1.
Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis
Robin, M., de Wreede, L. C., Wolschke, C., Schetelig, J., Eikema, D. J., Van Lint, M. T., Knelange, N. S., Beelen, D., Brecht, A., Niederwieser, D., et al
Haematologica. 2019
Abstract
Allogeneic hematopoietic stem cell transplant remains the only curative treatment for myelofibrosis. Most post-transplantation events occur during the first 2 years and hence we aimed to analyze the outcome of 2-year disease-free survivors. 1055 patients with myelofibrosis transplanted between 1995 and 2014 and registered in the registry of the European Society for Blood and Marrow Transplantation were included. Survival was compared to the matched general population to determine excess mortality and the risk factors that are associated. In the 2-year survivors, Disease-free survival was 64% (60-68%) and Overall Survival was 74% (71-78%) at 10 years, better in younger individuals and in women. Excess mortality was 14% (8-21%) in patients < 45 years and 33% (13-53%) in patients ≥ 65 years. The main cause of death was relapse of the primary disease. Graft versus Host Disease before 2 years decreased the risk of relapse. Multivariable analysis of excess mortality showed that age, male sex recipient, secondary myelofibrosis and no GVHD prior to the 2-year landmark increased the risk of excess mortality. This is the largest study to date analyzing long-term outcome in patients with myelofibrosis undergoing transplant. Overall it shows a good survival in patients alive and in remission at 2-years but the occurrence of late complications, including late relapses, infectious complications and secondary malignancies highlights the importance of screening and monitoring of long-term survivors.
2.
Family mismatched allogeneic stem cell transplantation for Myelofibrosis: Report from the Chronic Malignancies Working Party of EBMT
Raj, K., Eikema, D. J., McLornan, D. P., Olavarria, E., Blok, H. J., Bregante, S., Ciceri, F., Passweg, J., Ljungman, P., Schaap, N., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
This analysis includes 56 Myelofibrosis (MF) patients transplanted from family mismatched donor between 2009-2015 enrolled in the European Society for Blood and Marrow Transplantation (EBMT) database. The median age was 57 years (range, 38-72); 75% had primary MF and 25% had secondary MF. JAK2 V617F was mutated in 61%. Donors were HLA mismatched at 2 or more loci. Stem cells were sourced from bone marrow in 66% and peripheral blood in 34%. The median CD34+ cell dose was 4.8x10(6)/kg (1.7-22.9x10(6)/kg) (n=43). Conditioning was predominantly myeloablative (MAC) in 70% and reduced intensity (RIC) in the remainder. Regimens were heterogeneous with Thiotepa, Busulphan Fludarabine (TBF) and post-transplant cyclophosphamide (PTCy) used in 59%. The incidence of neutrophil engraftment by 28 days was 82% (range, 70-93%), at a median of 21 days (range,19-23). At 2 yrs. the CI of primary Graft failure was 9% (1-16%) and secondary graft failure was 13% (4-22%).The cumulative incidence (CI) of grades II-IV acute GvHD (aGvHD) and III-IV was 28% (16-40%) and 9% (2-17%) at 100 days. The CI of chronic GvHD (cGvHD) at 1 year was 45% (32-58%) but CI of death without cGVHD by 1 year was 20% (10-31%). With a median follow up of 32 months, the 1- and 2-year OS was 61% (48-74%) and 56% (41-70%) respectively. The 1- and 2- year PFS was 58% (45-71%) and 43% (28-58%) with a 2-year CI of relapse of 19% (7-31%). The 2-year non-relapse mortality (NRM) was 38% (24-51%). This retrospective study of MF allo-SCT utilising family mismatched donors, demonstrates feasibility of the approach, timely neutrophil engraftment in over 80% of cases and acceptable OS and PFS rates with relapse rates not dissimilar to the unrelated donor setting. However, strategies to minimise the risk of graft failure and the relatively high NRM need to be employed, ideally in a multicentre prospective fashion.