scholarly journals A unique pattern of central nervous system leukemia in acute myelomonocytic leukemia associated with inv(16)(p13q22)

Blood ◽  
1985 ◽  
Vol 65 (5) ◽  
pp. 1071-1078
Author(s):  
R Holmes ◽  
MJ Keating ◽  
A Cork ◽  
Y Broach ◽  
J Trujillo ◽  
...  
Keyword(s):  
Median Duration ◽  
Myeloid Leukemia ◽  
Chromosome Analysis ◽  
Leptomeningeal Disease ◽  
Brain Scan ◽  
Fab Classification ◽  
Additional Chromosome ◽  
Acute Myelomonocytic Leukemia ◽  
Immature Cells ◽  
Myelomonocytic Leukemia

Twenty-six patients with inv(16)(p13q22) or del(16)(q22) in association with acute myelomonocytic leukemia (AMML-M4, FAB classification), and abnormal marrow eosinophils have been treated at this institute. Initial bone marrow eosinophilia (greater than or equal to 4%) was observed in 22 of 26 patients (85%), and abnormal eosinophil morphology, characterized by immature cells with some interspersed basophilic granules, was evident in 26 of 26 (100%). Giemsa-banded chromosome analysis performed in all patients revealed 16 cases with inv(16)(p13q22) alone, and ten cases with additional chromosome changes. Twenty-five patients received combination induction chemotherapy, and 23 (92%) achieved complete remission (CR). The median duration of remission was 18 months (range, six to 72 + months), and the median duration of survival was 34 months (range, 0.5 to 133 months). Nine patients (35%) relapsed in the CNS at a median time of 19 months (range, six to 133 months) from first marrow CR. All patients had leptomeningeal disease, and in addition, six of nine (66%) demonstrated two or more enhancing lesions on computed tomography brain scan, consistent with intracerebral myeloblastomas. Review of 384 Giemsa-banded patients with acute myeloid leukemia revealed no other morphologic or cytogenetic subgroup with either an equivalent incidence of CNS leukemia or documented intracerebral myeloblastomas. This series of inv(16)(p13q22)/del(16)(q22) AMML reports a favorable prognosis for such patients and associates a specific clonal cytogenetic subgroup of acute leukemia with a distinct propensity for CNS relapse, manifesting as leptomeningeal disease and intracerebral myeloblastomas.

scholarly journals A unique pattern of central nervous system leukemia in acute myelomonocytic leukemia associated with inv(16)(p13q22)

Blood ◽  
1985 ◽  
Vol 65 (5) ◽  
pp. 1071-1078 ◽  
Author(s):  
R Holmes ◽  
MJ Keating ◽  
A Cork ◽  
Y Broach ◽  
J Trujillo ◽  
...  
Keyword(s):  
Median Duration ◽  
Myeloid Leukemia ◽  
Chromosome Analysis ◽  
Leptomeningeal Disease ◽  
Brain Scan ◽  
Fab Classification ◽  
Additional Chromosome ◽  
Acute Myelomonocytic Leukemia ◽  
Immature Cells ◽  
Myelomonocytic Leukemia

Abstract Twenty-six patients with inv(16)(p13q22) or del(16)(q22) in association with acute myelomonocytic leukemia (AMML-M4, FAB classification), and abnormal marrow eosinophils have been treated at this institute. Initial bone marrow eosinophilia (greater than or equal to 4%) was observed in 22 of 26 patients (85%), and abnormal eosinophil morphology, characterized by immature cells with some interspersed basophilic granules, was evident in 26 of 26 (100%). Giemsa-banded chromosome analysis performed in all patients revealed 16 cases with inv(16)(p13q22) alone, and ten cases with additional chromosome changes. Twenty-five patients received combination induction chemotherapy, and 23 (92%) achieved complete remission (CR). The median duration of remission was 18 months (range, six to 72 + months), and the median duration of survival was 34 months (range, 0.5 to 133 months). Nine patients (35%) relapsed in the CNS at a median time of 19 months (range, six to 133 months) from first marrow CR. All patients had leptomeningeal disease, and in addition, six of nine (66%) demonstrated two or more enhancing lesions on computed tomography brain scan, consistent with intracerebral myeloblastomas. Review of 384 Giemsa-banded patients with acute myeloid leukemia revealed no other morphologic or cytogenetic subgroup with either an equivalent incidence of CNS leukemia or documented intracerebral myeloblastomas. This series of inv(16)(p13q22)/del(16)(q22) AMML reports a favorable prognosis for such patients and associates a specific clonal cytogenetic subgroup of acute leukemia with a distinct propensity for CNS relapse, manifesting as leptomeningeal disease and intracerebral myeloblastomas.

