Donor Cell–Derived Hematologic Neoplasms after Hematopoietic Stem Cell Transplantation: A Systematic Review

Abstract

Development of de novo hematologic malignancies in donor cells after allogeneic stem cell transplantation (allo-SCT) provides a useful in vivo model to study the process of leukemogenesis. A systematic analysis of the cases reported in the literature was performed to identify risk factors and mechanisms involved in the pathogenesis of donor cell-derived hematologic neoplasms (DCHN) and leukemogenic transformation. Relevant data were extracted from 137 cases. Cases of DCHN show a wide heterogeneity with regard to recipient/donor age, sex mismatch, and conditioning regimen. Some characteristics, such as the type of primary disease, the type of hematologic malignancy of the DCHN, and the stem cell source used in the transplant procedure, differ from those expected. Mechanisms involved in the pathogenesis of DCHN are complex, and several hypotheses have been proposed, such as pre-existing hematologic neoplasms or premalignant clones in the donor, decreased immune surveillance, and damage to bone marrow microenvironment in the recipient. Most likely several if not all these mechanisms play a role in DCHN development. Novel approaches, such as next-generation sequencing to study consecutive samples after allo-SCT in these patients, appear to be promising to decipher the mechanisms of leukemogenesis.

Short Tandem Repeats (STRs) as Biomarkers for the Quantitative Follow-Up of Chimerism after Stem Cell Transplantation: Methodological Considerations and Clinical Application

“…However, despite MRD analyses being more specific than chimerism analyses, they can fail to detect relapse when expression of surface or molecular markers is lost due to clonal heterogeneity, which is not uncommon. Moreover, in the rare situation of donor cell leukemia [46][47][48], the presence of leukemic cells can be misdiagnosed as disease relapse if chimerism analysis is not performed. Therefore, we consider that monthly chimerism follow-up should be performed in unseparated PB in acute leukemia patients during the first year after HSCT and every three months during the second year.…”

Donor cell‐derived acute promyelocytic leukemia after allogeneic hematopoietic stem cell transplantation

“…7 Review of the literature identified more than 70 cases of AML DCL (Table S1). 8 The Figure 3). Another study reported that DCL appears earlier in patients transplanted with CB.…”

“…Review of the literature identified more than 70 cases of AML DCL (Table ) . The median time between allogenic HSCT and occurrence of AML DCL was 30 months (range 1‐279).…”

Clonal Hematopoiesis of Indeterminate Potential as a Novel Risk Factor for Donor-Derived Leukemia

“…Donor-derived leukemia (DDL) is a severe complication of HSCT in which patients later develop a secondary leukemia of donor origin ( Fialkow et al., 1971 ; Wiseman, 2011 ). Previously considered rare, DDL mayconstitute 5% or more of leukemia relapses, and the number of cases has continued to increase over the last 50 years, particularly since 2000 ( Suarez-Gonzalez et al., 2018a ; Wiseman, 2011 ). The median age of recipients with DDL ranges from 31 to 53 years, indicating that it may be more common in adults ( Suarez-Gonzalez et al., 2018a ; Wang et al., 2011 ; Wiseman, 2011 ).…”