Impact of T-cell chimerism on relapse after cord blood transplantation for hematological malignancies: Nagoya Blood and Marrow Transplantation Group study

Yokohata, Emi; Kuwatsuka, Yachiyo; Ohashi, Haruhiko; Terakura, Seitaro; Kawashima, Naomi; Seto, Aika; Kurahashi, Shingo; Ozawa, Yukiyasu; Goto, Tatsunori; Imahashi, Nobuhiko; Nishida, Tetsuya; Miyao, Kotaro; Sakemura, Reona; Kato, Tomonori; Sawa, Masashi; Kohno, Akio; Sao, Hiroshi; Iida, Hiroatsu; Kiyoi, Hitoshi; Naoe, Tomoki; Miyamura, Koichi; Murata, Makoto

doi:10.1038/bmt.2016.323

Cited by 6 publications

(9 citation statements)

References 14 publications

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“…Patients were planned to be followed up for at least 1 year after transplant or less if they satisfied one of the discontinuation criteria. Chimerism analyses were done at the National Hospital Organization Nagoya Medical Center using short tandem repeats by PCR assay in peripheral CD3+ T cells on days 14, 28, and 56 after transplantation as previously described 36 . BM mononuclear cells (BM‐MNCs) and BM‐derived MSCs were also assessed for chimerism status including MSC donor chimerism on days 14, 28, 56, and 84 after transplantation.…”

Section: Methodsmentioning

confidence: 99%

“…Patient age, median (range), y 47 (24-70) 44 (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52) .62…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…Platelets ≥20 × 10 9 /L 38 (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48) 39 (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47) 1.00…”

Section: Patient Characteristicsunclassified

“…Platelets ≥50 × 10 9 /L 52 (42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57) 46 (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53) .29…”

Section: Patient Characteristicsmentioning

confidence: 99%

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Phase I clinical trial of intra-bone marrow cotransplantation of mesenchymal stem cells in cord blood transplantation

Goto

Murata

Nishida

et al. 2020

Stem Cells Translational Medicine

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Mesenchymal stem cells (MSCs) have immunomodulatory properties and support hematopoiesis in the bone marrow (BM). To develop a new strategy to not only prevent graft-vs-host disease (GVHD) but also to enhance engraftment, a phase I trial of cord blood transplantation (CBT) combined with intra-BM injection of MSCs (MSC-CBT) was designed. Third-party BM-derived MSCs were injected intra-BM on the day of CBT. The conditioning regimen varied according to patient characteristics. GVHD prophylaxis was tacrolimus and methotrexate. The primary endpoint was toxicity related to intra-BM injection of MSCs. Clinical outcomes were compared with those of six controls who received CBT alone. Five adult patients received MSC-CBT, and no adverse events related to intra-BM injection of MSCs were observed. All patients achieved neutrophil, reticulocyte, and platelet recoveries, with median times to recoveries of 21, 35, and 38 days, respectively, comparable with controls. Grade II-IV acute GVHD developed in three controls but not in MSC-CBT patients. No patients developed chronic GVHD in both groups. At 1 year after transplantation, all MSC-CBT patients survived without relapse. This study shows the safety of MSC-CBT, and the findings also suggest that cotransplantation of MSCs may prevent GVHD with no inhibition of engraftment.

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Section: Methodsmentioning

confidence: 99%

“…Patient age, median (range), y 47 (24-70) 44 (35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52) .62…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…Platelets ≥20 × 10 9 /L 38 (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48) 39 (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47) 1.00…”

Section: Patient Characteristicsunclassified

“…Platelets ≥50 × 10 9 /L 52 (42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57) 46 (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53) .29…”

Section: Patient Characteristicsmentioning

confidence: 99%

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Phase I clinical trial of intra-bone marrow cotransplantation of mesenchymal stem cells in cord blood transplantation

Goto

Murata

Nishida

et al. 2020

Stem Cells Translational Medicine

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“…To assess the disease progression in detail, it is necessary to analyze each component of chimerism after separating blood cells into T lymphocytes and granulocytes. 13 A previous report demonstrated that 14% of patients had mixed chimera in the T-cell compartments in transplantation of cutaneous T-cell lymphoma. 14 The donor chimera in the T cell fraction decreased early at relapse of SS.…”

Section: Discussionmentioning

confidence: 99%

Long-term complete remission of early hematological relapse after discontinuation of immunosuppressants following allogeneic transplantation for Sezary syndrome

et al. 2018

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Sezary syndrome (SS) is a leukemic form of cutaneous T-cell lymphoma and is chemo-resistant. Allogeneic hematopoietic stem cell transplantation is a promising therapy for SS; however, relapse is common. Therapeutic options after relapse have not been established. We managed an SS patient with hematological relapse within one month after transplantation. After discontinuation of immunosuppressants, she achieved complete remission and remained relapse-free. The chimeric analyses of Tcells showed that the full recipient type became complete donor chimera after immunological symptoms. This clinical course suggested that discontinuation of immunosuppressants may result in a graftversus- tumor effect, leading to the eradication of lymphoma cells.

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Long-term persistent donor–recipient mixed chimerism without disease recurrence after myeloablative single-unit cord blood transplantation in adult acute myeloid leukemia following myelodysplastic syndrome

Tanoue

Konuma

Takahashi

et al. 2017

Leukemia & Lymphoma

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Impact of T-cell chimerism on relapse after cord blood transplantation for hematological malignancies: Nagoya Blood and Marrow Transplantation Group study

Cited by 6 publications

References 14 publications

Phase I clinical trial of intra-bone marrow cotransplantation of mesenchymal stem cells in cord blood transplantation

Phase I clinical trial of intra-bone marrow cotransplantation of mesenchymal stem cells in cord blood transplantation

Long-term complete remission of early hematological relapse after discontinuation of immunosuppressants following allogeneic transplantation for Sezary syndrome

Long-term persistent donor–recipient mixed chimerism without disease recurrence after myeloablative single-unit cord blood transplantation in adult acute myeloid leukemia following myelodysplastic syndrome

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