 200 patients (67%) were alive after a median follow-up of 42 months (range 3–112 months). The overall TRM rate was 17%. Outcome depended on indication. According to our results, allogeneic HSCT is potentially curative for hematological diseases, but it is a toxic approach for malignant disorders.

Bloodstream infections related to the use of central venous catheters are an important cause of patient morbidity, mortality, and increased health care costs. Catheter-related infection may be due to fibrin deposition associated with catheters. Interventions designed to decrease fibrin deposition have the potential to reduce catheter-related infections. This study was a randomized, controlled trial in which 246 patients with nontunneled central venous catheters were randomly assigned to receive a heparin-coated catheter with 50 mL/d of normal saline solution as a continuous infusion (heparin-coated group) or a noncoated catheter with a continuous infusion of low-dose unfractionated heparin (control group: continuous infusion of 100 U/kg/d). Catheter-related bloodstream infection occurred in 2.5% (3/120 catheters) in the heparin-coated group (0.9 events per 1,000 days) and in 9.1% (11/120 catheters) in the control group (3.5 events per 1,000 days; P = 0.027). No other risk factors were found for the development of catheter-related bloodstream infection. Six and seven patients experienced severe bleeding in the heparin-coated and control groups, respectively (P = 1.00). We did not observe heparin-induced thrombocytopenia. The use of heparin-coated catheters can be a safe and effective approach to the prevention of catheter-related bloodstream infection in patients with hematooncologic disease.

In the present study we report the clinical outcome of 27 patients with refractory or relapsed Hodgkin's lymphoma (HL) undergoing autologous peripheral stem-cell transplantation (ASCT).On transplant, 18 patients had sensitive disease (SD) and 9 resistant disease (RD). The median time between diagnosis and ASCT was 18 months (range, 7 to 96 months). The conditioning consisted of BEAM regimen.The 100-day mortality rate was 3%. Three months after transplant, 12 patients transplanted with SD were in complete remission (CR) and only one of the 9 patients transplanted with RD achieved CR. Overall survival and disease-free survival after 3 years were 68% and 60%, respectively.the present results confirm the efficacy and safety of the ASCT in refractory or relapsed HL patients with SD. Other strategies should be investigated for patients with RD.

A 55-year-old man with multiple myeloma developed sustained bleeding after bone marrow aspiration and cutaneous bleeding. Routine coagulation studies revealed a prolonged activated partial thromboplastin time and thrombin time (> 60 s) with a normal reptilase time. Further evaluation showed failure of the activated partial thromboplastin time to correct completely in a 1: 1 mixture with normal plasma. Treatment of the patient's plasma in vitro with protamine sulfate normalized the thrombin time. The presence of a heparin-like anticoagulant was suspected. The plasma heparin level was 0.73 IU/ml. Intravenous infusion of protamine sulfate appeared to neutralize the anticoagulant activity and stop the bleeding. The cancer cells themselves or the invasive nature of this type of cancer might result in a massive release of a heparinoid. Such coagulopathy appears to be a rare mechanism of bleeding and it is an important entity to consider since it is potentially reversible with protamine sulfate.

A pp65 antigenemia assay for polymorphonuclear leukocytes (PMNLs) (CINAkit Rapid Antigenemia), and a qualitative polymerase chain reaction (PCR) test for plasma 'PCR-P qual' (Amplicor cytomegalovirus [CMV] test) were performed for 126 samples (blood and plasma) obtained from 18 bone marrow transplant patients, over a 9-month surveillance period. Among those samples, 92 were assayed with a semi-quantitative PCR test for PMNLs 'PCR-L quant.' The number of samples with a positive CMV test for antigenemia and PCR-P qual assays was 20.63% and 12.7%, respectively, whereas the PCR-L quant assay was positive in 48 of the 92 samples assayed (52.17%). The rates of concordance of the results of PCR-P qual and antigenemia, PCR-P qual and PCR-L quant, antigenemia and PCR-L quant were 92%, 65.2% and 66.8%, respectively. The analysis of the results for the 92 specimens tested by all 3 methods showed a rate of concordance of 63% among all methods. Good agreement (kappa=0.72) was found only between pp65 Ag and PCR-P qual assays. Clinical disease correlates with an antigenemia high viral load. Three patients had CMV disease despite preemptive therapy, and all of them had graft-versus-host-disease (GVHD). PMNLs-based assays are more efficient in monitoring CMV reactivation, but for high-risk patients with GVHD, more sensitive assays (real-time PCR) must be done.

