Acute monocytic leukemia (French-American-British classification M5) does not have a worse prognosis than other subtypes of acute myeloid leukemia: a report from the Eastern Cooperative Oncology Group.

PURPOSE Acute monocytic leukemia is a distinct subtype of acute myeloid leukemia (AML) with characteristic biologic and clinical features. This study was designed to compare the outcome of patients with M5 to that of other subtypes of AML, and to identify differences in M5a and M5b. PATIENTS AND METHODS We reviewed all patients with AML M5 entered in three clinical trials for newly diagnosed AML conducted by the Eastern Cooperative Oncology Group between 1989 and 1998. Eighty-one patients, 21 with M5a and 60 with M5b, were identified. RESULTS The complete remission rate was 62% for all patients with M5; 52% for patients with M5a and 65% for patients with M5b (P =.3), and 60% for the 1122 patients with non-M5 AML entered on the same clinical trials (P =.8 for M5 v non-M5). The 3-year disease-free survival was 26% for all M5 patients; 18% for M5a and 28% for M5b (P =.31), and 33% for non-M5 patients (P =.13 for M5 v non-M5). The 3-year overall survival was 31% for all M5 patients; 33% for M5a and 30% for M5b (P =.65), and 30% for non-M5 (P =.74 for M5 v non-M5). The karyotypes of patients with AML M5 were heterogeneous. CD11b was the only leukemic cell antigen expressed differently in M5a (53%) compared to M5b (77%) to a significant degree (P =.02). CONCLUSION AML M5 represents an immunologically heterogeneous population similar to non-M5 AML with a prognosis that is not dependent on morphology. The disease-free survival and overall survival of patients with M5a, M5b, and non-M5 appear not to differ with currently available therapy.

[1]  D. Neuberg,et al.  A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: a trial by the Eastern Cooperative Oncology Group. , 2004, Blood.

[2]  W. Hiddemann,et al.  Distinct genetic patterns can be identified in acute monoblastic and acute monocytic leukaemia (FAB AML M5a and M5b): a study of 124 patients , 2002, British journal of haematology.

[3]  G. Ehninger,et al.  Analysis of Flt3-activating Mutations in 979 Patients with Acute Myelogenous Leukemia: Association with Fab Subtypes and Identification of Subgroups with Poor Prognosis , 2022 .

[4]  T. Ahmed,et al.  Secondary acute myelogenous leukemia and myelodysplasia without abnormalities of chromosome 11q23 following treatment of acute leukemia with topoisomerase II-based chemotherapy , 2001, Leukemia.

[5]  S. Raimondi,et al.  Experience with 2-chlorodeoxyadenosine in previously untreated children with newly diagnosed acute myeloid leukemia and myelodysplastic diseases. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  S. Brandt,et al.  Age and Cytogenetics as Predictors of Event Free Survival in Patients with Acute Non-Lymphocytic Leukemia Receiving High Dose Cytosine Arabinoside and Daunorubicin as Consolidation Chemotherapy , 2001, Leukemia & lymphoma.

[7]  Y. Honma.  A Novel Therapeutic Strategy Against Monocytic Leukemia with Deoxyadenosine Analogs and Adenosine Deaminase Inhibitors , 2001, Leukemia & lymphoma.

[8]  J. Reilly,et al.  FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group. , 2000 .

[9]  X. Thomas,et al.  Impact of pre-induction therapy leukapheresis on treatment outcome in adult acute myelogenous leukemia presenting with hyperleukocytosis , 2000, Annals of Hematology.

[10]  Y. Honma,et al.  Antileukemic efficacy of 2-deoxycoformycin in monocytic leukemia cells. , 2000, Blood.

[11]  B. Löwenberg,et al.  Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene , 2000, Leukemia.

[12]  P. Porcu,et al.  Hyperleukocytic Leukemias and Leukostasis: A Review of Pathophysiology, Clinical Presentation and Management , 2000, Leukemia & lymphoma.

[13]  Y. Honma,et al.  Myeloid and monocytoid leukemia cells have different sensitivity to differentiation-inducing activity of deoxyadenosine analogs. , 2000, Leukemia research.

[14]  T. Naoe,et al.  Prognostic implication of FLT3 and N-RAS gene mutations in acute myeloid leukemia. , 1999, Blood.

[15]  F. Appelbaum,et al.  Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. , 1998, The New England journal of medicine.

[16]  Y. Honma,et al.  Human monocytoid leukemia cells are highly sensitive to apoptosis induced by 2'-deoxycoformycin and 2'-deoxyadenosine: association with dATP-dependent activation of caspase-3. , 1998, Blood.

