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HSCT preparation
Photo by Chad McNeeley

VIENNA—Outcomes of hematopoietic stem cell transplant (HSCT) are encouraging in myelofibrosis (MF) patients who respond well to JAK inhibitors, according to researchers.

The group found that patients with the best response to JAK inhibition had a 2-year survival probability of 91% after HSCT, compared to 32% for patients with
leukemic transformation while on a JAK inhibitor.

In addition, receiving a JAK inhibitor until HSCT could prevent the return of MF-related symptoms.

Mohamed Shanavas, MD, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada, presented these findings at the 20th Congress of the European Hematology Association (abstract S450*).

The decision to undergo HSCT is a complex one in MF, particularly for those patients who are responding to JAK inhibitors. So Dr Shanavas and his colleagues undertook a retrospective, multicenter analysis to determine if there is an association between response to JAK inhibition and HSCT outcome.

The investigators analyzed the outcomes of 100 patients who had a first HSCT for primary MF, post-essential thrombocythemia MF, or post-polycythemia vera MF. Patients had to have exposure to a JAK inhibitor but no history of leukemic transformation prior to taking a JAK inhibitor.

Response criteria

The researchers stratified patients’ JAK1/2 response according to the following criteria:

  • Group A: Clinical improvement: Fifty percent or greater reduction in palpable spleen length for spleen palpable by ≥ 10 cm, or complete resolution of splenomegaly for spleen < 10 cm
  • Group B: Stable disease: Spleen response not meeting the criteria of clinical improvement
  • Group C: A 10% to 19% increase in blasts, new onset of anemia requiring transfusions, or intolerance to treatment due to side effects
  • Group D: Progressive disease: New splenomegaly > 5 cm, 100% increase in spleen 5-10 cm, or 50% increase in spleen > 10 cm
  • Group E: Leukemic transformation: Bone marrow or circulating blasts ≥ 20%.

Patient and treatment characteristics

Patients were a median age of 59 (range, 32–72). Fifty-seven had primary MF, 21 had post-essential thrombocythemia MF, and 22 had post-polycythemia vera MF. Sixty-two patients had JAK2V617F-mutated disease, 37 were wild-type, and 1 had unknown JAK status.

The majority of patients had intermediate-2 or high-risk disease according to their DIPSS scores, and 42 had a transplant comorbidity index score of 3 or greater.

Most patients (n=91) had ruxolitinib as their JAK inhibitor, 6 had momelotinib, and 3 had another inhibitor.

The median duration of JAK inhibitor therapy was 5 months (range, 1–36), and 66 patients were on treatment at the time of transplant. Thirty patients had previously discontinued JAK therapy, and the status of 4 was unknown.

In terms of their response to JAK inhibitors, 23 patients were in group A (clinical improvement), 31 in group B (stable disease), 15 in group C (increased blasts/transfusion need/intolerance), 18 in group D (progressive disease), and 13 in group E (leukemic transformation).

Fifty patients received a matched unrelated donor transplant, 36 had a matched sibling donor, and 14 had either a mismatched unrelated donor or a haploidentical transplant.

Fifty-six patients had a reduced-intensity conditioning regimen, and 44 had full intensity. Fifty percent of patients had T-cell depletion prior to transplant.


Patients who stopped JAK inhibitor therapy 6 or more days prior to transplant (n=20) experienced more “withdrawal symptoms”—the return of MF-related symptoms—than patients in whom the interval was less than 6 days (n=46). For the most part, withdrawal symptoms were non-severe in nature.

Two patients had fatal HSCT-related toxicity of venoocclusive disease, 4 had primary graft failure, and 4 had secondary graft failure. Forty-three percent of cytomegalovirus-seropositive patients had reactivation, 6 patients had Epstein-Barr virus reactivation, 6 had adenovirus or human polyomavirus BK infections, and 7 had invasive fungal infections.

Grade 2-4 acute graft-vs-host disease (GVHD) occurred in 37% of patients at day 100, and grade 3-4 occurred in 16%. Chronic GVHD of all grades occurred in 48% of patients, and extensive chronic GVHD occurred in 23%.

The cumulative incidence of relapse at 2 years was 17%, and non-relapse mortality was 28%. Overall survival (OS) was 61%.

“We analyzed this outcome based upon the response to JAK inhibitors,” Dr Shanavas said. “Patients who were deriving clinical improvement, group A, had a superior outcome, with a probability of survival of 91% at 2 years. Patients who had leukemic transformation, group E, had an inferior OS of 32% at 2 years.”

He noted that the outcomes appeared similar in the other 3 groups, so the researchers combined them for further analysis.

“As expected,” he said, “patients who had leukemic transformation had a significantly higher relapse rate than the other groups.”

The researchers then performed a multivariate analysis and found that response to JAK inhibitors, DIPSS score prior to JAK therapy, and donor type had a significant effect on OS.

The team concluded that prior exposure to JAK inhibitors does not have a negative effect on early HSCT outcomes. And actually, patients who undergo HSCT while responding to JAK inhibitors have encouraging outcomes. end hematology article

*Information in the abstract differs from that presented at the meeting.

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