[Prophylactic, preemptive and curative use of donor lymphocyte infusion in patients undergoing allogeneic stem cell transplantation: guidelines of the SFGM-TC]. / Recommandations de la SFGM-TC concernant l'injection prophylactique, préemptive et curative des lymphocytes du donneur (DLI) après allogreffe de cellules souches hématopoïétiques.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the fourth annual series of workshops which brought together practitioners from all member centers and took place in September 2013 in Lille. Here, we report our recommendations regarding the use of donor lymphocyte injection (DLI) in the prophylactic, pre-emptive and curative settings. This work has been limited to allogeneic stem cell transplantations from an HLA-matched (10/10) or -one antigen-mismatched (9/10) donor.

Nonbacterial purpura fulminans and severe autoimmune acquired protein S deficiency associated with human herpesvirus-6 active replication.

Nonbacterial purpura fulminans (PF) is rare, usually follows viral infection in young children, and is characterized by specific coagulation disorders, requiring specific therapy. Following a transient rash, a 2-year-old previously healthy girl developed PF without haemodynamic impairment. Laboratory data revealed disseminated intravascular coagulation and a severe transient protein S deficiency. Antiprotein S autoantibodies and active human herpesvirus-6 (HHV6) replication were demonstrated. Purpuric skin lesions spread very rapidly despite broad-spectrum antibiotics and right leg amputation. Plasmapheresis and intravenous immunoglobulins gave complete clinical recovery and normalization of protein S level within 10 days, with progressive clearance of antiprotein S autoantibodies. Transient severe protein S deficiencies have previously been reported in patients with nonbacterial PF, usually after varicella infection. This is the first documented case of PF after HHV6 infection.

The VAD chemotherapy regimen plus a G-CSF dose of 10 microg/kg is as effective and less toxic than high-dose cyclophosphamide plus a G-CSF dose of 5 microg/kg for progenitor cell mobilization: results from a monocentric study of 82 patients.

A study was conducted to compare the efficiency and toxicity of two peripheral blood stem cell (PBSC) mobilization procedures for newly diagnosed patients with multiple myeloma. Patients from group 1 (n=51) were treated by high-dose cyclophosphamide (HD-CY) plus G-CSF (5 microg/kg/day), and the second group (n=31) by VAD regimen plus G-CSF administration (10 microg/kg/day). Successful mobilization, defined by a minimal count of 2.5 x 10(6) CD34(+) cells/kg collected, was achieved in 96 and 90% of patients in groups 1 and 2, respectively (P=0.15). The mean peripheral blood CD34(+) cells concentration and the mean CD34(+) cells/kg collected were higher in group 2 than in the group 1 (P=0.05). The mean number of leukaphereses necessary to collect a count of 2.5 x 10(6) CD34(+) cells/kg was reduced in group 2 compared to group 1. Adverse events, blood products consumption and time spent in the hospital were significantly greater after HD-CY. In conclusion, VAD plus a G-CSF dose of 10 microg/kg administration seems preferential to HD-CY plus a G-CSF dose of 5 microg/kg for PBSC collection because of equivalent or better efficiency in stem cell mobilization, strong favorable toxicity profile and reduced cost.

Comparison of lenograstim vs filgrastim administration following chemotherapy for peripheral blood stem cell (PBSC) collection: a retrospective study of 126 patients.

Mobilization techniques for peripheral blood stem cell (PBSC) collection include the administration of chemotherapy followed by hematopoietic growth factors or growth factors alone. Two forms of recombinant human granulocyte colony-stimulating factor (rhG-CSF) are available for PBSC mobilization: lenograstim and filgrastim which are the glycosylated and non-glycosylated forms respectively. In order to determine the influence of the two forms of G-CSF following chemotherapy on PBSC collection, we conducted a retrospective study in 126 patients with various hematological malignancies: 65 and 61 for the lenograstim and filgrastim groups respectively. No significant differences between the two groups were observed in terms of sex, age and diagnosis. Prior therapies and PBSC mobilization regimen were also equivalent. No significant difference was observed between the groups for the median CD34+ cells harvested. The number of leukapheresis necessary to obtain a minimal number of 3 x 10(6) CD34+ cells/kg was equivalent for the two groups. The proportion of patients affected by a failure in PBSC collection was similar in the two groups. Our data suggest that lenograstim and filgrastim are equivalent for PBSC mobilization after chemotherapy.

