title: Effect of conditioning regimens on graft failure in myelofibrosis: a retrospective analysis.
abstract: In myelofibrosis, the introduction of reduced-intensity conditioning (RIC) preceding allogeneic stem cell transplantation (SCT) resulted in lower transplant-related mortality rates compared with myeloablative conditioning. However, lowering the intensity of conditioning may increase the risk of graft failure in myelofibrosis, although hitherto this has not been indisputably proven. We here report the outcome of 53 patients who underwent allogeneic SCT with different conditioning regimens (RIC and non-myeloablative (NMA)) in three transplantation centers in the Netherlands. The cumulative incidence of graft failure within 60 days after SCT was high (28%), and this was primarily associated with the intensity of the conditioning regimen. Cumulative neutrophil engraftment at 60 days was lower in patients who received NMA conditioning compared with those who received RIC (56% vs 84%, P=0.03). Furthermore, of six patients who received a second transplantation after graft failure, the three patients with RIC regimens subsequently engrafted, whereas the three patients who received a second NMA regimen did not. This study indicates that in myelofibrosis, NMA regimens result in high engraftment failure rates. We propose the use of more intensive conditioning regimens, incorporating busulfan or melphalan.
authors.affiliation: Department of Haematology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Slot
authors.affiliation: Department of Haematology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Smits
authors.affiliation: Department of Haematology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: N W C J
authors.initials: NW
authors.lastname: van de Donk
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: B I
authors.initials: BI
authors.lastname: Witte
authors.affiliation: Department of Haematology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Raymakers
authors.affiliation: Department of Haematology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: J J W M
authors.initials: JJ
authors.lastname: Janssen
authors.affiliation: Department of Haematology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: A E C
authors.initials: AE
authors.lastname: Broers
authors.affiliation: Department of Haematology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: P A W
authors.initials: PA
authors.lastname: Te Boekhorst
authors.affiliation: Department of Haematology, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Zweegman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002066:Busulfan / Q000627:therapeutic use; D037282:Calreticulin / Q000235:genetics; D003131:Combined Modality Therapy; D036101:Cord Blood Stem Cell Transplantation; D003520:Cyclophosphamide / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D006085:Graft Survival; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008558:Melphalan / Q000627:therapeutic use; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D009504:Neutrophils / Q000637:transplantation; D036102:Peripheral Blood Stem Cell Transplantation; D011087:Polycythemia Vera / Q000150:complications; D055728:Primary Myelofibrosis / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000628:therapy*; D053628:Receptors, Thrombopoietin / Q000235:genetics; D012189:Retrospective Studies; D013920:Thrombocythemia, Essential / Q000150:complications; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation; D055815:Young Adult
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; D019653:Myeloablative Agonists; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D003520:Cyclophosphamide; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan