Long-term outcome of allogeneic stem cell transplantation in chronic lymphocytic leukemia: analysis after a minimum follow-up of 5 years

2008 ◽  
Vol 49 (9) ◽  
pp. 1724-1730 ◽  
Author(s):  
Pankaj Malhotra ◽  
William J. Hogan ◽  
Mark R. Litzow ◽  
Michelle A. Elliott ◽  
Dennis A. Gastineau ◽  
...  
Blood ◽  
2010 ◽  
Vol 116 (14) ◽  
pp. 2438-2447 ◽  
Author(s):  
Peter Dreger ◽  
Hartmut Döhner ◽  
Matthias Ritgen ◽  
Sebastian Böttcher ◽  
Raymonde Busch ◽  
...  

Abstract The purpose of this prospective multicenter phase 2 trial was to investigate the long-term outcome of reduced-intensity conditioning allogeneic stem cell transplantation (alloSCT) in patients with poor-risk chronic lymphocytic leukemia. Conditioning was fludarabine/ cyclophosphamide-based. Longitudinal quantitative monitoring of minimal residual disease (MRD) was performed centrally by MRD-flow or real-time quantitative polymerase chain reaction. One hundred eligible patients were enrolled, and 90 patients proceeded to alloSCT. With a median follow-up of 46 months (7-102 months), 4-year nonrelapse mortality, event-free survival (EFS) and overall survival (OS) were 23%, 42%, and 65%, respectively. Of 52 patients with MRD monitoring available, 27 (52%) were alive and MRD negative at 12 months after transplant. Four-year EFS of this subset was 89% with all event-free patients except for 2 being MRD negative at the most recent assessment. EFS was similar for all genetic subsets, including 17p deletion (17p−). In multivariate analyses, uncontrolled disease at alloSCT and in vivo T-cell depletion with alemtuzumab, but not 17p−, previous purine analogue refractoriness, or donor source (human leukocyte antigen-identical siblings or unrelated donors) had an adverse impact on EFS and OS. In conclusion, alloSCT for poor-risk chronic lymphocytic leukemia can result in long-term MRD-negative survival in up to one-half of the patients independent of the underlying genomic risk profile. This trial is registered at http://clinicaltrials.gov as NCT00281983.


2007 ◽  
Vol 13 (8) ◽  
pp. 925-931 ◽  
Author(s):  
John Kuruvilla ◽  
John D. Shepherd ◽  
Heather J. Sutherland ◽  
Thomas J. Nevill ◽  
Janet Nitta ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5087-5087
Author(s):  
Herbert G. Sayer ◽  
Lars-Olof Muegge ◽  
Sebastian Scholl ◽  
Kristina Schilling ◽  
Anne Klink ◽  
...  

Abstract A total of 46 patients (24 female, 22 male) with acute myeloid leukemia (AML) received RIC allogeneic blood stem cell transplants from either fully HLA-compatible family donors (n=14) or unrelated HLA-compatible donors (n=32) between 3/1999 and 3/2007. The unselected consecutive single centre study patients (median age: 52 years, range: 22–64) were at high risk for treatment-related complications (older age, previous infectious complications, impaired organ function). 67% (n=31) of the cohort were not in first remisson but in an advanced status of AML. All patients received 30 mg·m−2 Fludarabine i.v. day −10 to −5, Busulfan 4mg·kg−1 orally day −5 to −4, and 10 mg·kg−1 i.v. Antithymocyteglobulin (ATG-Fresenius®) day −4 to −1 as RIC prior to allogeneic stem cell transplantation. A median of unselected 6.8 x 106 CD-34 positive stem cells (range: 1.9–14.3) were given. GvHD-prophylaxis consisted of Cyclosporin 3mg·kg−1 continuous infusion in case of 10/10 HLA compatibility donor situation (n=34), with the addition of mycophenolate mofetil 2gr. i.v. primarily starting from day +10 in one antigen mismatched HLA-unrelated donor situation (n=12). Nine patients (19.6%) died of therapy related mortality, due to GvHD (n=3), infections (n=4), or both (n=2). Relapses occurred in 18 patients (39%), in five patients even more than one year after transplantation. The median observation time of the study group was 19 months (range: 3–101), the product-limit estimates (Kaplan-Meier) of overall survival (OS) at 36 months were 0.48 (±0.08), of event-free survival (EFS) 0.44 (±0.08), respectively. Figure Figure Disease-status (remisson vs. advanced) failed to have a significant impact in OS or EFS, whereas donor status (related vs. unrelated) resulted in OS at 24 months 0.76 (±0.12) for related donors and 0.4 (±0.09) for unrelated donors (p=0.017, log-rank test). RIC with Fludarabine/Busulfan/ATG prior to allogeneic stem cell transplantation results in a consistently sustained long-term outcome for this otherwise adverse patient subgroup, favouring family-matched donor selection.


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