[Method and impact of allografts cryopreservation during the Covid-19 pandemic: guidelines from the SFGM-TC]. / Modalités et impact de la cryopréservation des greffons allogéniques en contexte pandémique : recommandations de la SFGM-TC.

The COVID-19 pandemic disorganized the allogeneic stem cell transplantation activities all over the world, with the necessity to cryopreserve allografts to secure the procedure for both the recipient and the donor. Cryopreservation, usually anecdotal, has been used by all the French speaking centers; data collected from 24 centers were assessed in order to determine the impact of cryopreservation on the quality of allografts. Our analysis clearly demonstrates that increasing transit time (more than 48hours) is deleterious for CD34+ recovery, legitimates the slight increase of the requested CD34+ cell dose with respect to the average recovery rate as well as the importance of the quality control on the infused product.

Prognostic Impact of 18F-FDG PET/CT in Patients With Aggressive B-Cell Lymphoma Treated With Anti-CD19 Chimeric Antigen Receptor T Cells.

PURPOSE OF THE REPORT: We aimed to evaluate the role of 18F-FDG PET/CT in predicting patient outcome following chimeric antigen receptor T (CAR T) cells infusion in aggressive B-cell lymphoma. METHODS: 18F-FDG PET/CT data before leukapheresis, before CAR T-cell infusion and 1 month (M1) after CAR T-cell infusion, from 72 patients were retrospectively analyzed. SUVmax, total lesion glycolysis (TLG), metabolic tumor volume (MTV), and parameters describing tumor kinetics were calculated for each 18F-FDG PET/CT performed. The aim was to evaluate the prognostic value of 18F-FDG PET/CT metabolic parameters for predicting progression-free survival (PFS) and overall survival (OS) following CAR T-cell therapy. RESULTS: Regarding PFS, ∆MTVpre-CAR and ∆TLGpre-CAR were found to be more discriminating compared with metabolic parameters at preinfusion. Median PFS in patients with a ∆MTVpre-CAR of less than 300% was 6.8 months (95% confidence interval [CI], 2.8 months to not reached) compared with 2.8 months (95% CI, 0.9-3.0 months) for those with a value of 300% or greater (P = 0.004). Likewise, median PFS in patients with ∆TLGpre-CAR of less than 420% was 6.8 months (95% CI, 2.8 months to not reached) compared with 2.7 months (95% CI, 1.3-3.0 months) for those with a value of 420% or greater (P = 0.0148). Regarding OS, metabolic parameters at M1 were strongly associated with subsequent outcome. SUVmax at M1 with a cutoff value of 14 was the most predictive parameter in multivariate analysis, outweighing other clinicobiological variables (P < 0.0001). CONCLUSIONS: Disease metabolic volume kinetics before infusion of CAR T cells seems to be superior to initial tumor bulk itself for predicting PFS. For OS, SUVmax at M1 might adequately segregate patients with different prognosis.

Umbilical cord blood transplants facilitated by the French cord blood banks network. On behalf of the Agency of Biomedicine, Eurocord and the French society of bone marrow transplant and cell therapy (SFGM-TC).

The public French Cord Blood Banks Network was established in 1999 with the objective of standardizing the practices governing umbilical cord blood (UCB) banking in France. The Network adopted a strategy to optimize its inventory and improve the quality of its banked units based on a quality improvement process using outcome data regularly provided by Eurocord. This study aimed to describe the results, over 10 years, of UCBT facilitated by a national network that used the same criteria of UCB collection and banking and to assess how modifications of banking criteria and unit selection might influence transplant outcomes. Nine hundred and ninety-nine units (593 single-unit and 203 double-unit grafts) were released by the Network to transplant 796 patients with malignant (83%) and non-malignant (17%) diseases. Median cell dose exceeded 3.5 × 107 TNC/kg in 86%. There was a trend to select units more recently collected and with higher cell dose. Neutrophil engraftment was 88.2% (85.7-90.7) and 79.3% (72.6-86.5) respectively for malignant and non-malignant diseases with a trend to faster recovery with higher cell doses. The respective 3-year transplant-related mortality were 31.1% (27.5-35.1) and 34.3% (27.0-43.5). OS was 49% ± 4 in malignant and 62% ± 4 in non-malignant disorders. In multivariate analysis, cell dose was the only unit-related factor associated with outcomes. Our results reflect the benefit on clinical outcomes of the strategy adopted by the Network to bank units with higher cell counts.

