Current Challenges in Stem Cell Transplantation in Myelofibrosis

Abstract

Primary or post-ET/PV myelofibrosis is one of the Philadelphia-negative myeloproliferative neoplasms with worst survival. Allogeneic stem cell transplantation (ASCT) can cure a substantial number of patients but is still not universally applicable due to toxicity which leads to therapy-related morbidity and mortality. In the more recent years, outcome of ASCT has improved by less toxic conditioning regimens and optimization of relapse prevention strategies. The introduction of novel therapies such as JAK2 inhibitors may also be helpful in preparation of the transplant by reducing spleen size and constitutional symptoms. To reduce the risk of relapse, molecular monitoring and adoptive immunotherapy with donor lymphocytes have been introduced. Despite lacking prospective randomized trials, it is justified to offer ASCT to eligible patients with PMF whose median survival is expected to be less than 5 years. This includes patients with intermediate-2 and high risk according to IPSS or DIPSS, respectively. The benefit/risk ratio should be considered in each patient taking also transplant- and patient-specific factors into account.

Myeloproliferative Neoplasms

“…Bone marrow transplantation is the only curative therapy for the myeloproliferative neoplasms, 110 but several questions remain unanswered. It is unclear whether full allogeneic or haploidentical transplantation should be performed, and there is uncertainty about the conditioning regimen.…”

Cell competition between wild-type and JAK2V617F mutant cells in a murine model of a myeloproliferative neoplasm

“…The co-existence of wild-type and JAK2V617F mutant cells in conditions that range from CHIP to chronic MPNs, which over long periods of time can remain stable or rapidly progress to frank malignancy, coupled with the high risk of relapse following curative allogeneic stem cell transplantation, [8][9][10][11][12][13][14][15][16][17][18][19] all make MPN a unique model disease to study the early stages of clonal competition and tumor progression. Using both in vitro co-culture and in vivo competitive marrow transplantation assays, we demonstrate that the presence of wild-type cells alters the behavior of co-existing JAK2V617F mutant cells (Figure 1-2).…”

“…[8][9][10] In others, the MPN can evolve to acute leukemia and patients experience high relapse rates following allogeneic stem cell transplantation, the only curative treatment for patients with MPNs. [11][12][13][14] JAK2V617F is also one of the common mutations associated with clonal hematopoiesis of indeterminate potential, which is defined as the presence of a somatic mutation in at least 2-4% blood cells without other hematologic abnormalities. Such clonal hematopoiesis is present in 10-20% of people older than 70 yrs and most of these individuals do not convert to advanced disease.…”

How I treat the blast phase of Philadelphia chromosome–negative myeloproliferative neoplasms

“…The same limitations preclude any definitive conclusions regarding the optimal conditioning regimen in this context. 82 Both reduced-intensity and myeloablative regimens have been used, and the choice of conditioning regimen has not been predictive of transplantation-related mortality, relapse, or survival in published retrospective series. 46,47,49,83,84 Donor source has not been an independent predictor of outcome in most reports, although there has been a trend toward increased transplantation-related mortality in some series in patients receiving transplants from MUDs when compared with matched related donors.…”