Allogeneic hematopoietic stem cell transplantation for acquired aplastic anemia using cyclophosphamide and antithymocyte globulin: a single center experience.

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.

Allogeneic hematopoietic stem cell transplantation in Tunisia.

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.

Detection of catheter-related bloodstream infections by the Gram stain-acridine orange leukocyte cytospin test in hematopoietic stem cell transplant recipients.

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.

Prospective randomised comparison of the COBE spectra version 6 and haemonetics MCS(+) cell separators for hematopoietic progenitor cells leucapheresis in patients with multiple myeloma.

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 was > 20 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, P < 0.01). 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.

Bone marrow transplantation from matched related donors for patients with Fanconi anemia using low-dose busulfan and cyclophosphamide as conditioning.

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.

Prevalence of inherited prothrombotic abnormalities and central venous catheter-related thrombosis in haematopoietic stem cell transplants recipients.

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 <24 h after, catheter removal, and in case of clinical signs of thrombosis. A total of 171 patients were included during the 28-month study period. Five (2.9%) and three (1.7%) patients had evidence of protein C and protein S deficiency, respectively. Only one patient had an antithrombin deficiency (0.6%). In total, 10 patients (5.8%) were heterozygous for the factor V Leiden mutation, and one patient had heterozygous prothrombin G20210A mutation (0.6%). We observed a CVC-related thrombosis in 13 patients (7.6%). Thrombosis was diagnosed in four out of 20 patients (20%) with a inherited prothrombotic abnormality compared to nine of 151 patients (6%) who did not have a thrombophilic marker (relative risk 3.3 CI 95% 1.1-9.9). Our results suggest that inherited prothrombotic abnormalities contribute substantially to CVC-related thrombosis in HSCT recipients. In view of physicians' reluctance to prescribe prophylactic anticoagulant treatment in these patients, a priori determination of inherited prothrombotic abnormalities may form a basis to guide these treatment decisions.

First-line thalidomide-dexamethasone therapy in preparation for autologous stem cell transplantation in young patients (<61 years) with symptomatic 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.

Difference in time to positivity is useful for the diagnosis of catheter-related bloodstream infection in hematopoietic stem cell transplant recipients.

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.

Rejection of the second allogeneic graft in a child with Fanconi anemia reversed by antilymphocyte globulin and donor lymphocyte infusion.

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.

[Infectious complications related to non-tunneled central venous catheters in immunocompromised patients: prospective study about 210 cases]. / Les infections liées aux cathéters veineux centraux non tunnélisés chez des patients immunodéprimés : étude prospective à propos de 210 cas.

OBJECTIVE: To evaluate infectious complications related to non-tunneled central venous catheter in immunocompromised patients, in a bone marrow unit. METHODS: From July to April 2002, we inserted 210 non-tunneled central venous catheters in 139 immunocompromised patients (52 F/87 M). The mean age was 26 years (3-56 years). Our study included 33 children aged from 3 to 15 years, on whom 46 catheters were placed. The catheters were placed for the following indications: 145 catheters were used in subjects who received a bone marrow transplantation, 58 catheters were placed in subjects who received chemotherapy for acute leukemia and seven catheters were used in patients who received immunosuppressive therapy. RESULTS: The mean duration of catheterization was 33 days (7-114 days). There were 3.1 catheter-related infections per 1000 catheter-days. Coagulase-negative Staphylococci were implicated in 64% of cases. We observed two pneumothorax (0.9%), one arterial puncture (0.4%) and two catheter-related thrombosis (0.9%). CONCLUSION: Non-tunneled catheters in immunocompromised patients (adults and children) is a safe technique, and is an alternative to the Hickman catheters which are most widely used today in patients undergoing bone marrow transplantation.

[Allogenic hematopoietic stem cell transplantation in acquired aplastic anemia: first experience of the National Center for Bone Marrow Grafting]. / Allogreffe de cellules souches hematopoietiques dans les aplasies medullaires acquises: experience initiale du Centre National de Greffe de Moelle Osseuse.

Bone marrow transplantation from HLA-identical sibling offers cure and leads to restoration of normal hematopoiesis and long-term survival in 60-80% of recipients. From february 1998 to october 1999, seven patients with aplastic anemia (2 very severe aplastic anemia and 5 severe aplastic anemia), with a median age of 22 years (14-39), received a transplant from an HLA-identical sibling donor. All patients had sustained engraftment. Only one patient developed grade IV acute graft-versus-host disease. One patient died in the 22th day of systemic mycobacterial infection and one in the 79th day of acute graft-versus-host disease. The remaining 5 patients are alive and have a complete hematological recovery, with a median follow-up of 6 months (1,5-12). There are at least two reasons for the improved survival of patients with aplastic anemia who where treated by HLA-indentical bone marrow transplantation. One is the decreased incidence of graft rejection that has resulted from the more judicious use of transfusions before bone marrow transplantation, and improvements in the immunosuppressive qualities of the conditioning programs. Another reason for improved survival is the decrease in the incidence and severity of acute graft-versus-host disease.