scholarly journals Specific Patterns of Molecular Mutations Determine the Morphologic Differentiation Stages in Acute Myeloid Leukemia (AML)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2388-2388
Author(s):  
Dominic Rose ◽  
Torsten Haferlach ◽  
Susanne Schnittger ◽  
Karolina Perglerová ◽  
Wolfgang Kern ◽  
...  
Keyword(s):  
Promyelocytic Leukemia ◽  
Mutation Rates ◽  
Employment Equity ◽  
Total Cohort ◽  
Fab Classification ◽  
Significance Levels ◽  
Acute Myelomonocytic Leukemia ◽  
Equity Ownership ◽  
Differentiation Stage ◽  
Myelomonocytic Leukemia

Abstract Background: The FAB classification of AML was based on the differentiation state and the involved cell lineages and recognized some close associations between genetic abnormalities and cytomorphology: CBFB-MYH11 and AML with abnormal eosinophils, PML-RARA and acute promyelocytic leukemia; RUNX1-RUNX1T1 and AML with maturation (FAB subtype M2). Associations with molecular mutations have not been examined in detail yet. Aim: Evaluate the impact of molecular mutations on the AML differentiation state. Material and Methods: The cohort comprized 3,703 patients with de novo AML (median age 67 yrs; range: 18.1-100.5 yrs). All cases were analyzed by cytomorphology and molecular mutation screening for 12 genes by next generation or Sanger sequencing in our laboratory. Based on cytomorphology and immunophenotyping we categorized the cohort into 11 subgroups: 1. AML with minimal differentiation (according to the FAB classification: M0; n=192), 2. AML without maturation (M1; n=1,015), 3. AML with maturation (M2; n=1,324), 4. acute promyelocytic leukemia (APL) with PML-RARA (M3; n=124), 5. the microgranular variant of APL (M3v, n=110), 6. acute myelomonocytic leukemia (M4; n=604), 7. acute myelomonocytic leukemia with abnormal eosinophils and CBFB-MYH11 (M4eo; n=81), 8. acute monoblastic leukemia (M5a; n=86), 9. acute monocytic leukemia (M5b; n=63), and 10. acute erythroid leukemia (M6; n=101). Cases with acute megakaryoblastic leukemia (M7; n=3) were not considered for statistical evaluation. All 3,703 cases were analyzed for FLT3-ITD and FLT3-TKD. All cases except M3/M3v and M4eo (n=3,487) were screened for NPM1 und MLL-PTD. Data on the mutation status of the following genes was available: FLT3-ITD (n=3,703), FLT3-TKD (n=3,703), CEBPA (n=2,684), RUNX1 (n=2,320), WT1 (n=2,224), ASXL1 (n=1,591), DNMT3A (n=1,294), NRAS (n=1,232), TP53 (n=1,046) and TET2 (n=974). Statistical significance of associations between the mutation frequencies and AML subtypes were assessed by Fisher’s exact test and corrected according to Benjamini-Hochberg (1995) to compensate for multiple testing. Results: The mutation rates of the analyzed genes are in line with published data. Total cohort: Significant associations were observed between the mutation frequencies of distinct genes and the differentiation stage of the AML. Figure 1 depicts genes showing significantly different mutation rates within distinct AML subtypes compared to the rate of the total cohort. In detail, mutations in RUNX1 were most frequently observed in M0 (43.6%) and M2 (24.0%) and were nearly absent in M5a (3.5%) and M5b (0%). The highest TP53 mutation rates were observed in M6 (35.3%) and M2 (15.0%), the lowest in M4 (3.0%) and M1 (5.7%). NPM1 mutations were significantly more frequent in M5b (69.8%), M4 (56.3%), M5a (47.7%) and M1 (42.1%) than in M2 (24.2%), M6 (20.8%), M0 (3.1%), and absent in M3, M3v, and M4eo, respectively. NPM1 mutated subcohort (n=1,200): The overall DNMT3A mutation rate in this subcohort was 49.1%. It was significantly higher in M5b (75.0%) and M4 (61.6%) and significantly lower in M1 (40.6%), M5a (22.2%), and M6 (13.3%). Contrary, RUNX1 (overall frequency in NPM1mut cases 1.2%) and ASXL1 (overall 2.5%) mutations were more frequent in M5a (8.3% and 34.8%, respectively), while FLT3-ITD was more frequent in M1 (52.5%), and WT1 mutations more frequent in M6 (26.7%). CEBPA double mutated subcohort (n=108): ASXL1 and RUNX1 mutations were 5- and 7-fold more frequent in M2 than in M1, but did not reach significance. Conclusions: Specific patterns of molecular mutations are linked to distinct AML differentiation stages: 1) RUNX1 and ASXL1 with M0 2) NPM1, ASXL1 and TET2 with M5a, and 3) NPM1 and DNMT3A with M5b. 4) The differentiation stage of NPM1 mutated AML is driven by the presence of additional mutations: DNMT3A mutations lead to a (myelo-)monocytic differentiation, while mutations in RUNX1 or ASXL1 lead to a monoblastic phenotype. 5) FLT3-ITD is most frequent in NPM1 mutated AML without maturation and WT1 mutations are most frequent in acute erythroid leukemia bearing NPM1mut. Figure 1: Morphologic classes and the identified genes with significantly different mutation rates compared to the total cohort: ▲ genes with a higher mutation frequency; ▼ genes with lower mutation rates (significance levels were corrected according to Benjamini-Hochberg, * indicates trends (0.05<p<0.13,), for all other p<0.05) Figure 1:. Morphologic classes and the identified genes with significantly different mutation rates compared to the total cohort: ▲ genes with a higher mutation frequency; ▼ genes with lower mutation rates (significance levels were corrected according to Benjamini-Hochberg, * indicates trends (0.05<p<0.13,), for all other p<0.05) Disclosures Rose: MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Perglerová:MLL2 s.r.o.: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

