Donor Cell Leukemia: A Review

Abstract

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.

Occurrence of Donor Cell-derived Lymphoid Blast Crisis 24 Years Following Related Bone Marrow Transplantation for Chronic Myeloid Leukemia

“…Rather, acquired "second hit" on susceptible donor cells with an intrinsic defect in the recipient microenvironment could be a more plausible mechanism for DCL (1, 3, 7). The microenvironment in the transplant recipient would be damaged by conditioning irradiation or chemotherapy, which may lead to impair immune surveillance or dysregulation of cytokines or homeostasis for hematopoiesis (1). The homeostatic imbalance between the stem cells and the stroma would eventually result in the proliferation of abnormal donor cells (1,10).…”

“…The microenvironment in the transplant recipient would be damaged by conditioning irradiation or chemotherapy, which may lead to impair immune surveillance or dysregulation of cytokines or homeostasis for hematopoiesis (1). The homeostatic imbalance between the stem cells and the stroma would eventually result in the proliferation of abnormal donor cells (1,10). According to the recent findings that mesenchymal stem cells (MSCs) remained of recipient origin over a period of several years after transplantation (11,12), we cultured the MSCs obtained from the BM sample at the diagnosis of DCL and then performed a chimerism evaluation using STRs.…”

“…Reported cases with DCL, mainly acute myeloid leukemia after umbilical cord blood transplantation, are increasing according to the recent advance of diagnostic procedures such as short tandem repeat (STR) testing (4)(5)(6)(7). Although multiple mechanisms for developing DCL have been proposed, considering the diversified phenotypes of DCL with varied latency periods in previously reported cases, the pathogenesis of DCL could involve more than a single pathway (1,3,7). We herein report a unique case of DCL, as donor cellderived lymphoid blast crisis (BC) of chronic myeloid leukemia (CML) was observed 24 years after related bone marrow transplantation (BMT) for CML in the chronic phase (CP).…”

“…Secondary leukemia-derived donor cells, designated donor cell leukemia (DCL), may occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT) (1)(2)(3). Reported cases with DCL, mainly acute myeloid leukemia after umbilical cord blood transplantation, are increasing according to the recent advance of diagnostic procedures such as short tandem repeat (STR) testing (4)(5)(6)(7).…”

An unusual case of donor‐derived myelodysplastic syndrome following double‐unit umbilical cord blood transplantation in acute lymphoblastic leukemia

“…A total of 51 cases of ddMDS and 13 cases of ddAML have been reported in the literature [8]. The median time from HSCT to the development of ddMDS/ddAML has been reported to be 24 months [9].…”