Clinical characteristics and outcome of patients with reports of bone marrow reticulin
| Patient no. . | 0331 . | 1202 . | 3231 . | 3851 . | 3630 . | 1131 . | 0123 . | 923 . |
|---|---|---|---|---|---|---|---|---|
| Age/sex* | 60/F | 31/M | 53/M | 54/F | 58/M | 37/M | 27/F | 44/F |
| Duration of ITP*† | 23.2 | 1.5 | 7.0 | 3.2 | 5.8 | 3.3 | 12.4 | 7.9 |
| Splenectomy* | Yes | Yes | Yes | No‡ | Yes | Yes | Yes | Yes |
| No. of prior ITP treatments | 8 | 3 | 9 | 4 | 8 | 8 | 8 | 4 |
| Current steroid treatment* | No | No | No | Yes | No | Yes | Yes | Yes |
| Romiplostim exposure in previous study | Placebo | 1322 μg on days 1 and 22 | 75-380 μg weekly for 24 weeks | 7-640 μg weekly for 24 weeks | 140-2063 μg weekly for 24 weeks | 100-630 μg weekly for 24 weeks | 262 μg weekly for 5 weeks | 48 μg weekly for 6 weeks |
| Cumulative romiplostim exposure in previous study | 0 μg | 2643 μg | 7740 μg | 5275 μg | 37 420 μg | 9390 μg | 1309 μg/kg | 286 μg |
| Maximum dose of romiplostim in this study; amount | 875 μg | 2270 μg | 600 μg | 1000 μg | 1980 μg | 800 μg | 1025 μg | 305 μg |
| Dosage | 11 μg/kg | 18 μg/kg | 8 μg/kg | 13 μg/kg | 15 μg/kg | 9 μg/kg | 11 μg/kg | 5 μg/kg |
| Study day event was reported | 317 | 154 | 78 | 53 | 50 | 24 | 259 | 829 |
| Platelet count at time event was reported§ | 31 × 109/L | 33 × 109/L | 86 × 109/L | —‖ | 12 × 109/L | 12 × 109/L | 14 × 109/L | 80 × 109/L |
| Maximum platelet count in this study | 157 × 109/L | 93 × 109/L | 88 × 109/L | 54 × 109/L | 280 × 109/L | 12 × 109/L | 565 × 109/L | 728 × 109/L |
| Median platelet count at maximum romiplostim dose in this study (range) | 45 × 109/L (21-74) | 35 × 109/L (33-36) | 68 × 109/L (46-84) | 4 × 109/L (single value) | 29 × 109/L (7-280) | 4 × 109/L (single value) | 20 × 109/L (16-21) | 204 × 109/L (7-354) |
| Baseline reticulin assessment | NA | No significant increase | NA | NA | Grade 0-1+ | Not dense | NA | NA |
| Reticulin event assessment | Mild to moderately increased | Moderate | Mildly increased | Diffuse grade 2-3 | Grade 1-2+ | Emphasis diffusely | Grade 2+ | Mild |
| Follow-up reticulin assessment | NA | Mild, diffuse | NA | NA | NA | Grade 1 | NA | NA |
| Event resolved¶ | NA | No | NA | NA | NA | No | NA | NA |
| Collagen fibrosis (trichrome stain) | NA | Negative | NA | Negative | NA | Negative | Negative | NA |
| Presence of NRBCs | Week 12, end of study | No | No | End of study | Weeks 4, 12, 44, 48, 56, 60, 64, 68, 72, 76, and 80 | Week 1, end of study | No | No |
| Elevated LDH# | Weeks 12-40 end of study | Week 24 | Week 40 | Weeks 1 and 4, end of study | Weeks 4, 8, 24, 28, 32, 36, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 92 | Week 1, day 23 | Weeks 24 and 36 | No |
| Event led to study discontinuation | Yes | Yes | No | No | No | No | No | No |
| Patient no. . | 0331 . | 1202 . | 3231 . | 3851 . | 3630 . | 1131 . | 0123 . | 923 . |
|---|---|---|---|---|---|---|---|---|
| Age/sex* | 60/F | 31/M | 53/M | 54/F | 58/M | 37/M | 27/F | 44/F |
| Duration of ITP*† | 23.2 | 1.5 | 7.0 | 3.2 | 5.8 | 3.3 | 12.4 | 7.9 |
| Splenectomy* | Yes | Yes | Yes | No‡ | Yes | Yes | Yes | Yes |
| No. of prior ITP treatments | 8 | 3 | 9 | 4 | 8 | 8 | 8 | 4 |
| Current steroid treatment* | No | No | No | Yes | No | Yes | Yes | Yes |
