Italian Bone Marrow Donor Registry Research Articles

HLA-A, -B, -C and -DRB1 Association with Autism Spectrum Disorder Risk: A Sex-Related Analysis in Italian ASD Children and Their Siblings.

Autism Spectrum disorders (ASD) are diagnosed more often in males than in females, by a ratio of about 3:1; this is likely to be due to a difference in risk burden between the sexes and/or to "compensatory skills" in females, that may delay the diagnosis of ASD. Identifying specific risk factors for ASD in females may be important in facilitating early diagnosis. We investigated whether HLA- class I: -A, -B, -C and class II -DRB1 alleles, which have been suggested to play a role in the development of ASD, can be considered as sex-related risk/protective markers towards the ASD. We performed HLA allele genotyping in 178 Italian children with ASD, 94 healthy siblings, and their parents. HLA allele distribution was compared between children with ASD, sex-matched healthy siblings, and a cohort of healthy controls (HC) enrolled in the Italian bone marrow donor registry. Allele transmission from parents to children with ASD and their siblings was also assessed. Our findings suggest that HLA-A*02, B*38, and C*12 alleles are more frequently carried by females with ASD compared to both HC and healthy female siblings, indicating these alleles as potential risk factors for ASD in females. Conversely, the HLA-A*03 allele was more commonly transmitted to healthy female siblings, suggesting it might have a protective effect. Additionally, the HLA-B*44 allele was found to be more prevalent in boys with ASD, indicating it is a potential risk factor for male patients. This is the first Italian study of sex-related HLA association with ASD. If confirmed, these results could facilitate early ASD diagnosis in female patients, allowing earlier interventions, which are crucial in the management of neurodevelopmental disorders.

SARS-COV-2 screening in allogeneic hematopoietic stem cell donors: Implications for the evaluation process and eligibility

IntroductionSoon after the onset of the SARS-CoV-2 pandemic, viral screening by nasopharyngeal swab became mandatory for allogeneic hematopoietic stem cell (HSC) donor eligibility.MethodsWe described our monocenter experience with allogeneic HSC donors from February 1 to the October 31, 2020 to verify whether the introduction of SARS-CoV-2 screening altered the donor eligibility and/or entailed a prolongation of the evaluation process.ResultsA total of 21 allogeneic HSC donors were screened during the above-mentioned period upon request by the local transplant physicians or by the Italian Bone Marrow Donor Registry; among the HSC donors (n = 17) who completed the eligibility process and further received the nasopharyngeal swab, all but one were negative for the presence of SARS-CoV-2. The positive donor remained asymptomatic for the whole duration of the infection, which lasted six weeks. However, he was temporarily excluded from donation. The median duration of the evaluation process was not significantly different, compared to the same period of 2019 (p-value = 0.11).ConclusionThe mandatory SARS-CoV-2 screening in allogeneic HSC donors allowed for the detection of 6% positivity in this monocenter series over a 9-month period. Despite the inconvenience of this unexpected non-eligibility, the exclusion of a SARS-CoV-2 positive donor represented an important safety measure for the donor, with respect to a new and still partially unknown virus. The screening did not alter the length of the donor evaluation and thus, did not cause a delay in the eligibility process.

Availability of HLA-allele-matched unrelated donors and registry size: Estimation from haplotype frequency in the Italian population

In Italy, an HLA-matched unrelated donor is currently the primary donor when a HLA matched sibling is not found for allogeneic haematopoietic stem cell transplantation (HSCT). Better outcomes for transplantation require optimal matching between donor and recipient at least at the HLA-A, -B, -C, and -DRB1 loci; therefore, the availability of HLA-matched unrelated donors is important. The enormous HLA polymorphism has always necessitated registries with a large number of individuals in order to be able to provide well-matched donors to a substantial percentage of patients. In order to increase the efficiency of the Italian Bone Marrow Donor Registry (IBMDR) in providing Italian patients with a suitable donor, the probability of finding an HLA-A, -B, -C, and -DRB1 allele-matched (8/8) or a single mismatch unrelated donor (7/8) was estimated in this study according to IBMDR size. Using a biostatistical approach based on HLA haplotype frequencies of more than 100,000 Italian donors enrolled in the IBMDR and HLA-typed at high-resolution level, the probability of finding an 8/8 HLA-matched donor was 23.8%; 33.4%; and 41.4% in simulated registry sizes of 200,000; 500,000; and 1,000,000 donors; respectively. More than 2 million recruited donors are needed to increase the likelihood of identifying an HLA 8/8 matched donor for 50% of Italian patients.If one single mismatch at HLA I class loci was accepted, the probability of finding a 7/8 HLA-matched donor was 62.8%; 73.7%; and 80.3% in 200,000 donors; 500,000; and 1,000,000 donors; respectively.Using the regional haplotype frequencies of IBMDR donors, the probability of recruiting a donor with a new HLA phenotype, in the different Italian regions, was also calculated. Our findings are highly relevant in estimating the optimal size of the national registry, in planning a cost-effective strategy for donor recruitment in Italy, and determining the regional priority setting of recruitment activity in order to increase the phenotypic variability of IBMDR as well as its efficiency.

