Early (Day −7) versus Conventional (Day −1) Inception of Cyclosporine-A for Graft-versus-Host Disease Prophylaxis after Unrelated Donor Hematopoietic Stem Cell Transplantation in Children. Long-Term Results of an AIEOP Prospective, Randomized Study

We carried out a randomized, multicenter study comparing the inception of cyclosporine- A (CsA) on day –7 to conventional CsA (on day –1) to evaluate the influence of this modification on graft-versus-host disease (GVHD), treatment-related mortality (TRM), relapse rate (RR), and event-free survival (EFS) in children with hematologic malignancies given unrelated donor (UD) hematopoietic stem cell transplantation (HSCT). Between 1997 and 2002, 152 children transplanted for acute leukemia (102), myelodysplastic syndromes (23), chronic myelogenous leukemia (20), and non-Hodgkin lymphoma (7) were enrolled in the study and randomized to receive either early CsA (group 1, N = 72) or conventional CsA (group 2, N = 80), after stratification according to HLA compatibility and disease phase. The cumulative incidence of both grade II-IV and grade II-IV acute GVHD (aGVHD), as well as of chronic GVHD (cGVHD), did not differ between the 2 groups. No significant differences were observed also with regard to TRM and RR. The 8-year Kaplan-Meier estimates of EFS were 56% in group 1, and 46% in group 2 (P = NS). In the Cox model, advanced disease phase, male recipient, older donor, and occurrence of grade III-IV aGVHD predicted inferior overall EFS. These data indicate that early inception of CsA does not improve posttransplantation outcome of children with hematologic malignancies given UD-HSCT

Allogeneic hematopoietic cell transplantation from unrelated donors in multiple myeloma: study from the italian bone marrow donor registry.

AbstractTo evaluate trends in allografting from unrelated donors, we conducted a study on 196 consecutive myeloma patients transplanted between 2000 and 2009 in Italy. Twenty-eight percent, 37%, and 35%, respectively, received myeloablative, reduced-intensity, and nonmyeloablative conditioning. In these 3 cohorts, 1-year and 5-year transplantation-related mortalities were 28.8% and 37.0%, 20.3% and 31.3%, and 25.0% and 30.3%, respectively (P = .745). Median overall survival (OS) and event-free survival from transplantation for the 3 cohorts were 29 and 10 months, 11 and 6 months, and 32 and 13 months, respectively (P = .039 and P = .049). Overall cumulative incidences of acute and chronic graft-versus-host-disease (GVHD) were 46.1% and 51.1%. By Cox multivariate analyses, chronic GVHD was significantly associated with longer OS (hazard ratio [HR], .51; P = .009), whereas the use of peripheral blood stem cells was borderline significant (HR, .55; P = .051). Better response posttransplantation was associated with longer event-free survival (HR, 2.13 to 4.25; P < .001). Acute GVHD was associated with poorer OS (HR, 2.53; P = .001). This analysis showed a strong association of acute and chronic GVHD and depth of response posttransplantation with clinical outcomes. Long-term disease control remains challenging regardless of the conditioning. In the light of these results, prospective trials may be designed to better define the role of allografting from unrelated donors in myeloma

Allelic HLA Matching and Pair Origin Are Favorable Prognostic Factors for Unrelated Hematopoietic Stem Cell Transplantation in Neoplastic Hematologic Diseases: An Italian Analysis by the Gruppo Italiano Trapianto di Cellule Staminali e Terapie Cellulari, Italian Bone Marrow Donor Registry, and Associazione Italiana di Immunogenetica e Biologia dei Trapianti

HLA molecules are important for immunoreactivity in allogeneic hematopoietic stem cell transplantation (HSCT). The Gruppo Italiano Trapianto di Cellule Staminali e Terapie Cellulari, Italian Bone Marrow Donor Registry, and Associazione Italiana di Immunogenetica e Biologia dei Trapianti promoted a retrospective observational study to evaluate HLA matching and the impact of allelic HLA mismatching and non-HLA factors on unrelated Italian HSCT outcomes. From 2012 to 2015, 1788 patients were enrolled in the study. The average donor age was 29 years and the average recipient age was 49 years. As a conditioning regimen, 71% of the patients received myeloablative conditioning. For GVHD prophylaxis, 76% received either antithymocyte or anti-T lymphocyte globulin, cyclosporine A, and methotrexate. Peripheral blood was the stem cell source in 80%. The median duration of follow-up was 53 months. Regarding HLA matching, 50% of donor-recipient pairs were 10/10 matched, 38% had 1 mismatch, and 12% had 2 or more mismatches. A total of 302 pairs shared Italian origin. Four-year overall survival (OS), progression-free survival, GVHD-free relapse-free survival, and relapse rates were 49%, 40%, 22%, and 34%, respectively. The 4-year NRM was 27%, and the 100-day cumulative incidence of grade 65II acute GVHD (aGVHD) was 26%. In multivariate analysis, 9/10 and 648/10 HLA allele-matched pairs were associated with worse OS (P = .04 and .007, respectively), NRM (P = .007 and P < .0001, respectively), and grade III-IV aGVHD (P = .0001 and .01, respectively). Moreover, the incidences of grade II-IV aGVHD (P = .001) and chronic GVHD (P = .002) were significantly lower in Italian pairs. In conclusion, 10/10 HLA matching is a favorable prognostic factor for unrelated HSCT outcome in the Italian population. Moreover, the presence of 2 HLA-mismatched loci was associated with a higher NRM (P < .0001) and grade II-IV aGVHD (P = .006) and a poorer OS (P = .001) compared with 1 HLA-mismatched locus in early or intermediate disease phases. Finally, we found that Italian donor and recipient origin is a favorable prognostic factor for GVHD occurrence

Early (Day -7) versus Conventional (Day -1) Inception of Cyclosporine-A for Graft-versus-Host Disease Prophylaxis after Unrelated Donor Hematopoietic Stem Cell Transplantation in Children. Long-Term Results of an AIEOP Prospective, Randomized Study.

