title: Donor lymphocyte infusions to leukemic bone lesions are therapeutically effective in a Ph+ ALL patient with post-HSCT relapse.
abstract: A Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) case was maintained in remission with the use of chemo-immunotherapy. The latter involved sibling bone marrow transplant (BMT) (three procedures) followed by intravenous (IV) donor lymphocyte infusion (DLI). The third relapse responded to routine chemotherapy and again DLI was employed. During hematological and molecular remission verified at the level of iliac crest aspiration, extra-medullary relapse in the bones was apparent. A novel procedure of donor lymphocyte injection to the bone leukemic lesions was developed and employed. A dose of 10(6) donor lymphocytes/kg body weight (BW) of the recipient were each time injected to the plane of the right and left tibia, the head of the humerus, and the calcaneus, which resulted in healing of the destructive process. In consequence of this novel approach, in addition to the healing of bone lesions, an accumulation of cytotoxic activated T-cells in the marrow was documented, which was mirrored by an increase in the number of transcripts for interferon (IFN)-γ, interleukin (IL)-17, as well as RORγt. The local administration of DLI directly to the leukemic lesions requires a lower dose that diminishes the toxicity due to the general immune system activation.
authors.affiliation: L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences , Wroclaw , Poland .
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lange
authors.forename: Dorota
authors.initials: D
authors.lastname: Dlubek
authors.forename: Robert
authors.initials: R
authors.lastname: Zdziarski
authors.forename: Anna
authors.initials: A
authors.lastname: Chodorowska
authors.forename: Monika
authors.initials: M
authors.lastname: Mordak-Domagala
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Klimczak
authors.forename: Janusz
authors.initials: J
authors.lastname: Lange
authors.forename: Emilia
authors.initials: E
authors.lastname: Jaskula
mesh_terms: D000293:Adolescent; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy; D017148:Infusions, Intraosseous; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D007519:Isoantigens / Q000378:metabolism; D017710:Lymphocyte Transfusion; D060046:Maintenance Chemotherapy; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D012074:Remission Induction; D035781:Siblings; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D020381:Interleukin-17; D007519:Isoantigens; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D007371:Interferon-gamma
keywords: ALL; DLI; Ph+ALL; bcr/abl e1a2; donor lymphocyte infusion; hematopoietic stem cell transplantation; intra-bone donor lymphocyte infusion; relapse