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 ≥II acute GVHD (aGVHD) was 26%. In multivariate analysis, 9/10 and ≤8/10 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.

Correlation of the two most frequent HLA haplotypes in the Italian population to the differential regional incidence of Covid-19

BackgroundUnderstanding how HLA polymorphisms may affect both susceptibility, course and severity of Covid-19 infection could help both at the clinical level to identify individuals at higher risk from the disease and at the epidemiological one to explain the differences in the epidemic trend among countries or even within a specific country. Covid-19 disease in Italy showed a peculiar geographical distribution from the northern most affected regions to the southern ones only slightly touched.MethodsIn this study we analysed the regional frequencies for the most common Italian haplotypes from the Italian Bone Marrow Donor Registry (HLA-A, -B, -C and -DRB1 at four-digit level). Then we performed Pearson correlation analyses among regional haplotypes estimated frequency in the population and Covid-19 incidence and mortality.ResultsIn this study we found that the two most frequent HLA haplotypes in the Italian population, HLA-A*:01:01g-B*08:01 g-C*07:01g-DRB1*03:01g and HLA-A*02.01g-B*18.01g-C*07.01g-DRB1*11.04g, had a regional distribution overlapping that of Covid-19 and showed respectively a positive (suggestive of susceptibility) and negative (suggestive of protection) significant correlation with both Covid-19 incidence and mortality.ConclusionsBased on these results, in order to define such HLA haplotypes as a factor effectively associated to the disease susceptibility, the creation of national networks that can collect patients’ samples from all regions for HLA typing should be highly encouraged.

Organ Procurement and Transplantation in Italy

Organ Procurement and Transplantation in Italy

High Resolution Donor/Recipient HLA Matching Level in Unrelated Hematopoietic Stem Cell Transplantation and Impact on the Transplant Outcome: The Italian Experience on Behalf of GITMO, IBMDR and Aibt

