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Clinical Trial
. 2019 Jan;25(1):56-62.
doi: 10.1016/j.bbmt.2018.07.038. Epub 2018 Aug 1.

Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies: Expanded Analysis and Long-Term Follow-Up

Erica Dahl Warlick  1 , Todd E DeFor  2 , Nelli Bejanyan  3 , Shernan Holtan  3 , Margaret MacMillan  4 , Bruce R Blazar  4 , Kathryn Dusenbery  5 , Mukta Arora  3 , Veronika Bachanova  3 , Sarah Cooley  3 , Aleksandr Lazaryan  3 , Philip McGlave  3 , Jeffrey S Miller  3 , Armin Rashidi  3 , Arne Slungaard  3 , Gregory Vercellotti  3 , Celalettin Ustun  3 , Claudio Brunsein  3 , Daniel Weisdorf  3
Affiliations
Clinical Trial

Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies: Expanded Analysis and Long-Term Follow-Up

Erica Dahl Warlick et al. Biol Blood Marrow Transplant. 2019 Jan.

Abstract

Reduced-intensity conditioning (RIC) extends the curative potential of allogeneic hematopoietic cell transplantation (HCT) to patients with hematologic malignancies unable to withstand myeloablative conditioning. We prospectively analyzed the outcomes of 292 consecutive patients, median age 58 years (range, 19 to 75) with hematologic malignancies treated with a uniform RIC regimen of cyclophosphamide, fludarabine, and total body irradiation (200 cGy) with or without antithymocyte globulin and cyclosporine and mycophenolate mofetil graft-versus-host disease (GVHD) prophylaxis followed by allogeneic HCT at the University of Minnesota from 2002 to 6. Probability of 5-year overall survival was 78% for patients with indolent non-Hodgkin lymphoma, 53% for chronic myelogenous leukemia, 55% for Hodgkin lymphoma, 40% for acute myelogenous leukemia, 37% for myelodysplastic syndrome, 29% for myeloma, and 14% for myeloproliferative neoplasms. Corresponding outcomes for relapse were 0%, 13%, 53%, 37%, 39%, 75%, and 29%, respectively. Disease risk index (DRI) predicted both survival and relapse with superior survival (64%) and lowest relapse (16%) in those with low risk score compared with 24% survival and 57% relapse in those with high/very-high risk scores. Recipient cytomegalovirus (CMV)-positive serostatus was protective from relapse with the lowest rates in those also receiving a CMV-positive donor graft (29%). The cumulative incidence of 2-year nonrelapse mortality was 26% and was lowest in those receiving a matched sibling graft at 21%, with low (21%) or intermediate (18%) HCT-specific comorbidity index, and was similar across age groups. The incidence of grades II to IV acute GVHD was 43% and grades III to IV 27%; the highest rates were found in those receiving an unrelated donor (URD) peripheral blood stem cell (PBSC) graft, at 50%. Chronic GVHD at 1 year was 36%. Future approaches incorporating alternative GVHD prophylaxis, particularly for URD PBSC grafts, and targeted post-transplant antineoplastic therapies for those with high DRI are indicated to improve these outcomes.

Keywords: AML; Aggressive and indolent non-Hodgkin lymphoma; Hematopoietic stem cell transplantation (HCT); Hodgkin lymphoma; MDS; Reduced-intensity conditioning (RIC).

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Figures

Figure 1:
Figure 1:
Survival by Donor Type Adjusted for DRI and Age
Figure 2:
Figure 2:
Relapse by DRI
Figure 3:
Figure 3:
Relapse by CMV Serostatus
See this image and copyright information in PMC

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