M. Akif Yesilipek

Cidofovir for BK Virus-Associated Hemorrhagic Cystitis: A Retrospective Study

BACKGROUND BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation (HSCT), but antiviral treatment for this condition has not been evaluated. METHODS We conducted a retrospective survey on the safety and outcome of cidofovir treatment for patients with BKV-HC in centers affiliated with the European Group for Blood and Marrow Transplantation. RESULTS From 1 April 2004 to 31 December 2007, 62 patients received a diagnosis of BKV-HC after a median interval of 35 days after HSCT (range, 3-577 days). Fifty-seven patients (92%) received intravenous cidofovir, whereas 5 patients received cidofovir intravesically. Complete response (CR) was recorded in 38 (67%) of 57 patients with HC treated with intravenous cidofovir, whereas partial response (PR) was documented in 7 patients (12%). CR was documented in 3 patients and PR in 1 patient with HC treated with intravesical cidofovir. A reduction of 1-3 logs in BKV load was documented in 8 of the 10 patients achieving CR. Mild-to-moderate toxic effects were recorded in 18 of 57 patients who received intravenous cidofovir administration. In a multivariate analysis, the factors significantly associated with response to cidofovir were the stem cell source (P = .01) and the use of total body irradiation (P = .03). After a median follow-up of 287 days, overall survival and total treatment-related mortality rates were 63% and 40% for patients achieving CR, compared with 14% and 72% for patients with PR or no response to cidofovir, respectively (P = .001 and P = .001, respectively). CONCLUSIONS Cidofovir may be a potentially effective therapy for BKV-HC, but evidence supporting its use requires randomized controlled trials.

Risk of complications during hematopoietic stem cell collection in pediatric sibling donors: a prospective European Group for Blood and Marrow Transplantation Pediatric Diseases Working Party study.

We investigated prospectively factors influencing the safety of hematopoietic stem cell (HSC) collection in 453 pediatric donors. The children in the study donated either BM or peripheral blood stem cells (PBSCs) according to center policy. A large variability in approach to donor issues was observed between the participating centers. Significant differences were observed between BM and PBSC donors regarding pain, blood allotransfusion, duration of hospital stay, and iron supplementation; however, differences between the groups undergoing BM vs PBSC donation preclude direct risk comparisons between the 2 procedures. The most common adverse event was pain, reported mainly by older children after BM harvest, but also observed after central venous catheter (CVC) placement for PBSC collection. With regard to severe adverse events, one patient (0.7%) developed a pneumothorax with hydrothorax after CVC placement for PBSC collection. The risk of allotransfusion after BM harvest was associated with a donor age of < 4 years and a BM harvest volume of > 20 mL/kg. Children < 4 years were at higher risk than older children for allotransfusion after BM harvest and there was a higher risk of complications from CVC placement before apheresis. We conclude that PBSC and BM collection are safe procedures in children.

New autoimmune diseases after cord blood transplantation : a retrospective study of EUROCORD and the Autoimmune Disease Working Party of the European Group for Blood and Marrow Transplantation

To describe the incidence, risk factors, and treatment of autoimmune diseases (ADs) occurring after cord blood transplantation (CBT), we analyzed both CBT recipients reported to EUROCORD who had developed at least 1 new AD and those who had not. Fifty-two of 726 reported patients developed at least 1 AD within 212 days (range, 27-4267) after CBT. Cumulative incidence of ADs after CBT was 5.0% +/- 1% at 1 year and 6.6% +/- 1% at 5 years. Patients developing ADs were younger and had more nonmalignant diseases (P < .001). ADs target hematopoietic (autoimmune hemolytic anemia, n = 20; Evans syndrome, n = 9; autoimmune thrombocytopenia, n = 11; and immune neutropenia, n = 1) and other tissues (thyroiditis, n = 3; psoriasis, n = 2; Graves disease, n 1; membranous glomerulonephritis, n = 2; rheumatoid arthritis, n = 1; ulcerative colitis, n = 1; and systemic lupus erythematosus, n = 1). Four patients developed 2 ADs (3 cases of immune thrombocytopenia followed by autoimmune hemolytic anemia and 1 Evans syndrome with rheumatoid arthritis). By multivariate analysis, the main risk factor for developing an AD was nonmalignant disease as an indication for CBT (P = .0001). Hematologic ADs were most often treated with steroids, rituximab, and cyclosporine. With a median follow-up of 26 months (range, 2-91), 6 of 52 patients died as a consequence of ADs. We conclude that CBT may be followed by potentially life-threatening, mainly hematologic ADs.

HLA‐matched family hematopoetic stem cell transplantation in children with beta thalassemia major: The experience of the Turkish Pediatric Bone Marrow Transplantation Group

Yesilipek MA, Ertem M, Cetin M, Öniz H, Kansoy S, Tanyeli A, Anak S, Kurekci E, Hazar V. HLA‐matched family hematopoetic stem cell transplantation in children with beta thalassemia major: The experience of the Turkish Pediatric Bone Marrow Transplantation Group.

Two novel mutations in the 3' untranslated region of the beta-globin gene that are associated with the mild phenotype of beta thalassemia.