[Extramammary carcinoid tumor metastatic to the breast. Apropos of a case]. / Les carcinoïdes d'origine extramammaire métastasiant au sein. A propos d'une observation.

We report the case of a 42-year-woman treated for an appendicular carcinoid tumor with bilateral ovary metastases and mesenteric node involvement. After a systematic mammography, an infraclinical lesion of the breast was detected. Mammographic and echographic images revealed nodular mass with possibly malignant features. Fine-needle aspiration biopsy indicated malignancy. The definitive diagnosis of breast metastasis of a carcinoid tumor was made by biopsy. This case is related to 14 previously published cases. The authors emphasize the importance of making a precise histological diagnosis to avoid overtreatment of a metastatic lesion.

[Post-transfusion hemochromatosis. Results of a study carried out in Blood Transfusion Centers. Analysis of 15 cases treated with subcutaneous perfusion of Desferal. Working group "Transfusion Techniques and Therapeutics"]. / L'hémochromatose post-transfusionnelle. Résultats d'une enquête menée auprès des Etablissements de Transfusion Sanguine en France. Analyse de 15 cas traités par perfusion sous-cutanée de Desféral. Groupe de travail Techniques et Thérapeutiques Transfusionnelles.

Post-transfusional iron overload is a real problem for doctors in charge of transfusions, as shown by the survey we led in twenty French blood banks. Deferoxamine remains the most efficient chelator, but can be prescribed only in a parenteral way. It is now proved that continuous infusions, intravenous or subcutaneous, are preferable to intermittent injections as far as iron excretion is concerned. In our study, we selected 15 polytransfused patients for dysmyelopoiesis. 13 cases were analysed by measuring the serum ferritin level. A clear decrease was noted, as well as a relative normalization of serum alanine amino transferases. However, if this treatment is effective and well tolerated, the problem is that it obviously requires the patient's compliance. It seems important to us to optimize prevention and treatment of post-transfusional iron overload through a consensus.

[Erythropoietin for autologous transfusion. Use in a case of severe anemia with allo-immunization]. / Erythropoiétine pour transfusion autologue. Utilisation dans un cas d'anémie grave avec allo-immunisation.

In view of the transfusional risks of viral transmission (notably HIV), autologous transfusion is increasingly used; it is often the only possible type of transfusion. A 42-year-old woman with lupus erythematosus, chronic renal failure and triple cardiac valve disease demanding surgery was admitted for multifactorial severe anaemia. Treatment with erythropoietin (8000 units/day) iron replenishment, corticosteroids and polyvalent immunoglobulins was initiated. The patient was operated upon in April 1990. A preoperative cell-saver autotransfusion was performed during surgery. The postoperative period was uneventful. Homologous transfusion was not necessary. In this case where homologous transfusion was ruled out, erythropoiesis stimulated by erythropoietin enabled autotransfusion and cardiac surgery to be performed.

[Quality and safety about hemapheresis practicing: from a self-evaluation of medical practices to a systematic risk management process]. / Qualité et sécurité des pratiques en hémaphérèse : d'un référentiel d'évaluation des pratiques professionnelles vers une démarche systématique de gestion des risques.

Hemapheresis is made up of a set of essential methods for modern medical practices. Applicated to donors, they allow production of labile blood products as well as raw material for plasma products industrial manufacturing; applicated to patients, they are indispensable for the treatment of many pathologies. Conditions for their implementation are very variable according to the teams who have few tools at their disposal to access, standardize and make reliable their activity. Therefore, an approach has been initiated by the Institut National de la Transfusion Sanguine and the Hemapheresis French Society to develop a guide which primary goal is to help teams evaluate themselves in different areas of their responsibilities. The generalization of the evaluation of professional practices in all activities and specialties required recently by the third iteration of the certification procedure of health institutions and a new law about French health system reinforce us in our approach. Finally, hemapheresis is not without risks, neither for donors nor for patients, which now encourages us to analyze sharply our procedures, to identify risk situations and develop means of prevention. This second step is already a current news for us.

Posttransplant prophylactic intravenous immunoglobulin in kidney transplant patients at high immunological risk: a pilot study.