[How to perform leukapheresis for procurement of the staring material used for commercial CAR T-cell manufacturing: A consensus from experts convened by the SFGM-TC]. / Condition de réalisation de la cytaphérèse pour la mise à disposition du matériel biologique nécessaire à la production de CAR T-cells commerciaux : avis d'experts proposé par la SFGM-TC.

Chimeric antigen receptor (CAR) T-cells are a new class of cancer treatments manufactured through autologous or allogeneic T cells genetic engineering to induce CAR expression directed against a membrane antigen present at the surface of malignant cells. In Europe, tisagenlecleucel (Kymriah™) has a marketing authorization for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia in children and young adults and for the relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The marketing authorization for axicabtagene ciloleucel (Yescarta™) is the treatment of relapsed/refractory DLBCL and mediastinal B-cell lymphoma. Both products are "living drugs" and genetically modified autologous T cells directed against CD19 which is an antigen expressed throughout B lymphoid differentiation and on many B malignancies. This collaborative work - part of a series of expert works on the topic - aims to provide practical advice to assist collection facilities that procure the starting material i.e. blood mononuclear cells for autologous CAR T-cell manufacturing.

Commercial anti-CD19 CAR T cell therapy for patients with relapsed/refractory aggressive B cell lymphoma in a European center.

Two autologous anti-CD19 chimeric antigen receptors (CAR) T cells (axicabtagene ciloleucel [axi-cel] and tisagenlecleucel [tisa-cel]) are commercially approved in Europe for relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). We performed a retrospective study to evaluate patterns of use, efficacy and safety for axi-cel and tisa-cel. Data from 70 patients who underwent apheresis for commercial CAR T cells between January 2018 and November 2019 in our institution were retrospectively collected. Sixty-one patients were infused. The median age at infusion was 59 years old (range 27-75 years). The median number of prior therapies was 3 (range, 2-6). The overall response rates (ORRs) at 1 month and 3 months were 63% and 45%, respectively, with 48% and 39% achieving a complete response (CR), respectively. After a median follow-up after infusion of 5.7 months, the median progression-free survival (PFS) was 3.0 months (95% CI, 2.8-8.8 months), and the median overall survival (OS) was 11.8 months (95% CI, 6.0-12.6 months). In multivariate analysis, factors associated with poor PFS were the number of previous lines of treatment before CAR T cells (≥4) (P = .010) and a C reactive protein (CRP) value >30 mg/L at the time of lymphodepletion (P < .001). Likewise, the only factor associated with a shorter OS was CRP >30 mg/L (P = .009). Cytokine release syndrome (CRS) of any grade occurred in 85% of patients, including 8% of patients with CRS of grade 3 or higher. Immune cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 28% of patients, including 10% of patients with ICANS of grade 3 or higher. Regarding efficacy and safety, no significant difference was found between axi-cel and tisa-cel. This analysis describes one of the largest real-life cohorts of patients treated with axi-cel and tisa-cel for R/R aggressive B cell lymphoma in Europe.

[Preservation/congelation of hematopoietic stem cell grafts in a pediatric context: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. / Conservation/congélation des greffons de CSH dans un contexte pédiatrique : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 7th allogeneic hematopoietic stem cell transplantation clinical practices harmonization workshop series in September 2016 in Lille, France. The objective of our workshop is to provide a discussion on the conservation and congelation of hematopoietic stem cells in a pediatric setting as well as our recommendations for this technique.

Management of psychiatric complications in unrelated donor before unrelated peripheral hematopoietic stem cell collections.

