TOPLINE

Among patients with chronic myelomonocytic leukemia (CMML), allogeneic stem cell transplantation (ASCT) was associated with longer median overall survival across BLAST risk groups, with the strongest and most consistent association seen in high- and intermediate-risk groups. Patients who underwent transplant before blast transformation had the longest median survival, at 119 months. However, the retrospective design and younger age of the transplant cohort limit causal interpretation.

METHODOLOGY

• CMML carries a risk for blast transformation, and current noncurative therapies offer limited survival benefits. ASCT is the only potentially curative treatment, but its benefits across modern risk groups, including BLAST and BLAST-Mol, remain uncertain.
• To evaluate this, researchers conducted a retrospective study of 775 patients with CMML (median age, 71 years; 68% men) diagnosed between 1994 and 2024 at Mayo Clinic sites in Rochester, Minnesota; Jacksonville, Florida; and Phoenix.
• Participants were stratified by ASCT status (ASCT cohort, n = 151; non-ASCT cohort, n = 624) and risk-adjusted using the BLAST clinical risk model (accounting for peripheral blood blasts ≥ 2%, white blood cell count ≥ 13 × 10⁹/L, and anemia severity) and BLAST-Mol, which incorporates molecular and cytogenetic features in addition to clinical variables.
• Overall survival and blast transformation-free survival were assessed. The median follow-up duration was 77 months.
• Molecular data were available for 593 patients, with next-generation sequencing identifying mutations in the TET2 (49%), ASXL1 (47%), and SRSF2 (42%) genes; cytogenetic data were available for 754 patients, with abnormal karyotypes identified in 21%. 

TAKEAWAY

• The ASCT cohort demonstrated longer median overall survival than the non-ASCT cohort (77 vs 28 months; hazard ratio [HR], 0.6; P < .01). Overall survival rates at 1 year, 5 years, and 10 years were higher in the ASCT cohort (93%, 56%, and 43%, respectively) than in the non-ASCT cohort (74%, 25%, and 7%, respectively).
• When adjusted for BLAST risk categories, ASCT vs non-ASCT was associated with longer median survival in the high-risk (50 vs 14 months; HR, 0.19; P < .01), intermediate-risk (81 vs 28 months; HR, 0.2; P < .01), and low-risk (111 vs 65 months; HR, 0.6; P = .04) groups. ASCT was also associated with longer blast transformation-free survival in the high-risk (not reached vs 12 months; HR, 0.19; P = .01), intermediate-risk (153 vs 24 months; HR, 0.2; P = .01), and low-risk (171 vs 63 months; HR, 0.4; P = .01) groups.
• In BLAST-Mol risk-adjusted analysis, ASCT was associated with improved median survival in the high-risk (50 vs 12 months; HR, 0.15; P < .01) and intermediate-risk (81 vs 23 months; HR, 0.3; P < .01) groups but not in the low-risk group (not reached vs 66 months; HR, 0.5; P = .08) compared with non-ASCT. Transplantation was associated with improved blast transformation-free survival in the high-, intermediate-, and low-risk groups.
• Median overall survival was the longest among patients who underwent ASCT before blast transformation (119 months), followed by those who underwent ASCT after blast transformation (44 months), non-transplanted patients without blast transformation (31 months), and non-transplanted patients with blast transformation (21 months).

IN PRACTICE

“These observations support the early use of ASCT in CMML, ideally before [blast transformation] and regardless of genetic characteristics,” the study authors wrote.

SOURCE

The study, led by Ali Alsugair of the Division of Hematology at Mayo Clinic in Rochester was published online in the American Journal of Hematology.

LIMITATIONS

The study was retrospective, and patients who underwent ASCT were younger than those who did not undergo transplant across all BLAST risk groups, with other baseline differences between cohorts. Although the survival difference persisted after excluding patients older than 75 years from the non-ASCT cohort, residual selection bias cannot be excluded.

DISCLOSURES

The authors did not disclose any funding information for the study. Three authors reported receiving research funding, honoraria, and consultancy fees from various pharmaceutical companies, including AbbVie, Astellas, Ascentage Pharma, Bristol Myers Squibb, Pfizer, and others. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.