Impact of Donor Epstein-Barr Virus Serostatus on the Incidence of Graft-Versus-Host Disease in Patients With Acute Leukemia After Hematopoietic Stem-Cell Transplantation: A Study From the Acute Leukemia and Infectious Diseases Working Parties of the European Society for Blood and Marrow Transplantation.
Styczynski J, Tridello G, Gil L, Ljungman P, Hoek J, Iacobelli S, Ward KN, Cordonnier C, Einsele H, Socie G, Milpied N, Veelken H, Chevallier P, Yakoub-Agha I, Maertens J, Blaise D, Cornelissen J, Michallet M, Daguindau E, Petersen E, Passweg J, Greinix H, Duarte RF, Kröger N, Dreger P, Mohty M, Nagler A, Cesaro S.
J Clin Oncol. 2016 Jul 1;34(19):2212-20
In this important study by the Infectious Disease Working Party from EBMT investigated the outcome of EBV Serostatus on outcome after allogeneic stem cell transplantation for acute leukemia. Therefore, 11,364 patients who underwent allogeneic peripheral-blood or bone marrow transplantation for acute leukemia between 1997 and 2012 were included.
Interestingly, patients receiving grafts from EBV-seropositive donors had the same overall survival as patients who received grafts from EBV-seronegative donors Seropositive donors also had no influence on relapse-free survival, relapse incidence, and nonrelapse mortality. However, in univariate analysis, recipients receiving grafts from seropositive donors had a higher risk of chronic GVHD than those with seronegative donors (40.8% v 31.0%, respectively; P < .001). When adjusting for confounders, higher risk was identified for both acute and chronic GVHD. In seronegative patients with seropositive donors, the HR for chronic GVHD was 1.30 (95% CI, 1.06 to 1.59; P = .039). In seropositive patients with seropositive donors, the HR was 1.24 (95% CI, 1.07 to 1.45; P = .016) for acute GVHD and 1.43 (95% CI, 1.23 to 1.67; P < .001) for chronic GVHD. The authors conclude that donor EBV status significantly influences development of acute and chronic GVHD after allo-HSCT.
High dose therapy and autologous stem cell transplantation in patients with POEMS syndrome: A retrospective study of the Plasma Cell Disorder sub-committee of the Chronic Malignancy Working Party of the European Society for Blood & Marrow Transplantation.
Cook G, Iacobelli S, van Biezen A, Ziagkos D, LeBlond V, Abraham J, McQuaker G, Schoenland S, Rambaldi A, Halaburda K, Rovira M, Sica S, Byrne J, Garcia Sanz R, Nagler A, van de Donk NW, Sinisalo M, Cook M, Kröger N, De Witte T, Morris C, Garderet L.
Haematologica. 2016 Sep 15. pii: haematol.2016.148460. [Epub ahead of print]
POEMS syndrome is a rare para-neoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment can control the disease-related symptom complex. The CMWP of EBMT performed a retrospective study investigating the clinical outcome of autologous stem cell transplantation for patients with POEMS syndrome.
127 patients, who underwent an autologous stem cell transplantation between 1997-2010 with a median age of 50 years (range 26-69) were included. The median time from diagnosis to ASCT was 7.5 months with 32% of patients receiving an autologous stem cell transplantation >12 months from diagnosis. Engraftment was seen in 97% patients and engraftment syndrome was documented in 23% of autologous stem cell transplantation recipients.
Haematological response was characterized as CR in 48.5%, PR in 20.8%, With a median follow-up of 48 months (95%CI 38.3, 58.6), 90% of patients are alive and 16.5% of patients have progressed. The 1-year non-relapse mortality was 3.3%. The 3-year probabilities of PFS and OS are 84% and 94%, respectively with 5-year probabilities of PFS and OS of 74% and 89%.
