Reduced intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia: long term results of a ‘donor’ versus ‘no donor’ comparison

Mohty, Mohamad; Lavallade, Hugues de; El-Cheikh, Jean; Ladaique, Patrick; Faucher, Catherine; Fürst, Sabine; Vey, Norbert; Coso, Diane; Stoppa, A. M.; Gastaut, J. A.; Chabannon, Christian; Blaise, Didier

doi:10.1038/leu.2008.164

Cited by 49 publications

(31 citation statements)

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“…18) are consistent with a report from CIBMTR suggesting 30% of patients aged .65 were living >3 years after RIC-HCT and that age had no effect on outcome (55 patients were aged .65 (median 67, range [65][66][67][68][69][70][71][72][73][74][75][76][77][78] [ (Fig. 19) [103] An analysis comparing patients with and without allo HCT donors ("genetic randomization") reported an advantage for the donor group as a surrogate for RIC [104]. However, donor vs. no donor methodology is less useful with the increasing use of alternative donors [105], emphasizing the important possibility of selection bias in comparisons of allo HCT vs. not [106].…”

Section: In Older Patientssupporting

confidence: 73%

Acute myeloid leukemia: 2016 Update on risk‐stratification and management

Estey

2016

American J Hematol

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Evidence suggest that even patients aged 70 or above benefit from specific AML therapy. The fundamental decision in AML then becomes whether to recommend standard or investigational treatment. This decision must rest on the likely outcome of standard treatment. Hence we review factors that predict treatment related mortality and resistance to therapy, the latter the principal cause of failure even in patients aged 70 or above. We emphasize the limitations of prediction of resistance based only on pre‐ treatment factors and stress the need to incorporate post‐treatment factors, for example indicators of minimal residual disease. We review various newer therapeutic options and considerations that underlie the decision to recommend allogeneic hematopoietic cell transplant. Am. J. Hematol. 91:825–846, 2016. © 2016 Wiley Periodicals, Inc.

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Section: In Older Patientssupporting

confidence: 73%

Acute myeloid leukemia: 2016 Update on risk‐stratification and management

Estey

2016

American J Hematol

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“…[2][3][4][5] Reduced-intensity conditioning (RIC) was introduced to allo-HCT more than a decade ago for patients who are older, had significant co-morbid conditions or poorer performance status. [6][7][8] The anti-neoplastic potency of these RIC HCT regimens relies primarily on the GVL effect rather than ablating all residual leukemic disease. 9 It is clear that patients with active leukemia had more relapse and worse OS after allo-HCT regardless of donor type or patient age.…”

Section: Introductionmentioning

confidence: 99%

Achieving stringent CR is essential before reduced-intensity conditioning allogeneic hematopoietic cell transplantation in AML

Üstün

Wiseman

DeFor

et al. 2013

Bone Marrow Transplant

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Reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (allo-HCT) can cure patients with AML in CR. However, relapse after RIC allo-HCT may indicate heterogeneity in the stringency of CR. Strict definition of CR requires no evidence of leukemia by both morphologic and flow cytometric criteria. We re-evaluated 85 AML patients receiving RIC allo-HCT in CR to test if a strict definition of CR had direct implications for the outcome. These patients had leukemia immunophenotype documented at diagnosis and analyzed at allo-HCT. Eight (9.4%) had persistent leukemia by flow cytometric criteria at allo-HCT. The patients with immunophenotypic persistent leukemia had a significantly increased relapse (hazard ratio (HR): 3.7; 95% confidence interval (CI): 1.3-10.3, P ¼ 0.01) and decreased survival (HR: 2.9; 95% CI: 1.3-6.4, Po0.01) versus 77 patients in CR by both morphology and flow cytometry. However, the pre-allo-HCT bone marrow (BM) blast count (that is, 0-4%) was not significantly associated with risks of relapse or survival. These data indicate the presence of leukemic cells, but not the BM blast count affects survival. A strict morphologic and clinical lab flow cytometric definition of CR predicts outcomes after RIC allo-HCT, and therefore is critical to achieve at transplantation. Keywords: allogeneic hematopoietic cell transplantation; reduced-intensity conditioning regimen; AML; relapse; minimal residual disease; CR INTRODUCTIONAllogeneic hematopoietic SCT (allo-HCT) remains the most effective treatment for most patients with AML. 1 The two main mechanisms by which allo-HCT can cure AML are through the immunologically based GVL effect and leukemic cell cytoreduction by HCT conditioning. 2-5 Reduced-intensity conditioning (RIC) was introduced to allo-HCT more than a decade ago for patients who are older, had significant co-morbid conditions or poorer performance status. [6][7][8] The anti-neoplastic potency of these RIC HCT regimens relies primarily on the GVL effect rather than ablating all residual leukemic disease. 9 It is clear that patients with active leukemia had more relapse and worse OS after allo-HCT regardless of donor type or patient age. [10][11][12][13][14][15] Following allo-HCT, 40-60% of AML patients in CR1 enjoy long-term OS, whereas o20% of refractory or relapsed AML patients survive. 1,11 Yet even for allo-HCT during CR, relapse remains the most frequent complication of allo-HCT. 16 As relapse has been reported more frequently after RIC allo-HCT compared with myeloablative conditioning (MAC) allo-HCT in patients with AML, this suggests heterogeneity in the interpretation of a CR, which may be more important after RIC allo-HCT. [17][18][19][20][21][22][23] The CR definition updated in 2003 24 clearly requires no evidence of leukemia by flow cytometry in addition to the morphologic remission as reported: 'The presence of a unique phenotype (by flow cytometry) identical to what was found in the pretreatment specimen (for example, CD34, CD7 coexpression) should be viewed ...

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“…were not significantly different between the two groups, confirming earlier studies, which had shown that RIC is a viable alternative for older or more comorbid acute myeloid leukemia patients. 3 Regarding NIH-defined GVHD, we found that the cumulative incidence of classic aGVHD was significantly lower in RIC than in MAC patients ( Figure 1a). Also, classic aGVHD occurred significantly later in the RIC cohort (31 days (range: 10-95) for RIC versus 23 days (9-86) for MAC, P ¼ 0.041).…”

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confidence: 85%

“…Patients with RARS and RARS-T were also found to have mutations in JAK2, MPL, TET2 and ASXL1. [3][4][5][6][7][8] However, the clinical relevance and etiology of RS in MDS and MDS/MPN remain unclear due to the lack of specific molecular defects, including recurrent chromosomal abnormalities or mutations. High throughput-next generation sequencing (HT-NGS) is being widely used to identify mutational events in leukemia and other cancers.…”

mentioning

confidence: 99%