Researchers Review Current Status of HSCT for Myelofibrosis

In a recent review, researchers describe what is currently known about allogenic hemopoietic stem cell transplant (HSCT) for myelofibrosis.

A recent review provided an update on the status of allogeneic hemopoietic stem cell transplants (HSCT) for patients with myelofibrosis (MF).

The authors, writing in Frontiers in Immunology, reviewed the latest evidence on indications for transplant, prognostic scoring systems, predicting outcomes, splenomegaly, and other issues, including relapse and monitoring. Currently, allogenic HSCT is the only curative therapy for MF.

Survival in MF can be predicted using one of the available scoring systems and other variables. Two are based on clinical data (international prognostic scoring system, or IPSS; and dynamic international prognostic scoring system, or DIPSS). DIPSS-plus includes cytogenetics data and another, mutation-enhanced international prognostic scoring system, or MIPSS70, includes mutational analysis.

Variables related to the success of a transplant include patients with an age of 70 to 75; comorbidities; good performance status, low transfusion burden, absence of a massive splenomegaly and portal hypertension and donor type.

DIPSS can identify low-risk patients, high-risk patients with DIPSS-plus. MIPSS can be used to identify patients with high risk mutations. Regardless of risk scores, patients who are triple negative (JAK2/CALR/MPL) or CALR wild type and ASXL1 mutated, should be considered for transplant, the authors said.

A common complication in patients with advanced MF is an enlarged spleen, or splenomegaly. Treatments include splenectomy; JAK inhibitors, typically ruxolitinib; or splenic irradiation.

However, splenectomy is linked with significant morbidity and mortality, the authors said, and splenic irradiation has some limitations as well, although it may be indicated for patients who are not eligible for surgery or who have stopped responding to JAK inhibitors.

Graft-versus-host disease (GVHD) is one of the main causes of death in transplant-related mortality, along with infections and organ failure. Donor type is an important predictor of MF outcomes, and an HLA-matched donor is the best predictor of success in HCST. One study of 233 transplants for MF showed that donor type is an independent risk factor for mortality, with a relative risk of death of 3.92 for matched unrelated donor (56% 5-year survival rate) and 9.37 for mismatched unrelated donor (48% 5-year survival rate), when compared with matched related donor (34% 5-year survival rate).

If not using an HLA matched donor, GVHD prophylaxis regimens may include various options, including post-transplant cyclophosphamide (PT-CY) or a combination of calcineurin inhibitor with ATG and PT-CY; the authors also noted that a pilot study also used ruxolitinib and PT-CY with promising results.

Before the transplant, the choice of conditioning regimen is also key what happens post-transplant, the authors wrote. The authors said that they recently showed that 2 alkylating agents—they used busulfan and thiotepa—in combination with fludarabine significantly reduced the risk of relapse when compared to regimen with 1 alkylating agent and fludarabine.

Patients with myelofibrosis may have 1 of 3 driver mutations (JAK2, CALR and MPL), or lack all 3. Patients who are triple negative patients cannot be followed after HSCT by minimal residual disease status and but chimerism studies may be helpful, the authors said.

In the case of MF relapse after HSCT, there are 3 options: ruxolitinib, donor leukocytes infusion (DLI), and a second allogenic HSCT. The authors said based on a small number of studies, dose-escalated DLI, or a second allogeneic HSCT for non-responders, seem to be the best available options.


Bacigalupo A, Innocenti I, Rossi E, et al. Allogeneic hemopoietic stem cell transplantation for myelofibrosis: 2021. Front Immunol. Published online May 4, 2021. doi: 10.3389/fimmu.2021.637512