Donor origin precursor B-cell lymphoblastic leukemia post beta-thalassemia haploidentical transplant – A rare case report

Secondary malignancy of donor origin in the form of acute lymphoblastic leukemia (ALL), post-allogeneic hematopoietic stem cell transplant (HSCT) for beta thalassemia (BT) major, is exceedingly rare. A10 year old male child, the first and only product of non-consanguineous conception, was diagnosed with BT major at the age of 9 months when he had diarrhea and his parents (both of whom had thalassemia minor) noticed yellowing of the skin. Until the age of 10 years, he received regular blood transfusion and iron chelation, when the requirements got escalated and he consequently had to undergo myeloablative haploidentical HSCT from his mother. The post-transplant period was uneventful, and follow up with short tandem repeat chimerism analysis revealed complete donor chimerism on all occasions. Five years after the transplant, he developed fever with pancytopenia. Peripheral smear (PS) and bone marrow revealed blasts that were immunophenotypically precursor B-ALL. Cytogenetics revealed twenty diploid female metaphases with modal karyotype 46, XX[20], and again, complete donor chimerism was noted. Thus, a diagnosis of donor cell leukemia (DCL) was considered. Induction chemotherapy was initiated; however, the patient succumbed to systemic sepsis midway through induction therapy. No evidence of leukemia was noted in the patient's mother, who was followed up with PSs for 5 years. DCL has a poor prognosis. Greater understanding of the disease biology could allow for appropriate donor screening, notification and shielding the recipient from DCL and its grave consequences.