Exploratory research for optimal GvHD prophylaxis after single unit CBT in adults: short-term methotrexate reduced the incidence of severe GvHD more than mycophenolate mofetil

Terakura, Seitaro; Wake, Atsushi; Inamoto, Yoshihiro; Murata, Makoto; Sakai, Rika; Yamaguchi, Takuhiro; Takahashi, Satoshi; Uchida, Naoyuki; Onishi, Yasushi; Ohashi, Kazuteru; Ozawa, Yukiyasu; Kanamori, Heiwa; Yamaguchi, Hiroki; Fukuda, Takahiro; Ichinohe, Tatsuo; Takanashi, Minoko; Atsuta, Yoshiko; Teshima, Takanori

doi:10.1038/bmt.2016.255

Cited by 36 publications

(19 citation statements)

References 51 publications

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“…The significant association between increased CRP levels and decreased 16-hour CCI may be explained by the frequent occurrence of PES after CBT. In addition, GVHD prophylaxis using methotrexate may contribute to better platelet transfusion responses found in our study, probably because using methotrexate for GVHD prophylaxis has been reported to reduce the incidence of PES and acute GVHD after CBT [28][29][30]. These findings suggested that development of PES may be strongly associated with PTR after CBT.…”

Section: Discussionsupporting

confidence: 54%

Platelet Transfusion Refractoriness in Single-Unit Cord Blood Transplantation for Adults: Risk Factors and Clinical Outcomes

Tanoue

Konuma

Kato

et al. 2018

Biology of Blood and Marrow Transplantation

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Platelet transfusion refractoriness (PTR) is frequently observed after allogeneic hematopoietic cell transplantation (HCT). However, the incidence of and risk factors for PTR, and impact of PTR on transplant outcomes after cord blood transplantation (CBT) have not been fully investigated. We retrospectively analyzed 185 adult patients who received single-unit CBT in our institute. The mean 16-hour corrected count increment (CCI) for the 5840 platelet transfusions was 3.68 × 10/L. Among them, 3196 transfusions (54.7%) were associated with a PTR with 16-hour-CCI <4.5 × 10/L. Results of multivariate analysis indicated that the following factors were significantly associated with decreased platelet transfusion responses: female sex with pregnancy history, male sex, the presence of HLA class I antibody, lower cord blood total nucleated cell dose, lower cord blood CD34 cell dose, 3 locus HLA disparities, body temperature ≥38°C, C-reactive protein ≥10 mg/dL, cytomegalovirus reactivation, use of foscarnet, and use of liposomal amphotericin B. By contrast, graft-versus-host disease prophylaxis including methotrexate, ABO minor mismatch, use of ganciclovir, and use of linezolid were significantly associated with better platelet transfusion responses. PTR had a significant effect on poor neutrophil and platelet recovery, and overall mortality after CBT. These data suggest that early phase PTR may be predictive of engraftment and mortality after single-unit CBT for adults.

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Section: Discussionsupporting

confidence: 54%

Platelet Transfusion Refractoriness in Single-Unit Cord Blood Transplantation for Adults: Risk Factors and Clinical Outcomes

Tanoue

Konuma

Kato

et al. 2018

Biology of Blood and Marrow Transplantation

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“…These results are better than previous studies of i.v. CBT for adult patients, but they may be inconsistent with animal experiments showing that intrabone transplantation is 10–15 times more efficient in the engraftment of cord blood cells than i.v. transplantation .…”

Section: Discussionmentioning

confidence: 97%

“…The median time to neutrophil recovery was 17–23 days, and platelet recovery was 32–41 days, which are much faster than i.v. CBT . A retrospective comparative study showed that neutrophil recovery was significantly faster in intrabone single CBT than in i.v.…”

