Hepatobiliary Infections After Solid Organ or Hematopoietic Cell Transplantation

Abstract Although hematopoietic cell transplantation is generally accomplished utilizing a single donor and recipient pair, multiple donors have been used to mediate engraftment, particularly in the case of low donor cell counts as in umbilical cord blood transplantation. The general engraftment outcome of HLA nonidentical cord blood transplantation is the predominance of one of the units over the other. Here we pose the question whether in the canine hematopoietic cell transplantation model, can we establish multiple donor chimerism using two DLA-identical donors and a single recipient. We identified 8 triplets of DLA-identical littermates by matching highly polymorphic microsatellite markers within DLA class I and class II regions and confirmed by DLA-DRB1 gene sequencing. The marrow recipients received 2 Gy total body irradiation followed by intravenous infusions of marrow cells from both donors 1 and 2. The median number of donor cells injected was 4.1 (range = 2.0–7.0) X 108 cells/kg. Post grafting immunosuppression consisted of cyclosporine (CSP) and mycophenolate mofetil (MMF) given for 35 and 28 days, respectively. The median time to hematological recovery (blood counts equivalent to pre-HCT levels) was 38 (range = 30–42) days. The degrees of chimerism were determined using variable number tandem repeat-polymerase chain reaction (VNTR-PCR) methods. As shown in the Table, sustained trichimerism occurred in 4 out of 8 dogs with engraftment for a period grater than 26 weeks. For G631, both donor grafts were rejected shortly following discontinuation of CSP and MMF. Dog G513 developed graft versus host disease (GvHD) which was successfully treated with a short course of CSP. Five dogs received kidney allografts from one of the respective HCT donors 6 months after HCT to assess donor specific immune tolerance. Chimerism Analysis of Dogs Receiving Marrow from Two Donors Duration of Engraftment in Weeks (% Chimerism) Recipient Donor 1 Donor 2 Recipient GVHD Accept Donor 1 Kidney Graft (wks) ND = not determined; [R] = rejection G158 >43 (5%) 37 (0%) [R] >43 (95%) No Yes (20) G193 >44 (72%) 16 (0%) [R] >44 (28%) No Yes (10) G362 >47 (28%) >47 (55%) >47 (17%) No Yes (16) G513 >47 (53%) >47 (22%) >47 (25%) Yes Yes (16) G551 >32 (35%) >32 (20%) >32 (45%) No ND G631 8 (10%) [R] 8 (12%) [R] 8 (>88%) No ND G643 >30 (28%) >30 (40%) >30 (23%) No Yes (4) G664 >26 (50%) 6 (2%) [R?] >26 (48%) No ND Kidney allografts were found to be essentially free of inflammation when assessed histologically on biopsy. Dog G643, was tested for immune function by a mixed leukocyte reaction and found to be competent against DLA nonidentical stimulator cells but nonresponsive against either of the donor stimulator cells. In summary, following nonmyeloablative conditioning, simultaneous administration of marrow stem cells from two DLA-identical littermates can result in trichimerism. Furthermore, immunological tolerance to multiple hematopoietic cell donors can include a solid organ graft from one of the marrow donors.

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Long-Term Tolerance to Kidney Allografts After Induced Rejection of Donor Hematopoietic Chimerism in a Preclinical Canine Model.

Blood ◽

10.1182/blood.v120.21.2991.2991 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2991-2991

Author(s):

David Mathes ◽

Scott Stoll Graves ◽

George E. Georges ◽

Christian Kuhr ◽

Jeff Chang ◽

...

Keyword(s):

Cell Transplantation ◽

Hematopoietic Cell Transplantation ◽

Conflicts Of Interest ◽

Organ Transplant ◽

Canine Model ◽

Hematopoietic Cell ◽

Mixed Chimerism ◽

Solid Organ ◽

Kidney Graft ◽

Marrow Graft

Abstract Abstract 2991 Allogeneic hematopoietic cell transplantation provides a reliable method for inducing tolerance towards solid organ grafts. However, this procedure can result in graft-versus-host disease (GVHD) thereby limiting its application. Here we test the hypothesis that mixed chimerism can be intentionally reverted to host hematopoiesis without rejection of a kidney graft. Recipient dogs were given 2 Gy total body irradiation (TBI) before and a short course of immunosuppression after marrow infusion from dog leukocyte antigen-identical littermates. All dogs achieved stable mixed chimerism. After a mean of 20 weeks, one cohort of dogs received kidney transplants from their respective marrow donors. Subsequently, recipients were reconditioned with 2 Gy TBI and given autologous granulocyte-colony stimulating factor-mobilized leukocytes (recipient leukocyte infusion) that had been collected before marrow transplant. Dogs receiving a second TBI and recipient leukocyte infusion without a kidney transplant rejected their donor hematopoietic graft within 3 weeks. Dogs that received kidney grafts, followed by a second TBI and recipient leukocyte infusion, rejected their marrow graft without rejecting their transplanted kidneys for periods greater than one year. Mixed chimerism may be clinically reverted to 100% recipient without rejection of a kidney allograft. This model has potential applications in understanding the mechanism of split tolerance. This finding may have application towards minimizing the risk of GVHD in solid organ transplant patients given hematopoietic cell transplantation from HLA-identical donors. Disclosures: No relevant conflicts of interest to declare.

