ImmunoSensation - the immune sensory system

Biol Blood Marrow Transplant. 2018 Dec 5.

Family mismatched allogeneic stem cell transplantation for Myelofibrosis: Report from the Chronic Malignancies Working Party of EBMT.

Raj K, Eikema DJ, McLornan DP, Olavarria E, Blok HJ, Bregante S, Ciceri F, Passweg J, Ljungman P, Schaap N, Carlson K, Zuckerman T, de Wreede LC, Volin L, Koc Y, Diez-Martin J, Brossart P, Wolf D, Blaise D, Bartolomeo PD, Vitek A, Robin M, I YA, Chalandon Y, Kroger N

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 4.8 × 10/kg (1.7-22.9 × 10/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.

PMID: 30408564