Genetically identical twin transplantation for chronic lymphocytic leukemia

Abstract

We identified 19 persons with B-cell chronic lymphocytic leukemia (CLL) who received genetically identical twin blood cell or bone marrow transplants after high-dose conditioning. Ten are alive (eight disease-free) with a median follow-up of 89 months (range, 31-171 months); 5-year relapse rate was 50% (95% confidence interval (CI), 26-73%). Estimated 5-year survival and disease-free survival were 61% (95% CI, 37-82%) and 45% (95% CI, 23-68%). In two of four patients tested at 12 and 21 months by polymerase chain reaction no evidence of residual CLL was detected post-transplant. In one recipient who relapsed at 6 years, molecular studies showed a different CLL clone from that detected pretransplant. This clone was subsequently identified in the donor suggesting transfer of occult leukemia at the time of transplant. Genetically identical twin transplants can result in long-term disease-free survival and molecular remissions, these data suggest the potential for CLL control in the absence of allogeneic graft-versus-leukemia effect. The case of leukemia transfer indicates the need for careful evaluation of donors prior to graft collection.

Monoclonal B-cell lymphocytosis in healthy blood donors: an unexpectedly common finding

“…30,31 To date, however, MBL has not been reported in any recipients following blood transfusion. Indeed, no MBL studies have been conducted in transfusion recipients.…”

Graft-versus-leukemia in chronic lymphocytic leukemia

“…Others have reached similar conclusions with less extensive analyses. 29,34,35 However, a more critical analysis of GvL in CLL requires considering detailed data from larger numbers of allograft recipients with and without GvHD, recipients of T-cell-depleted allograft and genetically identical twin transplant recipients.…”

“…Unfortunately, such data are reported few in number. Pavletic et al 34,35 reported 19 subjects transplanted between 1980 and 2001 with bone marrow or blood cell transplants after high doses of pretransplant anti-leukemia drugs with or without radiation. Four of 13 subjects achieving complete remission relapsed with a 5-year cumulative relapse risk of 52% (95% confidence interval, 27-77%).…”

Monoclonal B cell lymphocytosis: Clinical and population perspectives

“…There is both the theoretical and actual concern for transfer of MBL and leukemia stem cells to recipients, especially in the setting of an immunodepressed recipient. Several occurrences of transfer of MBL donor clones to a CLL patient undergoing transplant resulting in a second CLL in the recipient have been documented (40)(41)(42). Three case studies of potential population-screened MBL donors and a detailed review of ethical issues can be found in Hardy et al (29).…”