A randomised crossover trial of two separators was undertaken to compare the mononuclear cell, CD34(+) cell and CFU-GM yield, in patients (61 years) with previously untreated symptomatic multiple myeloma. After first-line therapy, all patients received mobilising chemotherapy (cyclophosphamide 4 g/m(2)) and daily G-CSF. The first leucapheresis was performed on the first day the peripheral blood absolute CD34(+) cell count was20 cells/microl. All patients underwent 2 leucaphereses on consecutive days. The patients were randomised to undergo either the first or second leucapheresis using the COBE Spectra. The target duration of the procedure on the COBE Spectra was 2 total blood volumes, and for the Haemonetics MCS(+) it was 20 cycles with four recirculations. Between September 2003 and March 2005, 60 patients were entered in the study. COBE Spectra version 6 processed significantly larger volumes of blood than the Haemonetics MCS(+) (8,845 and 5,680 ml, respectively, P0.01). The absolute yield of mononuclear cells (2.1 vs. 1.5 x 10(8)/kg, P = 0.04), CFU-GM (11 vs. 3 x 10(4)/kg, P = 0.01) and CD34(+) cells (3 vs. 1.7 x 10(6)/kg, P = 0.02) were all significantly higher with the COBE Spectra version 6, as were the yields per unit volume of blood processed. In conclusion, our study shows that COBE Spectra Version 6 is faster and has a better yield than the Haemonetics MCS(+), in patients with multiple myeloma.

Thalidomide-dexamethasone therapy was given in patients (61 years) with previously untreated symptomatic multiple myeloma. The aim of this study was to assess the efficacy and toxicity of this combination as first-line therapy, and to determine its effect on stem cell collection and engraftment. During first-line therapy, thalidomide and dexamethasone were administered for 75 days (200 mg/day) and 3 months, respectively. The monthly dose of dexamethasone was 20 mg/m2/day for 4 days, with cycles repeated on days 9 to 12 and 17 to 20 on the first and the third month of therapy. After first-line therapy, a collection of peripheral blood stem cells (PBSC) was performed. Between May 2003 and September 2004, 60 patients were included. On an intent-to-treat basis, the overall response (or =partial response) rate was 74%, including 24% of patients who obtained a complete remission. Grade 3-4 toxicities consisted of infections (12%), deep-vein thrombosis (3%), constipation (5%), and neuropathy (5%). A total of 58 patients (96%) proceeded to PBSC mobilisation and yielded a median number of 8 x 10(6) CD34+ cells/kg. First-line thalidomide-dexamethasone therapy is effective and relatively well tolerated in young patients with symptomatic multiple myeloma. This combination does not affect PBSC mobilisation.

Catheter-related bloodstream infections are associated with recognized morbidity and mortality. Accurate diagnosis of such infections results in proper management of patients and in reducing unnecessary removal of catheters. We carried out a prospective study in a bone marrow transplant unit to assess the validity of a test based on the earlier positivity of central venous blood cultures in comparison with peripheral blood cultures for predicting catheter-related bacteremia. Between May 2002 and June 2004, 38 bloodstream infections with positive simultaneous central venous catheter and peripheral vein blood cultures were included. A total of 22 patients had catheter-related bacteremias and 16 had noncatheter-related bacteremias, using the catheter-tip culture/clinical criteria as the criterion standard to define catheter-related bacteremia. Differential time to positivity of 120 min or more was associated with 86% sensitivity and 87% specificity. In conclusion, differential time to positivity of 120 min or more is sensitive and specific for catheter-related bacteremia in hematopoietic stem cell transplant recipients who have nontunnelled short-term catheters.

