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What is the impact of pre-treatment ruxolitinib on patients with MF receiving allo-HSCT? An EBMT CMWP study

Apr 14, 2021

Most patients (89%) diagnosed with myelofibrosis (MF) present with splenomegaly, and new or increasing splenomegaly is considered to be a marker of disease progression.1 Ruxolitinib was the first Janus kinase (JAK)1/2 inhibitor specifically approved to treat MF and has since become the cornerstone of therapy.2,3

Ruxolitinib reduces spleen size and improves constitutional symptoms in patients with MF, but the impact of pretreatment with ruxolitinib on outcome after allogeneic hematopoietic stem cell transplantation (allo-HSCT) requires examination.4

At the 47th Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), Nicolaus Kröger presented the results of a retrospective study in patients treated with ruxolitinib prior to receiving allo-HSCT for progressive MF, conducted by the EBMT Chronic Malignancy Working Party (CMWP).4 The results of this study were recently published in Leukemia.5   

 Methods and patient characteristics4

The study evaluated 551 patients with MF who received allo-HSCT between 2012 and 2016 either with (n = 277) or without (n = 274) pretreatment with ruxolitinib. The pretreatment cohort was further segmented by those responsive to ruxolitinib at transplantation and those who were not responsive or had lost response.

Regardless of pretreatment status, the median age was 58 and 63% of patients were male. A majority of pretreated patients had Dynamic International Prognostic Scoring System (DIPSS) scores of intermediate-2 (125 out of 277, 56%) or high risk (49 of 277, 22%). Further patient characteristics are detailed in Table 1.

Table 1. Patient characteristics*

Data given as n (%) unless otherwise stated

Prior ruxolitinib

No ruxolitinib


Number of patients

277 (50.3)

274 (47.9)


Median age, years (range)

58 (30–75)

58 (29–75)

p = 0.4

DIPSS at transplant
              High risk

125 (56)
49 (22)

76 (39)
41 (20)

p = 0.01

Karnofsky score at transplant

113 (42)
154 (58)

89 (33)
181 (67)

p = 0.03

DIPSS, Dynamic International Prognostic Scoring System.
*Data from Kröger et al.4

The median duration of pretreatment with ruxolitinib was 7.6 months, with the different spleen response rates prior to allo-HSCT shown in Table 2.

Table 2. Pretreatment with ruxolitinib and spleen response prior to allo-HSCT*

Spleen response

Patients, n (%)

Discontinuation of ruxolitinib prior to allograft

56 (23)

Response of ruxolitinib to spleen size at time of transplant
              Spleen response >50%
              Spleen response <50%
              No spleen response

25 (13)
66 (34)
81 (42)

allo-HSCT, allogeneic hematopoietic stem cell transplant.
*Data from Kröger et al.4


The incidence of relapse at 24 months post-transplant was relatively low among the three segmented patient groups (no ruxolitinib, lost/no response to ruxolitinib, and treatment-responsive) at approximately 16% for the entire study population. However, the treatment-responsive group demonstrated a significantly better response, with an incidence of relapse of 8% (p = 0.05).

Patients who were responsive to pretreatment with ruxolitinib experienced significantly improved event-free survival than the other two patient groups (p = 0.013).

Regarding overall survival, while there was no significant difference among the three treatment groups, there was a trend toward better survival among the responders to pretreatment with ruxolitinib. A longer follow-up (>24 months) may demonstrate a more significant difference among patient groups in this analysis segment.

In the multivariate analyses, it was demonstrated consistently that higher age (58 vs <58) and mismatched vs matched donor type both resulted in higher hazard ratios for non-relapse mortality, event-free survival, and overall survival; no factors had statistically significant impact on relapse risk.


This study demonstrated that treatment with ruxolitinib prior to allo-HSCT in patients with MF had no negative impact post-transplant on non-relapse mortality, relapse incidence, and event-free and overall survival.

Patients who responded to pretreatment with ruxolitinib experienced a lower incidence of graft failure compared to those who experienced no response to ruxolitinib or lost response.

Those patients with an ongoing spleen response to pretreatment with ruxolitinib experienced a lower relapse rate and improved event-free survival after receiving allo-HSCT than those who had not been treated with ruxolitinib.

The study results suggest that transplantation is preferable while the patient is still responsive to ruxolitinib, rather than waiting until a change in or loss of response.

Should patients with myelofibrosis be transplanted before or after ruxolitinib failure?

  1. Tefferi A, Cervantes F, Mesa R, et al. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood. 2013;122(8):1395-1398. DOI: 10.1182/blood-2013-03-488098
  2. Kröger NM, Deeg JH, Olavarria E, et al. Indication and management of allogeneic stem cell transplantation in primary myelofibrosis: a consensus process by an EBMT/ELN international working group. Leukemia. 2015;29:2125-2133. DOI: 10.1038/leu.2015.233
  3. Bose P, Versovstek S. JAK inhibition for the treatment of myelofibrosis: limitations and future perspectives. HemaSphere. 2020:4(4):e424. DOI: 10.1097/HS9.0000000000000424
  4. Kröger N. Impact of prior JAK inhibitor therapy with ruxolitinib after allogeneic hematopoetic stem cell transplantation for myelofibrosis. A CMWP study. 47th Annual Meeting of the EBMT; March 3, 2021; Virtual.
  5. Kröger N, Sbianchi G, Sirait T et al. Impact of prior JAK-inhibitor therapy with ruxolitinib on outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis: a study of the CMWP of EBMT. Leukemia. 2021;22:1-0. DOI: 10.1038/s41375-021-01276-4