Morphological classification, response to therapy, and survival in 263 adult patients with acute nonlymphoblastic leukemia

Mertelsmann, R; Thaler, H Tzvi; To, L; Gee, TS; McKenzie, S; Schauer, P; Friedman, A; Arlin, Z; Cirrincione, C; Clarkson, B

doi:10.1182/blood.v56.5.773.bloodjournal565773

Cited by 7 publications

(1 citation statement)

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“…Erythroleukaemia is an uncommon disease affecting 3–8% of all patients with acute myeloid leukaemia (AML) 1,2 . It is infrequently seen in patients below the pge of 15 years 3 .…”

Section: Introductionmentioning

confidence: 99%

Erythroleukaemia and daunorubicin‐induced cardiotoxicity in a young boy

Chopra

et al. 1990

Int J Clinical Practice

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“…Erythroleukaemia is an uncommon disease affecting 3–8% of all patients with acute myeloid leukaemia (AML) 1,2 . It is infrequently seen in patients below the pge of 15 years 3 .…”

Section: Introductionmentioning

confidence: 99%

Erythroleukaemia and daunorubicin‐induced cardiotoxicity in a young boy

Chopra

et al. 1990

Int J Clinical Practice

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Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710

Powell

Moser

Stock

et al. 2010

Blood

333

288

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Arsenic trioxide (As 2 O 3 ) is a highly effective treatment for patients with relapsed acute promyelocytic leukemia (APL); its role as consolidation treatment for patients in first remission has not been defined. We randomized 481 patients (age > 15 years) with untreated APL to either a standard induction regimen of tretinoin, cytarabine, and daunorubicin, followed by 2 courses of consolidation therapy with tretinoin plus daunorubicin, or to the same induction and consolidation regimen plus two 25-day courses of As 2 O 3 consolidation immediately after induction. After consolidation, patients were randomly assigned to one year of maintenance therapy with either tretinoin alone or in combination with methotrexate and mercaptopurine. Ninety percent of patients on each arm achieved remission and were eligible to receive their assigned consolidation therapy. Event-free survival, the primary end point, was significantly better for patients assigned to receive As 2 O 3 consolidation, 80% compared with 63% at 3 years (stratified logrank test, P < .0001). Survival, a secondary end point, was better in the As 2 O 3 arm, 86% compared with 81% at 3 years (P ‫؍‬ .059). Disease-free survival, a secondary end point, was significantly better in the As 2 O 3 arm, 90% compared with 70% at 3 years (P < .0001). The addition of As 2 O 3 consolidation to standard induction and consolidation therapy significantly improves event-free and diseasefree survival in adults with newly diagnosed APL. This trial was registered at clinicaltrials.gov (NCT00003934).

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Monocytic AML cells inactivate antileukemic lymphocytes: role of NADPH oxidase/gp91phox expression and the PARP-1/PAR pathway of apoptosis

Aurelius

Thorén

Akhiani

et al. 2012

Blood

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Dysfunction of T cells and natural killer (NK) cells has been proposed to deter- IntroductionAcute myeloid leukemia (AML) is characterized by a deficiency of hematopoietic progenitor and stem cell development with a resulting accumulation of immature myeloid cells in BM. [1][2][3] The current treatment in AML comprises an initial phase of intensive chemotherapy, induction, and consolidation that aims to achieve and maintain complete remission (CR). 4,5 Younger patients may subsequently undergo allogeneic stem cell transplantation, 6 whereas few therapeutic options are available in the postconsolidation phase for other patients. 7 The occurrence of relapse after CR along with the poor postrelapse survival significantly explains the dismal longterm survival of patients with AML. 4,8 In several studies investigators point to a role for lymphocytes, such as cytotoxic T cells and natural killer (NK) cells, in the surveillance of the malignant clone in AML and in determining prognosis. 9 T cells are considered to mediate the graft-versusleukemia reaction that significantly accounts for the reduced rate of leukemic relapse after allogeneic stem cell transplantation, 10,11 and several tumor-associated antigens of relevance to T-cell reactivity are expressed by AML cells. 12 A role for NK cells in surveillance of AML cells was demonstrated, as exemplified by the favorable outcome when authors used transplants with donor/recipient class I disparities, which facilitates NK cell-mediated destruction of residual leukemic cells. 13 In addition, multiple deficiencies of T-and NK-cell functions, with ensuing relapse risk and poor prognosis, have been observed in patients with AML who did not undergo transplantation. [14][15][16][17][18] In earlier studies, investigators demonstrated that nonmalignant phagocytic cells down-modulate lymphocyte functions by producing and releasing NADPH oxidase-derived reactive oxygen species (ROS). [19][20][21][22][23] These findings have formed the basis for the use of a NADPH oxidase inhibitor in conjunction with IL-2 as a relapsepreventive strategy in patients with AML. 24,25 In this study, we monitored the surface expression of gp91 phox , a component of the ROS-generating NADPH oxidase, 26 on leukemic cells recovered from BM and blood of newly diagnosed patients with AML and explored whether ROS produced by leukemic cells compromise Tand NK-cell function. These analyses were performed with cells recovered from patients with defined morphologic subtypes of AML cells on the basis of French-American-British (FAB) classification. 27 We report that AML cells from patients with monocytic forms of AML (FAB classes M4/M5), but not cells from patients with myeloblastic AML (FAB class M2) or immature AML (FAB class M1), express the NADPH oxidase, produce ROS, and trigger extensive apoptosis in adjacent T and NK cells. Our results are suggestive of a novel mechanism of immune evasion in myelomonocytic and monocytic AML. Methods Sampling of BM and peripheral bloodPeripheral blood or BM from 26 untreated...

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Morphological classification, response to therapy, and survival in 263 adult patients with acute nonlymphoblastic leukemia

Cited by 7 publications

References 0 publications

Erythroleukaemia and daunorubicin‐induced cardiotoxicity in a young boy

Erythroleukaemia and daunorubicin‐induced cardiotoxicity in a young boy

Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: North American Leukemia Intergroup Study C9710

Monocytic AML cells inactivate antileukemic lymphocytes: role of NADPH oxidase/gp91phox expression and the PARP-1/PAR pathway of apoptosis

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