We describe a case of Plasmodium falciparum infection in a 25-year-old male patient with a myelodysplastic syndrome, who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) in September 2003. Conditioning regimen consisted of total body irradiation (10 Gy) and cyclophosphamide 60 mg/kg for 2 days. A dose of 4 � 10 6 CD34 þ cells/kg was transfused. Engraftment was well documented on day 17 post-transplantation. Spiking fevers occurred on days 19 and 21, associated with a pancytopenia, hepatosplenomegaly and neurological signs. P. falciparum parasites were found on the peripheral blood smear (parasitemia ¼ 23%). Marrow aspiration showed P. falciparum parasites and proliferation of mature histiocytes with hemophagocytosis. Quinine 10 mg/kg i.v. three times a day for 10 consecutive days was given. The fever subsided within 3 days, and pancytopenia vanished in 14 days. Parasitemia cleared in 6 days. The patient left the unit on day 46 with no further complications. The screening of donors showed that infection was acquired from two blood units (from a single donor) given 5 days before transplantation. We report the first case of profound hemophagocytosis in immunosuppressed patient with malaria of high parasitemia after a bone marrow transplant. The Hematology Journal (2004) 5, 449–450. doi:10.1038/sj.thj.6200531

Although the equimolecular mixture of oxygen and nitrous oxide (EMONO) seems a good choice to relieve procedure-related pain in children, it has not been evaluated for insertion of central venous catheters in children. To assess the safety and the effectiveness of this gas mixture for insertion of central venous catheters, we conducted a prospective observational study.This study was performed by the "Centre National de Greffe de Moelle Osseuse." Procedure and inhalation characteristics, as well as pain evaluations and side effects, were reported.Fifty central venous catheters were inserted in 50 consecutive children. Median age was 7 (range, 4-13) years. An anesthesiologist was responsible for delivering EMONO, and provided constant surveillance throughout the procedure. EMLA cream was applied 2 hr before EMONO inhalation. No associated drugs were used. All catheters were inserted by the same experienced physician in the operating theater. Median inhalation length was 5 min (range, 3-6) before starting catheter's insertion and 12 min (range, 9-25) for the total inhalation. Median procedural pain evaluations were 10 (range, 0-30) for children on a 0-100 visual analog scale (VAS). Minor side effects were observed during eight (16%) inhalations. These side effects were euphoria (14%), deep sedation (4%), nausea and vomiting (2%), hallucinations (2%). All side effects were transient and resolved within 5 min after removing the inhalation device.This study which shows that EMONO is effective for insertion of central venous catheters in children and represents a simple and safe alternative to general anesthesia.

DMSO is used as a cryoprotectant for long-term storage of haematopoietic progenitor cells from the marrow or blood.1 Until recently, there has been little information on the neurological toxicity of DMSO other than headache.2 Recent reports suggest that this may be a more frequent problem than currently appreciated.3, 4, 5, 6, 7

Perforation of the superior vena cava after subclavian catheterization: a rare complication after autologous PBSCT

Rejection after allogeneic bone marrow transplantation for Fanconi anemia (FA) is a complication with a high risk of mortality. We describe a patient who, following a second episode of rejection after a second allogeneic stem cell transplantation, was successfully treated with antilymphocyte globulin, followed by donor lymphocyte infusion. At three and a half years after donor lymphocyte infusion, she is alive with a Karnofsky score of 90%. Her molecular chimerism is of donor origin. Thus, donor lymphocyte infusion can be considered as a therapy option for rejection after allogeneic bone marrow transplantation for FA. The Hematology Journal (2003) 4, 452–453. doi:10.1038/sj.thj.6200330

