Impact of spleen size and splenectomy on outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis: A retrospective analysis by the chronic malignancies working party on behalf of European society for blood and marrow transplantation (EBMT).
Allografts
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Busulfan
/ administration & dosage
Disease-Free Survival
Female
Follow-Up Studies
Hematopoietic Stem Cell Transplantation
Humans
Male
Melphalan
/ administration & dosage
Middle Aged
Organ Size
Primary Myelofibrosis
/ mortality
Registries
Retrospective Studies
Spleen
/ pathology
Splenectomy
Survival Rate
Vidarabine
/ administration & dosage
Journal
American journal of hematology
ISSN: 1096-8652
Titre abrégé: Am J Hematol
Pays: United States
ID NLM: 7610369
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
07
08
2020
revised:
07
10
2020
accepted:
12
10
2020
pubmed:
17
10
2020
medline:
26
1
2021
entrez:
16
10
2020
Statut:
ppublish
Résumé
The role of spleen size and splenectomy for the prediction of post-allogeneic hematopoietic stem cell transplant (allo-HCT) outcome in myelofibrosis remains under debate. In EBMT registry, we identified a cohort of 1195 myelofibrosis patients transplanted between 2000-2017 after either fludarabine-busulfan or fludarabine-melphalan regimens. Overall, splenectomy was performed in 202 (16.9%) patients and its use decreased over time (28.3% in 2000-2009 vs 14.1% in 2010-2017 period). By multivariate analysis, splenectomy was associated with less NRM (HR 0.64, 95% CI 0.44-0.93, P = .018) but increased risk of relapse (HR 1.43, 95% CI 1.01-2.02, P = .042), with no significant impact on OS (HR 0.86, 95% CI 0.67-1.12, P = .274). However, in subset analysis comparing the impact of splenectomy vs specific spleen sizes, for patients with progressive disease, an improved survival was seen in splenectomised subjects compared to those patients with a palpable spleen length ≥ 15 cm (HR 0.44, 95% CI 0.28-0.69, P < .001), caused by a significant reduction in NRM (HR 0.26, 95% CI 0.14-0.49, P < .001), without significantly increased relapse risk (HR 1.47, 95% CI 0.87-2.49, P = .147). Overall, despite the possible biases typical of retrospective cohorts, this study highlights the potential detrimental effect of massive splenomegaly in transplant outcome and supports the role of splenectomy for myelofibrosis patients with progressive disease and large splenomegaly.
Substances chimiques
Vidarabine
FA2DM6879K
Busulfan
G1LN9045DK
fludarabine
P2K93U8740
Melphalan
Q41OR9510P
Types de publication
Clinical Trial
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
69-79Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009;113(13):2895-2901.
Kroger NM, Deeg JH, Olavarria E, et al. Indication and management of allogeneic stem cell transplantation in primary myelofibrosis: a consensus process by an EBMT/ELN international working group. Leukemia. 2015;29(11):2126-2133.
Polverelli N, Breccia M, Benevolo G, et al. Risk factors for infections in myelofibrosis: role of disease status and treatment. A multicenter study of 507 patients. Am J Hematol. 2017;92(1):37-41.
Tefferi A, Partain DK, Palmer JM, et al. Allogeneic hematopoietic stem cell transplant overcomes the adverse survival effect of very high risk and unfavorable karyotype in myelofibrosis. Am J Hematol. 2018;93(5):649-654.
Guardiola P, Anderson JE, Bandini G, et al. Allogeneic stem cell transplantation for agnogenic myeloid metaplasia: a European Group for Blood and Marrow Transplantation, Societe Francaise de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study. Blood. 1999;93(9):2831-2838.
Li Z, Gooley T, Applebaum FR, Deeg HJ. Splenectomy and hemopoietic stem cell transplantation for myelofibrosis. Blood. 2001;97(7):2180-2181.
Robin M, Zine M, Chevret S, et al. The Impact of Splenectomy in Myelofibrosis Patients before Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2017;23(6):958-964.
Bacigalupo A, Soraru M, Dominietto A, et al. Allogeneic hemopoietic SCT for patients with primary myelofibrosis: a predictive transplant score based on transfusion requirement, spleen size and donor type. Bone Marrow Transplant. 2010;45(3):458-463.
Kroger N, Holler E, Kobbe G, et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Blood. 2009;114(26):5264-5270.
