Long term follow up of patients after allogeneic stem cell transplantation and transfusion of HSV-TK transduced T-cells

Abstract Abstract 1019 Allogeneic stem cell transplantation is the only curative treatment for myelofibrosis. Here we present a long–term follow up of patients with myelofibrosis treated with reduced-intensity allogeneic stem cell transplantation in the prospective multicenter study conducted by the MDS subcommittee of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT) (study registration NCT 00599547). From 2002 to 2007, a total of 103 patients with primary (63 pts) or post-polycythemia vera and –essential thrombocythemia myelofibrosis (40 pts) from seventeen transplantation centers in three nations were included in the study. There were 62 males and 41 females with a median age of 55 years (range, 32–68 years). Risk profile according to Lille score was low risk with constitutional symptoms (17%), intermediate risk (53%) and high risk (30%). All but three of the patients received peripheral stem cells as stem cell source from either related (n=33) or unrelated donor (n=70) and a conditioning with Busulfan (10mg/kg orally or 8mg/kg intravenously),Fludarabin (180 mg/m2) and antithymocyte-globulin (ATG-Fresenius®) according a previously published protocol. According to high-resolution HLA typing, 21 patients had at least one allele or antigen HLA mismatch. From 88 patients with a known JAK2V617F-status 63 harbored the mutation. After a median follow up of 60 months (range 9–109 months), 41 patients had chronic graft vs. host disease which was extensive in the half of cases. The 5-year and 8-year estimated overall survival (OS) was 68% and 65%, respectively with a stable plateau after 5,3 years follow up (Figure-1). Estimated 5-year disease-free survival was 40%. The cumulative incidence of relapse/progression at 3 and 5 years was 22% and 28% and the non-relapse mortality at 1 and at 3 years was 18% ands 21%, respectively.Figure-1Figure-1. Within the overall follow up period, relapse/progression occurred in 28 patients. Twenty one of them were treated with donor-lymphocyte infusions (DLI) and/or a second allogeneic transplantation (n=11). Sixteen of those were at the last follow up alive. The estimated OS of all relapsed patients after a median follow up of 46 months (range 4–62 months) beginning from the time of relapse was 55%. In multivariate analysis advanced age >55years (HR: 4.69, p=0.001), absence of JAK2V617F mutation (HR: 2.50, p=0.02), mismatched donor (HR: 3.62, p=0.002) were significant independent predictors for reduced OS. This update of a prospective trial using reduced intensity conditioning followed by allogeneic stem cell transplantation for myelofibrosis confirmed a very good long-term OS. Relapse still occurs in about 30% and remains the main problem after transplantation. However, with adoptive immunotherapy using DLI or even second allogeneic transplantation a second remission with long term survival can be induced in about 50% of the relapsed patients. Developing methods for remission monitoring and early prediction and treatment of relapse should be the focus of future studies. Disclosures: Kobbe: Celgene: Consultancy, Research Funding; Ortho Biotec: Consultancy. de Witte:Novartis: Consultancy, Honoraria, Speakers Bureau.

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Long-term follow up after allogeneic stem cell transplantation in patients with severe aplastic anemia after cyclophosphamide plus antithymocyte globulin conditioning

Haematologica ◽

10.3324/haematol.2011.050096 ◽

2011 ◽

Vol 97 (5) ◽

pp. 710-716 ◽

Cited By ~ 23

Author(s):

J. Konopacki ◽

R. Porcher ◽

M. Robin ◽

S. Bieri ◽

J.-M. Cayuela ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Aplastic Anemia ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Antithymocyte Globulin ◽

Severe Aplastic Anemia ◽

Long Term Follow Up

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Reduced Intensity Vs. Myeloablative Conditioning Followed By Allogeneic Stem Cell Transplantation for Patients with Myelodysplastic Syndrome: Long Term Follow-up of a Prospective Randomized EBMT Phase III Study (RICMAC-Trial)

Blood ◽

10.1182/blood-2018-99-113340 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1019-1019

Author(s):

