Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): results from Cancer and Leukemia Group B 8461.

Byrd, John C.; Weiss, R B; Arthur, DD; Lawrence, David; Baer, Maria R.; Davey, FR; Trikha, E S; Carroll, Andrew J.; Tantravahi, Ramana; Qumsiyeh, Mazin B.; Patil, S.; Moore, J O; Mayer, R. John; Schiffer, Charles A.; Cd, Bloomfield

doi:10.1200/jco.1997.15.2.466

Cited by 219 publications

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“…Byrd et al [10] reported that CD56 expression that was associated with a high incidence of extramedullary manifestations led to poor clinical outcomes in AML with t(8;21) [7,11,20,24]. We only had two patients with extramedullary leukemia at the time of diagnosis and did not evaluate the relationship between CD56 expression and adverse outcomes.…”

Section: Discussionmentioning

confidence: 99%

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Predictable prognostic factor of CD56 expression in patients with acute myeloid leukemia with t(8:21) after high dose cytarabine or allogeneic hematopoietic stem cell transplantation

et al. 2006

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CD56 expression in acute myeloid leukemia (AML) has been associated with extramedullary leukemia and multidrug resistance, but its clinical and prognostic significance has not been clearly identified. This study examined CD56 expression in 37 adult de novo AML patients with t(8:21). CD56 was expressed in 25 cases (67.6%). Complete remission (CR) rates were similar in both groups (91.7% vs. 88.7%; P = 0.73), but the relapse rates differed considerably (60% vs. 25%; P = 0.02). The median duration of disease-free survival (DFS) was significantly shorter in the CD56+ (median, 12.2 ± 6.4 months) than in the CD56À group (median, not reached) (P = 0.02). In addition, the median duration of survival differed significantly in the CD56+ group (median, 14.9 ± 4.4 months) compared with the CD56À group (median, not reached) (P = 0.01). Of the fifteen transplanted patients who achieved CR, allogeneic HST was performed from their siblings. The median duration of DFS in the CD56+ patients was significantly shorter than the CD56À patients (median, 24.4 ± 4.5 months vs. median, not reached; P = 0.02). We concluded that CD56 expression correlates to a reduced DFS and survival for AML patients with t(8:21), including those patients who underwent transplantation. Am. J.

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Section: Discussionmentioning

confidence: 99%

“…The expression of CD56 is one of the most adverse risk factors in patients with AML [5][6][7]. Although CD56 expression in AML with t(8;21) has been associated with extramedullary manifestations [8][9][10][11][12] and multidrug resistance [13,14], its clinical and prognostic significance has not been clearly defined.…”

Section: Introductionmentioning

confidence: 99%

Predictable prognostic factor of CD56 expression in patients with acute myeloid leukemia with t(8:21) after high dose cytarabine or allogeneic hematopoietic stem cell transplantation

et al. 2006

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“…5 Although specific situations exist in which the presence of myeloid sarcoma has little effect on outcome, in general it heralds a poor prognosis. 5,[49][50][51][52] Sites of involvement vary depending on the exact underlying disorder, age of patient and the presentation (eg preceding or concurrent with systemic disease). The tumors consist of populations of blasts, but mixtures of cell types are seen in the more differentiated subtypes.…”

Section: Differential Diagnosismentioning

confidence: 99%

Benign extramedullary myeloid proliferations

2007

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Extramedullary proliferations of bone marrow elements are infrequently encountered in routine pathology practice. On occasion, they can present diagnostic difficulties when seen in unusual or unanticipated sites. This review serves to cover aspects of underlying embryogenesis of myeloid elements, as well as sites and circumstance of benign proliferations of myeloid elements along with their occasional confusion with neoplastic myeloid proliferations. Benign proliferations associated with hematologic disorders and hematopoietic growth factors are discussed. Immunohistochemical evaluation of myeloid proliferations is considered as well. Modern Pathology (2007) 20, 405-415.

