Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison

Cornelissen, Jan J.; Holt, Bronno van der; Verhoef, Gregor; Veer, Mars B. van ‘t; Oers, Marinus H. J. van; Schouten, Harry C.; Ossenkoppele, Gert J.; Sonneveld, Pieter; Maertens, Johan; Kooy, Marinus van Marwijk; Schaafsma, M; Wijermans, Pierre W.; Biesma, Douwe H.; Wittebol, Shulamit; Voogt, P. J.; Baars, Joke W.; Zachée, Pierre; Verdonck, Leo F.; Löwenberg, Bob; Dekker, A. W.

doi:10.1182/blood-2008-07-168625

Cited by 157 publications

(131 citation statements)

References 33 publications

Supporting

Mentioning

119

Contrasting

Unclassified

Order By: Relevance

“…Because a high incidence of relapse is the main cause of treatment failure in adults with ALL, the use of allogeneic stem cell transplantation (SCT) as post-remission therapy has become a widely-accepted strategy. In the setting of myeloablative conditioning (MAC), the graft-versusleukemia (GVL) effect for adult ALL has been definitely confirmed from several "donor vs. no donor" comparisons [8][9][10]. However, nonrelapse mortality (NRM) may counterbalance that favorable overall outcome observed after MAC-SCT in patients with advanced age or comorbidities.…”

Section: Introductionmentioning

confidence: 99%

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

et al. 2013

View full text Add to dashboard Cite

The role of reduced-intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long-term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high-risk ALL in first or second complete remission. All transplants received a uniform strategy of pretransplant chemotherapy and GVHD prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P < 0.001) and higher proportions of transplantation using peripheral blood (93.3% vs. 13.3%; P < 0.001) but otherwise showed similar characteristics. After a median follow-up of 67 months, RIC transplants showed comparable nonrelapse mortality (21.2% vs. 24.3%) and disease-free survival (50.8% vs. 54.9%) to MAC transplants, although relapse risk was higher (34.2% vs. 26.4%; HR, 2.07; P 5 0.019) in multivariate analysis. Other independent factors associated with better outcomes were the presence of chronic GVHD and transplantation in first complete remission. Interestingly, the negative impact of RIC on relapse risk was seen only for Philadelphia-positive ALL transplants (32.7% vs. 19.6%; HR, 3.46; P 5 0.020), while no difference was found between RIC and MAC for Philadelphia-negative ALL transplants (35.0% vs. 32.1%; HR, 1.39; P 5 0.429). RIC can be considered as a reasonable choice for providing a sufficient long-term graft-versus-leukemia effect for adult high-risk ALL patients ineligible for MAC. Am. J. Hematol. 88:634-641,

show abstract

Section: Introductionmentioning

confidence: 99%

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The efficacy of this approach has been evaluated through clinical studies using genetic randomization, in which patients with a HLA-matched sibling donor are allocated to the allogeneic HSCT arm, and those without a donor are placed in the chemotherapy or autologous HSCT arm. [2][3][4][5][6][7][8][9][10] These studies, as well as a meta-analysis of seven similar studies, confirmed that the donor group had a superior outcome compared with the no-donor group, and that autologous HSCT was not superior to chemotherapy in patients with adult ALL in CR1. 11 However, the efficacy of unrelated HSCT in patients with ALL in CR1, who lack an HLA-matched sibling, is still unclear.…”

Section: Introductionmentioning

confidence: 52%

“…The TP of achieving CR2 after relapse in patients who decided to continue chemotherapy in CR1 was estimated to have a baseline value of 0.4 with a plausible range of 0.3-0.5 based on the literature. 10,20,23 Utilities were calculated based on a 10-year survival probability, which was the primary outcome measure, with or without adjusting for QOL. The survival curve nearly reaches a plateau after 5 years, and therefore 'Alive at 10 years' reflects 'Cure of leukemia', which is the primary goal of HSCT.…”