Patriarca F, Masciulli A, Bacigalupo A. et al; Gruppo Italiano Trapianti di Midollo Osseo. (GITMO)Busulfan- or thiotepa-based conditioning in myelofibrosis: a phase ii multicenter randomized study from the GITMO Group. Biol Blood Marrow Transplant. 2019;25(5):932-940.
Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799-807.
Harrison C, Vannucchi AM. Ruxolitinib: a potent and selective Janus kinase 1 and 2 inhibitor in patients with myelofibrosis. An update for clinicians. Ther Adv Hematol. 2012;3(6):341-354.
Elli EM, Barate C, Mendicino F, Palandri F, Palumbo GA. Mechanisms Underlying the Anti-inflammatory and Immunosuppressive Activity of Ruxolitinib. Front Oncol. 2019;9:1186.
Palandri FP, Palumbo GA, Bonifacio M, et al. Baseline factors associated with response to ruxolitinib: an independent study on 408 patients with myelofibrosis. Oncotarget. 2017;8:79073-79086.
McLornan DP, Yakoub-Agha I, Robin M, Chalandon Y, Harrison CN, Kroger N. State-of-the-art review: allogeneic stem cell transplantation for myelofibrosis in 2019. Haematologica. 2019;104(4):659-668.
Shanavas M, Popat U, Michaelis LC, et al. Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Myelofibrosis with Prior Exposure to Janus Kinase 1/2 Inhibitors. Biol Blood Marrow Transplant. 2016;22(3):432-440.
Tefferi A, Mesa RA, Nagorney DM, Schroeder G, Silverstein MN. Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients. Blood. 2000;95(7):2226-2233.
Bossard JB, Beuscart JB, Robin M, et al. Splenectomy before allogeneic hematopoietic cell transplantation for myelofibrosis: a French nationwide study. Am J Hematol. 2020;96(1):80-88. https://doi.org/10.1002/ajh.26034.
McLornan DP, Malpassuti V, Lippinkhof-Kozijn A, et al. Outcome of allogeneic haematopoietic stem cell transplantation in myeloproliferative neoplasm, unclassifiable: a retrospective study by the Chronic Malignancies Working Party of the EBMT. Br J Haematol. 2020;190:437-441.
Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405.
Robin M, Porcher R, Wolschke C, et al. Outcome after transplantation according to reduced-intensity conditioning regimen in patients undergoing transplantation for myelofibrosis. Biol Blood Marrow Transplant. 2016;22(7):1206-1211.
Baron F, Galimard JE, Labopin M, et al. Allogeneic peripheral blood stem cell transplantation with anti-thymocyte globulin vs allogeneic bone marrow transplantation without anti-thymocyte globulin. Haematologica. 2020;105(4):1138-1146.
Hernandez-Boluda JC, Pereira A, Kroger N, et al. Determinants of survival in myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation. Leukemia. 2020. https://doi.org/10.1038/s41375-020-0815-z. [Epub ahead of print].
McLornan DP, Szydlo R, Robin M, et al. Outcome of patients with Myelofibrosis relapsing after allogeneic stem cell transplant: a retrospective study by the Chronic Malignancies Working Party of EBMT. Br J Haematol. 2018;182(3):418-422.
Passamonti F, Cervantes F, Vannucchi AM, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood. 2010;115(9):1703-1708.
Passamonti F, Giorgino T, Mora B, et al. A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis. Leukemia. 2017;31:2726-2731.
Mesa RA, Nagorney DS, Schwager S, Allred J, Tefferi A. Palliative goals, patient selection, and perioperative platelet management: outcomes and lessons from 3 decades of splenectomy for myelofibrosis with myeloid metaplasia at the Mayo Clinic. Cancer. 2006;107(2):361-370.
Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib vs best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787-798.
Pardanani A, Tefferi A. How I treat myelofibrosis after failure of JAK inhibitors. Blood. 2018;132(5):492-500.
Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106(8):2912-2919.
Artz AS, Pollyea DA, Kocherginsky M, et al. Performance status and comorbidity predict transplant-related mortality after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2006;12(9):954-964.
Polverelli N, Tura P, Battipaglia G, et al. Multidimensional geriatric assessment for elderly hematological patients (≥60years) submitted to allogeneic stem cell transplantation. A French-Italian 10-year experience on 228 patients. Bone Marrow Transplant. 2020;55:2224-2233. https://doi.org/10.1038/s41409-020-0934-1.
Gagelmann N, Ditschkowski M, Bogdanov R, et al. Comprehensive clinical-molecular transplant scoring system for myelofibrosis undergoing stem cell transplantation. Blood. 2019;133(20):2233-2242.
