Table 1.
Major studies of ruxolitinib therapy prior to AHSCT for myelofibrosis.
| Study | No. of patients | Median age (range), year | Median exposure to ruxolitinib (range), months | Ruxolitinib tapering schedule | Response to ruxolitinib | Adverse events | Results | Conclusions |
|---|---|---|---|---|---|---|---|---|
| Jaekel78 | 14 | 67 (33–80) | 6.5 (2–12) | 14 days prior to conditioning | Ameliorate MF-related symptoms: 71.4% Reduce splenomegaly: 64% |
No unexpected adverse events |
Engraftment: 13 patients OS 78.6%, EFS 64%, TRM 7% (9-month follow-up). |
Ruxolitinib might improve AHSCT outcome |
| Stubig80 | 22 | 59 (42–74) | 3.2 (0.7–10.5) | No tapering schedule | Improvement of constitutional symptoms: 86% Spleen size reduction > 50%: 41%; <50%: 14%; No response or loss of response: 45% |
No unexpected adverse events |
Graft failure: none 1-year OS 81%, DFS 76%, NRM 14% OS was superior in patients who responded to ruxolitinib |
Patients who responded to ruxolitinib prior to AHSCT might have favorable transplant results |
| Hanif83 | 10 | 56 (47–60) | 5.7 (1.9–9) | 6 days prior to conditioning | Spleen size reduction in 5 of 9 patients | No unexpected adverse events |
After a median follow-up of 14.5 months, all 10 patients were alive | This study supported the safety of ruxolitinib therapy prior to AHSCT, provided a taper was used |
| Shanavas79 | 100 | 59 (32–72) | 5 (1–56) | 66 patients underwent different tapering schedule | Group-A: clinical improvement Group-B: stable disease Group-C: new cytopenia or increasing blasts Group-D: progressive disease: splenomegaly Group-E: progressive disease: leukemic transformation |
2 SAEs; 1 pulmonary infiltrate and rebound splenomegaly; 1
hypoxic respiratory failure Adverse events were more common in patients who stopped ruxolitinib ⩾6 days prior to conditioning |
4 patients each experienced primary and second graft
failure Grade II-IV, III-IV aGVHD were 37% and 16% 1-year OS was 61%, and was 91%, 54%, 54%, 60%, 32% in group-A, B, C, D, E, respectively |
Patients responded well to JAK1/2 inhibitors had better AHSCT
outcomes JAK1/2 inhibitors should be continued near to the start of conditioning to minimize the risk of withdrawal symptoms |
| Shahnaz Syed Abd Kadir81 | 159 | 59 (28–74) | 4.9 (0.4–39.1) | No tapering schedule | Splenic size response in 18 of 42 (42.9%) patients | No unexpected adverse events |
Engraftment, aGVHD, NRM and OS did not differ between the
ruxolitinib group (n = 46) and non-ruxolitinib
group (n = 113) CMV reactivation rate was higher in the ruxolitinib group |
Ruxolitinib pretreatment did not negatively influence outcome after AHSCT |
| Salit82 | 28 | 56 (43–68) | 7 (2–36) | Form the start of conditioning to Day -4 | No unexpected adverse events |
Graft failure: none 2-year OS: 86% |
Pre-AHSCT ruxolitinib was well tolerated and might improve
post-transplant outcome Overlap of ruxolitinib with conditioning did not result in unexpected adverse events |
aGVHD, acute graft-versus-host disease; AHSCT, allogeneic hematopoietic stem-cell transplantation; DFS, disease free survival; EFS, event free survival; NRM, nonrelapse mortality; OS, overall survival; SAEs, serious adverse events; TRM, transplant-related mortality.