title: Colony growth in cultures from bone marrow and peripheral blood after curative treatment for leukemia and severe aplastic anemia.
abstract: The recovery of colony-forming cell numbers after curative treatment for leukemia and severe aplastic anemia (SAA) was studied. We examined 191 patients (85 acute myeloid leukemia [AML], 48 acute lymphocytic leukemia [ALL], 32 chronic myeloid leukemia [CML], 17 SAA, and nine myelodysplastic syndrome [MDS]) who were in hematologic remission 6 months to 13 years after either curative chemotherapy (n = 69) or allogeneic bone marrow transplantation (BMT) (n = 122) by culturing their precursor cells from bone marrow (BM) (n = 548) and peripheral blood (PB) (n = 529) in methylcellulose. Thirty-six BM donors and 25 PB donors served as controls. BM colony-forming cell numbers were abnormally low in all patients (p < 0.002) irrespective of underlying disorder and type of treatment (chemotherapy or irradiation). These numbers did not normalize with time--colony-forming cells were still strongly reduced up to 10 years after therapy, whether or not the patient had received an allogeneic bone marrow graft (p < 0.002). We also compared patients who remained in stable hematologic remission with those who later relapsed (6 months to 2 years after treatment). BM colony-forming cell numbers were significantly lower in patients who subsequently relapsed (p = 0.004). In contrast to BM cultures, we found normal colony-forming capacity by PB precursors in all patients. We conclude that (1) after chemotherapy or BMT, colony-forming cell numbers of BM in culture are permanently reduced; (2) this defect is probably due to a dysfunction of the BM environment rather than to a numerical reduction of the precursor cell pool; and (3) very low colony-forming capacity may be related to relapse.
authors.affiliation: Department of Internal Medicine, University of Basel, Switzerland.
authors.forename: D C
authors.initials: DC
authors.lastname: Betticher
authors.forename: H
authors.initials: H
authors.lastname: Huxol
authors.forename: R
authors.initials: R
authors.lastname: Müller
authors.forename: B
authors.initials: B
authors.lastname: Speck
authors.forename: C
authors.initials: C
authors.lastname: Nissen
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000188:drug therapy / Q000473:pathology* / Q000628:therapy; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001773:Blood Cells / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation; D002452:Cell Count; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology* / Q000628:therapy; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000473:pathology / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology* / Q000628:therapy
chemical_list: D000970:Antineoplastic Agents