Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Chronic and Advanced Phase Myelofibrosis

Abstract

Myelofibrosis (MF) is a chronic progressive hematologic malignancy with a median overall survival (OS) of approximately 6 years. Allogeneic hematopoietic stem cell transplantation (HSCT) is the sole treatment approach that offers curative potential. The use of reduced-intensity conditioning regimens has expanded the application of HSCT to patients with MF up to age 70 years. Recent retrospective and prospective reports have suggested worse HSCT outcomes for patients with MF receiving an unrelated donor graft compared with those receiving a related donor graft. To identify patient- and HSCT-specific variables influencing outcomes, we conducted a retrospective analysis of 42 patients with chronic and advanced-phase MF who underwent HSCT at our institution. For this cohort, at a median follow-up of 43 months, progression-free survival (PFS) was 15 months and OS was 25 months. In multivariable analysis, the sole clinical variable that negatively influenced outcome was the use of an unrelated donor, with a median PFS and OS both of 11 months versus not yet reached in patients receiving a related donor graft. At 2 years, OS was 38% (95% confidence interval [CI], 20%-56%) and nonrelapse mortality (NRM) was 53% (95% CI, 36%-78%) in the unrelated donor graft group, compared with 75% (95% CI, 46%-90%) and 21% (95% CI, 9%-47%) in the related donor graft group. There was no difference in the rates of grade III-IV acute graft-versus-host disease between the unrelated and related donor groups (38% versus 38%). Despite a more aggressive disease state, 2-year PFS and OS were both 42% (95% CI, 15%-67%) in patients with myeloproliferative neoplasm-blast phase undergoing HSCT. Graft failure rate was higher in patients receiving a mismatched donor graft compared with those receiving a matched donor graft (60% versus 13%; P = .0398). Retransplantation of patients with graft failure resulted in long-term survival. Baseline splenomegaly did not affect transplantation outcomes. Given the particularly poor outcomes seen in the unrelated donor cohort here and elsewhere, a formal exploration of alternative hematopoietic stem cell sources is warranted.

Comparison of Outcomes of Allogeneic Transplantation for Primary Myelofibrosis among Hematopoietic Stem Cell Source Groups

“…Rather, several studies have demonstrated the importance of donor selection in decreasing NRM. In the retrospective studies from the CIBMTR, France, and the United States for patients with PMF or secondary myelofibrosis mainly with PB transplantation, unrelated donor grafts were associated with higher NRM and lower OS than related donor grafts [4,28,29]. In contrast, the present study demonstrated in patients with PMF, BM transplantation from an HLA-matched unrelated donor showed a trend toward higher NRM compared with transplantation from an HLA-matched related donor, but they were not significantly different.…”

Busulfan- or Thiotepa-Based Conditioning in Myelofibrosis: A Phase II Multicenter Randomized Study from the GITMO Group

“…In our study, the kinetics of hematopoietic engraftment was significantly influenced by the spleen size at the time of HSCT, as reported previously [33][34][35][36]. Only 15% of our patients had a spleen larger than 22 cm, but we observed that even a moderate splenic enlargement had a negative impact on hematopoietic engraftment, although it did not significantly influence overall outcome.…”

“…Our overall NRM of 21% at 2 years was similar to that reported in the EBMT study (16% at 1 year) and within the range of NRM rates reported in previous studies (Appendix 4); moreover, in the unrelated donor transplant recipients in our study, both conditioning regimens were apparently safer than the fludarabine + melphalan regimen of the MDPC trial. Nonetheless, in most studies, transplants from unrelated donors exhibited a higher risk of toxicity and mortality; in some of these, the increased risk was limited to mismatched donor transplants [14], whereas in others it included even transplants from matched unrelated donors [12,16,[23][24][25][26]31,35,36], in which a high risk of graft failure and related-mortality are reported [26]. In the present study, GVHD did not seem to contribute to NRM, given the very low GVHD rates in both arms.…”

Immunotherapy in Myeloproliferative Diseases

“…Most importantly, for MPN patients being at high risk of progressing and transforming into AML, allo-HSCT is the only curative modality if carried out before transformation [ 77 ]. The 5-year survival rate after allo-HSCT ranges from 30% to 70% and the regimen was reported to have the potential to achieve a resolution of bone marrow fibrosis [ 77 , 78 ]. A graft-versus-myelofibrosis effect could be increased by donor lymphocyte infusion (DLI) for patients relapsing after allo-HSCT and the bone marrow fibrosis was reverted within 12 months after transplantation [ 76 , 79 ].…”