Abstract 4648 Objectives A central venous access is always necessary for the management of patients receiving myeloablative conditioning followed by allogeneic stem cell transplantation (SCT). Tunnelled, cuffed silastic catheters are the device of choice for these patients. To our knowledge, there are no prospective studies investigating the use of totally implantable central venous access ports (TIAP) in patients receiving myeloablative conditioning followed by allogeneic SCT. The aim of this prospective study was to investigate the usefulness of a new “high flow” single lumen port device in these patients. <>Methods: Between December 2007 and July 2009, patients with haematological malignancies received a TIAP prior to allogeneic SCT. All patients received the same type of port [silicone, 10 French, high flow rate (3100ml/h), Reference 40010, Laboratoires Perouse, Ivry le Temple, France]. All devices were inserted under local anesthesia through direct puncture of the right subclavian vein using the Seldinger technique. A chest X-ray was always obtained to document correct positioning. All infusions, including the graft itself and all blood drawings, were performed via the port. Port-related bloodstream infection was defined according to Infectious Disease Society of America guidelines. All patients were examined by ultrasonography in case of clinical signs of thrombosis and systematically after discharge. Results Forty six TIAP were placed in 46 patients [median age: 25 years (20-41 years); 20 female and 26 male], and remained in place for a cumulative duration of 9756 days in situ (range 30-560 days). No pneumothorax occurred. Port-related bloodstream infection occurred in 2 cases (candida parapsilosis and staphylococcus aureus) [2/46, 4.3% ; 0.2 event per 1000 days]. These ports were removed. No port-related thrombosis occurred. No port-related deaths were observed. In conclusion, the use of “high flow” totally implantable ports has resulted in a good option for long-term access to central veins and delivery of myeloablative conditioning followed by allogeneic SCT, in spite of severe neutropenia and increased risk of sepsis in this category of patients. Although multicentre randomized clinical trials are needed to define the optimal device in this clinical setting, the results of this prospective study support the wider use of TIAP in patients receiving myeloablative conditioning followed by allogeneic SCT. Disclosures: No relevant conflicts of interest to declare.

This paper reported in part on a study of optimal timing of second transplantation in patients with multiple myeloma (http://clinicaltrials.gov/show/NCT00207805). It is being retracted with the consent of all the authors.

Central venous catheters (CVCs) are widely used in patients with hemato-oncological disease for indications such as administration of chemotherapy, parenteral nutrition, blood products and monitoring of hemodynamics. CVCs are a major source of hospital-acquired infection. The National Nosocomial Infections Surveillance System reported a rate of catheter-related bloodstream infection (CRBI) of five per 1000 central catheter-days. This study was a randomized trial in which patients with nontunneled catheters were randomly assigned to heparin-coated (7 French, polyurethane, double lumen; Arrow®, USA) or chlorhexidine and silver sulfadiazine impregnated CVCs (7 French, polyurethane, double lumen; Arrow®, USA). All CVCs were placed in the subclavian vein in the operating room. CRBI was defined according to Infectious Disease Society of America guidelines. The principal investigator determined whether infections were catheter related and had no knowledge of “the assigned arm” at the time of adjudication of the reference standard definition. Before catheter insertion, laboratory prothrombotic markers included factor V Leiden, the prothrombin gene Gly20210A mutation, plasma antithrombin levels, and protein C and S activity. In our study, all patients were systematically examined by ultrasonography just before, or less than 24 hours after, catheter removal and in case of clinical signs of thrombosis. Two radiologists performed the ultrasonography and were unaware of the allocation of the patients. Two hundred and twenty patients were randomly assigned. Eight patients were excluded after assignment. Ultimately, 212 patients were analyzed [median age: 28 years (7–60); 97 female and 115 male]. CRBI occurred in 6.7% (7/104) of those in the heparin-coated group (2.7 events per 1000 days) and in 4.6% (5/108) in the chlorhexidine and silver sulfadiazine group (2 events per 1000 days) (P=0.5). The microorganisms involved in CRBIs were coagulase-negative Staphylococcus (five cases in the heparin group and 3 cases in the antiseptic group), Staphylococcus aureus (one case in the heparin group), Candida parapsilosis (one case in the antiseptic group), Pseudomonas aeruginosa (one case in the heparin group and one case in the antiseptic group). We observed a CVC-related thrombosis in 11 patients (5.2%; 5 in the heparin group and 6 in the antiseptic group P=0.8). Catheter-related thrombosis and CRBI coincided in two patients and were not significantly correlated (P=0.6). Four (1.9%) and three (1.4%) patients had evidence of protein C and protein S deficiency, respectively. Only one patient had an antithrombin deficiency (0.5%). In total, 9 patients (4.2%) were heterozygous for the factor V Leiden mutation. Thrombosis was diagnosed in three out of 17 patients (17.6%) with a inherited prothrombotic abnormality compared to 8 out of 195 patients (4.1%) who did not have a thrombophilic marker (relative risk 4.3 CI 95% 1.2–14.7). Six and five patients experienced severe bleeding in the heparin and antiseptic groups, respectively. We did not observe heparin-induced thrombocytopenia and anaphylaxis to chlorhexidine was not reported. To our knowledge, this is the first randomized study comparing in haematological patients heparin-coated with antiseptic impregnated CVCs. Furthermore, our results suggest that inherited prothrombotic abnormalities contribute substantially to CVC-related thrombosis in hemato-oncological patients. Presently, the best options for reducing CRBI are heparin-coated and antibiotic-impregnated CVCs. A large, well designed randomized controlled trial is required to determine which of these is most effective.