Response Rates in Patients with Acute Myeloid Leukemia (AML), Treated with Azacitidine, Using WHO and International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1848-1848 ◽  
Author(s):  
Lewis R. Silverman ◽  
David R. McKenzie ◽  
Bercedis L. Peterson ◽  
Richard M. Stone ◽  
Bayard L. Powell ◽  
...  
Keyword(s):  
Supportive Care ◽  
Median Duration ◽  
Myeloid Leukemia ◽  
Response Criteria ◽  
Refractory Anemia ◽  
Care Group ◽  
Transfusion Independence ◽  
Best Response ◽  
Fab Classification ◽  
New Treatment

Abstract The CALGB conducted a series of clinical trials with azacitidine (Vidaza®) administered subcutaneously or intravenously in patients with MDS using the FAB classification (JCO2002;20:2429). Since completion of these CALGB studies (8421, 8921, 9221), a new classification system was developed by the WHO that distinguishes MDS from AML (blasts > 20%). Although studies with azacitidine in patients with AML had previously shown activity, the 75 mg/m2/day dose in the CALGB studies was lower than previously studied. Using the WHO system, the diagnosis for CALGB study patients was redefined and patients with AML were analyzed separately. Most of the 105 patients were previously considered refractory anemia with excess blasts in transformation (RAEB-T). Also, new treatment response criteria for MDS were published by the IWG (Blood2000; 96:3671). Using IWG response criteria, azacitidine patients with WHO AML in studies 8421, 8921, or 9221 had an overall response rate (CR+PR+HI) of 48% (12/25), 32% (9/28), and 37% (10/27), respectively. Best Response using IWG Response Criteria for WHO AML Patients in Studies 8421, 8921, and 9221 Median duration of any response (CR, PR or HI) in the 33 azacitidine-treated responders was 279 days (range: 61 to 724 days). The median duration of CR in the 8 azacitidine-treated responders was not achieved; however, the 25th percentile was 115 days (range: 92 to 274+ days). In Study 9221, the median duration of transfusion independence (defined as ≥56 days) in patients independent at baseline was significantly longer in the azacitidine group compared with supportive care for red blood cells (azacitidine [n=8]: 411 days vs. supportive care [n=9]: 133 days, p=0.02) and platelets (azacitidine [n=13]: 363 days vs. supportive care [n=18]: 125 days, p=0.004). In the azacitidine group, 22% (6/27) of patients had a hemoglobin improvement to >11 g/dL that was maintained for ≥56 days compared with 8% (2/25) in the supportive care group (p=0.2). The proportions of patients with ANC >1500/m3 and platelets >100,000/mm3 lasting for ≥56 days were similar between the treatment arms. Azacitidine patients with WHO AML had a longer median survival (19.3 months) compared with the supportive care group (12.9 months) (p=0.2). Further studies investigating azacitidine in patients with AML with dysplasia are warranted.

scholarly journals Post-remission therapy of adult acute myeloid leukemia: High dose cytosine-arabinoside versus other consolidation regimens

