Induction of graft-versus-host disease as immunotherapy of leukemia relapsing after allogeneic transplantation: single-center experience of 32 adult patients.
Thirty-two adults (median age 36 years) with leukemia (15 AML, eight CML, six ALL, three CLL) persisting or relapsing 1-40 months (median 4) after allogeneic BMT (20 matched siblings, eight unrelated, four family mismatch) underwent immunotherapy to elicit GVHD. This comprised one or more of: infusion of donor cells (n = 22), stopping cyclosporine (n = 14), and administration of interferon-alpha2b (n = 15) or interleukin-2 (n = 4). Eight acute leukemia patients received chemotherapy as well. The time from relapse to immunotherapy was 0-1344 days (median 4). Acute and/or chronic GVHD developed in 17 patients. Response was not evaluable in three patients due to early toxic death. There was no response in 10 patients, whereas 19 showed objective response. Nine patients died due to toxicity and 10 due to progressive disease. Thirteen patients are alive 4-58 months (median 14) after immunotherapy; 12 in remission (five AML, four chronic phase CML, one ALL, one accelerated phase CML, one CLL) and one with progressive disease (accelerated phase CML). Eleven of 13 patients who are alive had GVHD compared with six of 19 who died (P = 0.005, Fisher's exact test). We conclude that with the exception of CML in myeloid blast crisis, immunotherapy is active in most types of acute and chronic leukemia relapsing after allogeneic BMT. It is associated with considerable toxicity. Clinically obvious GVHD, especially chronic GVHD, results in a higher probability of survival.
Mehta
J
J
Leukaemia Unit, Royal Marsden Hospital, Surrey, UK.
Powles
R
R
Kulkarni
S
S
Treleaven
J
J
Singhal
S
S
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000139:chemically induced / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000628:therapy; D007945:Leukemia, Lymphoid / Q000276:immunology / Q000628:therapy*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy; D007951:Leukemia, Myeloid / Q000276:immunology / Q000628:therapy*; D007962:Leukocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy; D011994:Recombinant Proteins; D012008:Recurrence; D012074:Remission Induction / Q000379:methods
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D016572:Cyclosporine