Allogeneic hematopoietic stem cell transplantation can efficiently treat patients with severe hematological diseases. A human leukocyte antigen-compatible donor is required for performing transplantation. The occurrence of unexpected acute severe diseases in a donor can compromise the feasibility of allogeneic hematopoietic stem cell transplantation. However, when a severe health problem occurs in a donor while the recipient has already received a conditioning regimen, hematologists have to find the best solutions for the recipient, while the team in charge of the donor has to find the best medical solutions for the donor. We describe here the occurrence of psychiatric acute complications in an unrelated donor while the myeloablative conditioning regimen had already been given to the recipient. We report the successive decisions that were made in an emergency based upon the expertise of physicians specialized in hematology, apheresis, cell therapy, and psychiatry to preserve the donor's health and recipient's life.

Using EasyMatch® to anticipate the identification of an HLA identical unrelated donor: A validated efficient time and cost saving method.

In the absence of an HLA matched familial donor, a search for an unrelated donor or cord blood unit is initiated through worldwide registries. Although a first look-up on available HLA information of donors in the "book" at BMDW (Bone Marrow Donor Worldwide) can provide a good estimation of the number of compatible donors, the variety of resolution typing levels requires confirmatory typing (CT) which are expensive and time consuming. In order to help recipient centers in their work. The French donor registry (France Greffe de Moelle/Agence de la Biomedecine) has recently developed a software program called "EasyMatch®" that uses haplotype frequencies to compute the likelihood of phenotypic match in donors according to various typing resolution levels. The goal of our study is to report a single monocentric user-experience with EasyMatch®, demonstrating that its routine use reduced the cost and the delay of the donor search in our center, allowing the definition of a new strategy to search compatible unrelated donors. The strategy was first established on a retrospective cohort of 217 recipients (185 adults and 32 children=before score) and then validated on a prospective cohort of 171 recipients (160 adults and 11 children=after score). For all patients, we calculated the delay between the registration day and the donor identification day, and the number of CT requested to the donor centre. Considering both groups, we could observe a significant decrease of the number of CT from 8 to 2 (p<0,001), and a significant decrease of the median delay to identify a suitable donor from 43 to 31days (p<0.0001). EasyMatch® estimates the number of potentially identical donors, but doesn't foresee availability of the donors. It provides us an easy tracking of mismatches, an estimation of the number of potential donors, the selection of population following ethnic origin of patients and a high prediction when probability is high or low. It affords a new approach of donor search in our daily work and improves the efficiency in the great challenge of the compatible donor identification.

Impact of a change in protected environment on the occurrence of severe bacterial and fungal infections in children undergoing hematopoietic stem cell transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a procedure with a high infection risk. Strict isolation of patients is the rule to prevent such condition. OBJECTIVE: We compared the occurrence of severe infections (bacteremia and invasive fungal infection, IFI) in children undergoing alloHSCT before and after the move to a new protected unit with decreases in isolation methods. METHODS: The study was conducted over a 10-year period. Unit 1 (2002-2007) consisted of laminar airflow rooms where caregivers were required to wear a sterile outfit (gown, gloves, hat, and mask). Unit 2 (2008-2012) included spacious positive air pressure rooms with HEPA filters where only a clean gown and mask were required to be worn. RESULTS: Two hundred eighty-six alloHSCTs were performed (144 in Unit 1 and 142 in Unit 2). We reported a total incidence of 4.78 infections/1000 hospital-days including 4.4 episodes of bacteremia and 0.38 episodes of IFI. There was no statistical difference in the incidence of infections: n = 4.98/1000 hospital-days in Unit 1 vs. n = 4.6/1000 in Unit 2 (P = 0.63). CONCLUSION: The lack of difference in the occurrence of severe infection supports our decision to decrease unnecessary high protection in alloHSCT units to improve children's daily life.

Disease evolution and outcomes in familial AML with germline CEBPA mutations.