Abstract Introduction: HLA molecules play an important role for immunoreactivity in allogeneic hematopoietic stem cell transplantation (HSCT). To elucidate the effect and the potential identification of "permissive" and "non permissive" I and II class HLA mismatching (mm) loci on the early and long term transplant outcome, we conducted a retrospective/prospective observational analysis on 1789 patients transplanted with unmanipulated haematopoietic stem cells from a volunteer unrelated donor (URD). Methods Between January 2012 to December 2015, 1789 adult patients with a median age of 49 years (18-70) affected by haematological malignant diseases, performed an unrelated HSCT, coordinated by the Italian Bone Marrow Donor Registry (IBMDR). All patients have been typed by high resolution (HR) HLA typing for HLA-A/B/C/DRB1/DQB1 loci, at the start of the donor's search process. Patient and donor characteristics are shown in Table 1. As conditioning regimen and GVHD prophylaxis, 71% of patients received a myeloablative conditioning and 76% a combination of anti-Thymoglobuline, Cyclosporine and Metotrexate short course. Total Body Irradiation was part of conditioning regimen in 14% of cases and PBSC was used as stem cell source in 80% of transplants. Median follow for survivors was 38 months (1-76). Regarding to the allelic compatibility, 890 (50%) of donor/recipient (D/R) pairs were 10/10 HLA matched, 677 (38%) showed 1 mm for A, B, C, DRB1 or DQB1 in 249, 141, 173, 2 and 112 cases, respectively and 222 (12%) received HSCT from a 8/10 or less HLA matched donor. Results: Overall 90% and 79% of patients achieved PMN and PLTS engraftment within 30 and 90 days, respectively. Probabilities of 3-y Overall Survival (3-yr OS), Progression Free Survival (3-yr PFS), and Graft Relapse Free Survival (3-yr GRFS) were 52%, 42%, and 30%, respectively. The 3-y CI of Transplant Related Mortality (TRM) was 26%, with a 100-days CI of acute GVHD ≥2 of 26%, whereas the 3-yr CI of chronic GVHD was 30%, of which 10% extensive. Cox multivariate analysis showed that, compared to 10/10 HLA-matched HSCT, 9/10 and ≤8/10 HLA-matched HSCT were associated with worse outcomes in terms of OS (HR 1.16, p=0.04 and HR 1.3, p=0.007, respectively), GRFS (HR 1.2, p=0.005 and HR 1.2, p=0.07, respectively), TRM (HR 1.3, p=0.007 and HR 1.6, p&lt;0.0001, respectively), grade 3-4 aGVHD (HR 1.8, p=0.0001 and HR 1.8, p=0.01, respectively) and cGvHD (HR 1.3, p=0.005 and HR 1.1, p=0.35, respectively). Notably, no significant differences occurred through the comparison between ≤8/10 and 9/10 matching. Univariate comparisons are shown in Figure 1. Moreover, in order to identify permissive and non permissive allelic mismatching, we analyzed the donor/recipient pairs with a single HLA mm with a frequency &gt; 5%: the presence of A02:01 in the patient's HLA, after adjustment for HLA matching at the other loci and other clinical variables known to affect HSCT outcome, was associated with significant higher risk of TRM (HR 1.9, p= 0.03) and worst OS (HR 1.7, p=0.04). Patient's age &gt; 49 years (p&lt;0.0001), advanced disease stage (p&lt;0.0001), presence of 1 or more co- morbidity according to the Sorror Hematopoietic Cell Transplant-Comorbidity Index (p=0.01) were associated with a hazard risk of 1.4, 2, 1.2 for OS and 1.6, 1.75, 1.4 for TRM. Moreover, the Italian origin of recipient and donor resulted in reduced grade 2-4 acute (HR=0.6, p=0.001) and chronic GVHD (p=0.002, HR=0.4). Finally, the Transplant Program expertise (&gt;10 HSCT/year) is associated with reduced TRM (HR 0.8, p=0.0001), HSCT from female donor to male recipient was associated with higher risk of extensive cGvHD (HR 1.4, p=0.03), and CMV negative/negative status versus other combinations had protective effect on development of grade 3-4 aGVHD (HR 0.56, p=0.04). Conclusions: Our large cohort data of homogeneously treated 1789 URD transplants, show that 10/10 HLA matching remains a significantly favorable prognostic factor for OS, TRM, GRFS and acute/chronic GVHD, whereas there are no significant differences between 8/10 and 9/10 matching transplants. Moreover, the HLA A02:01 as single mm seems to play a "non permissive" role. Finally the Italian origin of recipient and donor is related to a reduced development of GVHD probably due to the matching of the extended MHC haplotypes in individuals of the same geographic origin. Disclosures Rambaldi: Amgen Inc.: Consultancy; Pfizer: Consultancy; Celgene: Consultancy; Omeros: Consultancy; Roche: Consultancy; Novartis: Consultancy; Italfarmaco: Consultancy. Vago:Moderna TX: Research Funding; GENDX: Research Funding. Patriarca:Janssen: Other: Advisory role; Jazz: Other: Travel, accommodations, expenses; Medac: Other: Travel, accommodations, expenses; Celgene: Other: Advisory Role; Travel, accommodations, expenses; MSD Italy: Other: Advisory Role.

Quality of harvest and role of cell dose in unrelated bone marrow transplantation: An Italian Bone Marrow Donor Registry–Gruppo Italiano Trapianto di Midollo Osseo Study

In this study, we investigated the factors affecting cell dose harvest and the role of cell dose on outcome. We analysed data from a cohort of 703 patients who underwent unrelated bone marrow transplantation facilitated by IBMDR in GITMO centers between 2002 and 2008. The median-infused cell doses is 3.7 × 108/kg, the correlation between the nucleated cells requested from transplant centers and those harvested by collection centers was adequate. A harvested/requested cells ratio lower than 0.5 was observed only in 3% of harvests. A volume of harvested marrow higher than the median value of 1270 ml was related to a significant lower infused cell dose (χ2: 44.4; P < 0.001). No patient- or donor-related variables significantly influenced the cell dose except for the recipient younger age (χ2: 95.7; P < 0.001) and non-malignant diseases (χ2: 33.8; P < 0.001).The cell dose resulted an independent predictor factor for a better outcome in patients affected by non-malignant disease (P = 0.05) while early disease malignant patients receiving a lower cell dose showed a higher risk of relapse (P = 0.05).

Allogeneic Hematopoietic Cell Transplantation from Unrelated Donors in Multiple Myeloma: Study from the Italian Bone Marrow Donor Registry

To 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.

Screening of related donors and peripheral blood stem cell collection practices at different Italian apheresis centres.

