Related hematopoietic cell donor care: is there a role for unrelated donor registries?

In almost half of allogeneic hematopoietic progenitor cell (HPC) transplants, a related donor (RD) is used, yet a lack of standardized guidelines means that their care is heterogeneous. Changes to regulatory standards aim to improve uniformity, but adherence to these regulations can prove logistically difficult for the transplant centers (TCs) managing RDs. Discussion has ensued around possible alternative models of related donor care and a session at the European Society for Blood and Marrow Transplantation (EBMT) annual meeting in 2013 debated the question of whether a role exists for unrelated donor registries in the management of 'related' donors.

Outcome of aplastic anaemia in children. A study by the severe aplastic anaemia and paediatric disease working parties of the European group blood and bone marrow transplant.

This study analysed the outcome of 563 Aplastic Anaemia (AA) children aged 0-12 years reported to the Severe Aplastic Anaemia Working Party database of the European Society for Blood and Marrow Transplantation, according to treatment received. Overall survival (OS) after upfront human leucocyte antigen-matched family donor (MFD) haematopoietic stem cell transplantation (HSCT) or immunosuppressive treatment (IST) was 91% vs. 87% (P 0·18).

T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis.

Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. "Haploidentical expert" centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period).

Current outcome of HLA identical sibling versus unrelated donor transplants in severe aplastic anemia: an EBMT analysis.

We have analyzed 1448 patients with acquired aplastic anemia grafted between 2005 and 2009, and compared outcome of identical sibling (n=940) versus unrelated donor (n=508) transplants. When compared to the latter, sibling transplants were less likely to be performed beyond 180 days from diagnosis (39% vs. 85%), to have a cytomegalovirus negative donor/recipient status (15% vs.

Low intensity lympho-ablative regimen followed by autologous hematopoietic stem cell transplantation in severe forms of multiple sclerosis: A MRI-based clinical study.

Background: Autologous hematopoietic stem cell transplantation (AHSCT) has been successfully used to treat aggressive forms of multiple sclerosis (MS) that are unresponsive to approved therapies. In the last years, in view of the risk of mortality related to the procedure, the utilization of low-intensity conditioning regimens has been considered.

Objective: To report magnetic resonance imaging (MRI) and clinical data in a small cohort of patients treated with a low-intensity lympho-ablative regimen, followed by AHSCT.

Bone marrow transplantation for acquired severe aplastic anemia.

This article addresses current transplant options for patients with acquired severe aplastic anemia (SAA). This discussion includes ongoing progress in the use of SAA in the setting of unrelated donor transplants, which now provide outcomes similar, though still not identical, to HLA-identical sibling transplants. Recent data on stem cell source, conditioning regimens, and graft-versus-host disease prophylaxis are outlined.

Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research.

Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome.

A survey on unmanipulated haploidentical hematopoietic stem cell transplantation in adults with acute leukemia.

The use of unmanipulated graft is increasingly adopted in the setting of allogeneic hematopoietic stem cell transplantation from haploidentical family donors (haplo-SCT) in acute leukemia (AL). We analyzed the outcome of 229 adult patients with de novo AL, who received an unmanipulated haploidentical transplant as their first allo-SCT between 2007 and 2011. Median follow-up was 30 months.

HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation.

Life-threatening graft-versus-host disease (GVHD) limits the use of HLA-C-mismatched unrelated donors in transplantation. Clinicians lack criteria for donor selection when HLA-C-mismatched donors are a patient's only option for cure. We examined the role for HLA-C expression levels to identify permissible HLA-C mismatches.

DLI after haploidentical BMT with post-transplant CY.

Forty-two patients relapsing after an unmanipulated haploidentical BM transplant and post-transplant CY (PT-CY), were given 108 DLI, with median interval from transplant of 266 days (range, 67-1372). DLI were given at escalating doses, expressed as CD3+ cells/kg, without GVHD prophylaxis, and ranged from 1 × 10(3) to 1 × 10(7) cells/kg (median 5 × 10(5) cells/kg). The average number of DLI per patient was 2.

Prolonged complete remission after induction chemotherapy followed by chemoradiation with tomotherapy in metastatic nasopharyngeal cancer.

Background: Nasopharyngeal carcinoma (NPC) is uncommon in the Western hemisphere and in Europe. The undifferentiated subtype has a relevant propensity to metastasize systemically, mostly in the skeleton. In patients with distant metastasis at presentation there is no consensus on the most appropriate approach.

New directions for rabbit antithymocyte globulin (Thymoglobulin(®)) in solid organ transplants, stem cell transplants and autoimmunity.

In the 30 years since the rabbit antithymocyte globulin (rATG) Thymoglobulin(®) was first licensed, its use in solid organ transplantation and hematology has expanded progressively. Although the evidence base is incomplete, specific roles for rATG in organ transplant recipients using contemporary dosing strategies are now relatively well-identified. The addition of rATG induction to a standard triple or dual regimen reduces acute cellular rejection, and possibly humoral rejection.

Outcome of aplastic anemia in adolescence: a survey of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation.

We analyzed the outcome of 537 adolescents (age 12-18 years) with idiopathic aplastic anemia included in the database of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation comparing: i) matched family donor hematopoietic stem cell transplantation performed as first-line treatment with ii) front-line immunosuppressive therapy not followed by subsequent transplant given for failure and with iii) hematopoietic stem cell transplantation performed after failed front-line immunosuppressive therapy. Overall survival was 86% in the matched family donor hematopoietic stem cell transplantation group, 90% in patients given front-line immunosuppressive alone (those who did not fail this treatment and who did not receive subsequent rescue with hematopoietic stem cell transplantation) and 78% in subjects who underwent hematopoietic stem cell transplantation post failed front-line immunosuppressive therapy (P=0.14).