Nicolaus Kroeger ◽

Simona Iacobelli ◽

Linda Koster ◽

Dietger Niederwieser ◽

Uwe Platzbecker ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Research Funding ◽

Phase Iii ◽

Long Term Follow Up

Abstract Introduction Retrospective studies in MDS/sAML suggest that reducing the intensity of the conditioning regimen prior to allogeneic stem cell transplantation reduces the risk of non-relapse mortality but is associated with a higher risk of relapse. A higher risk of relapse after RIC was confirmed in a prospective BMT CTN study but the prospective randomized studies from the EBMT for MDS and sAML did not show a difference in outcome after 2 years (J Clin Oncol. 2017 Jul 1;35(19):2157-2164). Here we present a long term follow-up of the study after a median follow-up of 75 months (range 4-150 months). Methods Within the European Society of Blood and Marrow Transplantation (EBMT) we conducted a prospective, multicenter, open label, randomized phase III trial comparing comparing a busulfan based (Busulfan 8mg/kg orally or equivalent dosis intravenously (iv) plus fludarabin 180mg/m²) reduced intensity conditioning regimen (RIC) and a standard myeloablative busulfan (Busulfan 16mg/kg orally or equivalent dosis iv plus cyclophosphamide 120mg/kg) based regimen (MAC) in patients with MDS or sAML (<20 % blasts). Between May 2004 and December 2012, a total of 129 patients were enrolled from 18 centers. Patients were randomly assigned in a 1 : 1 ratio and stratified according to donor, age and blast count. Results In the first report (JCO 2017) the CI of NRM after 1 year was 17% (95% CI 8-26%) after RIC and 25% (95% CI 15-36%) after MAC (p = 0.29). The CI of relapse at 2 years was 17% (95% CI 8-26%) after RIC and 15% (95% CI 6-24%) after MAC (p = 0.6), resulting in a 2 year relapse-free and overall survival of 62% (95% CI 50-74%) and 76% (95% CI 66-87%) after RIC and 58% (95% CI 46-71%) and 63% (95% CI 51-75%) after MAC (p = 0.58 and p = 0.08, respectively). In the current follow-up study, all cases but one who were alive at last report could be updated. The median follow-up is now 75 months in the MAC and 72 months in the RIC arm. Since last follow-up =18 death occurred in both arm (MAC n=8, RIC n=10) 8 relapses (MAC n=4; RIC n=4) and 6 NRM (MAC n=2; RIC n=4). Second allogeneic stem cell transplantation was performed in 18 patients (n=10 in RIC and n=8 in MAC) due to graft failure (n=4) relapse (n=11) and others (n=3). The CI of chronic GvHD at 5 years was 65% (95% CI: 53-78) after RIC and 68% after MAC ((95% CI: 55-81; p = 0.70). At 5 years there was no difference in CI of NRM (22%, 95%CI: 12-32 vs 30% , 95%CI : 19-42, p=0.5) in CI of Relapse (22% , 95% CI: 12-32 vs18%, 95% CI: 8-28, p= 0.7), Relapse free- (57%, 95% CI: 44-69 vs51%, 95% CI: 39-64, p=0.8) and Overall survival (69%, 95% CI: 58-80 vs 53%, 95% CI: 40-65, p=0.15) between RIC and MAC, respectively. Conclusion This long term follow-up of the prospective randomized EBMT trial confirmed early results that RIC resulted in at least similar long term relapse-free and overall survival as MAC in patients with MDS or sAML. The trial was registered under ClinicalTrials.gov Identifier: NCT01203228. Disclosures Niederwieser: Miltenyi: Speakers Bureau; Novartis: Research Funding. Platzbecker:Celgene: Research Funding. Scheid:Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; BMS: Honoraria; Amgen: Honoraria. Stelljes:MSD: Consultancy; Amgen: Honoraria; JAZZ: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Honoraria. Heim:Novartis: Research Funding. Bethge:Miltenyi Biotec GmbH: Consultancy, Honoraria, Research Funding; Neovii GmbH: Honoraria, Research Funding. Kobbe:Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Other: Travel Support, Research Funding.

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