Recommendations on eligibility criteria for donation of haematopoietic stem cells, management of collection of the cells and follow-up mainly concern unrelated donors. The aim of this study was to analyse the screening of related donors and collection practices at different Italian apheresis centres. A questionnaire regarding eligibility criteria for related haematopoietic stem cell donors, their peripheral blood collections and early follow-up was sent to several apheresis units. Data from the full charts of 500 candidates, screened between May 2005 and December 2009, were retrospectively evaluated. The donors' records, eligibility criteria, collections and follow-up are managed differently in each centre. Of the 500 evaluable candidates (51.2% male, 49.8% female; median age 47 years, range 13-77), 26.4% underwent thorough screening according to Italian Bone Marrow Donor Registry standards, while local protocols were applied to 73.6%; 91 candidates (18.2%) proved ineligible for donation. In the end, 352 donors (53.4% male, 46.6% female; median age 45 years, range 16-76) underwent 508 leukaphereses. Central venous catheters were used in 8.0% of donors, mainly in one centre. Unsuitable pre-apheresis peripheral blood parameters were reported in 38.7% of the aphereses. Leukapheresis-related adverse events were recorded in 23.0% of the procedures, with a drop-out rate of 0.2% for severe events. No donation-related fatalities occurred. The CD34+ cell yield was <2×10(6)/kg of recipient's body weight from 1.1% of donors ≥70 years old. More uniformity in donor screening procedures, management of peripheral blood collection and follow-up should be planned at a national level to maximise the safety of related donors.

Outcome of patients activating an unrelated donor search: the impact of transplant with reduced intensity conditioning in a large cohort of consecutive high-risk patients

An unrelated donor (UD) search was submitted to the Italian Bone Marrow Donor Registry between February 2002 and December 2004, for 326 consecutive patients with hematological malignancies, eligible for a reduced intensity conditioning (RIC) UD transplant. Only two regimens were allowed: melphalan, alemtuzumab, fludarabine and total body irradiation of 200 cGy (regimen A) and thiotepa, cyclophosphamide, anti-thymocyte globulin (regimen B). The outcome of patients receiving an UD transplant (n=121) was compared with patients who did not find a donor (n=205), in a time dependent analysis, correcting for time to transplant. The median follow up from activation of donor search was 6.1 years. UD transplant was associated with a significantly better survival in patients with acute leukemia and non-Hodgkin's lymphoma (NHL) whereas only a favorable trend was documented for Hodgkin's disease. No survival benefit was registered for chronic leukemias. The outcome of the two different conditioning regimens was comparable, in terms of survival, transplant-related mortality and graft versus host disease. In conclusion, finding an UD and undergoing a RIC transplant significantly improves survival of patients with acute leukemia and NHL. The advantage is less clear for HD and chronic leukemias. The role of different conditioning regimens remains to be elucidated by prospective clinical trials.

Estimation of human leukocyte antigen class I and class II high-resolution allele and haplotype frequencies in the Italian population and comparison with other European populations

The high-resolution (HR) allele and haplotype frequencies of class I and II human leukocyte antigen (HLA) system were determined in the Italian population from a sample of donors recruited in the Italian Bone Marrow Donor Registry (IBMDR). This study analyzed the HLA-A, -B, -C, -DRB1, and -DQB1 loci. Two different samples were used: donors HR typed at least for one allele, usually when selected for donor-recipient matching (respectively: 3596, 7591, 4715, 57345, and 8196), to make a list of the observed alleles and determine the relative frequencies of the alleles in each class of the corresponding antigen; donors HR randomly typed for both the alleles (respectively: 975, 1643, 1569, 22114, and 2087) to estimate the allele and haplotype frequencies, and two loci linkage disequilibrium. The number of alleles showing a frequency >1% on the total number of observed alleles are 18/75 HLA-A, 28/142 -B, 17/57 -C, 23/154 -DRB1, and 13/31 -DQB1. In each locus they account for more than 88% of the total cumulative frequencies. The most frequent alleles are A*02: 01, B*35: 01, C*04:01, DRB1*07:01, DQB1*03:01. The most frequent five-locus haplotype in the 338 donors randomly typed is A*01: 01-C*07:01-B*08: 01-DRB1*03:01-DQB1*02:01. The genetic comparison of the Italian population with 16 European populations shows a south-north gradient.

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.

