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Stem Cell Transplantation
Predictors of recovery following allogeneic CD34+-selected cell infusion without conditioning to correct poor graft function
Ferrata Storti Foundation
Haematologica 2020 Volume 105(11):2639-2646
Maria M. Cuadrado,1 Richard M. Szydlo,1,2 Mike Watts,3 Nishil Patel,4 Hanna Renshaw,4 Jude Dorman,5 Mark Lowdell,6 Stuart Ings,3 Chloe Anthias,1 Alejandro Madrigal,1 Stephen Mackinnon,5 Panagiotis Kottaridis,5 Ben Carpenter,5 Rachael Hough,5 Emma Morris,5 Kirsty Thomson,5 Karl S. Peggs5,7 and Ronjon Chakraverty5,7
1Anthony Nolan Research Institute; 2Department of Haematology, Imperial College London; 3Wolfson Cellular Therapy Unit, University College Hospital London NHS Trust; 4Department of Haematology, Royal Free London NHS Trust; 5Department of Haematology, University College Hospital NHS Trust; 6Centre for Cell, Gene & Tissue Therapeutics, Royal Free London NHS Trust and 7Department of Hematology, Cancer Institute, University College London, London, UK
ABSTRACT
Poor graft function is a serious complication following allogeneic hematopoietic stem cell transplantation. Infusion of CD34+-selected stem cells without pre-conditioning has been used to correct poor graft function, but predictors of recovery are unclear. We report the outcome of 62 consecutive patients who had primary or secondary poor graft function who underwent a CD34+-selected stem cell infusion from the same donor without further conditioning. Forty-seven of 62 patients showed hematolog- ic improvement and became permanently transfusion- and growth factor- independent. In multivariate analysis, parameters significantly associated with recovery were shared cytomegalovisur seronegative status of both the recipient and donor, the absence of active infection and matched recipient- donor sex. Recovery was similar in patients with mixed and full donor chimerism. Five-year overall survival rates were 74.4% (95% confidence interval [95% CI: 59-89]) in patients demonstrating complete recovery, 16.7% (95% CI: 3-46) in patients with partial recovery and 22.2% (CI 95% 5-47) in those who had no response. In patients with blood count recovery, those with poor graft function in one or two lineages had a better 5-year overall survival (93.8%, 95% CI: 82-99) than those with trilineage failure (53%, 95% CI: 34-88). New strategies including cytokine or agonist support, or a second transplant need to be investigated in patients whose blood counts do not recover.
Introduction
Graft failure is a severe complication of allogeneic hematopoietic stem cell trans- plantation (SCT), which is associated with reduced survival, especially in patients being treated for hematologic malignancies.1,2 Graft failure caused by rejection is relatively uncommon with an incidence of 4-6%3 and ensues as a result of an anti- donor response triggered by recipient T cells or NK cells or by pre-existing donor- specific antibodies (e.g., directed against human leukocyte antigens). Graft failure in the absence of rejection or tumor relapse is more common, with an incidence reported to be between 5-27%,4 and is referred to as poor graft function. In practice, graft rejection and poor graft function can be distinguished by measuring chimerism: donor cells are undetectable in the former but persist in the latter.5 Multiple risk factors are associated with poor graft function including issues related to the donor (low stem cell dose and ABO blood group incompatibility), the type of conditioning (reduced intensity or nonmyeloablative conditioning) or the patient (primary diseases such as aplastic anemia or myelofibrosis, viral infections, drugs or the presence of graft-versus-host disease [GvHD]).1,3
Currently, there are no clear recommendations for the treatment of poor graft
Correspondence:
RONJON CHAKRAVERTY
r.chakraverty@ucl.ac.uk
Received: May 16, 2019.
Accepted: November 20, 2019. Pre-published: November 21, 2019.
doi:10.3324/haematol.2019.226340 ©2020 Ferrata Storti Foundation
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haematologica | 2020; 105(11)
2639
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