Kerbauy DM, Gooley TA, Sale GE, et al. Hematopoietic cell transplantation as curative therapy for idiopathic myelofibrosis, advanced polycythemia vera, and essential thrombocythemia. Biol Blood Marrow Transplant. 2007;13(3):355-365.
Patriarca F, Bacigalupo A, Sperotto A, et al; on behalf of the GITMOAllogeneic hematopoietic stem cell transplantation in myelofibrosis: the 20-year experience of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Haematologica. 2008;93(10):1514-1522.
Ballen KK, Shrestha S, Sobocinski KA, et al. Outcome of transplantation for myelofibrosis. Biol Blood Marrow Transplant. 2010;16(3):358-367.
Alchalby H, Kroger N. Reduced-intensity conditioning followed by allogeneic hematopoietic stem cell transplantation in myelofibrosis. Curr Hematol Malig Rep. 2010;5(2):53-61.
Rondelli D, Goldberg JD, Isola L, et al. MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. Blood. 2014;124(7):1183-1191.
Gupta V, Gotlib J, Radich JP, et al. Janus kinase inhibitors and allogeneic stem cell transplantation for myelofibrosis. Biol Blood Marrow Transplant. 2014;20(9):1274-1281.
Scott BL, Gooley TA, Sorror ML, et al. The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantation. Blood. 2012;119(11):2657-2664.
Verstovsek S, Kantarjian HM, Estrov Z, et al. Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls. Blood. 2012;120(6):1202-1209.
Vannucchi AM, Kantarjian HM, Kiladjian JJ, et al. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015;100(9):1139-1145.
Mesa RA, Verstovsek S, Gupta V, et al. Effects of ruxolitinib treatment on metabolic and nutritional parameters in patients with myelofibrosis from COMFORT-I. Clin Lymphoma Myeloma Leuk. 2015;15(4):214-221. e211.
Palandri F, Breccia M, Bonifacio M, et al. Life after ruxolitinib: reasons for discontinuation, impact of disease phase, and outcomes in 218 patients with myelofibrosis. Cancer. 2020;126(6):1243-1252.
Elliott MA, Chen MG, Silverstein MN, Tefferi A. Splenic irradiation for symptomatic splenomegaly associated with myelofibrosis with myeloid metaplasia. Br J Haematol. 1998;103(2):505-511.
Ito T, Akagi K, Kondo T, Kawabata H, Ichinohe T, Takaori-Kondo A. Splenic irradiation as a component of a reduced-intensity conditioning regimen for hematopoietic stem cell transplantation in myelofibrosis with massive splenomegaly. Tohoku J Exp Med. 2012;228(4):295-299.
Zimran E, Tripodi J, Rampal R, et al. Genomic characterization of spleens in patients with myelofibrosis. Haematologica. 2018;103(10):e446-e449.
Mesa RA, Li CY, Schroeder G, Tefferi A. Clinical correlates of splenic histopathology and splenic karyotype in myelofibrosis with myeloid metaplasia. Blood. 2001;97(11):3665-3667.
Prakash S, Hoffman R, Barouk S, Wang YL, Knowles DM, Orazi A. Splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms: heterogeneous morphology and cytological composition. Mod Pathol. 2012;25(6):815-827.
Barosi G, Ambrosetti A, Centra A, et al. Splenectomy and risk of blast transformation in myelofibrosis with myeloid metaplasia. Italian Cooperative Study Group on Myeloid with Myeloid Metaplasia. Blood. 1998;91(10):3630-3636.
O'Neill HC, Griffiths KL, Periasamy P, et al. Spleen as a site for hematopoiesis of a distinct antigen presenting cell type. Stem Cells Int. 2011;2011:954275.
Filip S, Mokry J, Vavrova J, et al. Splenectomy influences homing of transplanted stem cells in bone marrow-ablated mice. Stem Cells and Development. 2012;21(5):702-709.
Kroger N, Panagiota V, Badbaran A, et al. Impact of molecular genetics on outcome in myelofibrosis patients after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2017;23(7):1095-1101.
Tefferi A, Cervantes F, Mesa R, et al. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood. 2013;122(8):1395-1398.
Snowden JA, Saccardi R, Orchard K, et al. Benchmarking of survival outcomes following haematopoietic stem cell transplantation: A review of existing processes and the introduction of an international system from the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Bone Marrow Transplant. 2020;55(4):681-694.