[17]  K Wheatley,et al.  The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. , 1998, Blood.

[18]  C. Bloomfield,et al.  Acute myeloid leukemia with 11q23 translocations: myelomonocytic immunophenotype by multiparameter flow cytometry , 1998, Leukemia.

[19]  J. Bennett,et al.  Acute myeloid leukaemia expressing the leucocyte integrin CD11b — a new leukaemic syndrome with poor prognosis: result of an ECOG database analysis , 1998 .

[20]  J. Magaud,et al.  Clinical and biological characteristics of adult de novo and secondary acute myeloid leukemia with balanced 11q23 chromosomal anomaly or MLL gene rearrangement compared to cases with unbalanced 11q23 anomaly: confirmation of the existence of different entities with 11q23 breakpoint , 1998, Leukemia.

[21]  C. Bloomfield,et al.  Adult patients with de novo acute myeloid leukemia and t(9; 11)(p22; q23) have a superior outcome to patients with other translocations involving band 11q23: a cancer and leukemia group B study. , 1997, Blood.

[22]  S. Granter,et al.  Leukemic vasculitis: a feature of leukemia cutis in some patients. , 1997, American journal of clinical pathology.

[23]  R. Gray,et al.  Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia. Results of the Medical Research Council's 10th AML trial (MRC AML10). Adult and Childhood Leukaemia Working Parties of the Medical Research Council. , 1997, Blood.

[24]  C. Bloomfield,et al.  Adult patients with de novo acute myeloid leukemia and t(9; 11)(p22; q23) have a superior outcome to patients with other translocations involving band 11q23: a cancer and leukemia group B study. , 1997, Blood.

[25]  Y. Kaneko,et al.  Differentiation inhibitory factor nm23 as a new prognostic factor in acute monocytic leukemia. , 1996, Blood.

[26]  D. Hirschstein,et al.  Effects of flt3 ligand on acute myeloid and lymphocytic leukemic blast cells from children. , 1996, Experimental hematology.

[27]  F. Behm,et al.  11q23 rearrangements in acute leukemia. , 1996, Leukemia.

[28]  S. Raimondi,et al.  Epipodophyllotoxin-related acute myeloid leukemia: a study of 35 cases. , 1995, Leukemia.

[29]  D. Horsman,et al.  Acute monocytic leukemia: a single institution experience. , 1995, Leukemia & lymphoma.

[30]  T. Lister,et al.  Prevalence and clinical correlations of MLL gene rearrangements in AML-M4/5. , 1994, Blood.

[31]  E. Estey,et al.  Abnormalities in the long arm of chromosome 11 (11q) in patients with de novo and secondary acute myelogenous leukemias and myelodysplastic syndromes. , 1994, Leukemia.

[32]  R. Mayer,et al.  Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. , 1994, The New England journal of medicine.

[33]  J. Rowley,et al.  Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. , 1993, The New England journal of medicine.

[34]  F. Behm,et al.  Translocation t(9;11)(p21;q23) in pediatric de novo and secondary acute myeloblastic leukemia. , 1992, Leukemia.

[35]  C. Preudhomme,et al.  Acute monocytic leukemia with (8;22)(p11;q13) translocation. Involvement of 8p11 as in classical t(8;16)(p11;p13). , 1992, Cancer genetics and cytogenetics.

[36]  M. Slovak,et al.  Acute monoblastic leukemia (FAB-M5b) with t(8;14)(p11;q11.1). , 1991, Cancer genetics and cytogenetics.

[37]  P. Fenaux,et al.  Acute monocytic leukaemia in adults: treatment and prognosis in 99 cases , 1990, British journal of haematology.

[38]  J. Buckley,et al.  Acute monoblastic leukemia: a unique subtype--a review from the Childrens Cancer Study Group. , 1990, Leukemia research.

[39]  J. Roberts,et al.  Testicular enlargement as a presenting feature of monocytic leukemia in an infant. , 1989, Journal of pediatric surgery.

[40]  R. Silverman,et al.  Transient blueberry muffin appearance of a newborn with congenital monoblastic leukemia. , 1989, Journal of the American Academy of Dermatology.

[41]  H. Preisler,et al.  Acute myelogenous leukemia with leukemia cutis. Eighteen cases seen between 1969 and 1986 , 1989, Cancer.

[42]  J. Hainsworth,et al.  Therapy-related acute nonlymphocytic leukemia with monocytic features and rearrangement of chromosome 11q. , 1989, Annals of internal medicine.

