A basis for updating our approach to resistant acute leukemia

Abstract

No studies exist documenting that chemotherapy alone eradicates tumors composed of leukemic cells in a large group of patients with tumors at any one site. Yet, its use has continued over 40 years in the absence of data. Consensus protocols exist only for testis and meningeal tumors, relying on local therapy. To constitute a body of knowledge about tumors at one site, the breast was chosen and all published cases were analyzed, with follow-up obtained, to document the behavior of acute leukemia tumors and survival after presentation. Among 235 cases (52% published since 2000), overall survival was poor, particularly for the 43% with concurrent morphologic marrow relapse, with 66-73% one-year mortality. Only 4 of 106 patients treated with chemotherapy alone survived 4 years. The majority of AML and ALL tumors were only transiently responsive to anti-leukemia treatments, including transplant, and next relapses were as, or more, common in further tumors than in marrow. A pattern of tumors similar to the metastases of invasive lobular breast cancer was revealed. When relapse occurred in marrow, durable remission was only rarely obtained. These data suggest a potential benefit of incorporating extent of disease workup at diagnosis and relapse into prospective trials. This could yield an accurate incidence of extramedullary tumors and a means to identify occult residual disease which could lead to marrow relapse. This approach could potentially result in greater success in curing acute leukemias. Am. J. Hematol. 87:251-257, 2012. V

Primary Intracerebral Myeloid Sarcoma

“…The t(8;21) translocation is themostcommonlyreportedcytogeneticabnormality;others includet(11q23),t(9;11),del(16q),t(8;17),t(8;16),t(1;11),and (q22;q22). Molecularly, t(8;21) and inv (16) are regarded as carryingafavorableprognosis [6,16].Inthisreview,genetic Case Report A22-year-oldmalepresentedtoourhospitalwithheadache.Physicaland neurological examination, as well as blood cell count were completely normal: hemoglobin 13.8 mg/dl, white blood cells 7,300/mm 3 , 60% neutrophils, 12% eosinophils, 2% basophils, 20% lymphocytes, 6% monocytes, and platelets 324,000/mm 3 . Biochemical panel and computed tomography (CT) of thorax and abdomen were also normal.…”

“…The diseasewasinitiallyreferredtoas'granulocyticsarcoma'and 'chloroma', and later, in the classification of myeloid neoplasms by the 2008 World Health Organization, these terms werereplacedwith'myeloidsarcoma'asasubgroupof'acute myeloid leukemias, not otherwise categorized' [1]. MS may occurinpatientswithacutemyeloidleukemia(AML),acute lymphocytic leukemia, myeloproliferative disease, or myelodysplasia, yet rarely presents in the absence of a myeloid disease [2,3].Itmayinvolveanyorgansystem,fromcommon involvement of the skin, bone, orbitae, and lymph nodes to rarecasesinvolvingheart,smallintestines,orbrain [2].Here, we present a patient with intracerebral MS (ICMS) with no hematological disease. Radiologically, the mass had the appearanceofameningioma.…”

Letter to the Editor Isolated extramedullary breast relapses in inv(16) positive and c-KIT negative acute myeloid leukemia after allogenic hematopoietic stem cell transplantation – description of two cases

“…central nervous system, ovary and testis, as well as other anatomical locations including skin, muscle, body cavities, mammary glands, gastrointestinal tract and urinary tract [4–7]. Up to 2010 as many as 163 cases of AML breast relapse were described but only 36% had karyotype evaluation [8]. We present two patients with AML favorable cytogenetics – inv(16)(p13;q22); CBFB (core binding factor β-chain) -MYH11 (myosin heavy chain 11 gene) – and EMR in breast after allo-HSCT.…”

“…Moreover, previous GvHD seems to occur more frequently in EMR compared with bone marrow relapse [6, 14]. The latest meta-analysis of AML extramedullary relapses in the breast, reported by Cunningham [8], included 163 cases published between 1969 and 2010. All FAB subtypes were nearly equally observed, but karyotypes were available only in 55 cases (36%).…”

Acquired resistance of leukemic cells to AraC is associated with the upregulation of aldehyde dehydrogenase 1 family member A2

“…Cytosine arabinoside (1-β-D-arabinofuranosylcytosine [AraC]) is one of the most effective drugs in the chemotherapeutic treatment of acute myeloid leukemia [3]. AraC is also active against other hematologic malignancies, such as acute lymphoblastic leukemia and non-Hodgkin lymphoma [4].…”