| Romiplostim exposure in previous study | Placebo | 1322 μg on days 1 and 22 | 75-380 μg weekly for 24 weeks | 7-640 μg weekly for 24 weeks | 140-2063 μg weekly for 24 weeks | 100-630 μg weekly for 24 weeks | 262 μg weekly for 5 weeks | 48 μg weekly for 6 weeks |
| Cumulative romiplostim exposure in previous study | 0 μg | 2643 μg | 7740 μg | 5275 μg | 37 420 μg | 9390 μg | 1309 μg/kg | 286 μg |
| Maximum dose of romiplostim in this study; amount | 875 μg | 2270 μg | 600 μg | 1000 μg | 1980 μg | 800 μg | 1025 μg | 305 μg |
| Dosage | 11 μg/kg | 18 μg/kg | 8 μg/kg | 13 μg/kg | 15 μg/kg | 9 μg/kg | 11 μg/kg | 5 μg/kg |
| Study day event was reported | 317 | 154 | 78 | 53 | 50 | 24 | 259 | 829 |
| Platelet count at time event was reported§ | 31 × 109/L | 33 × 109/L | 86 × 109/L | —‖ | 12 × 109/L | 12 × 109/L | 14 × 109/L | 80 × 109/L |
| Maximum platelet count in this study | 157 × 109/L | 93 × 109/L | 88 × 109/L | 54 × 109/L | 280 × 109/L | 12 × 109/L | 565 × 109/L | 728 × 109/L |
| Median platelet count at maximum romiplostim dose in this study (range) | 45 × 109/L (21-74) | 35 × 109/L (33-36) | 68 × 109/L (46-84) | 4 × 109/L (single value) | 29 × 109/L (7-280) | 4 × 109/L (single value) | 20 × 109/L (16-21) | 204 × 109/L (7-354) |
| Baseline reticulin assessment | NA | No significant increase | NA | NA | Grade 0-1+ | Not dense | NA | NA |
| Reticulin event assessment | Mild to moderately increased | Moderate | Mildly increased | Diffuse grade 2-3 | Grade 1-2+ | Emphasis diffusely | Grade 2+ | Mild |
| Follow-up reticulin assessment | NA | Mild, diffuse | NA | NA | NA | Grade 1 | NA | NA |
| Event resolved¶ | NA | No | NA | NA | NA | No | NA | NA |
| Collagen fibrosis (trichrome stain) | NA | Negative | NA | Negative | NA | Negative | Negative | NA |
| Presence of NRBCs | Week 12, end of study | No | No | End of study | Weeks 4, 12, 44, 48, 56, 60, 64, 68, 72, 76, and 80 | Week 1, end of study | No | No |
| Elevated LDH# | Weeks 12-40 end of study | Week 24 | Week 40 | Weeks 1 and 4, end of study | Weeks 4, 8, 24, 28, 32, 36, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 92 | Week 1, day 23 | Weeks 24 and 36 | No |
| Event led to study discontinuation | Yes | Yes | No | No | No | No | No | No |
F indicates female; M, male; ITP, idiopathic thrombocytopenia purpura; NA, not available; ND, not done; NRBC, nucleated red blood cell; WBC, white blood cell; and LDH, lactate dehydrogenase.
Age, sex, splenectomy status, and current steroid treatment for the study population as a whole at baseline are given in Table S1. These values were: median age, 53 years; proportion of females, 67%; proportion splenectomized, 60%; proportion receiving concurrent ITP treatment, 22%.
Years between ITP diagnosis and initial dose in previous studies.
Patient underwent splenectomy near the time the bone marrow aspirate and biopsy were taken.
If the platelet count at the time of the event was not available, the closest preceding platelet count was used.
Study ended on day 30. No platelet count reported at time event was reported.
NA entered when no follow-up was available.
LDH level higher than 250 U/L. (The reference range for LDH was 100-250 U/L.)
**Romiplostim treatment interrupted for approximately 15 weeks because of increased bone marrow reticulin.