Background: Thalidomide which represents an effective treatment strategy for relapsed/refractory multiple myeloma, actually represents a standard of care also for newly diagnosed multiple myeloma patients. Methods: In the present study, we adopted a gene expression profiling (GEP) strategy in an attempt to predict response (> 50% reduction in serum M protein) to primary therapy with thalidomide-dexamethasone for newly diagnosed multiple myeloma. Plasma cells (CD138+) were purified from bone marrow aspirates from 17 patients at diagnosis, before initiation of treatment with thalidomide-dexamethasone. GEP was performed using the Affymetrix U133 Plus_2 microarray platform. The Affymetrix output (CEL files) was imported into Genespring 7.3 (Agilent technologies) microarray analysis software, where data files were normalized across chips using GCRMA and to the 50th percentile, followed by per gene normalization to median. Criteria of response were those established by Bladè et al. Results: After sufficient follow-up, responders (n=9) and nonresponders (n=8) were identified, and gene expression differences in baselines samples were examined. Of the 11000 genes surveyed, Wilcoxon rank sum test identified 149 genes that distinguished response from non response. A multivariate step-wise discriminant analysis (MSDA) revealed that 14 of the 149 genes could be used in a response predictor model (see table). Of interest, the gene list encompasses WXSC1, known to be involved in the chromosomal translocation t(4;14) (p16.3;q32.3) in multiple myeloma. Conclusion: These results could be the first step to adopt microfluidic cards, in an attempt to select at diagnosis patients who will respond favourably to a particular treatment strategy. List of 14 genes able to predict response to primary therapy with thalidomide-dexamethasone for newly diagnosed multiple myeloma. Gene ID Gene Name Chromosomal location 212771_at C10orf38 10p13 229874_x_at LOC400741 1p36.13 219690_at U2AF1L4 19q13.12 202207_at ARL7 2q37.1 243819_at GNG2 14q21 203753_at TCF4 18q21.1 235400_at FCRLM1 1q23.3 211474_s_at SERPINB6 6p25 226785_at ATP11C Xq27.1 215440_s_at BEXL1 Xq22.1–q22.3 209054_s_at WXSC1 4p16.3 227168_at FLJ25967 22p12.1 213355_at ST3GAL6 3q12.1 223218_s_at NFKBIZ 3p12–q12

Background: Autologous stem cell transplantation (ASCT) is now considered standard therapy in young patients ( Methods: From May 2003 to April 2006, 140 patients with symptomatic MM (de novo) and less than 60 years of age, were randomly assigned to receive either tandem transplantation up-front (within 6 months of the first transplantation) [Arm A, n=69] or one ASCT followed by a consolidation therapy with thalidomide (day +90, 100 mg/per day during 5 months) [Arm B, n=71]. Patients included in the arm B received a second transplant in case of disease progression on consolidation therapy, or in case of relapse in responders. Clinical characteristics of each group were similar. In both arms of the study, ASCT was preceded by first-line therapy with thalidomide-dexamethasone and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide (4 g/m2) and G-CSF. Data were analyzed on an intent-to-treat basis. Results: With a median follow-up of 23 months (range: 6–34), the 2-year overall survival was 55% in the arm A and 75% in the arm B. Survival curves were not different (P=0.28, log-rank test). The 2-year event-free survival was 41% in the arm A and 60% in the arm B (P=0.4, log-rank-test). In the arm B, relapse-free survival of ≥ 16 months following the first transplantation was an important predictor of overall survival (p< 0.001). Conclusion: Data from the present study suggest that up-front single ASCT followed by a consolidation therapy with thalidomide and a second ASCT after relapse or progression is a safe and effective global strategy to treat MM patients. Longer follow-up is needed before definite conclusions can be given concerning the optimal timing of second autologous transplantations in patients with MM.