Transplacental trafficking of maternal and fetal cells during pregnancy establishes long-term reciprocal microchimerism in both mother and child. Consequently, the maternal immune system may become... Show moreTransplacental trafficking of maternal and fetal cells during pregnancy establishes long-term reciprocal microchimerism in both mother and child. Consequently, the maternal immune system may become sensitized to paternal histocompatibility antigens. It has been hypothesized that mother's "exposure" to paternal HLA haplotype antigens during pregnancy may affect the outcome of hematopoietic stem cell transplantation (HSCT) when the mother serves as a donor for the child. In T cell-depleted HLA-haploidentical HSCT, maternal donors have been associated with improved transplantation outcomes. The present retrospective multicenter study, conducted on behalf of the Cellular Therapy and Immunobiology Working Party of the European Society of Blood and Marrow Transplantation, involved 409 patients (102 pediatric and 307 adult) with acute leukemia who underwent HLA-haploidentical HSCT. The goal of the study was to evaluate the role of maternal donors in a large cohort of haploidentical transplantation recipients. Transplantation from maternal donors was associated with a lower relapse incidence in T cell-depleted HSCTs (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.16 to 3.92; P = .018) as well as in a limited series of unmanipulated in vivo T cell-depleted HSCTs (HR, 4.15; 95% CI, 0.94 to 18.35; P= .06), along with better graft-versus-host disease/relapse-free survival (GRFS) in T cell-depleted HSCT (HR, 1.67; 95% CI, 1.02 to 2.73; P = .04). These results indicate that the mother is the preferred donor to provide better GRFS in T cell-depleted HLA-haploidentical HSCT for acute leukemia. Show less
Felber, M.; Steward, C.G.; Kentouche, K.; Fasth, A.; Wynn, R.F.; Zeilhofer, U.; ... ; European Soc Immunodeficiencies ES 2020
Reduced-intensity/reduced-toxicity conditioning and allogeneic T-cell replete hematopoietic stem cell transplantation are curative in patients with hemophagocytic lymphohistiocytosis (HLH).... Show moreReduced-intensity/reduced-toxicity conditioning and allogeneic T-cell replete hematopoietic stem cell transplantation are curative in patients with hemophagocytic lymphohistiocytosis (HLH). Unstable donor chimerism (DC) and relapses are clinical challenges. We examined the effect of a reduced-intensity conditioning regimen based on targeted busulfan to enhance myeloid DC in HLH. The European Society for Bone and Marrow Transplantation-approved reduced-intensity conditioning protocol comprised targeted submyeloablative IV busulfan, IV fludarabine, and serotherapy comprising IV alemtuzumab (0.5-0.8 mg/kg) for unrelated-donor and IV rabbit anti-T-cell globulin for related-donor transplants. We assessed toxicity, engraftment, graft-versus-host disease (GHVD), DC in blood cell subtypes, and overall survival/event-free survival. Twenty-five patients from 7 centers were treated (median age, 0.68 year). The median total dose and cumulative area under the curve of busulfan was 13.1 mg/kg (6.4-26.4) and 63.1 mg/L x h (48-77), respectively. Bone marrow, peripheral blood stem cell, or cord blood transplants from HLA-matched related (n = 7) or unrelated (n = 18) donors were administered. Donor cells engrafted in all patients (median: neutrophils d+20/platelets d128). At last follow-up (median, 36 months; range, 8-111 months), the median DC of CD151 neutrophils, CD3(+) T cells, and CD16(+)56(+) natural killer cells was 99.5% (10-100), 97% (30-100), and 97.5% (30-100), respectively. Eight patients (32%) developed sinusoidal obstruction syndrome, resolving after defibrotide treatment. The 3-year overall survival and event-free survival rates were both 100%. None of the patients developed acute grade III to IV GHVD. Limited chronic GVHD was encountered in 4%. This regimen achieves excellent results with stable DC in patients with HLH. Show less
Halkes, C.; Wreede, L.C. de; Knol, C.; Simand, C.; Aljurf, M.; Tbakhi, A.; ... ; European Soc Blood Marrow 2019
To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to... Show moreTo specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n = 3), acquired hemo- philia (n = 3), autoimmune thrombocytopenia (n = 3), antiphospholipid syndrome (n = 2), thyroiditis (n = 12), blocking thyroid-stimulating hormone receptor antibody (n = 1), Graves disease (n = 2), myasthenia gravis (n = 1), rheumatoid arthritis (n = 2), sarcoidosis (n = 2), vasculitis (n = 1), psoriasis (n = 1), and psoriatic arthritis (n = 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% +/- 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34(+) graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT. (Blood. 2011;118(6):1693-1698) Show less
Daikeler, T.; Labopin, M.; Gioia, M. di; Abinun, M.; Alexander, T.; Miniati, I.; ... ; Farge, D. 2010
