Clinical characteristics of patients with MDS-RS and SF3B1 mutation with and without TN and during EPO response
| Variable . | At diagnosis . | At follow-up . | ||||||
|---|---|---|---|---|---|---|---|---|
| NTN . | TN (before EPO) . | P* . | Receiving EPO during response . | P† . | ||||
| No. (%) . | Median (IQR) . | No. (%) . | Median (IQR) . | No. (%) . | Median (IQR) . | |||
| Total no. of patients | 27 | 30 | 16 | |||||
| Age, y | 72 (67-77) | 76 (69-82) | .26 | |||||
| Sex | .79 | |||||||
| Male | 15 | 12 | ||||||
| Female | 12 | 18 | ||||||
| Blood | ||||||||
| Hemoglobin, g/dL‡ | 10.8 (10.2-11.6) | 9.0 (8.0-10.0) | <.001 | 10.7 (10.3-11.7) | <.001 | |||
| White blood cell count × 109/L | 4.7 (4.1-7.4) | 5.3 (4.8-6.7) | .53 | 4.9 (4.1-6.5) | .50 | |||
| Absolute neutrophil count × 109/L | 2.7 (2.0-5.2) | 3.4 (2.2-4.5) | .94 | 2.7 (1.6-4.1) | .61 | |||
| Platelet count × 109/L | 282 (205-312) | 277 (211-376) | .68 | 305 (238-375) | .79 | |||
| S-EPO, U/L | 32 (16-48) | 40 (29-62) | .13 | NA | NA | |||
| S-ferritin, µg/L | 358 (246-519) | 480 (281-756) | .43 | 472 (264-790) | .54 | |||
| BM | ||||||||
| Cellularity (%) | 60 (45-70) | 60 (50-70) | .58 | 70 (70-90) | .03 | |||
| Blasts (%) | 2.0 (1.0-3.5) | 2.5 (1.5-3.5) | .09 | 1.5 (0-2.5) | .04 | |||
| Erythropoiesis (%) | 34 (15-43) | 28 (18-40) | .30 | 32 (26-55) | .54 | |||
| Ring sideroblasts (%) | 40 (29-53) | 35 (25-52) | .64 | 40 (38-55) | .13 | |||
| IPSS-R (% of known) | ||||||||
| Very low | 17 (63) | 5 (18) | <.001 | NA | NA | |||
| Low | 10 (37) | 21 (75) | NA | |||||
| Intermediate | 0 (0) | 2 (7) | NA | |||||
| Not known/missing cytogenetics | 0 (0) | 2 (NA) | NA | |||||
| Mutations (% of known) | ||||||||
| SF3B1 only | 17 (63) | 16 (53) | .81 | 11 (69) | .47 | |||
| SF3B1 + 1 | 7 (26) | 9 (30) | 2 (12) | |||||
| SF3B1 + ≥2 | 3 (11) | 5 (17) | 3 (19) | |||||
| SF3B1 VAF | 36 (27-43) | 35 (30-39) | .85 | 36 (31-43) | .63 | |||
| Variable . | At diagnosis . | At follow-up . | ||||||
|---|---|---|---|---|---|---|---|---|
| NTN . | TN (before EPO) . | P* . | Receiving EPO during response . | P† . | ||||
| No. (%) . | Median (IQR) . | No. (%) . | Median (IQR) . | No. (%) . | Median (IQR) . | |||
| Total no. of patients | 27 | 30 | 16 | |||||
| Age, y | 72 (67-77) | 76 (69-82) | .26 | |||||
| Sex | .79 | |||||||
| Male | 15 | 12 | ||||||
| Female | 12 | 18 | ||||||
| Blood | ||||||||
| Hemoglobin, g/dL‡ | 10.8 (10.2-11.6) | 9.0 (8.0-10.0) | <.001 | 10.7 (10.3-11.7) | <.001 | |||
| White blood cell count × 109/L | 4.7 (4.1-7.4) | 5.3 (4.8-6.7) | .53 | 4.9 (4.1-6.5) | .50 | |||
| Absolute neutrophil count × 109/L | 2.7 (2.0-5.2) | 3.4 (2.2-4.5) | .94 | 2.7 (1.6-4.1) | .61 | |||
| Platelet count × 109/L | 282 (205-312) | 277 (211-376) | .68 | 305 (238-375) | .79 | |||
| S-EPO, U/L | 32 (16-48) | 40 (29-62) | .13 | NA | NA | |||
| S-ferritin, µg/L | 358 (246-519) | 480 (281-756) | .43 | 472 (264-790) | .54 | |||
| BM | ||||||||
| Cellularity (%) | 60 (45-70) | 60 (50-70) | .58 | 70 (70-90) | .03 | |||
| Blasts (%) | 2.0 (1.0-3.5) | 2.5 (1.5-3.5) | .09 | 1.5 (0-2.5) | .04 | |||
| Erythropoiesis (%) | 34 (15-43) | 28 (18-40) | .30 | 32 (26-55) | .54 | |||
| Ring sideroblasts (%) | 40 (29-53) | 35 (25-52) | .64 | 40 (38-55) | .13 | |||
| IPSS-R (% of known) | ||||||||
| Very low | 17 (63) | 5 (18) | <.001 | NA | NA | |||
| Low | 10 (37) | 21 (75) | NA | |||||
| Intermediate | 0 (0) | 2 (7) | NA | |||||
| Not known/missing cytogenetics | 0 (0) | 2 (NA) | NA | |||||
| Mutations (% of known) | ||||||||
| SF3B1 only | 17 (63) | 16 (53) | .81 | 11 (69) | .47 | |||
| SF3B1 + 1 | 7 (26) | 9 (30) | 2 (12) | |||||
| SF3B1 + ≥2 | 3 (11) | 5 (17) | 3 (19) | |||||
| SF3B1 VAF | 36 (27-43) | 35 (30-39) | .85 | 36 (31-43) | .63 | |||
Patients were diagnosed with (1) MDS-RS with single lineage dysplasia or multiple lineage dysplasia (MDS-RS-SLD/MLD) or (2) MDS/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T); all patients had SF3B1 mutation. Disease progression was rarely observed. Transformation to acute myeloid leukemia (AML) occurred in 1 of 57 patients; this patient had mutations in SF3B1, TET2, and RUNX1 at time of diagnosis, responded to EPO for more than 4 years, and developed AML after 7 years. A total of 20 patients were sequenced at 2 time points. In patients re-evaluated while receiving successful EPO treatment (at a median treatment period of 26 months [range, 10-80 months]), only 1 of 9 patients acquired additional mutations (ZRSF2 and TP53 in the same patient). In patients re-sequenced at time of loss of response to EPO, 1 of 11 gained an additional mutation (TET2).
IQR, interquartile range; NA, not applicable.
NTN vs TN (before EPO); Wilcoxon rank sum test for continuous variables, Fisher’s exact test for categorical variables.
Receiving EPO during response vs TN (before EPO).
Hemoglobin for transfused patients entered as 8.0 g/dL.