[Long-term survival and prognostic factors in multiple myeloma treated with conventional chemotherapy. Report of 109 cases]. / Survie a long terme et facteurs pronostiques du myelome multiple traite par chimiotherapie conventionnelle. A propos de 109 cas.

Our study is retrospective. We report the results of conventional chemotherapy ins previosly untreated patients with myeloma. Survival and prognostic factors were analysed in 109 patients diagnosed from 1983 to 1992. The median age was 65 years, 87 patients (80%) were including in the stage III according the Durie Salmon staging system. The median survival time was 27 months and 10 years survival rate is 3.66%. In the univariate analysis, two prognostic variables were retained namely the hemoglobin and creatinine level. The study suggest that conventional therapy is a good treatment for old patients. However, patients younger than 55 years, must benefit from intensive chemotherapy supported by autologous bone marrow, pheripheral blood stem cells, or allogenic bone marrow transplantation. A considerable encrace in duration of remission and survival is possible.

[Indications and complications of central venous catheters in hematologic oncology: report of 81 cases]. / Indications et complications des voies veineuses centrales en onco-hematologie: a propos de 81 cas.

From february 1998 to july 1999, 81 central venous catheters were placed in 41 patients 28 years old (5 to 51 years). We used the subclavicular anatomic way (Aubaniac) in all cases. The total duration of catheter placement was 2905 days (median of 31 days, range 1 to 165 days). We observed 1 pneumothorax (1.2%), 3 venous thrombosis (3.7%) and 1 arterial puncture (1.2%). Catheter-related infections were seen in 8 catheters (2.7 per 1000 catheter-days). Candida was encountered in 4 cases (50%), Gram-positive cocci in 2 cases (25%), and Gram-negative bacilli in 2 cases (25%). The improvement of preventive ways, diagnosis techniques (simultaneous quantitative cultures, differential positivity time), and therapeutic methods (treatment without removal of the catheter, antibiotic lock technique, catheter exchange by guidewire) should allow a better treatment of catheter-related infections.

[Value of hematopoietic stem cell autotransplantation in the treatment of multiple myeloma: initial experience at the National Bone Marrow Transplantation Center and review of the literature]. / Place de l'autogreffe de cellules souches hematopoïetiques dans le traitement du myélome multiple: expérience initiale du Centre National de Greffe de Moelle Osseuse et revue de la littérature.

Alkylating agents administered with predisone have been the standard therapy for myeloma over the lost three decades. Intensive treatment with autologous hematopoietic support has become the treatment of choice for multiple myeloma patients up to 60 years of age. From march 1999 to january 2000, seven patients with multiple myeloma (stage III) with a median age of 43 years (34-56) received an autologous stem cell transplantation. The myeloablative treatment regimen consisted of high-dose melphalan. All patients had sustained engraftment. The median duration of neutropenia (< 500/mm3) was 12 days (11-140) and the median duration of thrombocytopenia (< 20,000/mm3) was 13 days (11-110). One patient had a complete remission, one a very good partial remission, and 5 patients had a partial remission. With a median follow-up of 8 months (2-12), all patients are alive, without relapse.

[Kikuchi-Fujimoto subacute necrotizing lymphadenitis: two histologic forms observed in the same patient]. / Lymphadénite subaiguë nécrosante de Kikuchi-Fujimoto: deux formes histologiques observées chez la même patiente.

Histiocytic necrotizing lymphadenitis, also known as Kikuchi-Fujimoto disease is a rare self-limited condition of young adults usually misdiagnosed as malignant hematologic disease. The diagnosis depends on microscopic findings. Two histologic types are classically described, proliferative and necrotic types. This is a case report of 17 year-old girl who presented cervical lymphadenopathy. The first lymph node biopsy was in favor of malignant lymphoma. The second lymph node biopsy, done one month later, showed typical histiocytic necrotizing lymphadenitis. To our knowledge, this is the first time that the two forms of this disease are described in the same patient.

[HbC/beta-thalassemia association. Eleven cases observed in Tunisia]. / Association HbC/beta-thalassémie. A propos de onze cas observés en Tunisie.

Eleven cases of simultaneous HbC hemoglobinopathy and beta-thalassemia were detected during a study of 11,200 subjects at high risk for inherited hemoglobin anomalies. In seven cases, main clinical manifestations were anemia and enlargement of the spleen, whereas the four other patients were apparently free of symptoms and were diagnosed during routine tests in family members of affected patients. Microcytosis and hypochromia were found in every case. Most of the patients were from the North-Western part of Tunisia. Blood transfusions were required in only one patient, who was an infant with HbC/beta + thalassemia.