STANDARD INDUCTION CHEMOTHERAPY IN CHILDREN WITH MLL-AF9 ACUTE MYELOID LEUKEMIA AND SEVERE DISSEMINATED INTRAVASCULAR COAGULATION IS ASSOCIATED WITH HIGH MORTALITY
(Abstract release date: 05/19/16)
EHA Library. Colita A. 06/09/16; 134569; PB1669
Assoc. Prof. Anca Colita
Contributions
Contributions
Abstract
Abstract: PB1669
Type: Publication Only
Background
MLL-AF9 AML is a rare subgroup of unfavorable prognostic leukemia secondary to t(9;11)(p22;q23) with particular clinical aspects, mainly severe coagulopathy.
Aims
To analyze the clinical, hematological and coagulation parameters at diagnosis and correlation with the outcome after chemotherapy initiation in children with MLL-AF9 leukemia treated according to a BFM 2004 AML protocol in a single center.
Methods
Six consecutive patients with MLL-AF9 AML were identified by fluorescence in situ hybridization and Nested PCR in our center in the last 10 years. The diagnostic was completed by bone marrow morphology and immunophenotyping, standard kariotype and coagulation tests (AP, aPTT, INR, D-Dimers, PDF, Fbg, PC, PS, AT III). Patients were treated according to the BFM 2004 AML protocol. All patients received fresh frozen plasma. Informed consent has been obtained from parents.
Results
Between 2006-2015 we treated 74 patients with AML, 6 (8,1%) being diagnosed with MLL-AF9 AML, fusion type 6A in all cases. The kariotype has been performed in all patients, but we obtained interpretable result only in 2 patients, all of them without abnormal cytogenetics. The patient characteristics are shown in table 1. All patients had laboratory signs of variable degrees of DIC at diagnosis documented by prolonged coagulation times, presence of fibrin degradation products (FDP) and elevated D-Dimer levels. Three patients developed during the first 2 days after chemotherapy initiation a respiratory distress syndrome and seizures associated with cerebral hemorrhage with fatal outcome in the next 2-5 days. The initial hemostasis/coagulation analysis in these patients showed platelet counts 30x109/L, 70x109/L, respectively 165x109/L, but with high D-Dimer levels 1670, 2430, respectively > 60.000 µg/L (upper detection limit for our laboratory). The other 3 patients completed the induction chemotherapy without special complications. The BM aspirate and MLL-AF9 monitoring confirmed the complete remission (CR). The hemostasis/coagulation analysis in these patients showed similar platelet counts (60 x109/L, 54 x109/L, 30 x109/L), but associated with lower levels of D-Dimers (1070, 960, 1020µg/L).Table 1.
Conclusion
MLL-AF9 is a poor prognostic AML subtype, associated with a higher mortality at induction treatment. Half of the patients in our cohort had a severe DIC associated at onset, with high D-Dimers levels (more than twice upper normal limit) that worsened after chemotherapy initiation leading to respiratory failure and cerebral hemorrhage in absence of severe thrombocytopenia. For our cohort the presence of significant coagulopathy at onset is associated with poor prognosis, suggesting a clinical evolution of this syndrome that is similar with AML M3 outcome in the absence of all-trans retinoic acid associated chemotherapy.
Session topic: E-poster
Keyword(s): AML, Children, DIC, MLL
Type: Publication Only
Background
MLL-AF9 AML is a rare subgroup of unfavorable prognostic leukemia secondary to t(9;11)(p22;q23) with particular clinical aspects, mainly severe coagulopathy.
Aims
To analyze the clinical, hematological and coagulation parameters at diagnosis and correlation with the outcome after chemotherapy initiation in children with MLL-AF9 leukemia treated according to a BFM 2004 AML protocol in a single center.
Methods
Six consecutive patients with MLL-AF9 AML were identified by fluorescence in situ hybridization and Nested PCR in our center in the last 10 years. The diagnostic was completed by bone marrow morphology and immunophenotyping, standard kariotype and coagulation tests (AP, aPTT, INR, D-Dimers, PDF, Fbg, PC, PS, AT III). Patients were treated according to the BFM 2004 AML protocol. All patients received fresh frozen plasma. Informed consent has been obtained from parents.