Section: Discussionmentioning

confidence: 99%

Phase II study of intrabone single unit cord blood transplantation for hematological malignancies

et al. 2017

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The outcomes of cord blood transplantation with non‐irradiated reduced‐intensity conditioning for hematological malignancies need to be improved because of graft failure and delayed engraftment. Intrabone infusion of cord blood cells has the potential to resolve the problems. In this phase II study, 21 adult patients with hematological malignancy received intrabone transplantation of serological HLA‐A, B, and DR ≥4/6 matched single cord blood with a median number of cryopreserved total nucleated cells of 2.7 × 107/kg (range, 2.0–4.9 × 107/kg) following non‐irradiated fludarabine‐based reduced‐intensity conditioning. Short‐term methotrexate and tacrolimus were given as graft‐versus‐host disease prophylaxis, and granulocyte colony‐stimulating factor was given after transplantation. No severe adverse events related to intrabone injection were observed. The cumulative incidences of neutrophils ≥0.5 × 109/L, reticulocytes ≥1%, and platelets ≥20 × 109/L recoveries were 76.2%, 71.4%, and 76.2%, respectively, with median time to recoveries of 17, 28, and 32 days after transplantation, respectively. The probability of survival with neutrophil engraftment on day 60 was 71.4%, and overall survival at 1 year after transplantation was 52.4%. The incidences of grade II–IV and III–IV acute graft‐versus‐host disease were 44% and 19%, respectively, with no cases of chronic graft‐versus‐host disease. The present study showed the safety of direct intrabone infusion of cord blood. Further analysis is required to confirm the efficacy of intrabone single cord blood transplantation with non‐irradiated reduced‐intensity conditioning for adult patients with hematological malignancy. This study was registered with UMIN‐CTR, number 000000865.

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“…Thus, fludarabine plus busulfan might be preferable in patients who receive Moga before allo‐HSCT. In terms of GVHD prophylaxis in the setting of CBT, TAC plus MTX was associated with a lower incidence of GVHD than TAC plus mycophenolate mofetil . Thus, TAC plus MTX might be preferable in patients who receive Moga before allo‐HSCT.…”

Section: Key Scientific Statement To the Clinical Questions Regardingmentioning

confidence: 99%

Pre- and posttransplant use of mogamulizumab in patients with aggressive adult T-cell leukemia-lymphoma: A statement from key opinion leaders in Japan

et al. 2018

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Recently, the anti-CCR4 antibody mogamulizumab (Moga, Kyowa Hakko Kirin Co., Ltd, Tokyo, Japan) was approved as a treatment for CCR4-positive adult T-cell leukemialymphoma (ATL) in Japan. We use Moga before or after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aggressive ATL. A recent retrospective analysis using a database from a nationwide survey showed that the use of Moga before allo-HSCT was associated with an increased risk of severe/steroid-refractory acute GVHD and inferior overall survival. Meanwhile, it was reported that a number of patients with chemotherapy-refractory ATL achieved disease control with Moga, including those who subsequently underwent allo-HSCT. To address these issues pertaining to Moga in transplant-eligible patients with ATL, a key opinion leader (KOL) meeting comprising hematologists and transplant physicians was conducted by Kyowa Hakko Kirin Co., Ltd. in Japan. The goal of this KOL meeting was to design a framework to guide decision-making on the use of Moga in transplant-eligible patients with ATL. KOLs first presented their experiences, and after a subsequent discussion, the KOLs agreed on the key scientific statement as summarized in this Expert Commentary. Our experiences suggest that a good number of patients benefited from Moga, achieving disease control that was often unattainable by conventional chemotherapies. However, as our statement is based largely on retrospective studies and real clinical practice, it requires further validation. Nevertheless, we believe that this statement should help efficiently guide decision-making concerning Moga use in transplant-eligible patients with ATL.

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Exploratory research for optimal GvHD prophylaxis after single unit CBT in adults: short-term methotrexate reduced the incidence of severe GvHD more than mycophenolate mofetil

Cited by 36 publications

References 51 publications

Platelet Transfusion Refractoriness in Single-Unit Cord Blood Transplantation for Adults: Risk Factors and Clinical Outcomes

Platelet Transfusion Refractoriness in Single-Unit Cord Blood Transplantation for Adults: Risk Factors and Clinical Outcomes

Phase II study of intrabone single unit cord blood transplantation for hematological malignancies

Pre- and posttransplant use of mogamulizumab in patients with aggressive adult T-cell leukemia-lymphoma: A statement from key opinion leaders in Japan

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