NON-Permissive HLA-DPB1 T CELL Epitope Disparities Correlate with Engraftment and Survival after Unrelated Stem Cell Transplantation

Over 80% of stem cell transplantations (SCT) from unrelated donors (UD) are performed across allelic HLA-DPB1 disparities which have been associated with acute graft-versus-host disease (aGvHD) and, in 10/10 matched pairs, protection from disease relapse, while no significant correlation with overall survival (OS) could be revealed so far. We have previously developed an algorithm for non-permissive HLA-DP disparities involving an immunogenic T cell epitope (TCE) encoded by DPB1*0901, *1001 and *1701 (group 1), and, in a weaker form, by DPB1*0301, *1401 and *4501 (group 2) (Zino et al, Blood 2004). Here we report on the analysis of this algorithm in 627 UD SCT facilitated through the Italian Bone Marrow Donor Registry (IBMDR) and the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) between 1999 and 2006, performed for malignant disorders including acute myeloid or lymphoid leukaemia (n=320; 51%) and Hodgkin's or non-Hodgkin's lymphoma (n=86; 13.7%). 242 pairs (38.5%) were matched at the allelic level for HLA-A, B, C, DRB1 and DQB1 (10/10 allele-matched pairs), while the remaining 385 pairs (61.5%) presented at least one mismatch at either of these loci (<10/10 matched pairs). Non-permissive DPB1 TCE disparities were determined by either considering both group 1 and group 2 DPB1 alleles (“2-group model”), or group 1 alleles only (“1-group model”). In line with DPB1 allelic frequencies in the Italian population, non-permissive DPB1 TCE disparities were present in 40% of pairs according to the 2-group model, and in 16% of pairs according to the 1-group model. In the 10/10 matched pairs, the Cox regression probability of engraftment was significantly reduced by the presence of non-permissive TCE disparities in the 2-group model (HR=0.23; C.I. 0.07–0.70, p=0.01) and in the 1-group model (HR=0.25; C.I. 0.08–0.75, p=0.01). Importantly, in the 10/10 matched pairs, the adjusted Cox regression hazards of transplant related mortality (TRM) were significantly increased by the presence of non-permissive TCE disparities in the 2-group model (HR=1.72; C.I. 1.09–2.70, p=0.02) and in the 1-group model (HR=1.71; C.I. 1.01–2.92, p=0.05), resulting in a significant increase in the hazards of overall mortality in the 1-group model (HR=1.66; C.I. 1.07–2.58, p=0.02) which was marked but not statistically significant in the 2-group model (HR=1.38; C.I. 0.96–1.98, p=0.08). These effects of non-permissive TCE DPB1 disparities were completely abrogated by the additional presence of one or more mismatches at either of the other five HLA loci in the <10/10 matched group. Interestingly, the estimated cumulative incidence probability of TRM and OS was similar in the 10/10 matched pairs with non-permissive DPB1 TCE disparities according to the 2-group model and in the <10/10 matched pairs regardless of DPB1 matching status, and worse in the presence of DPB1 TCE disparities according to the 1-group model. No impact of non-permissive DPB1 disparities on the hazards of aGvHD grade 2–4 or disease relapse were observed in neither of the two models. Taken together, our data show, for the first time, a significant association between HLA-DP matching status and survival in UD SCT, suggesting that the avoidance of non-permissive DPB1 TCE disparities according to the 2-group model and, even more so, according to the 1-group model, could significantly improve the clinical success of this treatment by reducing transplant mortality.

Unrelated allogeneic bone marrow donation: short- and long-term follow-up of 103 consecutive volunteer donors.

Between 1992 and 1999, 105 unrelated allogeneic bone marrow collections from 103 volunteer donors (65 males and 38 females; median age 33 years) were carried out in three northern Italian centers (Verona, Bolzano and Padova) affiliated with the Italian Bone Marrow Donor Registry (IBMDR). The average volume of BM collected was equivalent in both genders (1143.1 ml for males and 1054.2 ml for females; P = 0.1), although the average volume collected for unit of body weight and the average post-collection blood volume depletion was higher in females (respectively 17.1 ml/kg and 14.2% in females, 14.8 ml/kg and 12% in males; P= 0.01 and 0.03). There was no statistically significant difference between males and females in the total number of nucleated cells collected. We did not record any acute life-threatening event during or after the bone marrow collections. The most frequent complaint was pain at the collection site (77%) followed by the onset of fatigue (38%) and nausea and vomiting (25%); all of these were short-term problems. Hospitalization was short (average 20.2 h) and donors started their normal daily activities after an average of 5.4 days. We also monitored Hb, serum ferritin levels, WBC and platelet counts in the post-collection period (average follow-up 40.1 months). All donors signed a written informed consent for a further bone marrow collection, if needed. Our findings confirm the short- and long-term safety of allogeneic bone marrow collection in volunteer donors.