Acute myelogenous leukemia in Down's syndrome: report of a single pediatric institution using a BFM treatment strategy

Zubizarreta, Pedro; Felice, Marı́a Sara; Alfaro, Elizabeth M.; Fraquelli, Lidia; Casak, Sandra J.; Quinteros, Rubén; Cygler, Ana M.; Gallego, Marta S.; Pérez, Laura; Sackmann‐Muriel, Federico

doi:10.1016/s0145-2126(98)00016-2

Cited by 25 publications

(18 citation statements)

References 24 publications

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“…6,14,40 Several collaborative pediatric group studies have found that approximately half of all pediatric cases of AMKL occur in patients with DS. 8,13,40 In contrast, only 17% of our patients with de novo AMKL had DS. This disparity may reflect a low rate of referral of patients with DS to our institution.…”

Section: Discussionmentioning

confidence: 57%

“…6,8,[12][13][14] AMKL in other children appears to be more heterogeneous, and its prognostic factors have not been well defined. 5,6 Since 1984, our institution has used systematic criteria to establish the diagnosis of AMKL.…”

Section: Introductionmentioning

confidence: 99%

“…Only 2.6% of the patients diagnosed at our institution during the study period as having AML had DS, whereas the proportion at other institutions is comparable to the 9.8% reported by the Children's Cancer Group (CCG). 6,8,13 Alternatively, because the diagnosis of non-DS AMKL is difficult in many cases, patients in this category may be more likely to be referred to a research institution; such referrals would reduce the relative percentage of DS-AMKL cases.The prognosis of children who have de novo AMKL in the absence of DS has been difficult to determine. Findings increasingly suggest that these patients have a poorer prognosis than do patients with other FAB subtypes of AML.…”

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confidence: 99%

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Biology and outcome of childhood acute megakaryoblastic leukemia: a single institution's experience

Athale

Razzouk

Raimondi

et al. 2001

Blood

193

173

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To describe the clinical and biologic features of pediatric acute megakaryoblastic leukemia (AMKL) and to identify prognostic factors, experience at St Jude Children's Research Hospital was reviewed. Of 281 patients with acute myeloid leukemia treated over a 14-year period, 41 (14.6%) had a diagnosis of AMKL. Six patients had Down syndrome and AMKL, 6 had secondary AMKL, and 29 had de novo AMKL. The median age of the 22 boys and 19 girls was 23.9 months (range, 6.7-208.9 months). The rate of remission induction was 60.5%, with a 48% rate of subsequent relapse. Patients with Down syndrome had a significantly higher 2-year event-free survival (EFS) estimate (83%) than did other patients with de novo AMKL (14%) or with secondary AMKL (20%; P < .038). Among patients who had de novo AMKL without Down syndrome, 2-year EFS was significantly higher after allogeneic bone marrow transplantation (26%) than after chemotherapy alone (0%; P ‫؍‬ .019) and significantly higher when performed during remission (46%) than when performed during persistent disease (0%; P ‫؍‬ .019). The 5-year survival estimates were significantly lower for de novo AMKL (10%) than for other forms of de novo AML (42%; P < .001). Treatment outcome is very poor for patients with AMKL in the absence of Down syndrome. Remission induction is the most important prognostic factor. Allogeneic transplantation during remission offers the best chance of cure; in the absence of remission, transplantation offers no advantage over chemotherapy alone. IntroductionAcute megakaryoblastic leukemia (AMKL) is a biologically heterogeneous form of acute myeloid leukemia (AML) and is recognized as the seventh subtype of AML (M7) within the FrenchAmerican-British (FAB) cooperative group classification system. 1 AMKL has a bimodal age distribution that peaks in early childhood (age Ͻ 3 years) and adulthood. [2][3][4][5][6] Between 1% and 10% of cases of AML in adults are identified as AMKL. 2,7 Although initially thought to be rare among children, AMKL has been diagnosed with increasing frequency in this age group, largely because of improvements in immunophenotyping. 5 Contemporary cooperative group studies have found that 3.1% to 10% of all cases of childhood AML are AMKL. [8][9][10][11] However, the exact incidence of AMKL in children remains undetermined.Acute megakaryoblastic leukemia is the most common form of AML in children with Down syndrome (DS), and its prognosis is excellent in this group of patients. 6,8,[12][13][14] AMKL in other children appears to be more heterogeneous, and its prognostic factors have not been well defined. 5,6 Since 1984, our institution has used systematic criteria to establish the diagnosis of AMKL. We reviewed the clinical and biologic characteristics and the outcomes of all 41 cases of childhood AMKL diagnosed at our institution since that time. Patients, materials, and methods PatientsAll cases of AMKL diagnosed between January 1985 and December 1998 at St Jude Children's Research Hospital were reviewed. Details of clinical presentation...