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“…Among these are certain secondary cytogenetic aberrations, leukocytosis, CD56 expression and extramedullary manifestations. Review of the literature found that some suggested indicators, most notably CD56 9 and extramedullary involvement, 10 were identified in a single or relatively small studies; others were based on the patients treated with different protocols [11][12][13][14] or included secondary leukemia, 15 rendering it difficult to compare and draw consistent conclusions. This is particularly true regarding implications of additional cytogenetic aberrations.…”

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confidence: 99%

Acute myeloid leukemia harboring t(8;21)(q22;q22): a heterogeneous disease with poor outcome in a subset of patients unrelated to secondary cytogenetic aberrations

Lin¹,

Chen

Luthra³

et al. 2008

Modern Pathology

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Acute myeloid leukemia with t(8;21)(q22;q22) is a distinct type of leukemia considered to have a favorable prognosis. However, some patients rapidly succumb to disease despite chemotherapy. We studied 56 patients with acute myeloid leukemia associated with t(8;21) and correlated clinicopathologic, cytogenetic and molecular findings with outcome to identify markers of prognosis. In a subset of patients, we also assessed the status of the c-KIT, FLT3 and RAS genes. There were 31 men and 25 women, with a median age of 38 years (range 4-76). The follow-up period ranged from 17 to 104 months (median 52). At the last follow-up, 29 patients had died, 25 patients were in complete remission and two patients were alive with disease. The median survial was 38 months. The 5-year overall survival rate of newly diagnosed patients was 56%. Most patients (39/56, 70%) had chromosomal aberrations in addition to t(8;21), with loss of a sex chromosome (39%) being most common followed by del(9q)(q21-22) (11%) and trisomy 8 (7%). These aberrations, however, did not predict survival. C-KIT (D816V or D816Y), FLT3 (ITD or D835) and RAS mutations were detected in 26, 10 and 7%, respectively, of cases assessed. The 5-year overall survival rate of patients with mutated leukemia was 20%. No mutations were observed in three patients who died within 7 months of diagnosis. Leukocytosis or CD56 expression did not correlate with a poor survival nor did the levels of CD19 expression predict c-KIT mutation status. We conclude that acute myeloid leukemia associated with t(8;21) is a heterogeneous disease with poor survival in a subset of patients unrelated to common secondary cytogenetic aberrations. Keywords: t(8;21); cytogenetics; c-KIT mutation The t(8;21)(q22;q22) is the most common cytogenetic abnormality in acute myeloid leukemia (AML), occurring in up to 12% of patients. 1 As a result of t(8;21), the ETO (MTG8) gene on chromosome 8 is fused to the AML1 (RUNX1) gene on chromosome 21, producing a novel chimeric gene, AML1-ETO. The AML1 gene encodes the alpha subunit of core-binding factor (CBF) that is essential for normal hematopoiesis. AML1-ETO fusion gene disrupts the CBF transcription complex, thus initiating the first step of leukemogenesis. 2 The AML1-ETO fusion protein is a multifunctional cellular protein that affects cell differentiation, proliferation, apoptosis and self-renewal. 3 Evidence suggests that additional cytogenetic aberrations may act synergistically with AML-ETO in leukemogenesis. 3 AML with t(8;21), similar to AML with inv(16) or t(15;17), is generally considered a disease with an overall favorable prognosis characterized by a higher response rate and longer median survival compared with other types of AML. This concept is adopted in the current World Health Organization Classification. 4 Of the two references cited by the WHO classification, both published in 1998, 5,6 one was a British study of 1612 AML patients in which 122 patients had AML with t(8;21). The 5-year overall survival (OS) rate of patients with t(8;21) ...

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Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): results from Cancer and Leukemia Group B 8461.

Abstract: Patients with t(8;21) and EML have a low CR rate and overall survival. An aggressive local and systemic induction therapy should be considered for this patient subset. The effectiveness of HDAC intensification in t(8;21) patients with EML is uncertain and warrants further study.

Cited by 219 publications

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Predictable prognostic factor of CD56 expression in patients with acute myeloid leukemia with t(8:21) after high dose cytarabine or allogeneic hematopoietic stem cell transplantation

Predictable prognostic factor of CD56 expression in patients with acute myeloid leukemia with t(8:21) after high dose cytarabine or allogeneic hematopoietic stem cell transplantation

Benign extramedullary myeloid proliferations

Acute myeloid leukemia harboring t(8;21)(q22;q22): a heterogeneous disease with poor outcome in a subset of patients unrelated to secondary cytogenetic aberrations

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