Concise Review: The Role of Hematopoietic Stem Cell Transplantation in the Treatment of Acute Myeloid Leukemia

Hamilton, Betty K.; Copelan, Edward A.

doi:10.1002/stem.1140

Cited by 47 publications

(29 citation statements)

References 59 publications

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“…1,2 However, even in the absence of morphologically detectable disease at the time of transplantation, relapse remains a major cause of treatment failure post-HCT, 2 demonstrating that microscopy-based evaluations are incapable of detecting clinically relevant amounts of tumor cells. Over the last 2 decades, several techniques were developed that enable the sensitive quantification of minimal residual disease (MRD) amounts in patients with AML in morphological remission.…”

Section: Introductionmentioning

confidence: 99%

Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission

Walter

Buckley²,

Pagel

et al. 2013

Blood

327

258

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• The negative impact of pre-HCT flow cytometrically determined MRD is similar for AML in CR1 and CR2.• Even minute levels of MRD (#0.1%) are associated with adverse outcome.Minimal residual disease (MRD) before myeloablative hematopoietic cell transplantation (HCT) is associated with adverse outcome in acute myeloid leukemia (AML) in first complete remission (CR1). To compare this association with that for patients in second complete remission (CR2) and to examine the quantitative impact of MRD, we studied 253 consecutive patients receiving myeloablative HCT for AML in CR1 (n 5 183) or CR2 (n 5 70) who had pre-HCT marrow aspirates analyzed by 10-color flow cytometry. Three-year estimates of overall survival were 73% (64%-79%) and 32% (17%-48%) for MRD neg and MRD pos CR1 patients, respectively, and 73% (57%-83%) and 44% (21%-65%) for MRD neg and MRD pos CR2 patients, respectively. Similar estimates of relapse were 21% (14%-28%) and 58% (41%-72%) for MRD neg and MRD pos CR1 patients, respectively, and 19% (9%-31%) and 68% (41%-85%) for MRD neg and MRD pos CR2 patients, respectively. Among the MRD pos patients, there was no statistically significant evidence that increasing levels of MRD were associated with increasing risks of relapse and death. After multivariable adjustment, risks of death and relapse were 2.61 times and 4.90 times higher for MRD pos patients (P < .001). Together, our findings indicate that the negative impact of pre-HCT MRD is similar for AML in CR1 and CR2 with even minute levels (£0.1%) as being associated with adverse outcome. (Blood. 2013;122(10):1813-1821

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Section: Introductionmentioning

confidence: 99%

Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission

Walter

Buckley²,

Pagel

et al. 2013

Blood

327

258

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“…5,6 Recently, with the introduction of high-dose chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the application of several novel therapeutic agents, significant advances have been made in the outcomes of patients with AL. [7][8][9] However, AL currently remains an incurable malignancy due to the presence of minimal residual disease (MRD). Previous studies have demonstrated that sensitive MRD detection could better estimate the total body burden of leukemic cells and allow for earlier therapeutic intervention prior to overt relapse, which would help to improve clinical outcome of patients with AL.…”

Section: Introductionmentioning

confidence: 99%

Quantitative detection of the human cervical cancer oncogene for monitoring the minimal residual disease in acute leukemia

Qiao

Guo

Ren

et al. 2014

Exp Biol Med (Maywood)

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The human cervical cancer oncogene (HCCR) has been shown to be over-expressed in some solid tumors, and its function is involved in negative regulation of p53 tumor suppressor gene. However, the roles of HCCR in leukemia remain unclear. The present study is to investigate whether the expression levels of HCCR mRNA are associated with clinical prognosis in patients with acute leukemia (AL) and to explore the potential use as a biomarker for monitoring minimal residual disease (MRD) in AL. The mRNA levels of HCCR1 and HCCR2 were quantified by real-time reverse transcription polymerase chain reaction in bone marrow samples from 80 adult de novo AL patients and 20 normal healthy donors. The expressions of HCCR1 and HCCR2 were significantly higher in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) than those in healthy donors (P < 0.01), but there was no significant difference between AML and ALL (P > 0.05). Besides white blood cell count, we did not find any significant correlation between HCCR expression and clinical characteristics, such as age, sex, CD34 antigen expression, and response to chemotherapy. HCCR was monitored in 12 cases during remission and/or relapse. Significant reductions of both HCCR1 and HCCR2 mRNA levels were observed in patients who had achieved complete remission after chemotherapy but not in patients with non-responsive. However, an increased HCCR expression was detected in these patients who relapsed. Our findings suggest that HCCR gene is over-expressed in AL patients and may be as a useful biomarker for monitoring MRD in AL.

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“…Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most effective therapy for leukemia and other malignant diseases [1]. Its major complications are graft-versus-host disease (GvHD), infections, and leukemia relapse [2,3].…”

Section: Introductionmentioning

confidence: 99%

Donor Natural Killer Cells and Their Therapeutic Potential in Allogeneic Hematopoietic Stem Cell Transplantation

Hu¹,

Liu²

2017

Natural Killer Cells

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Natural killer (NK) cells were first identified and named for their "natural" cytotoxicity to reject bone-marrow allografts in lethally irradiated mice. Different from T cells, NK cells require no prior sensitization or immunization to lyse transformed or virally infected target cells and are non-major histocompatibility complex (MHC)-restricted. However, recent progress in understanding of NK cells biology has proved that NK cells share some similar characteristics with T cells. During development, NK cells also undergo "education" according to "missing self" principle, thereby become mature and acquire effector function. The discovery that NK cells are able to "remember" prior certain stimulations indicates they may also contribute to adaptive immunity. After hematopoietic stem cell transplantation (HSCT), NK cells are the first donor-derived lymphogenous cells to reconstitute and alloreactivitiy of donor-derived NK cells have been shown to mediate graft-versus-leukemia (GvL) effect rather than to induce graft-versus-host disease (GvHD). These properties make donor-derived NK cells appealing for applications to benefit the outcome of HSCT. Here, we will review the improved understanding of NK cell biology, discuss characteristics of donor-derived NK cells which are associated with beneficial outcome of HSCT and explore novel methodologies that enhance the therapeutic effect of donor NK cells.

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Concise Review: The Role of Hematopoietic Stem Cell Transplantation in the Treatment of Acute Myeloid Leukemia

Cited by 47 publications

References 59 publications

Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission

Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission

Quantitative detection of the human cervical cancer oncogene for monitoring the minimal residual disease in acute leukemia

Donor Natural Killer Cells and Their Therapeutic Potential in Allogeneic Hematopoietic Stem Cell Transplantation

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