In a cohort of graft recipients, detailed organ-specific symptom response demonstrated clear symptom benefit after autologous stem cell transplantation especially in relation to neurological symptom control. The data analyzed in this study demonstrates the clinical utility of autologous stem cell transplantation for patients with POEMS syndrome.
A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis.
Speckmann C, Doerken S, Aiuti A, Albert MH, Al-Herz W, Allende LM, Scarselli A, Avcin T, Perez-Becker R, Cancrini C, Cant A, Di Cesare S, Finocchi A, Fischer A, Gaspar HB, Ghosh S, Gennery A, Gilmour K, González-Granado LI, Martinez-Gallo M, Hambleton S, Hauck F, Hoenig M, Moshous D, Neven B, Niehues T, Notarangelo L, Picard C, Rieber N, Schulz A, Schwarz K, Seidel MG, Soler-Palacin P, Stepensky P, Strahm B, Vraetz T, Warnatz K, Winterhalter C, Worth A, Fuchs S, Uhlmann A, Ehl S; P-CID study of the Inborn Errors Working Party of the EBMT.
J Allergy Clin Immunol. 2016 Sep 19. pii: S0091-6749(16)30965-4. doi: 10.1016/j.jaci.2016.07.040. [Epub ahead of print
Absent T-cell immunity resulting in life-threatening infections provides a clear rationale for hematopoetic stem cell transplantation (HSCT) in patients with severe combined immunodeficiency (SCID). Combined immunodeficiencies (CIDs) and "atypical" SCID show reduced, not absent T-cell immunity. If associated with infections or autoimmunity, they represent profound combined immunodeficiency (P-CID), for which outcome data are insufficient for unambiguous early transplant decisions. The Inborn Errors Working Party (IEWP) of EBMT compared natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome. Therefore, the IEWP performed a prospective and retrospective observational study. They recruited nontransplanted patients with P-CID aged 1 to 16 years to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome. A total of 51 patients were includued (median age, 9.6 years). Thirteen of 51 had a genetic diagnosis of "atypical" SCID and 14 of 51 of CID. About half of the patients had less than 10% naive T cells, reduced/absent T-cell proliferation, and at least 1 significant clinical event/year, demonstrating their profound immunodeficiency. Nineteen patients (37%) underwent transplantation within 1 year of enrolment, and 5 of 51 patients died. Analysis of the HSCT decisions revealed the anticipated heterogeneity, favoring an ongoing prospective matched-pair analysis of patients with similar disease severity with or without transplantation. Importantly, so far neither the genetic diagnosis nor basic measurements of T-cell immunity were good predictors of disease evolution. The P-CID study for the first time characterizes a group of patients with nontypical SCID T-cell deficiencies from a therapeutic perspective. Because genetic and basic T-cell parameters provide limited guidance, prospective data from this study will be a helpful resource for guiding the difficult HSCT decisions in patients with P-CID.
Allogeneic stem cell transplantation for patients with myelodysplastic syndrome 70 years of age or older: A retrospective study of the MDS subcommittee of the Chronic Malignancies Working Party (CMWP) of the EBMT.
Heidenreich S, Ziagkos D, de Wreede LC, van Biezen A, Finke J, Platzbecker U, Niederwieser D, Einsele H, Bethge W, Schleuning M, Beelen DW, Tischer J, Nagler A, Glass B, Maertens J, Yáñez L, Beguin Y, Sill H, Scheid C, Stelljes M, Ganser A, Zachée P, Selleslag D, de Witte T, Robin M, Kröger N.
