Allogeneic hematopoietic cell transplantation for myelofibrosis using fludarabine-, intravenous busulfan- and low-dose TBI-based conditioning

• Published in: Bone marrow transplantation (Basingstoke) Vol. 49; no. 9; pp. 1162 - 1169
• Main Authors: Shanavas, M, Messner, H A, Atenafu, E G, Kim, D H, Kuruvilla, J, Lipton, J H, Uhm, J, Seftel, M, Alam, N, Gupta, V
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-09-2014; Nature Publishing Group
• Subjects: 692/699/67/1990/2331; 692/700/565/1436; 692/700/565/545/576/1955; Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antimitotic agents; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Busulfan; Busulfan - administration & dosage; Cell Biology; Combined Modality Therapy; Conditioning; Confidence intervals; Dosage and administration; Engraftment; Failure; Female; Fludarabine; Graft rejection; Graft-versus-host reaction; Grafts; Health aspects; Hematologic and hematopoietic diseases; Hematology; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Humans; Inhibitors; Internal Medicine; Intravenous administration; Irradiation; Janus kinase; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes (neutrophilic); Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Myelofibrosis; original-article; Primary Myelofibrosis - drug therapy; Primary Myelofibrosis - radiotherapy; Primary Myelofibrosis - therapy; Public Health; Radiation; Radiation dosage; Retrospective Studies; Statistical analysis; Stem cell transplantation; Stem Cells; Survival Analysis; Therapy; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation Conditioning - methods; Transplantation, Homologous; Transplants & implants; Vidarabine - administration & dosage; Vidarabine - analogs & derivatives; Whole-Body Irradiation - methods; Canada; Antineoplastic agent; Intravenous administration; Stem cell; Hematopoietic cell; Homograft; Nucleotide analog; Myeloproliferative syndrome; Allogeneic hematopoietic stem cell transplantation; Graft; Busulfan; Conditioning; Purine nucleotide; Total body irradiation; Myelofibrosis; Hematology; Low dose; Alkanediol; Malignant hemopathy; Alkanesulfonic acid; Alkylating agent; Fludarabine; Antimetabolic; Nitrogen mustard; Fluorine Organic compounds; Cancer
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2014.131

Graft failure is one of the major barriers to the success of allogeneic hematopoietic cell transplantation (HCT) in myelofibrosis (MF). We report our institutional experience with 27 MF patients who underwent HCT using fludarabine-, intravenous BU- and low-dose total body irradiation (FBT)-based reduced-intensity (
n
=20) or full-intensity (
n
=7) conditioning regimens. Eight patients had prior exposure to JAK1/2 inhibitor therapy; six patients received JAK1/2 inhibitors leading on to HCT and two patients received transplant at the failure of JAK1/2 inhibitor therapy. No adverse impact of JAK1/2 inhibitor therapy was observed on early post-transplant outcomes. All evaluable patients had neutrophil recovery, and no primary graft failure was observed. Cumulative incidence of grades II–IV acute GVHD at day 100 was 48% (95% confidence interval (CI), 29–67%) and chronic GVHD at 2 years was 66% (95% CI, 49–84%). Cumulative incidences of nonrelapse mortality (NRM), relapse and probability of OS at 2 years were: 43% (95% CI, 12–74%), 10% (95% CI, 0–39%) and 56% (95% CI, 28–77%), respectively. FBT-based conditioning regimen has a favorable impact on engraftment; however, further efforts are required to reduce NRM.