In-depth molecular investigation of familial leukemia has been limited by the rarity of recognized cases. This study examines the genetic events initiating leukemia and details the clinical progression of disease across multiple families harboring germ-line CEBPA mutations. Clinical data were collected from 10 CEBPA-mutated families, representing 24 members with acute myeloid leukemia (AML). Whole-exome (WES) and deep sequencing were performed to genetically profile tumors and define patterns of clonal evolution. Germline CEBPA mutations clustered within the N-terminal and were highly penetrant, with AML presenting at a median age of 24.5 years (range, 1.75-46 years). In all diagnostic tumors tested (n = 18), double CEBPA mutations (CEBPAdm) were detected, with acquired (somatic) mutations preferentially targeting the C-terminal. Somatic CEBPA mutations were unstable throughout the disease course, with different mutations identified at recurrence. Deep sequencing of diagnostic and relapse paired samples confirmed that relapse-associated CEBPA mutations were absent at diagnosis, suggesting recurrence was triggered by novel, independent clones. Integrated WES and deep sequencing subsequently revealed an entirely new complement of mutations at relapse, verifying the presentation of a de novo leukemic episode. The cumulative incidence of relapse in familial AML was 56% at 10 years (n = 11), and 3 patients experienced ≥3 disease episodes over a period of 17 to 20 years. Durable responses to secondary therapies were observed, with prolonged median survival after relapse (8 years) and long-term overall survival (10-year overall survival, 67%). Our data reveal that familial CEBPA-mutated AML exhibits a unique model of disease progression, associated with favorable long-term outcomes.

Pharmacokinetic drug interaction between cyclosporine and imatinib in bone marrow transplant children and model-based reappraisal of imatinib drug interaction profile.

BACKGROUND: Previous reports have suggested that imatinib may increase cyclosporine exposure by CYP3A4 inhibition. However, the magnitude of this drug interaction remains unclear. At present, quantitative information about the interaction profile of imatinib is scarce. METHODS: The authors report the effect of imatinib on cyclosporine exposure in 6 pediatric patients with Philadelphia chromosome-positive acute lymphoblastic leukemia who received cyclosporine after hematopoietic stem-cell transplantation. Dose-normalized cyclosporine trough blood concentrations (TBC) were obtained before and after imatinib introduction. In addition, a validated model-based approach was used to derive quantitative predictions of CYP3A4-mediated drug interactions with imatinib as a victim or precipitant drug. RESULTS: The mean dose-normalized cyclosporine TBC significantly increased after 3 to 7 days of imatinib therapy. The modeling approach predicted weak-to-moderate effect of major CYP3A4 inhibitors on imatinib exposure. However, the inhibitory potency of imatinib was found to be similar to that of verapamil, suggesting significant influence of imatinib on the pharmacokinetics of drugs highly metabolized by CYP3A4. Observed increases in cyclosporine dose-normalized TBC of the 6 patients were compatible with model predictions. The observations and predictions suggest that imatinib may substantially increase cyclosporine exposure. CONCLUSIONS: Cyclosporine dose reduction may be necessary to avoid excessive immunosuppressive effect in case of coadministration of imatinib.

Academic difficulties and occupational outcomes of adult survivors of childhood leukemia who have undergone allogeneic hematopoietic stem cell transplantation and fractionated total body irradiation conditioning.

We studied academic and employment outcomes in 59 subjects who underwent allogeneic hematopoietic stem cell transplantation (a-HSCT) with fractionated total body irradiation (fTBI) for childhood leukemia, comparing them with, first, the general French population and, second, findings in 19 who underwent a-HSCT with chemotherapy conditioning. We observed an average academic delay of 0.98 years among the 59 subjects by Year 10 of secondary school (French class Troisième), which was higher than the 0.34-year delay in the normal population (P < .001) but not significantly higher than the delay of 0.68 years in our cohort of 19 subjects who underwent a-HSCT with chemotherapy. The delay was dependent on age at leukemia diagnosis, but not at fTBI. This delay increased to 1.32 years by the final year of secondary school (Year 13, Terminale) for our 59 subjects versus 0.51 years in the normal population (P = .0002), but did not differ significantly from the 1.08-year delay observed in our cohort of 19 subjects. The number of students who received their secondary school diploma (Baccalaureate) was similar to the expected rate in the general French population for girls (observed/expected = 1.02) but significantly decreased for boys (O/E = 0.48; CI: 95%[0.3-0.7]). Compared with 13.8% of the general population, 15.3% of the cancer survivors received no diploma (P = NS). Reported job distribution did not differ significantly between our cohort of childhood cancer survivors and the general population except that more female survivors were employed in intermediate-level professional positions. Academic difficulties after fTBI are common and their early identification will facilitate educational and professional achievement.