2014 ◽  
Vol 67 (3-4) ◽  
pp. 83-90 ◽  
Author(s):  
Vanja Zeremski ◽  
Aleksandar Savic
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cytosine Arabinoside ◽  
Myeloid Leukemia ◽  
Acute Myeloblastic Leukemia ◽  
High Dose ◽  
Study Group ◽  
Consolidation Therapy ◽  
Acute Myelomonocytic Leukemia ◽  
Myelomonocytic Leukemia ◽  
Acute Myeloid

Introduction. Modern therapy makes it possible for 60-80% patients with acute myeloid leukemia to achieve complete remission after induction therapy. However, most of them will relapse within six months to a year without additional cytostatic therapy. The questions regarding post-remission therapy remain unanswered. The objective of this study was to compare the survival and relapse rate among the patients who had received high dose cytosine-arabinoside during consolidation therapy and the patients who had not received high dose cytosine- arabinoside during consolidation therapy. Material and Methods. The study included 59 patients aged 18-60 years with de novo acute myeloid leukemia (except for Acute promyelocytic leukemia, which was excluded according to the French- American-British classification) who achieved complete remission. Thirty-nine patients who received high dose cytosine-arabinoside during consolidation were included in the study group and twenty patients who did not receive high dose cytosinearabinoside during consolidation were in the control group. Results. The results show a statistically significantly longer survival rate (p= 0.003) and a lower relapse rate (p= 0.02) among the study group patients, who received high dose cytosine-arabinoside during consolidation, compared to the controls, who did not receive high dose cytosine-arabinoside. The univariate analysis in the study group suggests that the affiliation to Acute myeloblastic leukemia with maturation and Acute myelomonocytic leukemia subgroups, as well as achieving complete remission after a single induction therapy has the prognostic significance. In the multivariate analysis, only the affiliation to Acute myeloblastic leukemia with maturation and Acute myelomonocytic leukemia subgroups retained the independent prognostic significance. Conclusion. This study has demonstrated that high dose cytosine-arabinoside used for consolidation therapy results in the higher survival rate and lower relapse rate compared to consolidation therapy without high dose cytosine-arabinoside. Only the patients within Acute myeloblastic leukemia with maturation and Acute myelomonocytic leukemia subgroups benefited significantly from high dose cytosine-arabinoside.

scholarly journals Hematologic Abnormalities Preceding Myeloid Leukemia in Three Cats

1979 ◽  
Vol 16 (5) ◽  
pp. 510-519 ◽  
Author(s):  
B. R. Madeweix ◽  
N. C. Jain ◽  
R. E. Weller
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Leukemia Virus ◽  
The Other ◽  
Feline Leukemia Virus ◽  
Acute Myelomonocytic Leukemia ◽  
Blast Cells ◽  
Myelomonocytic Leukemia

Cytopenia were recognized in three cats infected with feline leukemia virus. In one cat, marrow blast cells were increased in number, and a diagnosis of aleukemic leukemia was made. The disease progressed slowly for 31/2 months before terminating in acute myelomonocytic leukemia, recognized as a blast crisis in blood. In the other two cats, neutropenia and altered granulopoiesis in bone marrow preceded development of myeloid leukemia.

scholarly journals A pericentric inversion of chromosome 16 is associated with dysplastic marrow eosinophils in acute myelomonocytic leukemia

Blood ◽  
1984 ◽  
Vol 63 (4) ◽  
pp. 800-802 ◽  
Author(s):  
R Tantravahi ◽  
M Schwenn ◽  
C Henkle ◽  
M Nell ◽  
PR Leavitt ◽  
...  
Keyword(s):  
Pericentric Inversion ◽  
Surface Marker ◽  
Leukemic Cells ◽  
Acute Nonlymphocytic Leukemia ◽  
Chromosome 16 ◽  
Cytogenetic Studies ◽  
Fab Classification ◽  
Acute Myelomonocytic Leukemia ◽  
Surface Marker Analysis ◽  
Myelomonocytic Leukemia

Abstract Cytogenetic studies were performed in 18 consecutive children with acute nonlymphocytic leukemia (ANLL) between 1981 and 1983. Three children with acute myelomonocytic leukemia (AMMoL; M4, FAB classification) had the following unique bone marrow morphology and cytogenetic abnormality: eosinophilic precursors with dysplastic violaceous granules and a pericentric inversion of chromosome 16. Surface marker analysis of leukemic cells from these patients, using a panel of monoclonal antibodies, revealed the expression of a series of monocyte markers. The association of an inversion of chromosome 16 with abnormal eosinophil morphology in the M4 subtype of ANLL appears to represent a unique subgroup of patients.