[43]  V. Diehl,et al.  Phenotyping of acute myelomonocytic (AMMOL) and monocytic leukemia (AMOL): association of T-cell-related antigens and skin-infiltration in AMOL. , 1989, Leukemia research.

[44]  M. Pettenati,et al.  Translocation (8;16)(p11;p13) in patients with acute monocytic leukemias. An evolving syndrome? , 1988, Cancer genetics and cytogenetics.

[45]  O. Haas,et al.  Translocation t(8;16) in acute monocytic leukemia. , 1988, Cancer genetics and cytogenetics.

[46]  C. S. Scott,et al.  Diagnostic and prognostic factors in acute monocytic leukaemia: an analysis of 51 cases , 1988, British journal of haematology.

[47]  J. Huret,et al.  The 8p11 anomaly in "monoblastic" leukaemia. , 1988, Leukemia research.

[48]  J. Ritter,et al.  Early deaths due to hemorrhage and leukostasis in childhood acute myelogenous leukemia. Associations with hyperleukocytosis and acute monocytic leukemia , 1987, Cancer.

[49]  H. Higashino,et al.  Acute monocytic leukemia in children: Response to VP‐16‐213 as a single agent , 1987, Cancer.

[50]  C. Bloomfield,et al.  Central nervous system involvement in acute nonlymphocytic leukemia. A prospective study of adults in remission. , 1987, The American journal of medicine.

[51]  J. Dutcher,et al.  Hyperleukocytosis in adult acute nonlymphocytic leukemia: impact on remission rate and duration, and survival. , 1987, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[52]  F. Mitelman,et al.  A new specific chromosomal rearrangement, t(8;16) (p11;p13), in acute monocytic leukaemia , 1987, British journal of haematology.

[53]  D. Graham,et al.  Infiltrative polyneuropathy due to acute monoblastic leukemia in hematologic remission , 1987, Neurology.

[54]  M. Pinto,et al.  A unique 8;16 translocation in two infants with poorly differentiated monoblastic leukemia. , 1987, Cancer genetics and cytogenetics.

[55]  M. Auger,et al.  A quantitative study of monocyte procoagulant activity in acute monoblastic and chronic myelomonocytic leukaemias. , 1987, Acta haematologica.

[56]  A. Hertler,et al.  Isolated anterior chamber relapse in acute monoblastic leukemia , 1986, American journal of hematology.

[57]  D. Hossfeld,et al.  Translocation (9;11)(p21;q23) in a child with acute monoblastic leukemia following 2 1/2 years after successful chemotherapy for neuroblastoma. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[58]  R. L. Font,et al.  Acute monocytic leukemia recurring as bilateral perilimbal infiltrates. Immunohistochemical and ultrastructural confirmation. , 1985, Ophthalmology.

[59]  G Flandrin,et al.  Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. , 1985, Annals of internal medicine.

[60]  L. Odom,et al.  Acute monoblastic leukemia in infancy and early childhood: successful treatment with an epipodophyllotoxin. , 1984, Blood.

[61]  L. Vickars,et al.  Disseminated intravascular coagulation in acute monoblastic leukemia: response to heparin therapy. , 1984, Canadian Medical Association journal.

[62]  Denis R. Miller,et al.  A heparin‐like anticoagulant in an 8‐month‐old boy with acute monoblastic leukemia , 1984, American journal of hematology.

[63]  G. Dewald,et al.  A possible specific chromosome marker for monocytic leukemia: three more patients with t(9;11)(p22;q24) and another with t(11;17)(q24;q21), each with acute monoblastic leukemia. , 1983, Cancer genetics and cytogenetics.

[64]  C. Begg,et al.  Eastern Cooperative Oncology Group study of the cytochemistry of adult acute myeloid leukemia by correlation of subtypes with response and survival. , 1981, Cancer research.

[65]  L. Peterson,et al.  Extramedullary masses as presenting features of acute monoblastic leukemia. , 1981, American journal of clinical pathology.

[66]  J. Goldberg,et al.  Association of monocytic leukemia in patients with extreme leukocytosis. , 1980, The American journal of medicine.

[67]  M. Boiron,et al.  Acute monoblastic leukemia: a clinical and biologic study of 74 cases. , 1980, Blood.

[68]  H. Gralnick,et al.  Proposals for the Classification of the Acute Leukaemias French‐American‐British (FAB) Co‐operative Group , 1976, British journal of haematology.

[69]  L. Ganguli.  Acute monocytic leukaemia. , 1957, Journal of the Indian Medical Association.