Donor cell leukemia: a review

Relapse of acute leukemia following hematopoietic stem cell transplantation (HSCT) usually represents return of an original disease clone, having evaded eradication by pretransplant chemo-/radiotherapy, conditioning, or posttransplant graft-versus-leukemia (GVL) effect. Rarely, acute leukemia can develop de novo in engrafted cells of donor origin. Donor cell leukemia (DCL) was first recognized in 1971, but for many years, the paucity of reported cases suggested it to be a rare phenomenon. However, in recent years, an upsurge in reported cases (in parallel with advances in molecular chimerism monitoring) suggest that it may be significantly more common than previously appreciated; emerging evidence suggests that DCL might represent up to 5% of all posttransplant leukemia "relapses." Recognition of DCL is important for several reasons. Donor-derivation of the leukemic clone has implications when selecting appropriate therapy, because seeking to enhance an allogeneic GVL effect would intuitively not have the same role as in standard recipient-derived relapses. There are also broader implications for donor selection and workup, particularly given the growing popularity of nonmyeloblative HSCT and corresponding rising age of the potential donor pool. Identification of DCL raises potential concerns over future health of the donor, posing ethical dilemmas regarding responsibilities toward donor notification (particularly in the context of cord blood transplantation). The entity of DCL is also of research interest, because it might provide a unique human model for studying the mechanisms of leukemogenesis in vivo. This review presents and collates all reported cases of DCL, and discusses the various strategies, controversies, and pitfalls when investigating origin of posttransplant relapse. Putative etiologic factors and mechanisms are proposed, and attempts made to address the difficult ethical questions posed by discovery of donor-derived malignancy within a HSCT recipient.