Section: Transition Probabilities and Utilitiesmentioning

confidence: 99%

The role of HLA-matched unrelated transplantation in adult patients with Ph chromosome-negative ALL in first remission. A decision analysis

Kako

Morita

Sakamaki

et al. 2013

Bone Marrow Transplant

View full text Add to dashboard Cite

The efficacy of unrelated transplantation for patients with ALL who lack an HLA-matched sibling remains unclear. We performed a decision analysis to determine the efficacy of myeloablative transplantation from a genetically HLA-A, -B, -DRB1 allele-matched unrelated donor for patients with Ph chromosome-negative ALL aged 21-54 years. The transition probabilities were estimated from the Japan Adult Leukemia Study Group studies (ALL93; n ¼ 80, ALL97; n ¼ 82), and the Japan Marrow Donor Program database (transplantation in first CR (CR1): n ¼ 177). The primary outcome measure was the 10-year survival probability with or without quality of life (QOL) adjustment. Subgroup analyses were performed according to risk stratification based on the WBC count and cytogenetics, and according to age stratification. In all patients, unrelated transplantation in CR1 was shown to be superior in analyses both with and without QOL adjustment (40.8 vs 28.4% and 43.9 vs 29.0%, respectively). A similar tendency was observed in all subgroups. The decision model was sensitive to the probability of leukemia-free survival following chemotherapy and the probability of survival after transplantation in standard-risk and higher-aged patients. Unrelated transplantation in CR1 improves the long-term survival probability in patients who lack an HLA-matched sibling. However, recent improvements in treatment strategies may change this result.

show abstract

“…The 7-year probabilities of DFS for patients receiving zero, one, two and three maintenance chemotherapy agents were 15%, 29%, 58% and 61%, respectively (P ¼ 0.0001). 34 Only four prospective studies designed patients to receive maintenance therapy after auto-SCT, 4,6,7,10 and only 12 --52% patients actually took maintenance therapy. This may lead to an underestimation of the real potency of auto-SCT.…”

Section: Discussionmentioning

confidence: 99%

An auto-SCT-based total therapy resulted in encouraging outcomes in adolescents and young adults with acute lymphoblastic leukemia: report from a single center of China

Huang

et al. 2011

Bone Marrow Transplant

View full text Add to dashboard Cite

Application of auto-SCT in the post-remission therapy for adolescents and young adults (AYAs) with ALL is controversial. We analyzed the outcomes of 79 AYAs (15 --24 years) with ALL who received our designed total therapy protocol with auto-SCT in first CR from 1990 to 2009. The estimated OS and EFS at 5 years for the cohort were 62.8±5.9 and 61.5±5.7%. The cumulative non-relapse mortality and relapse rate at 5 years for the cohort were 7.2 ± 3.1 and 33.6 ± 5.8%. Time to CR 44 weeks was the only independent unfavorable factor associated with OS, EFS and relapse in multivariate analysis. Patients in standard risk (SR) group and high risk (HR) group had better OS (78.3±7.4, 63.8±10.2 vs 38.1±11.6%) and EFS (78.0±7.4, 63.4±9.4 vs 32.4±11.3%), and lower relapse rate (15.9±6.5, 31.5±9.5 vs 65.7±11.8%) compared with patients in very high risk (VHR) group. Our data confirmed that auto-SCT-based total therapy might be an optional treatment strategy for AYAs with ALL in SR. Patients in HR also could get benefit from such schedule. But for those in VHR, allogenetic SCT is still the prior recommendation for the frequent recurrence after auto-SCT.

show abstract

Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison

Cited by 157 publications

References 33 publications

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

The role of HLA-matched unrelated transplantation in adult patients with Ph chromosome-negative ALL in first remission. A decision analysis

An auto-SCT-based total therapy resulted in encouraging outcomes in adolescents and young adults with acute lymphoblastic leukemia: report from a single center of China

Contact Info

Product

Resources

About