The effects of posttransplant prophylactic intravenous immunoglobulin (IVIg) were investigated in renal transplant recipients at high immunological risk. Thirty-eight deceased-donor kidney transplant recipients with previous positive complement-dependent cytotoxicity crossmatch (n=30), and/or donor-specific anti-HLA antibodies (n=14) were recruited. IVIg (2 g/kg) was administrated on days 0, 21, 42 and 63 with quadruple immunosuppression. Biopsy-proven acute cellular and humoral rejection rates at month 12 were 18% and 10%, respectively. Glomerulitis was observed in 31% and 60% of patients at months 3 and 12, respectively, while allograft glomerulopathy rose from 3% at month 3 to 28% at 12 months. Interstitial fibrosis/tubular atrophy increased from 18% at day 0 to 51% and 72% at months 3 and 12 (p<0.0001). GFR was 50 +/- 17 mL/min/1.73 m(2) and 48 +/- 17 mL/min/1.73 m(2) at 3 and 12 months. PRA decreased significantly after IVIg (class I: from 18 +/- 27% to 5 +/- 12%, p<0.01; class II: from 25 +/- 30% to 7 +/- 16%, p<0.001). Patient and graft survival were 97% and 95%, respectively and no graft was lost due to rejection (mean follow-up 25 months). In conclusion, prophylactic IVIg in high-immunological risk patients is associated with good one-year outcomes, with adequate GFR and a profound decrease in PRA level, but a significant increase in allograft nephropathy.

[Prevalence of hepatitis B viral markers in Vietnamese blood donors]. / Prévalence des marqueurs du virus de l'hépatite B chez des donneurs de sang vietnamiens.

Serum samples were assayed using radioimmunoassay in 573 Vietnamese blood donors living in Hanoï (North Viet Nam). 66 (11.5%) subjects were HBsAg-positive. Of these 66 HBsAg carriers, 17 (25,8%) were positive for hepatitis B e antigen (HBeAg) and 43 (65.1%) for antibody to HBeAg (anti-HBe). 22 (3.8%) subjects were positive for antibody to hepatitis B core antigen (anti-HBc) alone. 402 (70.2%) subjects were positive for antibody to HBsAg (anti-HBs). This anti-HBs percentage increased with age. Only 83 (14.5%) subjects were negative for all hepatitis B viral (HBV) markers. This no HBV markers percentage decreased with age. The chi 2 test showed a non significant difference for frequencies of HBsAg, anti-HBc alone, anti-HBs but a significant one for frequencies of no HBV markers in men and women.

The timing of granulocyte-colony-stimulating factor administration after chemotherapy does not affect stem and progenitor cell apheresis yield: a retrospective study of 65 cases.

BACKGROUND: The optimal time for postchemotherapy granulocyte-colony stimulating factor (G-CSF) administration before peripheral blood stem and progenitor cell (PBPC) collection is not well defined. The impact of G-CSF scheduling on the number of CD34+ cells collected by leukapheresis from 65 patients with malignant disease was studied retrospectively. STUDY DESIGN AND METHODS: Chemotherapy was performed on Days 1 and 2 and was followed by G-CSF to mobilize PBPCs. In Group 1, 30 patients received the first dose of G-CSF immediately after the end of chemotherapy, as commonly recommended. In Group 2, 35 patients received the first G-CSF dose after the end of chemotherapy (Days 7 or 8). RESULTS: No difference was observed between the two groups in white cell recovery and the median number of CD34+ cells harvested. The number of leukapheresis procedures necessary to obtain the minimal number of 3 x 10(6) CD34+ cells per kg was the same. The proportion of patients with a failure of PBPC collection was similar, and G-CSF consumption was reduced in Group 2 without increasing infectious risks. CONCLUSION: Early administration of G-CSF after chemotherapy appears not to be a prerequisite for satisfactory PBPC collection. This approach could allow significant savings in terms of medical cost. A randomized and prospective study would be necessary, however, to assess the validity of these conclusions.

[Screening of carriers of antitetanus antibodies in blood donors]. / Dépistage des porteurs d'anticorps antitétaniques chez les donneurs de sang.

A screening of antitetanic antibody (AcAT) carriers has been carried out in 4770 blood donors. The percentage of "positive" subjects (with a rate of AcAT greater than or equal to 5 U.I./ml according to Laurell's method) is relatively high: 6,62%. The aim of a statistical study is to find out the distribution of AcAT carriers according to different factors: the chi 2 test allows us to conclude that the relation between the frequency of "positive" AcAT carriers and the blood groups is not significant but there is a significant connection between the frequency of "positive" AcAT carriers, sex and age. Our conclusions agree with those of authors having performed the study after vaccination. Our study has a double advantage: it allows us to know the vaccination state of the blood donors before any vaccination and allows the collecting of "positive" serum samples without having to wait for the vaccination.