Allogeneic hematopoietic stem cell transplantation in Fanconi anemia: the European Group for Blood and Marrow Transplantation experience.

Although allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for patients with Fanconi anemia (FA), published series mostly refer to single-center experience with limited numbers of patients. We analyzed results in 795 patients with FA who underwent first HSCT between May 1972 and January 2010. With a 6-year median follow-up, overall survival was 49% at 20 years (95% confidence interval, 38-65 years). Better outcome was observed for patients transplanted before the age of 10 years, before clonal evolution (ie, myelodysplastic syndrome or acute myeloid leukemia), from a matched family donor, after a conditioning regimen without irradiation, the latter including fludarabine. Chronic graft-versus-host disease and secondary malignancy were deleterious when considered as time-dependent covariates. Age more than 10 years at time of HSCT, clonal evolution as an indication for transplantation, peripheral blood as source of stem cells, and chronic graft-versus-host disease were found to be independently associated with the risk for secondary malignancy. Changes in transplant protocols have significantly improved the outcome of patients with FA, who should be transplanted at a young age, with bone marrow as the source of stem cells.

French multicenter 22-year experience in stem cell transplantation for beta-thalassemia major: lessons and future directions.

Although hematopoietic stem cell transplantation (HSCT) offers curative potential for beta-thalassemia major (beta-TM), it is associated with a variable but significant incidence of graft rejection. We studied the French national experience for improvement over time and the potential benefit of antithymocyte globulin (ATG). Between December 1985 and December 2007, 108 patients with beta-TM underwent HSCT in 21 different French transplantation centers. The majority of patients received a matched sibling transplant (n = 96) and a busulfan- and cyclophosphamide-based conditioning regimen (n = 95), also with ATG in 57 cases. Ninety-five of the 108 patients survived, with a median follow-up of 12 years. Probabilities of 15-year survival and thalassemia-free survival after first HSCT were 86.8% and 69.4%, respectively. Graft failure occurred in 24 patients, 11 of whom underwent a second HSCT. The use of ATG was associated with a decrease in rejection rate from 35% to 10%. Thalassemia-free survival improved significantly with time, reaching 83% in the 54 patients undergoing HSCT after 1994 (median time of HSCT). In view of the increased risk of graft rejection after matched sibling HSCT, current French national guidelines recommend, for all children at risk for beta-TM, the systematic addition of ATG to the myeloablative conditioning regimen and special attention to optimize transfusion and chelation therapy in the pretransplantation period.

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.

Long-term outcomes of hematopoietic stem cell transplantation for severe treatment-resistant autoimmune cytopenia in children.

We analyzed the long-term outcomes of pediatric patients registered in the European Group for Blood and Marrow Transplantation database who underwent hematopoietic stem cell transplantation (HSCT) for severe treatment refractory autoimmune cytopenia. With a median follow-up of 100 months, event-free survival was 54% overall, with no significant difference between allogeneic HSCT (n = 15) and autologous HSCT (n = 7) recipients (58% versus 42%; P = .50). Despite a trend toward failure of response or relapse after autologous HSCT compared with allogeneic HSCT, the difference was not significant (43% versus 13%; P = .30). Treatment-related mortality was high in both HSCT groups (29% and 16%; P = .09). Based on the limited numbers of subjects in this retrospective analysis, both allogeneic and autologous HSCT may induce complete and persistent responses in approximately one-half of pediatric patients with severe refractory autoimmune cytopenia, although treatment-related toxicity is high.

Final height and body mass index after fractionated total body irradiation and allogeneic stem cell transplantation in childhood leukemia.