Results
Between 2006-2015 we treated 74 patients with AML, 6 (8,1%) being diagnosed with MLL-AF9 AML, fusion type 6A in all cases. The kariotype has been performed in all patients, but we obtained interpretable result only in 2 patients, all of them without abnormal cytogenetics. The patient characteristics are shown in table 1. All patients had laboratory signs of variable degrees of DIC at diagnosis documented by prolonged coagulation times, presence of fibrin degradation products (FDP) and elevated D-Dimer levels. Three patients developed during the first 2 days after chemotherapy initiation a respiratory distress syndrome and seizures associated with cerebral hemorrhage with fatal outcome in the next 2-5 days. The initial hemostasis/coagulation analysis in these patients showed platelet counts 30x109/L, 70x109/L, respectively 165x109/L, but with high D-Dimer levels 1670, 2430, respectively > 60.000 µg/L (upper detection limit for our laboratory). The other 3 patients completed the induction chemotherapy without special complications. The BM aspirate and MLL-AF9 monitoring confirmed the complete remission (CR). The hemostasis/coagulation analysis in these patients showed similar platelet counts (60 x109/L, 54 x109/L, 30 x109/L), but associated with lower levels of D-Dimers (1070, 960, 1020µg/L).Table 1.
| Patient characteristics | No. 6 cases |
| Sex ratio M/F | 5/1 |
| Age median | 2y 6 mo |
| FAB type | M1:1/M5:3/M7:2 |
| Hg median | 7.6 g/dl |
| PLT median | 62 x109/L |
| WBC median | 19.13 x109/L |
| Blasts median | 13.88x109/L |
| Hepatomegaly | 4/6 |
| Splenomegaly | 3/6 |
Conclusion
MLL-AF9 is a poor prognostic AML subtype, associated with a higher mortality at induction treatment. Half of the patients in our cohort had a severe DIC associated at onset, with high D-Dimers levels (more than twice upper normal limit) that worsened after chemotherapy initiation leading to respiratory failure and cerebral hemorrhage in absence of severe thrombocytopenia. For our cohort the presence of significant coagulopathy at onset is associated with poor prognosis, suggesting a clinical evolution of this syndrome that is similar with AML M3 outcome in the absence of all-trans retinoic acid associated chemotherapy.
Session topic: E-poster
Keyword(s): AML, Children, DIC, MLL
Abstract: PB1669
Type: Publication Only
Background
MLL-AF9 AML is a rare subgroup of unfavorable prognostic leukemia secondary to t(9;11)(p22;q23) with particular clinical aspects, mainly severe coagulopathy.
Aims
To analyze the clinical, hematological and coagulation parameters at diagnosis and correlation with the outcome after chemotherapy initiation in children with MLL-AF9 leukemia treated according to a BFM 2004 AML protocol in a single center.
Methods
Six consecutive patients with MLL-AF9 AML were identified by fluorescence in situ hybridization and Nested PCR in our center in the last 10 years. The diagnostic was completed by bone marrow morphology and immunophenotyping, standard kariotype and coagulation tests (AP, aPTT, INR, D-Dimers, PDF, Fbg, PC, PS, AT III). Patients were treated according to the BFM 2004 AML protocol. All patients received fresh frozen plasma. Informed consent has been obtained from parents.
Results
Between 2006-2015 we treated 74 patients with AML, 6 (8,1%) being diagnosed with MLL-AF9 AML, fusion type 6A in all cases. The kariotype has been performed in all patients, but we obtained interpretable result only in 2 patients, all of them without abnormal cytogenetics. The patient characteristics are shown in table 1. All patients had laboratory signs of variable degrees of DIC at diagnosis documented by prolonged coagulation times, presence of fibrin degradation products (FDP) and elevated D-Dimer levels. Three patients developed during the first 2 days after chemotherapy initiation a respiratory distress syndrome and seizures associated with cerebral hemorrhage with fatal outcome in the next 2-5 days. The initial hemostasis/coagulation analysis in these patients showed platelet counts 30x109/L, 70x109/L, respectively 165x109/L, but with high D-Dimer levels 1670, 2430, respectively > 60.000 µg/L (upper detection limit for our laboratory). The other 3 patients completed the induction chemotherapy without special complications. The BM aspirate and MLL-AF9 monitoring confirmed the complete remission (CR). The hemostasis/coagulation analysis in these patients showed similar platelet counts (60 x109/L, 54 x109/L, 30 x109/L), but associated with lower levels of D-Dimers (1070, 960, 1020µg/L).Table 1.