AML-M4: Role of Eosinophilia and Cytogenetics on Treatment Response and Survival. The GIMEMA Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4501-4501
Author(s):  
Alessandro Pulsoni ◽  
Simona Iacobelli ◽  
Paola Fazi ◽  
Paolo Falcucci ◽  
Marco Vignetti ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Myeloid Leukemia ◽  
Standard Treatment ◽  
Univariate Analysis ◽  
Good Prognosis ◽  
Event Free Survival ◽  
Free Survival ◽  
Acute Myelomonocytic Leukemia ◽  
Myelomonocytic Leukemia

Abstract Background: The acute myeloid leukemia (AML)-M4 subtype is frequently associated to eosinophilia and/or to the cytogenetic alteration inv(16)/t(16;16). The presence of these features is generally associated with good prognosis, but the studies concerning their exact role are hampered by the low number of cases. We retrospectively analyzed patients with AML-M4 enrolled in two consecutive GIMEMA studies to assess the influence of eosinophilia and of the inv(16) cytogenetic abnormality on the prognosis of acute myelomonocytic leukemia (M4) and acute myelomonocytic leukemia with abnormal eosinophils (M4eos). Setting: A retrospective study, conducted over 9 years in patients affected by AML, admitted to 35 Italian hematological divisions. Patients and methods: Between December 1993 and December 2002, 1686 patients aged over 15 years with a diagnosis of AML were admitted to the EORTC-GIMEMA AML10 and AML 99p trials; of these, 400 patients (355 M4 and 45 M4Eo) were studied. The diagnosis of M4 and M4eos was first established at each institution and subsequently centrally reviewed at the time of study entry. The following parameters were evaluated: morphology, immunophenotype, cytogenetics performed at the onset of the disease, complete remission achievement and duration, overall survival (OS) and event-free survival (EFS) from AML diagnosis. Patients with M4eo were younger and more frequently associated with inv(16) compared to M4. Cytogenetic analisis failed or was not carried out in 40% of cases, while it was successfully analyzed in 240 cases; inv(16) was found in 17% of them. Results: Concerning the probability of obtaining a CR after standard treatment, at univariate analysis M4Eo had a non significant advantage compared to M4, while presence of inv(16) was significantly correlated to a higher CR probability; multivariate analysis showed a significant advantage only of M4Eo+ inv(16) compared to M4-without eosinophilia and without inv(16). DFS was not different in univariate analysis between patients carrying or not inv(16), while a borderline advantage of M4Eo was observed with respect of M4, not confirmed at multivariate analysis. OS curves showed at univariate analysis a significant advantage both of the presence of eosinophilia (P=0.004) and of inv(16) (P=0.01); at multivariate analysis, patients with M4Eo+ inv(16) had a highly significant advantage compared to M4 without eosinophilia and without inv(16) (P=0.004), but also compared to M4+ inv(16) (P=0.045), and M4Eo-without inv(16) (P=0.076). Conclusions: AML-M4 with or without eosinophilia represent 23.7% of AML. The presence of eosinophilia and of inv(16)/t(16;16) can be both considered favorable prognostic factors; however, only the association of both features allows a highly significant advantage in terms of CR and OS.

scholarly journals Human acute myelomonocytic leukemia: serologic studies with simian antisera

Blood ◽  
1976 ◽  
Vol 48 (3) ◽  
pp. 339-350 ◽  
Author(s):  
T Mohanakumar ◽  
DS Miller ◽  
RS Metzgar
Keyword(s):  
Myeloid Leukemia ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Human Leukemia ◽  
Lymphatic Leukemia ◽  
Acute Myelomonocytic Leukemia ◽  
Blast Cells ◽  
Myelomonocytic Leukemia

Abstract Simian antisera to human leukemia cells were able to distinguish antigens specific for lymphocytic types of leukemia from those expressed on certain myeloid leukemia cells. In this investigation, cells from acute myelomonocytic leukemia patients (AMML) were examined for their membrane-associated leukemia antigens. Simian antisera to both lymphocytic and myelogenous leukemia cells lysed cells from AMML donors. Monkey antisera to AMML cells, by direct microcytotoxicity testing, were cytotoxic for cells from all AMML patients, as well as for cells of certain patients with myeloid leukemia. Cells from patients with lymphatic leukemia were nonreactive. However, absorption studies indicated an antigen present on cells from patients with chronic lymphocytic leukemia which cross-reacted with AMML cell antigens. Sequential analyses of the serologic reactivity of cells from AMML patients undergoing chemotherapy corresponded with the clinical course of the patient, even though there was little correlation between the percentage of blast cells present and the per cent cytotoxicity with the antisera. At certain times a higher percentage of seropositive cells could be detected over that seen on morphological evaluation. The estimation of leukemic cells by serologic means could aid in the diagnosis and management of AMML patients during chemotherapy.

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