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Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Biology and outcome of childhood acute megakaryoblastic leukemia: a single institution's experience

Athale

Razzouk

Raimondi

et al. 2001

Blood

193

173

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“…They concluded that intensity of chemotherapy should be lowered and the clinical support be improved. 17 Lange et al reported on higher mortality in DS patients treated in the intensively timed induction arm (32%) than in those treated in the standard induction arm (2%) in the CCG studies 2861/2891. They also stated that bone marrow transplantation was too toxic and less effective in children with DS.…”

Section: Discussionmentioning

confidence: 99%

AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity

et al. 2005

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Despite improved prognosis in acute myelogenous leukaemia (AML) children with Down syndrome (DS), therapy-related toxicity remained a problem. We compared 67 DS patients from study AML-BFM 98 with 51 DS patients of the previous study AML-BFM 93, and the non-DS groups of both studies. Compared to non-DS patients, DS patients were treated with reduced anthracycline doses, without high-dose cytarabine/ mitoxantrone and without cranial irradiation. AML-DS patients were in median 1.8 years old, and 102/118 (86%) showed the typical morphology of acute megakaryoblastic leukaemia. In study 93, seven DS patients did not receive AML-specific chemotherapy, and treatment modifications were more common. Results improved significantly for patients treated in study 98 with a 3-year survival of 9174 vs 7077% in study 93 (P ¼ 0.001). There were no differences in outcome concerning the age groups 0-p2 and 2-p4 years (event-free survival for treated patients 0-p2 years 8374%, 2-p4 years 8177%). The cumulative incidence of relapses was significantly lower in DS (773%) than in non-DS patients (2877%). Therapy-related toxicity was generally lower in DS patients treated according to study 98. We conclude that a standardised and dose-reduced treatment schedule including the main components of AML treatment is advisable for AML children with DS.

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“…16 Outcomes are best in children with Down syndrome. [16][17][18] Postremission therapy must be improved. It has been suggested that autologous and allogeneic bone marrow transplantation (BMT) might offer the best chance of cure for patients in remission, but available clinical data are scant.…”

Section: Introductionmentioning

confidence: 99%

Hematopoietic stem cell transplantation for de novo acute megakaryocytic leukemia in first complete remission: a retrospective study of the European Group for Blood and Marrow Transplantation (EBMT)

Garderet

Labopin

Gorin

et al. 2005

Blood

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Acute megakaryoblastic leukemia (M7 AML) is a highly aggressive disease. We evaluated outcomes in 57 children (11 with Down syndrome) and 69 adults with M7 AML after first complete remission (CR1) following autologous or HLA-identical allogeneic transplantation. Characteristics of the recipients of autologous transplants (38 children, 37 adults) were, respectively: median age, 1.7 and 46 years; non-total body irradiation (non-TBI) conditioning regimen, 97% and 70%; bone marrow as stem cell source, 74% and 43%. Characteristics of the recipients of allogeneic transplants (19 children, 32 adults) were, respectively: median age, 2.8 and 37 years; non-TBI regimen, 63% and 42%; bone marrow as stem cell source, 95% and 69%. Autologous transplantation benefited children more; the relapse rate was high in adults. Results for autologous transplantation were (children and adults, respectively): engraftment, 90% and 100%; 3-year treatmentrelated mortality (TRM) rate, 3% and 8%; relapse rate, 45% and 64%; leukemia-free survival (LFS) rate, 52% and 27%; overall survival (OS) rate, 61% and 30%. After allogeneic transplantation, TRM was fairly low in children and adults, and relapse rates were lower than after autologous transplantation. Results for allogeneic transplantation were, respectively: engraftment, 95% and 90%; TRM, 0% and 26%; relapse rate, 34% and 28%; LFS, 66% and 46%; OS, 82% and 43% IntroductionAcute megakaryoblastic leukemia (M7 AML) is a rare subtype of acute myeloid leukemia (AML) that develops from primitive megakaryoblasts. It was first described by Van Boros and Korenyi in 1931, and it is the seventh AML subtype in the 1985 FrenchAmerican-British (FAB) classification. 1-3 Developments in cytochemistry and immunophenotyping have improved its diagnosis and differentiation from acute myelosclerosis. 4-6 M7 AML has a bimodal age distribution that peaks in early childhood (younger than 3 years) and in adulthood. 7 Approximately 1% of AML cases in adults and 5% to 10% in children are M7 AML. 8,9 Its incidence is higher in children with Down syndrome. 10,11 The prognosis for patients with M7 AML is poor. Although remission rates are not much lower than those for other myeloid leukemia subtypes, the relapse rate is high. Approximately half the patient population achieves complete remission (CR) with conventional chemotherapy, but few patients survive beyond 3 years. [12][13][14][15] Median overall survival (OS) is estimated to be 40 weeks in adults, 15 and the 2-year event-free survival is 14% in children. 16 Outcomes are best in children with Down syndrome. [16][17][18] Postremission therapy must be improved. It has been suggested that autologous and allogeneic bone marrow transplantation (BMT) might offer the best chance of cure for patients in remission, but available clinical data are scant. Published reports are often case reports 19,20 or small clinical series with inconsistent results. 15,16,21,22 The aim of this retrospective study is to evaluate outcomes after hematopoietic stem cell transplantation (HSCT...

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Acute myelogenous leukemia in Down's syndrome: report of a single pediatric institution using a BFM treatment strategy

Cited by 25 publications

References 24 publications

Biology and outcome of childhood acute megakaryoblastic leukemia: a single institution's experience

Biology and outcome of childhood acute megakaryoblastic leukemia: a single institution's experience

AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity

Hematopoietic stem cell transplantation for de novo acute megakaryocytic leukemia in first complete remission: a retrospective study of the European Group for Blood and Marrow Transplantation (EBMT)

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