Biol Blood Marrow Transplant. 2016 Oct 5. pii: S1083-8791(16)30390-1. doi: 10.1016/j.bbmt.2016.09.027. [Epub ahead of print
The median age at diagnosis of many hematological malignancies is between 60 and 70 years of age. The introduction of reduced toxicity regimen and better supportive care has led to an increase use of allogeneic stem cell transplantation in older patients with hematological malignancies. In this retrospective analysis the MDS subcommittee of the CMWP evaluated the outcome of 313 patients aged 70 years or older in the EBMT registry with MDS (n=221) and secondary acute myeloid leukemia (sAML) (n= 92) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from related (n=79) or unrelated donors (n=234). Median age at HSCT was 72 years (70-78 years). Conditioning regimen was non-myeloablative (NMA, n=54), reduced-intensity (RIC, n=207) or standard-intensity (MAC, n=52). Allogeneic HSCT for MDS patients' ≥ 70 years was increasingly performed over time. While during 2000-2004 only 16 patients received HSCT, during the period of 2011 to 2013, the number of transplantations increased to 181. The cumulative incidence of non-relapse mortality (NRM) at 1 year and relapse at 3 years was 32% and 28%, respectively, with a 3-year overall survival (OS) of 34%. Good performance, determined by Karnofsky performance status (KPS), and recipients´ sero-negativity for cytomegalovirus (CMV) was associated with a 3-year estimated OS of 43% (p=0.01) and 46% (p=0.002), respectively. Conditioning intensity did not impact survival. The authors concluded that after careful patient selection, allogeneic HSCT can be offered to patients older than 70 years with MDS.
Outcomes after use of two standard ablative regimens in patients with refractory acute myeloid leukaemia: a retrospective, multicentre, registry analysis.
Nagler A, Savani BN, Labopin M, Polge E, Passweg J, Finke J, Kyrcz-Krzemien S, Volin L, Anagnostopoulos A, Aljurf M, Beelen DW, Vigouroux S, Milpied N, Suarez F, Mohty M.
Lancet Haematol. 2015 Sep;2(9):e384-92.
Refractory leukemia can be cured by allogeneic stem cell transplantation However , the best conditioning regimen is still a matter of debate. The Acute Leukemia Working Party (ALWP) of EBMT compared Cyclophosphamide plus intravenous busulfan with cyclophosphamide plus total body irradiation (TBI) in adults with advanced refractory acute myeloid leukaemia before allogeneic haemopoietic stem-cell transplantation (HCT). In this retrospective, multicentre, registry-based study, we obtained data for patients (aged >18 years) with refractory acute myeloid leukaemia in active phase of disease, who had received HCT from an HLA-identical sibling or an unrelated donor after intravenous busulfan plus cyclophosphamide or cyclophosphamide plus TBI conditioning between 2000 and 2012. We obtained data for 514 patients who had received intravenous busulfan plus cyclophosphamide and 338 patients who had received cyclophosphamide plus TBI. The median percentage of blasts before HCT did not differ significantly between groups (20%) in the intravenous busulfan plus cyclophosphamide group vs 16% in the cyclophosphamide plus TBI group. Overall survival at 2 years did not differ between the groups in the univariate analysis (31·2% [95% CI 26·8-35·5] with intravenous busulfan plus cyclophosphamide vs 33·4% [28·1-38·7] wth cyclophosphamide plus TBI; p=0·65). Leukaemia-free survival at 2 years also did not differ between groups (25·0% [95% CI 21·0-29·0] vs 28·4% [23·4-33·5]; p=0·47). In multivariable analysis adjusting for differences between both groups, no difference was noted between the two groups in terms of overall survival (hazard ratio [HR] 0·99 [95% CI 0·83-1·20]; p=0·95) or leukaemia-free survival (HR 0·97 [0·81-1·16]; p=0·71). The authors concluded that the use of intravenous busulfan plus cyclophosphamide is likely to be a valid and efficient alternative to cyclophosphamide plus TBI conditioning regimen for patients with refractory acute myeloid leukaemia, especially for those transplant centres without access to radiation facilities.
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Bone Marrow Transplantation publishes high quality, peer reviewed original research and reviews that address all aspects of basic biology and clinical use of haemopoietic cell transplantation.
The journal also covers all aspects of the research and treatment of transplant-related complications and consequences including quality of life and psychological issues. Basic research studies on topics of relevance are also covered.
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