Durability of responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia.
An analysis was performed of the response to treatment with donor lymphocyte infusions (DLI) and the survival in 66 consecutive patients who relapsed after primary treatment by allogeneic stem cell transplantation for BCR-ABL-positive chronic myeloid leukemia. The transplant donor was an HLA-identical sibling (n = 35) or a "matched" unrelated volunteer (n = 31). Fifty-seven patients were transplanted in chronic phase, eight in accelerated phase, and one in second chronic phase. The recognition of relapse was based on precise molecular, cytogenetic, or hematologic criteria. The median interval from transplant to relapse was 12 months (range 3-85). The median interval from relapse to initiation of DLI was 9.4 months (range 1-70). Patients received DLI from their original transplant donors on a bulk-dose (n = 34) or on an escalating-dose (n = 32) regimen. Patients were monitored serially by hematologic, cytogenetic, and molecular criteria. Molecular remission was defined by the finding of negative results by nested primer reverse transcriptase polymerase chain reaction (RT-PCR) for BCR-ABL transcripts on two consecutive occasions, subject to satisfactory controls. Forty-four patients (67%) achieved molecular remission. Patients who had relapsed to advanced phase disease and patients with short intervals between transplant and relapse had significantly lower probabilities of achieving molecular remission. Of the 44 patients who achieved molecular remission, 4 reverted to a PCR-positive status at 15, 18, 37, and 87 weeks after remission. The probability of survival for patients who achieved molecular remission was significantly better than for those who failed to do so (95% versus 53% at 3 years post-DLI, P = .0001). We conclude that the majority of molecular remissions after DLI are durable, and thus the majority of responding patients may prove to have been cured. (Blood. 2000;96:2712-2716)
Dazzi
F
F
Department of Haematology, Hammersmith Hospital/ICSM, London, United Kingdom. f.dazzi@ic,ac,uk
Szydlo
R M
RM
Cross
N C
NC
Craddock
C
C
Kaeda
J
J
Kanfer
E
E
Cwynarski
K
K
Olavarria
E
E
Yong
A
A
Apperley
J F
JF
Goldman
J M
JM
D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000706:statistics & numerical data; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000628:therapy*; D015993:Life Tables; D017710:Lymphocyte Transfusion; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D009679:Nuclear Family; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood; D012334:RNA, Neoplasm / Q000097:blood; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016879:Salvage Therapy; D016019:Survival Analysis; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000706:statistics & numerical data; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016044:Fusion Proteins, bcr-abl