Allo-HCT outcomes for AML patients with NUP98 rearrangements: A study on behalf of the global committee, the ALWP and the PDWP of the EBMT

Abstract Background Acute myeloid leukemia (AML) with NUP98 rearrangements on chromosome 11p15 is a high-risk subtype with poor prognosis. Due to its rarity, the impact of allogeneic hematopoietic cell transplantation (allo-HCT) in these patients remains unclear. Patients and Methods Data from 147 AML patients with NUP98 rearrangements or chromosomal translocations on chromosome 11p15 who underwent their first allo-HCT, collected from 87 centers between 2010 and 2022, were analyzed. Results Among 147 patients, 109 were adults with a median transplant age of 46.3 years (range: 18.1–73.5), and 38 were children with a median transplant age of 9.4 years (range: 0.4–18). In adults, the most prevalent chromosomal translocation was t(5;11)(q35;p15) NUP98-NSD1 (24.8%), followed by t(7;11)(p15;p15) NUP98-HOXA9 (19.3%), whereas in children, t(5;11)(q35;p15) NUP98-NSD1 was the most common (68.4%), followed by t(11;12)(p15;p13) NUP98-KDM5A (13.2%). At the time of transplantation, 112 patients were in first complete remission (CR1), 14 were in second or subsequent complete remission (≥CR2), and 21 had active disease. Among adults, 72.5% (n=79) were in CR1, 9.2% (n=10) in ≥CR2, and 18.3% (n=20) had active disease, while among children, 86.8% (n=33) were in CR1, 10.5% (n=4) in ≥CR2, and 2.6% (n=1) had active disease (P = 0.04). Myeloablative conditioning was administered to 67.1% (n=98) of AML patients undergoing allo-HCT, with 59.3% (n=64) of adults and 89.5% (n=34) of children receiving it, the difference being statistically significant (P < 0.001). Donor types included haploidentical relatives (30 cases), HLA-matched sibling (34 cases), unrelated donors (68 cases: 44 with 10/10 HLA match, 15 with 9/10, 1 with 8/10, and 8 with missing HLA data), umbilical cord blood (12 cases), HLA-matched other relatives (2 cases), and mismatched relatives at one locus (1 case). In adults, the primary stem cell graft source was peripheral blood (n=88), while in children, bone marrow was predominantly used (n=22), followed by peripheral blood (n=8) and umbilical cord blood stem cells (n=8). In vivo T-cell depletion (TCD) was performed in 91 patients, while 53 did not receive TCD. The median follow-up duration was 2.9 years (95%CI: 2–3.5 years). The 30-day neutrophil recovery was 93.0% (95% CI: 87.2–96.2), with adults achieving 95.2% and children 86.5%. At 2 years, the overall survival (OS) was 69.9% (95% CI: 60.3–77.6), and the leukemia-free survival (LFS) was 52.0% (95% CI: 42.6–60.7). The 2-year GVHD-free, relapse-free survival (GRFS) was 40.6% (95% CI: 31.4–49.6). The 2-year cumulative incidence of relapse was 39.1% (95% CI: 30.1–48.0), and non-relapse mortality was 8.9% (95% CI: 4.8–14.4). The cumulative incidence of grade II–IV acute graft-versus-host disease (GVHD) at 100 days was 22.6% (95% CI: 16.1–29.7), with grade III–IV acute GVHD occurring in 9.9% (95% CI: 5.7–15.5). At 2 years, the cumulative incidence of chronic GVHD was 23.2% (95% CI: 16.0–31.3), with extensive chronic GVHD observed in 8.2% of patients (95% CI: 3.9–14.3). In univariate analysis, children had a 2-year OS of 78.7% (95% CI: 60.2–89.3) vs. 66.4% (95% CI: 54.5–75.8) for adults (P = 0.16). LFS was 55.8% (95% CI: 37.3–70.8) in children and 50.6% (95% CI: 39.4–60.8) in adults (P = 0.65). RI was 41.6% (95% CI: 24.4–58.0) in children vs. 38.2% (95% CI: 27.7–48.7) in adults (P = 0.58). NRM was 2.6% (95% CI: 0.2–12.0) in children and 11.1% (95% CI: 5.8–18.3) in adults (P = 0.10). Acute GVHD (grade II–IV) at 100 days occurred in 13.2% (95% CI: 4.7–26.0) of children and 26.0% (95% CI: 18.0–34.8) of adults (P = 0.11), with grade III–IV rates of 7.9% (95% CI: 2.0–19.3) and 10.6% (95% CI: 5.6–17.4), respectively (P = 0.63). Chronic GVHD at 2 years was 9.6% (95% CI: 2.4–23.1) in children vs. 28.3% (95% CI: 19.0–38.2) in adults (P = 0.045). Extensive chronic GVHD was 0.0% in children and 11.3% (95% CI: 5.4–19.6) in adults (P = 0.14). GRFS was 52.1% (95% CI: 33.8–67.6) in children vs. 36.1% (95% CI: 25.6–46.7) in adults (P = 0.28). Transplantation in patients with active disease was associated with inferior LFS, higher RI, and reduced GRFS, and myeloablative conditioning significantly improved the 2-year OS.Conclusion This is the largest cohort of allogeneic transplantation for AML patients with NUP98 rearrangements, a rare subset, with both adult and pediatric patients. Allo-HCT is an effective treatment for AML patients with NUP98 rearrangements.