Biomaterial Database

Myelodysplastic syndromes and acute myeloid leukemia in connective tissue disease after single-agent chemotherapy. 1996

N S Rosenthal, and D C Farhi

University Hospitals of Cleveland, Institute of Pathology, Case Western Reserve University, Ohio 44106-5077, USA.

Cytopenias are typical of patients with connective tissue disease (CTD) and are usually related to autoimmune phenomena. In some cases, cytopenia may be the result of treatment with cytotoxic agents. Although multi-drug therapy is known to produce myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) in patients with CTD, treatment with single-agent therapy, particularly methotrexate, has rarely been associated with secondary MDS or AML. Blood and marrow samples were studied from 3 men and 5 women with rheumatoid arthritis (5 cases), Behcet's disease (2 cases), and systemic lupus erythematosus (1 case) developing MDS or AML after methotrexate (5 cases), chlorambucil (2 cases), and cytoxan (1 case). The durations of CTD ranged from less than 6 months to more than 10 years. Five patients (63%) presented with MDS including refractory anemia (RA), refractory thrombocytopenia (RT), refractory anemia with excess blasts (RAEB), chronic myelomonocytic leukemia (CMML), and RAEB in transformation. Patients with RT, CMML, and RAEB in transformation developed AML. Of six patients presenting with or developing AML, four had AML with differentiation (FAB M2), one acute myelomonocytic leukemia (FAB M4), and one M4Eo. Inv 16 was seen in the M4Eo and t(8;21) in one case of M2. Four of six patients are alive up to 6 years after diagnosis of AML. One of three patients with MDS is alive 6 months after diagnosis of MDS. Cytopenias in patients with CTD may be due to therapy-related MDS or AML occurring in a setting of single-agent chemotherapy, including methotrexate.

UI	MeSH Term	Description	Entries
D007951	Leukemia, Myeloid	Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.	Granulocytic Leukemia,Leukemia, Granulocytic,Leukemia, Myelocytic,Leukemia, Myelogenous,Myelocytic Leukemia,Myelogenous Leukemia,Myeloid Leukemia,Leukemia, Monocytic, Chronic,Monocytic Leukemia, Chronic,Chronic Monocytic Leukemia,Chronic Monocytic Leukemias,Granulocytic Leukemias,Leukemia, Chronic Monocytic,Leukemias, Chronic Monocytic,Leukemias, Granulocytic,Leukemias, Myelocytic,Leukemias, Myelogenous,Leukemias, Myeloid,Monocytic Leukemias, Chronic,Myelocytic Leukemias,Myelogenous Leukemias,Myeloid Leukemias
D007970	Leukopenia	A decrease in the number of LEUKOCYTES in a blood sample below the normal range (LEUKOCYTE COUNT less than 4000).	Leukocytopenia,Leukocytopenias,Leukopenias
D008297	Male		Males
D008727	Methotrexate	An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.	Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009190	Myelodysplastic Syndromes	Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.	Dysmyelopoietic Syndromes,Hematopoetic Myelodysplasia,Dysmyelopoietic Syndrome,Hematopoetic Myelodysplasias,Myelodysplasia, Hematopoetic,Myelodysplasias, Hematopoetic,Myelodysplastic Syndrome,Syndrome, Dysmyelopoietic,Syndrome, Myelodysplastic,Syndromes, Dysmyelopoietic,Syndromes, Myelodysplastic
D002699	Chlorambucil	A nitrogen mustard alkylating agent used as antineoplastic for chronic lymphocytic leukemia, Hodgkin's disease, and others. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed)	4-(Bis(2-chloroethyl)amino)benzenebutanoic Acid,Amboclorin,CB-1348,Chloraminophene,Chlorbutin,Leukeran,Lympholysin,N,N-Di-(2-chloroethyl)-p-aminophenylbutyric Acid,NSC-3088,CB 1348,CB1348,NSC 3088,NSC3088
D003240	Connective Tissue Diseases	A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides.	Connective Tissue Disease,Disease, Connective Tissue,Diseases, Connective Tissue
D003520	Cyclophosphamide	Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.	(+,-)-2-(bis(2-Chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-Oxide Monohydrate,B-518,Cyclophosphamide Anhydrous,Cyclophosphamide Monohydrate,Cyclophosphamide, (R)-Isomer,Cyclophosphamide, (S)-Isomer,Cyclophosphane,Cytophosphan,Cytophosphane,Cytoxan,Endoxan,NSC-26271,Neosar,Procytox,Sendoxan,B 518,B518,NSC 26271,NSC26271
D003582	Cytogenetics	A subdiscipline of genetics which deals with the cytological and molecular analysis of the CHROMOSOMES, and location of the GENES on chromosomes, and the movements of chromosomes during the CELL CYCLE.	Cytogenetic