Allogeneic haematopoietic cell transplantation for myelofibrosis: proposed definitions and management strategies for graft failure, poor graft function and relapse: best practice recommendations of the EBMT Chronic Malignancies Working Party

Abstract

Allogeneic Haematopoietic Cell Transplantation (allo-HCT) remains the only curative approach in Myelofibrosis (MF). Despite advances over recent decades, relapse and non-relapse mortality rates remain significant. Relapse rates vary between 15% and 25% across retrospective studies and management strategies vary widely, ranging from palliation to adoptive immunotherapy and, in some cases, a second allo-HCT. Moreover, in allo-HCT, there is a higher incidence of poor graft function and graft failure due to splenomegaly and a hostile 'pro-inflammatory' marrow niche. The Practice Harmonisation and Guidelines subcommittee of the Chronic Malignancies Working Party (CMWP) of EBMT convened an international panel consisting of transplant haematologists, histopathologists and molecular biologists to propose practical, clinically relevant definitions of graft failure, poor graft function and relapse as well as management strategies following allo-HCT. A systematic approach to molecular monitoring, histopathological assessment and chimerism testing is proposed. These proposed recommendations aim to increase the accuracy and uniformity of reporting and to thereby facilitate the development of more consistent approaches to these challenging issues. In addition, we propose management strategies for these complications.

Impact of molecular profiling on the management of patients with myelofibrosis

“…MPN driver mutations are present in most MF patients and can therefore be useful to monitor minimal residual disease posttransplantation. Definition of molecular persistence or relapse after allo-HCT in MF patients is complicated due to the variable clearance kinetics of detectable mutations [94]). However, persistent detection of MPN driver mutations by quantitative high-sensitivity assays has been associated with higher risk of relapse and worse survival in several studies [95,96].…”

The Incidence, Outcomes, and Risk Factors of Secondary Poor Graft Function in Haploidentical Hematopoietic Stem Cell Transplantation for Acquired Aplastic Anemia

“…Poor graft function (PGF) was defined as sustained cytopenia of 2 or 3 lineages (neutrophil count <.5 × 10 9 /L, hemoglobin < 70 g/L, and platelet count < 20 × 10 9 /L) for over 2 weeks with full donor chimerism of > 95%, hypoplastic-aplastic BM, and absence of severe GvHD, active infection and drug toxicity. Primary PGF referred to PGF that failed to achieve initial engraftment, and sPGF was defined as a decrease of blood counts after prompt recovery ( 16 , 17 ). Chimerism analysis was evaluated using PB at 1, 2, 3, 6, 12 months post-transplantation and at annual outpatient visits thereafter.…”

Innovative strategies to improve hematopoietic stem cell transplant outcomes in myelofibrosis

“…HCT is recommended by the American Society of Transplant and Cellular Therapy and the EBMT‐European LeukaemiaNet (ELN) guidelines for patients aged under 70 years with intermediate‐2 or high‐risk disease based on IPSS, DIPSS, or DIPSS+. 16 , 17 , 18 The ELN additionally considers HCT for intermediate‐1 disease with adverse genetics, transfusion dependence or >2% circulating blasts. Patients ineligible for HCT may be offered a JAKi, clinical trial, transfusion support, splenectomy, or splenic irradiation.…”