Page 139 - 2019_06-Haematologica-web

Stem Cell Transplantation
Total body irradiation dose escalation decreases risk of progression and graft rejection after hematopoietic cell transplantation for myelodysplastic syndromes or myeloproliferative neoplasms
Ferrata Storti Foundation
Haematologica 2019 Volume 104(6):1221-1229
Federico Monaco,1 Bart L. Scott,1,2 Thomas R. Chauncey,1,2,3 Finn B. Petersen,4 Barry E. Storer,1,2 Frederic Baron,5 Mary E. Flowers,1,2 H. Joachim Deeg,1,2 David G. Maloney,1,2 Rainer Storb1,2 and Brenda M. Sandmaier1,2
1Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 2University of Washington, Seattle, WA, USA; 3VA Puget Sound Health Care System, Seattle, WA, USA; 4LDS Hospital, Salt Lake City, UT, USA and 5University of Liege, Belgium
ABSTRACT
Anon-myeloablative regimen of fludarabine and 200 cGy total body irradiation combined with post-grafting immunosuppression with mycophenolate mofetil and a calcineurin inhibitor facilitates allo- geneic hematopoietic cell transplantation from HLA-matched related or unrelated donors in older patients and/or those with comorbidities. However, outcomes of prior studies have been disappointing in patients with myelodysplastic syndromes or myeloproliferative neoplasms due to high incidences of progression or graft failure (together termed hematopoi- etic cell transplantation-failure). We hypothesized that escalating the total body irradiation dose may improve the outcomes and subsequently per- formed a phase II total body irradiation dose-escalation trial. Patients with median age 66 years were enrolled in two arms to receive non-myeloabla- tive conditioning followed by hematopoietic cell transplantation with total body irradiation dose escalation for excessive hematopoietic cell transplan- tation-failure: Arm A: myeloproliferative neoplasm/myelodysplastic syn- drome low risk (n=36); and Arm B: myelodysplastic syndrome high- risk/chronic myelomonocytic leukemia (n=41). Total body irradiation dose levels were: Level-1 (300 cGy), Level-2 (400 cGy), or Level-3 (450 cGy). Patients received intravenous fludarabine 30 mg/m2 for three days. Total body irradiation was administered on day 0 followed by infusion of periph- eral blood stem cells from HLA-matched related (n=30) or unrelated (n=47) donors. Post-grafting immunosuppression with mycophenolate mofetil and cyclosporine was administered. The primary end point was day 200 hematopoietic cell transplant failure, with the objective of reducing the inci- dence to <20%. The primary end point was reached on Arm A at dose Level-1 (300 cGy total body irradiation) with a cumulative incidence of day 200 hematopoietic cell transplant failure of 11%, and on Arm B at dose Level-3 (450 cGy) with a cumulative incidence of day 200 hematopoietic cell transplant failure of 9%. Increasing the total body irradiation dose leads to a higher success rate with non-myeloablative conditioning by reducing relapse and rejection. Further studies are necessary to decrease non-relapse mortality, especially among patients with high-risk disease. Trial registered under clinicaltrials.gov identifier: NCT00397813.
Introduction
Hematopoietic cell transplantation (HCT) is the only curative option for patients with myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN).1 While these disorders are usually seen in older individuals, conventional HCT after
Correspondence:
BRENDA M. SANDMAIER
bsandmai@fredhutch.org
Received: June 7, 2018. Accepted: January 2, 2019. Pre-published: January 10, 2019.
doi:10.3324/haematol.2018.199398
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/6/1221
©2019 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
haematologica | 2019; 104(6)
1221
ARTICLE