Impaired linear growth has been reported in patients treated during childhood with allogeneic stem cell transplantation and fractionated total body irradiation (fTBI). The objective of this study was to determine the final height and body mass index (BMI) achieved. Forty-nine patients with leukemia were included and surveyed for more than 5 years. Median age at follow-up was 24.3 years (range, 18.9-35.8) and median follow-up time from allograft was 14.4 years (range, 4.5-21.9). Mean height standard deviation score (s.d.s.) at final examination (-1.1 ± 1.3,) was significantly lower than at fTBI (0.3 ± 1.2; P = .001). Final height s.d.s. was significantly correlated with age at diagnosis, age at fTBI, and target height (P = .001; P < .001; P < .001, respectively). Final height was significantly lower in children transplanted before age 5 (P = .006). Growth hormone treatment (n = 6) had only a modest effect on growth velocity. Mean BMI at follow-up was normal at 19.6 kg/m(2) for boys and 21.2 for girls, but with a significant decrease since allograft only for boys (-1.2 ± 1.5 s.d.s.) (P = .003). In conclusion, final height is decreased; BMI is normal but decreased from fTBI in boys.

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome.

BACKGROUND: Patients with the Shwachman-Diamond syndrome often develop hematologic complications. No risk factors for these complications have so far been identified. The aim of this study was to classify the hematologic complications occurring in patients with Shwachman-Diamond syndrome and to investigate the risk factors for these complications. DESIGN AND METHODS: One hundred and two patients with Shwachman-Diamond syndrome, with a median follow-up of 11.6 years, were studied. Major hematologic complications were considered in the case of definitive severe cytopenia (i.e. anemia <7 g/dL or thrombocytopenia <20 × 10(9)/L), classified as malignant (myelodysplasia/leukemia) according to the 2008 World Health Organization classification or as non-malignant. RESULTS: Severe cytopenia was observed in 21 patients and classified as malignant severe cytopenia (n=9), non-malignant severe cytopenia (n=9) and malignant severe cytopenia preceded by non-malignant severe cytopenia (n=3). The 20-year cumulative risk of severe cytopenia was 24.3% (95% confidence interval: 15.3%-38.5%). Young age at first symptoms (<3 months) and low hematologic parameters both at diagnosis of the disease and during the follow-up were associated with severe hematologic complications (P<0.001). Fifteen novel SBDS mutations were identified. Genotype analysis showed no discernible prognostic value. CONCLUSIONS Patients with Shwachman-Diamond syndrome with very early symptoms or cytopenia at diagnosis (even mild anemia or thrombocytopenia) should be considered at a high risk of severe hematologic complications, malignant or non-malignant. Transient severe cytopenia or an indolent cytogenetic clone had no deleterious value.

Bone marrow versus peripheral blood as the stem cell source for sibling transplants in acquired aplastic anemia: survival advantage for bone marrow in all age groups.

BACKGROUND: Bone marrow has been shown to be superior to peripheral blood, as a stem cell source, in young patients (<20 years of age) with acquired aplastic anemia undergoing a matched sibling transplant. The aim of this study was to test whether this currently also holds true for older patients with acquired aplastic anemia. DESIGN AND METHODS: We analyzed 1886 patients with acquired aplastic anemia who received a first transplant from a human leukocyte antigen identical sibling between 1999 and 2009, with either bone marrow (n=1163) or peripheral blood (n=723) as the source of stem cells. RESULTS: In multivariate Cox analysis negative predictors for survival were: patient's age over 20 years (RR 2.0, P<0.0001), an interval between diagnosis and transplantation of more than 114 days (RR 1.3, P=0.006), no anti-thymocyte globulin in the conditioning (RR 1.6, P=0.0001), a conditioning regimen other than cyclophosphamide (RR=1.3, P=0.008) and the use of peripheral blood as the source of stem cells (RR 1.6, P<0.00001). The survival advantage for recipients of bone marrow rather than peripheral blood was statistically significant in patients aged 1-19 years (90% versus 76% P<0.00001) as well as in patients aged over 20 years (74% versus 64%, P=0.001). The advantage for recipients of bone marrow over peripheral blood was maintained above the age of 50 years (69% versus 39%, P=0.01). Acute and chronic graft-versus-host disease were more frequent in peripheral blood transplants. Major causes of death were graft-versus-host disease (2% versus 6% in bone marrow and peripheral blood recipients, respectively), infections (6% versus 13%), and graft rejection (1.5% versus 2.5%). CONCLUSIONS: This study shows that bone marrow should be the preferred stem cell source for matched sibling transplants in acquired aplastic anemia, in patients of all age groups.