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HCT Remains Best Bet for High-Risk Primary Myelofibrosis

December 30, 2021

Physicians treating patients with primary myelofibrosis have one curative treatment option: hematopoietic cell transplantation (HCT). The procedure, can be associated with significant morbidity and mortality, though, so accurate patient selection and counseling are vital. Which patients are better suited for transplant, and who would benefit more from non-transplant approaches?

In a recent Blood article, a team of European researchers, led by Nicolaus Kröger, MD, of the University Hospital Hamburg in Germany, analyzed 438 patients with clonal myeloproliferative neoplasms stratified according to risk, as determined by the Dynamic International Prognostic Scoring System (DIPSS).1

Using the DIPSS, patients with primary myelofibrosis fall into four risk categories: low, intermediate 1 (int-1), intermediate 2 (int-2), and high.

"In general, selecting a patient according to DIPSS is helpful in deciding which therapy will offer the best chance of survival," Dr.  Kröger told ASH Clinical News. However, he cautioned, "more research is necessary to reach a more ‘individualized' recommendation for each patient, which would include other tests, such as molecular genetics."

Among the 438 patients, 190 underwent HCT, and the remaining 248 patients received conventional therapies, such as cytoreductive agents (like hydroxyurea or interferon-alpha), immunomodulating drugs, and erythropoiesis-stimulating agents.

Although JAK inhibitors can be used to treat primary myelofibrosis, the patients in the non-transplant cohort of this retrospective study did not receive this therapy, the authors pointed out.

Survival was the study's primary outcome, while the DIPSS risk status was the main criterion for defining comparison groups, the authors explained.

According to the investigators' report, the relative risk (RR) of dying among patients receiving HCT over those receiving conventional therapies was:

  • 6 for low-risk (95% CI 1.7-19; p=0.0051)
  • 6 for int-1 (95% CI 0.79-3.2; p=0.19)
  • 55 for int-2 (95% CI 0.36-0.83; p=0.005)
  • 37 for high-risk (95% CI 0.21-0.66; p=0.0007)

As seen in the TABLE, the survival benefit of either approach changed according to the DIPSS risk category. The number of patients who survived at 1, 5, and 10 years after undergoing HCT was greater in patients at higher risk, compared with higher-risk patients who received conventional therapies. Int-2 and high-risk patients experienced the greatest survival benefit, with 32 percent of int-2 patients and 27 percent of high-risk patients surviving to year 10 after HCT, compared with 11 percent and 1 percent, respectively, in the non-transplant cohort.

However, 10-year survival benefits were the opposite for low-risk patients (60 percent for transplant and 92 percent for non-transplant patients).

"This study indicates that non–ruxolitinib-treated primary myelofibrosis patients younger than 65 years of age at diagnosis with [DIPSS] intermediate-2 or high-risk disease are likely to benefit from HCT," Dr. Kröger and co-authors wrote. "For patients with low-risk disease, non-transplant approaches may be appropriate." Individual counseling is indicated for lower-risk patients.

However, the authors did note some caveats to their findings. Patients enrolled in this study were younger than age 65 at diagnosis, so the results may not apply to an older population. Dr. Kr̦ger told ASH Clinical News that, in recent years, a greater number of older patients have received HCT Рbegging for a similar study in this population.

Also, the analysis did not include patients treated with JAK inhibitors like ruxolitinb, which may affect life expectancy in patients with primary myelofibrosis. A retrospective 2014 study published in Blood found that patients with primary myelofibrosis and int-2 or high DIPSS risk scores had a median life expectancy of ≤4 years, while patients with higher DIPSS risks who received ruxolitinib treatment (95% CI 0.41-0.91; p=0.0148).2

Dr. Kröger explained that his group's study was "performed in the ‘pre-ruxolitinib era,' so [results] may change if ruxolitinib pre-treatment was included." In the current study, this inclusion was not possible because the follow-up for ruxolitinib-treated patient is currently too short. He added that a study with ruxolitinib is "mandatory" and that his group is planning a prospective trial.

Although the study was limited by a small number of patients, the findings confirm the benefit for HCT in patients with high-risk and int-2 disease. Hazard ratios were not consistent over time, though, and Dr. Kröger acknowledged that the survival curves crossed around the 15-year mark in the int-1 risk group. "In the long run, [HCT] seems better in this setting. But in the short run, non-transplant approaches look better," he stated. "We need more research to advise primary myelofibrosis patients properly."


  1. Kröger N, Giorgino T, Scott BL, et al. Impact of allogeneic stem cell transplantation on survival of patients less than 65 years with primary myelofibrosis. Blood. 2015 March 17. [Epub ahead of print]
  2. Passamonti F, et al. Impact of ruxolitinib on the natural history of primary myelofibrosis: a comparison of the DIPSS and the COMFORT-2 cohorts. Blood. 2014;123:1833-35.

TABLE. Results of patients with primary myelofibrosis receiving ASCT (data at the time of transplant) or non-experimental conventional therapy (data at the time of diagnosis)

Allogeneic SCT

Conventional Therapy

Survival proportion (95% CI)

Year 1

Year 5 Year 10 Year 1 Year 5

Year 10

Low risk


69% (48-99) 60% (38-95) 98% (96-100) 95% (90-99)

92% (86-99)

Intermediate-1 risk

78% (55-100)

52% (33-83) 41% (24-70) 97% (93-100) 77% (67-89)

63% (51-77)

Intermediate-2 risk

82% (68-98)

50% (37-67) 32% (21-48) 77% (67-88) 41% (32-54)

11% (5-22)

High risk

65% (46-92)

32% (19-56) 27% (15-49) 67% (30-100) 11% (3-44)

1% (0-10)

Source: Kröger N, et al. Blood. 2015 March 17. [Epub ahead of print]


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