Background: For patients with Trisomy 21/Down Syndrome (DS), advances in chemotherapy regimens have increased the 5-year overall survival (OS) of myeloid leukemia– DS (ML-DS) and DS-acute lymphoblastic leukemia (DS-ALL) to over 85%. However, outcomes remain poor for relapsed/refractory disease, with 5-year OS in ML-DS and DS-ALL at 25% and 64%, respectively. Hematopoietic stem cell transplantation (HSCT) has been associated with increased survival, especially in patients who are in complete remission (CR) prior to HSCT. However, in DS-ALL, HSCT is not routinely performed due to concern for increased chemotherapy toxicity and subsequent intolerance for high dose conditioning regimens, which are compounded by common comorbidities. In this population, HSCT is saved for very high-risk, relapsed cases only. Overall, there is limited current data on HSCT outcomes and comorbidities associated with pediatric and adolescent/young adult (AYA) patients with Trisomy 21 (T21).

Methods: A retrospective chart review was performed at the University of Texas MD Anderson Cancer Center of three AYA patients with T21 who received allogeneic HSCT for relapsed acute leukemia. Characteristics noted include the peri-transplant course, occurrence of graft-vs-host-disease (GvHD), transplant-related toxicities, and treatment response.

Results:Among the three, two were female and one was male, aged 17, 24, and 28 years, respectively. In the 24-year-old patient, T21-associated congenital abnormalities included aortic coarctation and spina bifida; in the 28-year-old male, congenital hypothyroidism and seizure disorder. Two patients underwent transplantation between 13–36 months from diagnosis, while the third more than 36 months after diagnosis. All three were in second complete remission (CR2) at the time of transplant, with Karnofsky performance scores >70. The 17-year-old female underwent a haploidentical transplant for Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) after two prior relapses, followed by a second haploidentical transplant due to graft failure. The 24-year-old female received a haploidentical transplant for high-risk, relapsed B-ALL with a TP53 mutation which failed treatment to CD19-directed chimeric antigen receptor T-cell therapy. The 28-year-old male received a matched unrelated donor transplant for relapsed acute myeloid leukemia with unfavorable cytogenetics. All patients received a myeloablative conditioning with post-transplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis. Median time to neutrophil engraftment was noted by D+14 and median platelet engraftment by D+19 following HSCT. Day+30 engraftment studies were available for two patients, which illustrated quick reconstitution, with 100% T and Myeloid cells of donor origin. Transplant-related comorbidities in our 17-year-old patient included severe engraftment syndrome with the development of pericardial effusion requiring pericardiocentesis, transient acute kidney injury. She also developed viral reactivation with CMV as well as parvovirus reactivation, which was treated, but subsequently caused secondary graft failure. Infections included HHV6 in the same patient, and BKV in another patient that did not require treatment. Two patients experienced mucositis, with one requiring patient-controlled analgesia and another requiring parenteral nutrition. One patient developed steroid refractory grade III skin GvHD requiring prednisone, ruxolitinib, and topical tacrolimus, and experienced eventual improvement with extracorporeal photopheresis. Another patient experienced grade 1 gut GVHD that did not require treatment. Two patients remain alive at the time of publication at an average time of 1 year. One patient who received HSCT following failure of CAR T cell therapy died of relapsed disease on D+90, indicating highly treatment-resistant disease.

Conclusion:Here we describe three patients with T21 who underwent HSCT for relapsed/refractory leukemia. Two patients are surviving, including one with multiply relapsed disease who had initial graft failure, and remains disease free 2 years and 7 months following HSCT. Toxicities following HSCT were manageable and did not significantly impact engraftment. Viral reactivations and infections were manageable with appropriate therapy. HSCT should be considered as a curative option for patients with T21 in areas where resources and close follow up are available to manage morbidities and toxicities.

This content is only available as a PDF.
2025
Sign in via your Institution