The feasibility of peripheral blood stem cell collection for autograft following failure in bone marrow aspiration.

High doses of cytotoxic drugs may impair stem cell collection. Failure in stem cell collection by bone marrow aspiration can be rescued by harvesting Peripheral Blood Stem Cell (PBSC) after a combination of chemotherapy and hematopoietic growth factor. We, therefore, retrospectively evaluated the possibility of collecting PBSC after chemotherapy and/or G-CSF administration in 12 patients with insufficient Granulocyte-macrophage colony-forming unit (CFU-GM) counts after bone marrow aspiration (all patients had previously received heavy chemotherapy for hematologic malignancies); median collection of CFU-GM/kg count was 2,9 x 10(4)/kg (range 0,4 to 8 x 10(4)/kg) whereas the minimal count required for autografting is 10 x 10(4)/kg. Median collections of CFU-GM from PBSC were 5,8 x 10(4)/kg. While the CFU-GM collected in PBSC was higher than after bone marrow aspiration, only 5 patients had enough PBSC for autografting. In another case, addition of cells collected from both PBSC and bone marrow aspiration yielded a sufficient number of CFU-GM to allow autografting. Therefore in this selected and small group of patients, failure in bone marrow aspiration does not seem to be predictive of a low PBSC collection but a long therapy free interval and use of G-CSF alone for PBSC mobilization could constitute a valuable alternative. Three patients had a successful short term hematologic reconstitution out of the four patients having had an autograft.

The dose of granulocyte-colony-stimulating factor after chemopriming treatment does not influence apheresis yield of progenitor cells: a retrospective study of 91 cases.

BACKGROUND: The optimal dose of post-chemotherapy granulocyte-colony-stimulating factor (G-CSF) administration before peripheral blood progenitor cell (PBPC) collection has not been determined as yet, although 5 microg per kg per day has been recommended as the standard dose. This study retrospectively analyzed the effect of G-CSF dose on peripheral blood CD34+ cell collection from 91 patients with hematologic malignancies. STUDY DESIGN AND METHODS: Various doses of G-CSF were administered after several chemotherapeutic PBPC mobilization regimens. According to the dose of G-CSF administered, patients were assigned to two groups. Group 1 included 46 patients who received a low dose of G-CSF (median, 3.6 [range, 2.8-4.6] microg/kg/day). Group 2 included 45 patients who received a standard G-CSF dose of 6.0 (5.5-8. 1) microg per kg per day. Patients in the two groups were matched for age, diagnosis, previous therapy, and chemotherapeutic PBPC mobilization regimens. RESULTS: No difference was observed in the median number of CD34+ cells harvested from each group. The number of leukapheresis procedures necessary to obtain a minimum of 3 x 10(6) CD34+ cells per kg was the same in both groups, and the percentage of patients who failed to achieve adequate PBPC collections was similar in the two groups. CONCLUSION: The administration of low-dose G-CSF after chemotherapy appears equivalent to administration of the standard dose in achieving satisfactory PBPC collection. This approach could allow significant savings in medical cost. A randomized and prospective study is necessary, however, to assess the validity of these conclusions.

Passive immunotherapy in AIDS: a double-blind randomized study based on transfusions of plasma rich in anti-human immunodeficiency virus 1 antibodies vs. transfusions of seronegative plasma.

A randomized double-blind controlled trial was conducted to determine the efficacy of passive immunotherapy in the treatment of symptomatic human immunodeficiency virus (HIV) infection. This trial included 86 symptomatic patients randomized to receive plasma rich in anti-HIV-1 antibody or standard seronegative plasma. Each patient in both groups received a 300-ml infusion every 14 days over a 1-year period, and every 28 days thereafter, in addition to zidovudine and other conventional prophylactic treatments. Plasma donors were selected among symptomless seropositive individuals with a CD4 lymphocyte count > or = 400 x 10(6) cells per liter, a negative p24 antigen assay, and a high concentration of anti-p24 antibody. The plasmas were heat-inactivated before infusion. During the study period (day 28-day 365) scheduled by the protocol, clinical benefit from passive immunotherapy was observed in delaying the appearance of the first AIDS-defining event (P < 0.009) and reducing the cumulative incidence of such events, which was estimated 3-fold higher in the control group compared to the treatment group. Seven deaths occurred in the treatment group vs. 11 in the control group (P = 0.27). A total of 47 patients died or exhibited new AIDS-defining events, 18 in the treatment group and 29 in the control group (P = 0.009). No clinical benefit was observed after the 1-year period with infusions performed every 4 weeks. These results indicate a favorable effect of passive immunotherapy on the evolution of advanced AIDS.

