Double Umbilical Cord Blood Transplantation: Relevance of Persistent Mixed-Unit Chimerism

Allogeneic hematopoietic stem cell transplantation (HSCT) is one of curative treatment options for patients with hematologic malignancies. Although GVHD mediated by the donor's T lymphocytes remains the most challenging toxicity of allo-HSCT, graft-versus-leukemia (GVL) effect targeting leukemic cells, has an important role in affecting the overall outcome of patients with AML. Here we comprehensively characterized the TCR repertoire in patients who underwent matched donor or haplo-cord HSCT using next-generation sequencing approach. Our study defines the functional kinetics of each TCRA and TCRB clone, and changes in T-cell diversity (with identification of CDR3 sequences) and the extent of clonal expansion of certain T-cells. Using this approach, our study demonstrates that higher percentage of cord-blood cells at 30 days after transplant was correlated with higher diversity of TCR repertoire, implicating the role of cord-chimerism in enhancing immune recovery. Importantly, we found that GVHD and relapse, exclusive of each other, were correlated with lower TCR repertoire diversity and expansion of certain T-cell clones. Our results highlight novel insights into the balance between GVHD and GVL effect, suggesting that higher diversity early after transplant possibly implies lower risks of both GVHD and relapse following the HSCT transplantation.

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“…These approaches include manipulation of post-transplantation immune suppression, source of stem cells and cytokine use. 22 , 23 …”

Section: Discussionmentioning

confidence: 99%

Quantitative characterization of T-cell repertoire in allogeneic hematopoietic stem cell transplant recipients

Yew

Alachkar

Yamaguchi

et al. 2015

Bone Marrow Transplant

117

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“…Pediatric allogeneic HCT from unrelated CBU transplants has similar outcomes in children to adult marrow or PBSC transplants . Furthermore, double‐cord transplants in adults have comparable outcomes to MUD transplants …”

Section: Discussionmentioning

confidence: 96%

Successful long‐term hematological and immunological reconstitution by autologous cord blood transplantation combined with post‐transplant immunosuppression in two children with severe aplastic anemia

Georgia

Oikonomopoulou

Kaisari

et al. 2018

Pediatric Transplantation

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aUCBT is a valuable curative option in pediatric patients with refractory idiopathic SAA and no available matched sibling or unrelated donors. Experience in the use of autologous cord blood units in patients with SAA is limited and private for‐profit cord blood‐banking programs are controversial. We report the successful treatment of two patients with SAA, aged 15 and 24 months, with autologous cord blood combined with immunosuppression. After conditioning with 200 mg/kg cyclophosphamide and ATG, 7.5 mg/kg, 32.2 × 107/kg, and 3.8 × 107/kg autologous cord blood nucleated cells were infused, respectively. One of our patients underwent transplantation after failure of IST. Both patients received post‐transplant immunosuppression with cyclosporine for 12 months. They remain disease‐free 6 years post‐transplantation.

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“…An unusual feature of this case was persistent coengraftment of both umbilical cord units, which can be associated with relapse [6]. Persistent coengraftment is rare in dUCBT and has been reported in a small number of case reports [7]. Following relapse 16 months after transplant, a second remission was achieved with a repeat course of alemtuzumab and pentostatin, which lasted 6 months before relapse occurred again.…”

Section: Introductionmentioning

confidence: 96%

Persistent Mixed Donor Chimerism following Double Umbilical Cord Transplantation in a Patient with T-Cell Prolymphocytic Leukemia

Mistry

Hexner

Mangan

2019

Case Reports in Hematology

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T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive postthymic T-cell neoplasm with an associated survival time of 1 year when left untreated. Current standard of care for T-PLL is with alemtuzumab, followed by allogeneic or autologous stem cell transplant. Little is found in the literature about alternative donor transplantation in T-PLL. Here, we present the case of a patient treated with double umbilical cord blood transplantation, which resulted in initial complete remission. An unusual outcome of this case is that coengraftment of both cords was established. After 16 months, the patient had relapse of the disease, unfortunately, prompting treatment with alemtuzumab and pentostatin, which resulted in remission once again. Here, we report a unique phenomenon whereby single-cord dominance occurred after treatment with these agents, suggesting that anti-T-cell therapy after transplant may help achieve single-unit dominance. A second relapse of the disease occurred six months thereafter, ultimately resulting in the patient’s death, highlighting the aggressive nature of this disease.

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Double Umbilical Cord Blood Transplantation: Relevance of Persistent Mixed-Unit Chimerism

Cited by 17 publications

References 57 publications

Quantitative characterization of T-cell repertoire in allogeneic hematopoietic stem cell transplant recipients

Quantitative characterization of T-cell repertoire in allogeneic hematopoietic stem cell transplant recipients

Successful long‐term hematological and immunological reconstitution by autologous cord blood transplantation combined with post‐transplant immunosuppression in two children with severe aplastic anemia

Persistent Mixed Donor Chimerism following Double Umbilical Cord Transplantation in a Patient with T-Cell Prolymphocytic Leukemia

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