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Prophylaxis vs preemptive therapy in prevention of CMV infection: new insight on prophylactic strategy after allogeneic hematopoietic cell transplantation

Acta Haematologica Polonica ◽

10.2478/ahp-2020-0005 ◽

2020 ◽

Vol 51 (1) ◽

pp. 17-23 ◽

Cited By ~ 2

Author(s):

Jan Styczyński

Keyword(s):

Cell Transplantation ◽

Hematopoietic Cell Transplantation ◽

Primary Prophylaxis ◽

Hematopoietic Cell ◽

Allogeneic Hematopoietic Cell Transplantation ◽

Preemptive Therapy ◽

Solid Organ ◽

Cell Transplant ◽

Cmv Infection ◽

American Society

AbstractCytomegalovirus (CMV), the beta-human herpesvirus type 5 (HHV-5), is a major cause of morbidity in immunocompromised hosts, especially recipients of allogeneic hematopoietic cell transplantation (HCT) or solid organ transplantation. The standard-of-care approach to CMV prevention based on CMV surveillance-guided preemptive therapy is being challenged by the recent approval of letermovir (LMV) for primary prophylaxis. Real-word clinical data show dramatic improvement in the reduction of risk of CMV infection and any CMV viremia in all studies performed so far. LMV is the drug that is breaking the paradigm of preemptive therapy with shift to prophylaxis. A summary of reported data presented in 2019 annual meetings of American Society of Transplantation and Cellular Therapy (ASTCT), European Society for Blood and Marrow Transplantation (EBMT) and American Society of Hematology (ASH), as well as already published results, is presented in this review. A total number of 401 adult high-risk patients on primary prophylaxis after HCT were reported in 11 studies up to January 1, 2020. It was shown that fewer patients in the LMV arms had any CMV reactivation or need for CMV treatment compared with the any other prophylactic or preemptive approaches. In conclusion, LMV is much highly effective than CMV-guided preemptive therapy in preventing CMV infection and CMV disease. The use of LMV in prophylaxis results in an improvement in overall survival during the first 24 and 48 weeks. LMV has a favorable safety profile, as it does not cause myelotoxicity. Current guidelines of European Conference on Infections in Leukemia (ECIL7) recommend LMV for the use in prophylaxis of CMV infection in patients after allogeneic hematopoietic cell transplant.

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Tolerance after Solid Organ and Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2011.11.005 ◽

2012 ◽

Vol 18 (1) ◽

pp. S193-S200 ◽

Cited By ~ 5

Author(s):

Paul Szabolcs ◽

William J. Burlingham ◽

Angus W. Thomson

Keyword(s):

Cell Transplantation ◽

Hematopoietic Cell Transplantation ◽

Hematopoietic Cell ◽

Solid Organ

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Donor-Derived Smoldering Multiple Myeloma following a Hematopoietic Cell Transplantation for AML

Case Reports in Hematology ◽

10.1155/2017/3728429 ◽

2017 ◽

Vol 2017 ◽

pp. 1-3

Author(s):

Bita Fakhri ◽

Mark Fiala ◽

Michael Slade ◽

Peter Westervelt ◽

Armin Ghobadi

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Cell Transplantation ◽

Monoclonal Gammopathy ◽

Hematopoietic Cell Transplantation ◽

Plasma Cells ◽

Hematopoietic Cell ◽

Unrelated Donor ◽

Solid Organ ◽

Smoldering Multiple Myeloma

Posttransplant Lymphoproliferative Disorder (PTLD) is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT). Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML). Eighteen months following her transplant, she developed a monoclonal gammopathy. Bone marrow studies revealed 10% plasma cells, but the patient lacked clinical defining features of multiple myeloma (MM); thus a diagnosis of smoldering multiple myeloma (SMM) was established. Cytogenetic and molecular studies of the bone marrow confirmed the plasma cells were donor-derived. The donor lacks a diagnosis of monoclonal gammopathy of undetermined significance, SMM, or MM.

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