Quantitation of passively acquired human immunodeficiency virus (HIV) antibodies in AIDS patients transfused with a plasma that is rich in HIV antibodies.

BACKGROUND: Passive immunotherapy in human immunodeficiency virus (HIV) infection is based on transfusions of plasma that is rich in HIV antibodies. STUDY DESIGN AND METHODS: To verify whether the clearance of transfused antibodies will maintain an elevated titer of specific antibodies between biweekly transfusions of plasma, the titers of anti-HIV-1 in plasma and in transfusion recipients were measured. Samples from 12 recipients were analyzed by automated scanning of Western blot, before transfusion and at Days 2, 7, and 14 after transfusion. RESULTS: The p24 antibody became detectable or higher than the baseline after transfusion and remained detectable until the second transfusion. Anti-p24 titers were variable and dependent on the antibody titer of the transfused plasma and the baseline p24 antigen titer. CONCLUSION: Biweekly transfusion of plasma with a high anti-HIV titer maintains a high anti-p24 titer between transfusions in AIDS patients treated with passive immunotherapy.

Sustained complete cytologic and molecular remission induced by donor leucocyte infusions alone in an acute myeloblastic leukaemia in relapse after bone marrow transplantation.

Therapeutic options for treatment of recurrence of leukaemia after allogeneic bone marrow transplantation (BMT) are limited. A beneficial effect of donor lymphocyte infusions (DLI) has not previously been described in acute myeloid leukaemia (AML) relapse. We report a case of AML with t(8;21), relapsing 3 months after BMT, who received DLI without adjuvant chemotherapy or growth factors. The patient developed acute GVHD and achieved a rapid complete remission of his AML by both cytologic and molecular criteria of at least 14 months duration, thereby showing that DLI for AML in relapse after BMT is an alternative therapeutic option.

Autologous blood donation for elective surgery in children weighing 8-25 kg.

To determine whether autologous blood donation can be used safely and efficiently in children weighing 8-25 kg, we studied children whose perioperative blood losses were expected to exceed 25% of total blood volume. Blood donations were performed in pediatric units, under the direction of an anesthesiologist and a blood bank physician experienced in paediatric care. Twenty-four children, median age 6 years (1-13), were included. They underwent surgery mainly for digestive or urological disorders, and for orthopedic defects. Forty blood collections were performed of the 46 prescribed. Phlebotomies could not be performed in 1 child because of the mother's apprehension, and in 5 cases because of venous access problems. All phlebotomies were hemodynamically well tolerated. Hemodilution was also performed in 17 children, and cell saver used in 2. Allogeneic blood transfusion was avoided in 21/24 children.

Virological and immunological data of AIDS patients treated by passive immunotherapy (transfusions of plasma rich in HIV-1 antibodies).

BACKGROUND AND OBJECTIVES: In human immunodeficiency virus (HIV) infections, passive immunotherapy can be carried out through infusions of virus-inactivated plasma from symptomless HIV-infected persons with abundant HIV antibodies. MATERIALS AND METHODS: We carried out a prospective, randomized, double-blind, controlled, passive immunotherapy study, which compared two groups. One received plasma rich in HIV antibodies, the other a standard seronegative plasma. RESULTS: Measurement of the plasma HIV RNA load showed in both groups a significant decrease in the mean viral copy number at the end of the first month, followed by an increase at the third month. Beyond the third months, a significant decrease in viral load was observed only in the treatment group. A significant difference in favor of the treatment group was observed for plasma viremia by HIV culture. For the cytokines involved in the viral replication and for the immune activation markers such as neopterin and beta 2-microglobulin, the biological analysis in plasma failed to show a significant difference in either group. Clinically, the treatment group benefited by delay in the appearance of the first AIDS-defining event and reduction in the cumulative incidence of such events. CONCLUSION: One possible interpretation is that passive immunotherapy affects plasma viral load, but there is no evidence that HIV-specific antibodies are exclusively responsible for the observed effects.