We carried out a randomized, multicenter study comparing the inception of cyclosporine- A (CsA) on day -7 to conventional CsA (on day -1) to evaluate the influence of this modification on graft-versus-host disease (GVHD), treatment-related mortality (TRM), relapse rate (RR), and event-free survival (EFS) in children with hematologic malignancies given unrelated donor (UD) hematopoietic stem cell transplantation (HSCT). Between 1997 and 2002, 152 children transplanted for acute leukemia (102), myelodysplastic syndromes (23), chronic myelogenous leukemia (20), and non-Hodgkin lymphoma (7) were enrolled in the study and randomized to receive either early CsA (group 1, N = 72) or conventional CsA (group 2, N = 80), after stratification according to HLA compatibility and disease phase. The cumulative incidence of both grade II-IV and grade II-IV acute GVHD (aGVHD), as well as of chronic GVHD (cGVHD), did not differ between the 2 groups. No significant differences were observed also with regard to TRM and RR. The 8-year Kaplan-Meier estimates of EFS were 56% in group 1, and 46% in group 2 (P = NS). In the Cox model, advanced disease phase, male recipient, older donor, and occurrence of grade III-IV aGVHD predicted inferior overall EFS. These data indicate that early inception of CsA does not improve posttransplantation outcome of children with hematologic malignancies given UD-HSCT

Donor safety: the role of the WMDA in ensuring the safety of volunteer unrelated donors: clinical and ethical considerations

Since the beginning of hematopoietic stem cell harvesting from volunteer unrelated donors, ensuring donor safety has been a necessary goal of all parties involved in the process. As donation of BM or PBSCs is not in the interest of the donor's own physical health, donor registries and transplantation centers must take into account both medical and ethical aspects involved in the donation procedure. One of the principal goals leading to the formation of the World Marrow Donor Association (WMDA) was to establish internationally acceptable standards for all aspects of unrelated donor care. Bone Marrow Transplantation (2010) 45, 832-838; doi:10.1038/bmt.2010.2; published online 22 February 201

Donor safety: the role of the WMDA in ensuring the safety of volunteer unrelated donors: clinical and ethical considerations

Since the beginning of hematopoietic stem cell harvesting from volunteer unrelated donors, ensuring donor safety has been a necessary goal of all parties involved in the process. As donation of BM or PBSCs is not in the interest of the donor's own physical health, donor registries and transplantation centers must take into account both medical and ethical aspects involved in the donation procedure. One of the principal goals leading to the formation of the World Marrow Donor Association (WMDA) was to establish internationally acceptable standards for all aspects of unrelated donor care. Bone Marrow Transplantation (2010) 45, 832-838; doi:10.1038/bmt.2010.2; published online 22 February 2010Transplantation and immunomodulatio

HLA matching affects clinical outcome of adult patients undergoing haematopoietic SCT from unrelated donors: a study from the Gruppo Italiano Trapianto di Midollo Osseo and Italian Bone Marrow Donor Registry.

The importance of HLA donor-recipient matching in unrelated haematopoietic SCT (HSCT) is the subject of debate. In this retrospective study, we analyzed 805 adult patients from the Italian Registry receiving HSCT for a haematological malignancy from January 1999 to June 2006 and correlated the degree of HLA matching with transplant outcome. All patient-donor pairs had high-resolution typing at HLA-A, -B, -C, -DRB1 and -DQB1. There was a significantly higher risk of overall mortality, non-relapse mortality, graft failure and acute GVHD (aGVHD) for patients receiving HSCT from an unrelated donor with one or more low- or high-resolution mismatch/es (Mm/s). When only a single HLA Mm is present (9/10 matched pairs), mortality risk is higher than among 10/10 matched pairs in patients transplanted with acute leukaemia in the first CR ('early' patients) but not in the other patients (advanced patients): HR = 1.69, 95% CI = 0.94-3.02, P = 0.08; HR = 1.03, 95% CI = 0.80-1.32, P = 0.82, for early and advanced patients, respectively. These results confirm that the advantage of a 10/10 match has a greater effect in early patients, thus suggesting that a 9/10 matched donor can be chosen in patients with advanced disease lacking a rapidly available 10/10 matched one

Donor safety: the role of the WMDA in ensuring the safety of volunteer unrelated donors: clinical and ethical considerations

Since the beginning of hematopoietic stem cell harvesting from volunteer unrelated donors, ensuring donor safety has been a necessary goal of all parties involved in the process. As donation of BM or PBSCs is not in the interest of the donor's own physical health, donor registries and transplantation centers must take into account both medical and ethical aspects involved in the donation procedure. One of the principal goals leading to the formation of the World Marrow Donor Association (WMDA) was to establish internationally acceptable standards for all aspects of unrelated donor care. Bone Marrow Transplantation (2010) 45, 832-838; doi:10.1038/bmt.2010.2; published online 22 February 201