EBMT NEWSLETTER | July 2014 | Volume 42 - Issue 3

Important dates

Cancer. 2014 May 7. doi: 10.1002/cncr.28768. [Epub ahead of print]

Extreme heterogeneity of myeloablative total body irradiation techniques in clinical practice: A survey of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

Giebel S, Miszczyk L, Slosarek K, Moukhtari L, Ciceri F, Esteve J, Gorin NC, Labopin M, Nagler A, Schmid C, Mohty M.

This survey of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation was designed to explore the current clinical practice in the use of total body irradiation (TBI) in terms of methodology as part of the conditioning regimen of hematopoietic stem cell transplantation. TBI containing protocols are widely used in this setting. A total of 56 centers belonging to 23 countries answered the questionnaire. As one might expect, the final analysis of the survey indicated that TBI was an extremely heterogeneous modality. Total dose (from 8 to 14.4 Gy) as well as dose per fraction (1.65 Gy and 8 Gy) and dose rate were quite variable amongst centers. Treatment unit was not homogenous either. Approximately 93% of the centers used in vivo dosimetries. In most centers lungs were shielded during the radiation procedure but maximum dose accepted to the lungs ranged between 6 to 14.4 Gy). In summary, TBI is a highly heterogeneous procedure in the clinical practice and this fact has to be taken into consideration when designing prospective clinical trials and when analyzing results of retrospective analysis basically in terms of toxicities and side effects. If possible, efforts should be done to try to homogenize this widely used procedure in the transplant field.

Haematologica. 2014 May 9. [Epub ahead of print]
Intravenous busulfan for autologous stem cell transplantation in adult patients with acute myeloid leukemia: a survey of 952 patients on behalf of the Acute Leukemia Working Party of the EBMT.

Nagler A, Labopin M, Gorin NC, Ferrara F, Sanz MA, Wu D, Torres Gomez A, Lapusan S, Irrera G, Guimaraes JE, Botelho Sousa A, Carella AM, Vey N, Arcese W, Shimoni A, Berger R, Rocha V, Mohty M.

This retrospective analysis of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation tries to shed some light in the use of intravenous busulfan combined with cyclophosphamide as conditioning regimen for patients with acute leukemias candidates for an autologous stem cell transplantation. Historically, cyclophosphamide was combined with busulfan administered orally and this combination was the most frequently used in this setting. Intravenous busulfan has more predictable pharmacokinetics and less toxicity than oral busulfan. The analysis included almost 1000 patients with acute myeloid leukemia and autografted with intravenous busulfan-containing protocols, most of them male, median age of 50.5 years, 815 of them in first complete remission and the remaining 137 in second complete remission. This study confirms the efficacy of autologous stem cell transplantation in patients with acute myeloid leukemia, confirms age and cytogenetics as significant prognostic factor for long term outcome, indicates that the combination of intravenous busulfan with melphalan seems to have better disease control and that the use of the intravenous formulation simplifies the autologous procedure making it less toxic with only a minority of patients presenting with severe veno-oclussive disease.


Biol Blood Marrow Transplant. 2014 Jun 6. pii: S1083-8791(14)00328-0. doi: 10.1016/j.bbmt.2014.05.028. [Epub ahead of print]

Outcome of Allogeneic Stem Cell Transplantation for Patients Transformed to Myelodysplastic Syndrome or Leukemia from Severe Aplastic Anemia: A Report from the MDS Subcommittee of the Chronic Malignancies Working Party and the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation.

Hussein AA, Halkes CM, Socié G, Tichelli A, Borne PA, Schaap MN, Foa R, Ganser A, Dufour C, Bacigalupo A, Locasciulli A, Aljurf M, Peters C, Robin M, van Biezen AA, Volin L, De Witte T, Marsh J, Passweg JR, Kröger N; for the Severe Aplastic Anemia and Chronic Malignancies Working Parties of the European Group for Blood and Marrow Transplantation.

This joint effort of the Severe Aplastic Anemia and the Chronic Malignancies Working Parties of the European Group for Blood and Marrow Transplantation investigates the outcome of 140 patients that were allografted for an acute myelogenous leukemia or myelodisplastic syndrome occurring after a severe aplastic anemia. Median age was 29 years and half of the patients were allografted from unrelated donors. As expected, patients allografted in remission or untreated did have a better long- term outcome than patients with refractory disease. Major problem of the procedure was a high non-relapse mortality; 41% at 5 years after transplantation. Nevertheless, the allogeneic procedure was able to prolong survival in almost one half of this population with an otherwise fatal disorder.


 JAMA2014;311(24):2490-2498. doi:10.1001/jama.2014.6368.

Autologous Hematopoietic Stem Cell Transplantation vs Intravenous Pulse Cyclophosphamide in Diffuse Cutaneous Systemic Sclerosis

A Randomized Clinical Trial

Jacob M. van Laar, MD, PhD; Dominique Farge, MD, PhD; Jacob K. Sont, PhD; Kamran Naraghi, MD; Zora Marjanovic, MD; Jérôme Larghero, PharMD, PhD; Annemie J. Schuerwegh, MD, PhD; Erik W. A. Marijt, MD, PhD; Madelon C. Vonk, MD, PhD; Anton V. Schattenberg, MD, PhD; Marco Matucci-Cerinic, MD, PhD; Alexandre E. Voskuyl, MD, PhD; Arjan A. van de Loosdrecht, MD, PhD; Thomas Daikeler, MD; Ina Kötter, MD, PhD; Marc Schmalzing, MD; Thierry Martin, MD, PhD; Bruno Lioure, MD; Stefan M. Weiner, MD; Alexander Kreuter, MD; Christophe Deligny, MD; Jean-Marc Durand, MD, PhD; Paul Emery, MD; Klaus P. Machold, MD; Francoise Sarrot-Reynauld, MD, PhD; Klaus Warnatz, MD; Daniel F. P. Adoue, MD; Joël Constans, MD; Hans-Peter Tony, MD; Nicoletta Del Papa, MD, PhD; Athanasios Fassas, MD; Andrea Himsel, MD; David Launay, MD, PhD; Andrea Lo Monaco, MD, PhD; Pierre Philippe, MD; Isabelle Quéré, MD, PhD; Éric Rich, MD; Rene Westhovens, MD, PhD; Bridget Griffiths, MD; Riccardo Saccardi, MD; Frank H. van den Hoogen, MD, PhD; Willem E. Fibbe, MD, PhD; Gérard Socié, MD, PhD; Alois Gratwohl, MD; Alan Tyndall, MD ;for the EBMT/EULAR Scleroderma Study Group


The publication of the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) Trial in Journal of the American Medical Association (JAMA) represents the happy end of a huge collaborative effort between The European Group for Blood and Marrow Transplantation (EBMT) and the EULAR Scleroderma Study Group. It represents a clear example of how two societies can work together and be partners in order to move forward the specific field and a very interesting model to compare a transplant-based treatment strategy with a non-transplant-based one. In this study, high dose immunosuppressive therapy and autologous stem cell transplantation (ASCT) was compared in terms of efficacy and safety with 12 successive monthly intravenous pulses of cyclophosphamide in patients with early diffuse cutaneous systemic sclerosis. It was a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a EBMT–registered transplant facility.156 patients with early diffuse cutaneous systemic sclerosis were recruited. The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. Seventy-nine patients were randomly assigned to ASCT and the remaining 77 patients to monthly pulses of cyclophosphamide. Not entirely surprisingly, during the first year, there were more events in the ASCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group.  In summary and although ASCT was associated with increased treatment-related mortality in the first year after treatment, it conferred a significant long-term event-free survival benefit.


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