Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies

Expanded Analysis and Long-Term Follow-Up

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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.

Original languageEnglish (US)
Pages (from-to)56-62
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2019

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Hematologic Neoplasms
Allografts
Graft vs Host Disease
Cell Transplantation
Transplants
Recurrence
Unrelated Donors
Survival
Cytomegalovirus
Mycophenolic Acid
Antilymphocyte Serum
Whole-Body Irradiation
Myelodysplastic Syndromes
Incidence
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Hodgkin Disease
Acute Myeloid Leukemia
Antineoplastic Agents
Non-Hodgkin's Lymphoma
Cyclophosphamide

Keywords

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

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

Cite this

@article{087b7dbf0871473bac0c89d4dd4e58ad,
title = "Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies: Expanded Analysis and Long-Term Follow-Up",
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)",
author = "Warlick, {Erica D} and {De For}, {Todd E} and Nelli Bejanyan and Holtan, {Shernan G} and MacMillan, {Margaret L} and Blazar, {Bruce R} and Dusenbery, {Kathryn E} and Mukta Arora and Veronika Bachanova and Cooley, {Sarah A} and Aleksandr Lazaryan and {Mc Glave}, {Philip B} and Miller, {Jeffrey S} and Armin Rashidi and Arne Slungaard and Vercellotti, {Gregory M} and Celalettin Ustun and Claudio Brunsein and Weisdorf, {Daniel J}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.bbmt.2018.07.038",
language = "English (US)",
volume = "25",
pages = "56--62",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "1",

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T1 - Reduced-Intensity Conditioning Followed by Related and Unrelated Allografts for Hematologic Malignancies

T2 - Expanded Analysis and Long-Term Follow-Up

AU - Warlick, Erica D

AU - De For, Todd E

AU - Bejanyan, Nelli

AU - Holtan, Shernan G

AU - MacMillan, Margaret L

AU - Blazar, Bruce R

AU - Dusenbery, Kathryn E

AU - Arora, Mukta

AU - Bachanova, Veronika

AU - Cooley, Sarah A

AU - Lazaryan, Aleksandr

AU - Mc Glave, Philip B

AU - Miller, Jeffrey S

AU - Rashidi, Armin

AU - Slungaard, Arne

AU - Vercellotti, Gregory M

AU - Ustun, Celalettin

AU - Brunsein, Claudio

AU - Weisdorf, Daniel J

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - AML

KW - Aggressive and indolent non-Hodgkin lymphoma

KW - Hematopoietic stem cell transplantation (HCT)

KW - Hodgkin lymphoma

KW - MDS

KW - Reduced-intensity conditioning (RIC)

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U2 - 10.1016/j.bbmt.2018.07.038

DO - 10.1016/j.bbmt.2018.07.038

M3 - Article

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EP - 62

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

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