Conclusion
MLL-AF9 is a poor prognostic AML subtype, associated with a higher mortality at induction treatment. Half of the patients in our cohort had a severe DIC associated at onset, with high D-Dimers levels (more than twice upper normal limit) that worsened after chemotherapy initiation leading to respiratory failure and cerebral hemorrhage in absence of severe thrombocytopenia. For our cohort the presence of significant coagulopathy at onset is associated with poor prognosis, suggesting a clinical evolution of this syndrome that is similar with AML M3 outcome in the absence of all-trans retinoic acid associated chemotherapy.
Session topic: E-poster
Keyword(s): AML, Children, DIC, MLL
Type: Publication Only
Background
MLL-AF9 AML is a rare subgroup of unfavorable prognostic leukemia secondary to t(9;11)(p22;q23) with particular clinical aspects, mainly severe coagulopathy.
Aims
To analyze the clinical, hematological and coagulation parameters at diagnosis and correlation with the outcome after chemotherapy initiation in children with MLL-AF9 leukemia treated according to a BFM 2004 AML protocol in a single center.
Methods
Six consecutive patients with MLL-AF9 AML were identified by fluorescence in situ hybridization and Nested PCR in our center in the last 10 years. The diagnostic was completed by bone marrow morphology and immunophenotyping, standard kariotype and coagulation tests (AP, aPTT, INR, D-Dimers, PDF, Fbg, PC, PS, AT III). Patients were treated according to the BFM 2004 AML protocol. All patients received fresh frozen plasma. Informed consent has been obtained from parents.
Results
Between 2006-2015 we treated 74 patients with AML, 6 (8,1%) being diagnosed with MLL-AF9 AML, fusion type 6A in all cases. The kariotype has been performed in all patients, but we obtained interpretable result only in 2 patients, all of them without abnormal cytogenetics. The patient characteristics are shown in table 1. All patients had laboratory signs of variable degrees of DIC at diagnosis documented by prolonged coagulation times, presence of fibrin degradation products (FDP) and elevated D-Dimer levels. Three patients developed during the first 2 days after chemotherapy initiation a respiratory distress syndrome and seizures associated with cerebral hemorrhage with fatal outcome in the next 2-5 days. The initial hemostasis/coagulation analysis in these patients showed platelet counts 30x109/L, 70x109/L, respectively 165x109/L, but with high D-Dimer levels 1670, 2430, respectively > 60.000 µg/L (upper detection limit for our laboratory). The other 3 patients completed the induction chemotherapy without special complications. The BM aspirate and MLL-AF9 monitoring confirmed the complete remission (CR). The hemostasis/coagulation analysis in these patients showed similar platelet counts (60 x109/L, 54 x109/L, 30 x109/L), but associated with lower levels of D-Dimers (1070, 960, 1020µg/L).Table 1.
| Patient characteristics | No. 6 cases |
| Sex ratio M/F | 5/1 |
| Age median | 2y 6 mo |
| FAB type | M1:1/M5:3/M7:2 |
| Hg median | 7.6 g/dl |
| PLT median | 62 x109/L |
| WBC median | 19.13 x109/L |
| Blasts median | 13.88x109/L |
| Hepatomegaly | 4/6 |
| Splenomegaly | 3/6 |
Conclusion
MLL-AF9 is a poor prognostic AML subtype, associated with a higher mortality at induction treatment. Half of the patients in our cohort had a severe DIC associated at onset, with high D-Dimers levels (more than twice upper normal limit) that worsened after chemotherapy initiation leading to respiratory failure and cerebral hemorrhage in absence of severe thrombocytopenia. For our cohort the presence of significant coagulopathy at onset is associated with poor prognosis, suggesting a clinical evolution of this syndrome that is similar with AML M3 outcome in the absence of all-trans retinoic acid associated chemotherapy.
Session topic: E-poster
Keyword(s): AML, Children, DIC, MLL
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