Pediatric Donor Cell Acute Lymphoblastic Leukemia Following Bone Marrow Transplant for GATA2 Mutation

Abstract

Donor cell leukemia is a rare complication following hematopoietic stem cell transplant (HSCT). There are currently few reports in children and only rare, reported cases of donor-derived myelodysplastic syndrome/acute myeloid leukemia in patients with an underlying germline GATA2 mutation. Most reported cases are myeloid in origin and occur following related HSCT. We present a 3-year-old female who developed a donor-derived B-cell acute lymphoblastic leukemia 2 years post unrelated HSCT for GATA2 germline mutation.

GATA2 deficiency detected by newborn screening for SCID: A case report

“…The clinical presentation of our patient adds to the wide range of clinical manifestations of GATA2 deficiency, and suggests how a stepwise, multidisciplinary diagnostic approach can aid in timely diagnosis and management for infants with severe T-cell lymphopenia. There is much more to learn about GATA2 deficiency and its interaction with additional genetic or environmental factors, that predisposes them to severe complications even after curative therapies ( 10 , 18 – 20 ).…”

“…She has mild, chronic skin GVHD but is currently 13 months post-second transplant and doing well ( Figure 1 ). The patient's donor derived leukemia case has been reported elsewhere ( 10 ).…”

Cancer-associated fibroblasts in acute leukemia

“…The trouble is that LSCs remodel the BMM into a leukemia-permissive microenvironment while suppressing a hematopoietic-permissive microenvironment (50,60,(62)(63)(64)(65)(66)(67). Clinically, this hypothesis is best supported by donor cell leukemia, in which leukemia originates from engrafted donor cells after allogeneic HSC transplantation, i.e., the leukemiapermissive microenvironment may initiate leukemogenesis in healthy cells (68)(69)(70)(71)(72). Therefore, targeting of the leukemiapermissive BMM to restore hematopoietic-permissive BMM can be a useful strategy for overcoming R/R leukemia.…”