Long-term follow-up of relapsed acute leukemia treated with immunotherapy after allogeneic transplantation: the inseparability of graft-versus-host disease and graft-versus-leukemia, and the problem of extramedullary relapse.
Long-term outcome of 23 acute myeloid (AML, n=16) or lymphoblastic (ALL, n=7) leukemia patients who had received immunotherapy for treatment of persistent or recurrent disease 1.5-26 (median 4) months after allogeneic transplantation was studied to determine eventual survival. Immune manipulation comprised donor leukocyte infusion (n=18), interferon-alpha2b and/or interleukin-2 (n=15), and cyclosporine withdrawal (n=11) in various combinations. Graft-versus-host disease (GVHD) developed in 12 patients. Thirteen of 20 evaluable patients responded; 6 relapsing again. Eight patients died of toxicity, and 10 of progressive disease at 3-206 weeks (median 11). Five patients (3 AML, 2 ALL) are alive in remission with GVHD 2-46 months (median 23) after immunotherapy with Karnofsky scores of 70-100% (median 80). The overall survival of the whole group is 1-206 weeks (median 12), with an actuarial survival of 22% at 2 years. The development of GVHD was associated with superior survival in multivariate analysis (P=.007). Seven patients received immunosuppression because of the severity of GVHD (grade III/IV acute or extensive chronic): 3 died of GVHD, 3 improved but relapsed concomitantly, and 1 is alive in remission with extensive chronic GVHD. Four episodes of extramedullary relapse (granulocytic sarcomas) were seen in 3 patients with AML whose marrow remained in remission. We conclude that GVHD appears to be inseparable from graft-versus-leukemia in relapsed acute leukemia patients undergoing immunotherapy with a high proportion of patients dying due to toxicity or progressive disease, and isolated extramedullary relapse seems to be unusually common.
Leukaemia Unit, Royal Marsden Hospital, Surrey, UK. ssinghal@exchange.uams.edu
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Singhal
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Powles
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Kulkarni
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Treleaven
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Saso
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Mehta
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology; D020350:Graft vs Tumor Effect / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D007951:Leukemia, Myeloid / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D012008:Recurrence; D015996:Survival Rate; D016896:Treatment Outcome