Autologous hematopoietic stem cell transplantation in neuromyelitis optica: a registry study of the EBMT Autoimmune Diseases Working Party.

Background: Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the central nervous system, hallmarked by pathogenic anti-aquaporin 4 antibodies. NMO prognosis is worse compared with multiple sclerosis.

Objective: The European Group for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) conducted a retrospective survey to analyze disease outcome following autologous stem cell transplantation (ASCT).

Contouring of the Pharyngeal Superior Constrictor Muscle (PSCM). A cooperative study of the Italian Association of Radiation Oncology (AIRO) Head and Neck Group.

Background And Purpose: Irradiation of the Pharyngeal Superior Constrictor Muscle (PSCM) seems to play a crucial role in radiation-related swallowing dysfunctions. Purpose of our study was to quantify operator-related variability in the contouring of PSCM on Computed Tomography (CT) scans and adherence with contours derived from MR images.

Materials And Methods: Three sets of treatment planning CT and their corresponding MR images were selected.

Bloodstream infections are an improbable cause of positive serum (1,3)-β-D-glucan in hematology patients.

Ninety-one serum samples from 51 hematology patients with bacteremia infections were tested for (1,3)-β-d-glucan (BG). Eleven samples (15%) from 7 patients (14%) were positive for BG. Of these 7 patients with positive BG results, 4 (8%) had invasive aspergillosis and 3 (6%) had no invasive fungal disease.

Liposomal daunorubicin, fludarabine, and cytarabine (FLAD) as bridge therapy to stem cell transplant in relapsed and refractory acute leukemia.

Therapeutic options for patients with relapsed or refractory acute leukemia are still undefined and often unsatisfactory. We report the outcome of 79 patients with relapsed-refractory acute leukemia treated with fludarabine, cytarabine, and liposomal daunorubicin (FLAD regimen) followed by hematopoietic stem cell transplantation (HSCT), when clinically indicated, between May 2000 and January 2013. Forty-one patients had acute myeloid leukemia (AML), and 38 had acute lymphoblastic leukemia (ALL).

MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis.

From 2007 to 2011, 66 patients with primary myelofibrosis or myelofibrosis (MF) preceded by essential thrombocythemia or polycythemia vera were enrolled into a prospective phase 2 clinical trial of reduced-intensity allogeneic hematopoietic stem cell transplantation (AHSCT), Myeloproliferative Disorder Research Consortium 101 trial. The study included patients with sibling donors (n = 32) receiving fludarabine/melphalan (FluMel) as a preparative regimen and patients with unrelated donors (n = 34) receiving conditioning with FluMel plus anti-thymocyte globulin (ATG). Patient characteristics in the 2 cohorts were similar.

Outcome of allogeneic stem cell transplantation for patients transformed to myelodysplastic syndrome or leukemia from severe aplastic anemia: a report from the MDS Subcommittee of the Chronic Malignancies Working Party and the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation.

One hundred and forty patients who had undergone hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) transformation after treatment of severe aplastic anemia (SAA) were identified in the European Group for Blood and Marrow Transplantation (EBMT) database. The median age at HSCT was 29 years (range, 1 to 66 years). The transplant donor was related in 49% cases and unrelated in 51% cases.

Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts.

We studied 459 consecutive patients with hematologic malignancies, median age 44 years (range, 15 to 71 years), who underwent transplantation with grafts from identical sibling donors (SIB; n = 176), matched unrelated donors (MUD; n = 43), mismatched unrelated donors (mmUD; n = 43), unrelated cord blood (UCB; n = 105) or HLA-haploidentical family donors (HAPLO; n = 92). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in the SIB recipients; antithymocyte globulin for the MUD, mmUD, and UCB recipients; and post-transplantation cyclophosphamide, cyclosporine, and mycophenolate in the HAPLO recipients. Conditioning regimens were mostly myeloablative (69%).

CD34 selected cells for the treatment of poor graft function after allogeneic stem cell transplantation.

Poor graft function (PGF) is characterized by pancytopenia and a hypoplastic marrow, with complete donor chimerism, usually without severe graft-versus-host disease (GVHD). We report 41 patients with PGF, treated with granulocyte colony-stimulating factor-mobilized CD34 selected cells, at a median interval from transplant of 140 days, without conditioning and without GVHD prophylaxis. Donors were HLA matched siblings (n = 12), unrelated donors (n = 18), or mismatched family members (n = 11).

Experts' considerations on HLA-haploidentical stem cell transplantation.

Recently, novel strategies to control graft-versus-host disease and facilitate engraftment have allowed an increasing number of human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (haploHSCT) to be performed. A meeting was convened to review the biological rationale and the clinical results of various T-cell-depleted (TCD) and T-cell-replete (TCR) HLA-haploidentical 'transplant platforms'. The objective of the meeting was to promote discussion and consent among leading researchers in the field on three main crucial issues for haploHSCT: (i) eligibility criteria, (ii) choice of the most suitable donor, and (iii) choice of the most appropriate transplant platform.

Incidence and outcome of invasive fungal diseases after allogeneic stem cell transplantation: a prospective study of the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

Epidemiologic investigation of invasive fungal diseases (IFDs) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be useful to identify subpopulations who might benefit from targeted treatment strategies. The Gruppo Italiano Trapianto Midollo Osseo (GITMO) prospectively registered data on 1858 consecutive patients undergoing allo-HSCT between 2008 and 2010. Logistic regression analysis was performed to identify risk factors for proven/probable IFD (PP-IFD) during the early (days 0 to 40), late (days 41 to 100), and very late (days 101 to 365) phases after allo-HSCT and to evaluate the impact of PP-IFDs on 1-year overall survival.