Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission

Koreth, John; Schlenk, Richard F.; Kopecky, Kenneth J.; Honda, Sumihisa; Sierra, Jorge; Djulbegoviĉ, Benjamin; Wadleigh, Martha; DeAngelo, Daniel J.; Stone, Richard; Sakamaki, Hisashi; Appelbaum, Frederick R.; Döhner, Hartmut; Antin, Joseph H.; Soiffer, Robert J.; Cutler, Corey

doi:10.1001/jama.2009.813

Cited by 784 publications

(590 citation statements)

References 40 publications

(33 reference statements)

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“…In contrast to the results of meta-analysis studies of the prospective donor vs no-donor comparison, [8][9][10] our patients with and without a related donor had comparable OS. Similar results were obtained if the outcome was compared in terms of RFS (data not shown).…”

Section: Discussioncontrasting

confidence: 99%

“…[2][3][4][5][6][7][8] If we combine the results from those studies, we find that allogeneic HCT during CR1 confers a survival advantage in patients with cytogenetically intermediate and unfavorable risk. [8][9][10] However, such 'donor vs no-donor' studies do not provide an accurate picture of clinical practice, because an HLA-identical sibling is not the only donor source and a substantial proportion of patients without a related donor receive allogeneic HCT from an unrelated donor.…”

Section: Introductionmentioning

confidence: 99%

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Effect of related donor availability on outcome of AML in the context of related and unrelated hematopoietic cell transplantation

Yanada

Kurosawa²,

Yamaguchi

et al. 2012

Bone Marrow Transplant

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Although allogeneic hematopoietic cell transplantation (HCT) from a related donor is effective therapy for younger patients with AML, it remains unknown how the availability of a related donor affects the outcome when unrelated HCT is a treatment option for patients without a related donor. To address this issue, we retrospectively analyzed 605 cytogenetically non-favorable AML patients younger than 50 years for whom a related donor search was performed during first CR (CR1). The 4-year OS was 62% in 253 patients with a related donor and 59% in 352 patients without a related donor (P ¼ 0.534). Allogeneic HCT was performed during CR1 in 62% and 41% of patients with and without a related donor, respectively. Among patients transplanted in CR1, the cumulative incidence of non-relapse mortality was significantly higher in patients without a related donor (P ¼ 0.022), but there was no difference in posttransplant OS between the groups (P ¼ 0.262). These findings show the usefulness of unrelated HCT in younger patients with cytogenetically non-favorable AML who do not have a related donor. The extensive use of unrelated HCT for such patients may minimize the potential disadvantage of lacking a related donor.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of related donor availability on outcome of AML in the context of related and unrelated hematopoietic cell transplantation

Yanada

Kurosawa²,

Yamaguchi

et al. 2012

Bone Marrow Transplant

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“…1 Advances in genomic technologies have identified AML as a genetically heterogenous disease: many patients can now be classified into prognostic subgroups on the basis of their underlying molecular genetic defects, 2 although the indication for HSCT in all intermediate-risk patients in first remission of AML is still debated. 3 The major limitation of HSCT is the risk of treatment-related mortality (TRM), especially among older candidates with comorbidities. 4 As the incidence of AML is highest in people older than 60, reduced-intensity conditioning (RIC) regimens have been developed for over a decade in order to decrease TRM.…”

Section: Introductionmentioning

confidence: 99%

Equivalent outcomes using reduced intensity or conventional myeloablative conditioning transplantation for patients aged 35 years and over with AML

Sébert

Porcher

Robin

et al. 2014

Bone Marrow Transplant

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Allogeneic hematopoietic stem cell transplantation provides the best chance of long-term survival for patients with AML, but is associated with an unpredictable risk of treatment-related mortality. From January 2000 to December 2010, we compared the outcomes for patients with AML aged 35 and over using reduced-intensity conditioning (RIC, N = 60) or conventional myeloablative conditioning (MAC) regimen (N = 72) transplantation. The median follow-up was 47 months (10-134). The 4-year cumulative incidence of non-relapse mortality was 21%. After adjusting for cytogenetic risk, gender donor/recipient mismatch and CD34+ cells, non-relapse mortality was significantly lower with the RIC regimen (P = 0.027). The 4-year cumulative incidence of relapse was 38% and no difference was observed in the adjusted relapse rate between the two groups. The 4-year OS rate was 46%. Using both Cox regression and inverse probability-of-treatment weighted (IPTW) method, a similar OS rate was found with both regimens (adjusted hazard ratios for conventional vs reduced of 1.14 (95% CI 0.67-1.93, P = 0.64) with Cox regression, and 1.14 (95% CI 0.55-2.34, P = 0.73) with IPTW). Until prospective trials are completed, this study supports the use of a reduced-intensity regimen prior to transplantation for patients with AML aged 35 and over. INTRODUCTIONAllogeneic hematopoietic stem cell transplantation (HSCT) provides the best chance for long-term survival and offers the lowest risk of relapse for patients with high-risk AML. 1 Advances in genomic technologies have identified AML as a genetically heterogenous disease: many patients can now be classified into prognostic subgroups on the basis of their underlying molecular genetic defects, 2 although the indication for HSCT in all intermediate-risk patients in first remission of AML is still debated. 3 The major limitation of HSCT is the risk of treatment-related mortality (TRM), especially among older candidates with comorbidities. 4 As the incidence of AML is highest in people older than 60, reduced-intensity conditioning (RIC) regimens have been developed for over a decade in order to decrease TRM. 5 These regimens are now increasingly used to facilitate HSCT in patients with advanced age or medical comorbidities, primarily because RIC regimens are well tolerated and are associated with less toxicity. 6,7 Previously published retrospective analyses suggested similar survival rates, but with a significantly higher risk of relapse after RIC regimen for patients aged 50 and over with AML 8 or for patients with myelodysplastic syndromes. 9 Using unrelated donors (URDs), another retrospective study reported a higher relapse rate in AML patients younger than 50 years after RIC regimen, with a similar leukemia-free survival between the two regimens. 10

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“…Most showed no benefit or marginal benefit with allogeneic SCT [119][120][121][122][123]. A meta-analysis combining the results of many of the randomized trials confirmed the significant benefit of allogeneic SCT in CR in the average patient [124]. The results of the single and randomized studies were limited by several factors: (1) the limited number of patients in each of the studies (not large enough to detect modest but clinically significant benefits); (2) the lead time bias in performing allogeneic SCT; (3) a signification fraction of patients allocated to allogeneic SCT could not undergo the procedure; and (4) the benefit of allogeneic SCT performed in second CR among patient allocated to chemotherapy in first CR.…”

Section: Allogeneic (Or Autologous) Stem Cell Transplantmentioning

confidence: 99%

Acute myeloid leukemia—Major progress over four decades and glimpses into the future

2015

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Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission

Cited by 784 publications

References 40 publications

Effect of related donor availability on outcome of AML in the context of related and unrelated hematopoietic cell transplantation

Effect of related donor availability on outcome of AML in the context of related and unrelated hematopoietic cell transplantation

Equivalent outcomes using reduced intensity or conventional myeloablative conditioning transplantation for patients aged 35 years and over with AML

Acute myeloid leukemia—Major progress over four decades and glimpses into the future

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