There are approximately 800 different genomic alterations of the β‐globin gene described in the human hemoglobin variant (HbVar) database. In this study, we have identified two novel putative mutations (HBB:c.*+108 A>G and HBB:c.*+132 C>T) in the 3′ untranslated region (3′‐UTR) of the β‐globin gene and describe their clinical implications.

Deviating from safety guidelines during deferiprone therapy in clinical practice may not be associated with higher risk of agranulocytosis

A risk associated with the iron chelator deferiprone is the development of neutropenia or agranulocytosis. Accordingly, the product label recommends weekly blood monitoring and immediate interruption of treatment upon detection of an absolute neutrophil count (ANC) <1.5 × 109/L, out of concern that continued therapy might lead to a more severe drop. However, it is uncertain how these recommendations are followed under real‐life conditions and, if they are not followed, whether continuation of therapy results in increased incidence of agranulocytosis.

POSTTRANSPLANT ORAL IRON-CHELATING THERAPY IN PATIENTS WITH β-THALASSEMIA MAJOR

Allogeneic hematopoetic stem cell transplantation (HSCT) is the only radical cure of β-thalassemia. However, iron overload remains a cause of morbidity and mortality in posttransplant period. The authors present 7 patients as a preliminary report who underwent bone marrow transplant (BMT) and received oral chelating therapy (deferasirox) because of poor compliance to phlebotomy and desferrioxamine. The patients investigated mainly for possible side effects of deferasirox. No negative effect was seen in aspartate aminotransferase (AST), alanine aminotransferase (ALT), hemoglobin (Hb), and donor chimerism of the patients while serum ferritin levels significantly reduced (P = .018). Although serum creatinin significantly increased (P = .034), it was in normal limits in all patients. The authors believe that this report shows promising findings to plan further studies to clarify clinical safety and efficacy of deferasirox in posttransplant period.

Unrelated cord blood transplantation in children with severe congenital neutropenia.

Abstract:  SCN is an inherited hematological disorder with severe neutropenia and recurrent infections. Although there are some reports that recombinant rhG‐CSF improves clinical outcome, allogeneic HSCT appears to be the only curative treatment for these patients. We report here two children with SCN successfully treated by CBT from unrelated donors. They were refractory to rhG‐CSF treatment and have no identical family donor. Bu + CY were given as conditioning. Case 1 and Case 2 received 6/6 and 5/6 HLA‐matched unrelated umbilical cord blood, respectively. The number of infused nucleated cells was 6, 18 × 107/kg and CD34+  cell number was 3, 74 × 105/kg in Case 1. Those cell numbers were 8, 8 × 107/kg and 5, 34 × 105/kg for Case 2, respectively. Neutrophil/platelet engraftments were 45/49 days in Case 1 and 24/36 days in Case 2. Grade II cutaneous acute GVHD was seen in Case 2 that was treated successfully with prednisolone. Both patients are well with normal hematological findings and full donor chimerism for post‐transplant 20 and 24 months, respectively. We conclude that UCB can be considered as a safe source of stem cell in patients with SCN who need urgent HSCT.

Stem cell transplantation in hemoglobinopathies.

β-Thalassemia (thal) and sickle cell disease are the most common genetic diseases worldwide. Although supportive therapies such as regular transfusion and chelation for β-thal and hydroxyurea (HU) for sickle cell disease have significantly improved clinical manifestations and the quality of life, they cannot eliminate disease and therapy-related complications. Today, hematopoietic stem cell transplantation (HSCT) is the only curative treatment for patients with hemoglobinopathies. The first successful HSCT was reported in 1981. At that time, more than 1,000 patients underwent HSCT in Pesaro, Italy. Sixty β-thal patients underwent HSCT at the Department of Pediatric Hematology-Oncology, Akdeniz University School of Medicine, Antalya, Turkey between 1998 and 2006. We found stable mixed chimerism in 14 patients out of 45 (31%) in our transplanted thalassemia patients. The thalassemia free survival and overall survival rates were found to be 84.0 and 91.0%, respectively. The literature and our results indicate that HSCT can offer a cure for hemoglobinopathy patients.beta-Thalassemia (thal) and sickle cell disease are the most common genetic diseases worldwide. Although supportive therapies such as regular transfusion and chelation for beta-thal and hydroxyurea (HU) for sickle cell disease have significantly improved clinical manifestations and the quality of life, they cannot eliminate disease and therapy-related complications. Today, hematopoietic stem cell transplantation (HSCT) is the only curative treatment for patients with hemoglobinopathies. The first successful HSCT was reported in 1981. At that time, more than 1,000 patients underwent HSCT in Pesaro, Italy. Sixty beta-thal patients underwent HSCT at the Department of Pediatric Hematology-Oncology, Akdeniz University School of Medicine, Antalya, Turkey between 1998 and 2006. We found stable mixed chimerism in 14 patients out of 45 (31%) in our transplanted thalassemia patients. The thalassemia free survival and overall survival rates were found to be 84.0 and 91.0%, respectively. The literature and our results indicate that HSCT can offer a cure for hemoglobinopathy patients.

The value of donor lymphocyte infusions in thalassemia patients at imminent risk of graft rejection following stem cell transplantation.

The aim was to evaluate the feasibility of donor lymphocyte infusion (DLI) in transplanted patients with thalassemia who were at imminent risk of graft rejection (GR).