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

Le résumé fourni par la source

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.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.