Impact of graft-versus-host disease on outcomes after unrelated cord blood transplantation

Kanda, Junya; Morishima, Yasuo; Terakura, Seitaro; Wake, Atsushi; Uchida, Naoyuki; Takahashi, Satoshi; Ono, Yuju; Onishi, Yasushi; Kanamori, Heiwa; Aotsuka, Nobuyuki; Ozawa, Yukiyasu; Ogawa, Hiroyasu; Sakura, Toru; Ohashi, Kazuteru; Ichinohe, Tatsuo; Kato, Keisuke; Atsuta, Yoshiko; Teshima, Takanori; Murata, Makoto

doi:10.1038/leu.2016.288

Cited by 56 publications

(40 citation statements)

References 26 publications

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“…We have previously shown that high-dose PTCy is an effective single-agent prophylactic strategy after HLA-matched BMT [10–13] and seems to reduce severe aGVHD and cGVHD without concomitant decreases in the incidence of grade II aGVHD. Similar to recent studies in haplo BMT with PTCy [9] and umbilical cord transplantation [30] we demonstrate that grade II aGVHD is associated with significantly improved OS and PFS in HLA-matched BMT with PTCy. We believe that this is due to retention of the graft-versus-tumor effect with grade II aGVHD, but absence of the long-term morbidity and late mortality associated with moderate and severe cGVHD.…”

Section: Discussionsupporting

confidence: 90%

“…Given the improvements in survival associated with grade II aGVHD in this and prior studies [1,30,38], we propose that grade II aGVHD be distinguished from grades III to IV aGVHD as a clinical trial endpoint in studies of malignant disease to avoid cataloging “the good” with “the bad” [9]. We also note that the rate of progression from grade II aGVHD to grades III to IV aGVHD is low with PTCy platforms, particularly with skin-only grade II aGVHD.…”

Section: Discussionmentioning

confidence: 73%

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Development of Grade II Acute Graft-versus-Host Disease Is Associated with Improved Survival after Myeloablative HLA-Matched Bone Marrow Transplantation using Single-Agent Post-Transplant Cyclophosphamide

McCurdy

Kanakry

Tsai

et al. 2019

Biology of Blood and Marrow Transplantation

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Post-transplant cyclophosphamide (PTCy) can be used as the sole immunosuppression after myeloablative conditioning (MAC) for HLA-matched bone marrow transplantation (BMT). However, the effects of graft-versus-host disease (GVHD) with this platform are undefined. We retrospectively analyzed 298 consecutive adult patients with hematologic malignancies who engrafted after MAC HLA-matched sibling donor (MSD; n = 187) or HLA-matched unrelated donor (MUD; n = 111) T-cell-replete BMT with PTCy 50 mg/kg on days +3 and +4. After MSD and MUD BMT, 35% and 57% of patients, respectively, developed grade II acute GVHD (aGVHD) by 100 days, 11% and 14% grade III to IV aGVHD by 100 days, and 9% and 16% chronic GVHD (cGVHD) by 1 year. In landmark analyses at 100 days after HLA-matched BMT, 4-year overall survival (OS) and progression-free survival (PFS) were 57% (95% confidence interval [CI], .49 to .67) and 40% (95% CI, .31 to .51) in patients without grades II to IV aGVHD, and 68% (95% CI, .59 to .78) and 54% (95% CI, .44 to .65) in patients with grade II aGVHD. In adjusted time-dependent multivariable analyses, grade II aGVHD was associated with improved OS (hazard ratio, .58; 95% CI, .37 to .89; P = .01) and PFS (hazard ratio, .50; 95% CI, .34 to .74; P < .001) after HLA-matched BMT with PTCy. The ability of PTCy to limit grades III to IV aGVHD and cGVHD while maintaining grade II aGVHD may contribute to its effectiveness, and further attempts to reduce aGVHD may be detrimental.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 73%

Development of Grade II Acute Graft-versus-Host Disease Is Associated with Improved Survival after Myeloablative HLA-Matched Bone Marrow Transplantation using Single-Agent Post-Transplant Cyclophosphamide

McCurdy

Kanakry

Tsai

et al. 2019

Biology of Blood and Marrow Transplantation

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“…These studies assessed the impact of GVHD on transplantation outcomes throughout the study period and reported conflicting results [20][21][22]. Here we assessed the impact of GVHD on early (the first 18 months after transplantation) and late (thereafter) transplantation outcomes in a large cohort of AML patients given single or double UCBT by calculating the rate of relapse per patient-year for each condition within sequential 90-day intervals after allo-SCT (this method allows assessment of the evolution of the HR for the risk of relapse over time and is not affected by competing risks [23]) and by performing conventional Cox models where acute and chronic GVHD were handled as time-dependent covariates.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, chronic GVHD was associated with a lower risk of relapse, but only in the subgroup of patients receiving double UCBT. More recently, Kanda et al observed that acute and chronic GVHD each decreased the risk of relapse in a large cohort of UCBT recipients (n = 2558) [21]. However, only milder forms of GVHD (grade 1-2 acute and limited chronic GVHD) were associated with better survival due to a strong association between severe forms of GVHD and nonrelapse mortality.…”

Section: Introductionmentioning

confidence: 99%

Occurrence of graft‐versus‐host disease increases mortality after umbilical cord blood transplantation for acute myeloid leukaemia: a report from Eurocord and the ALWP of the EBMT

et al. 2017

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Background The efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukaemia (AML) relies on immune‐mediated graft‐versus‐leukaemia effects. Previous studies have suggested a strong association between graft‐versus‐host disease (GVHD) occurrence and graft‐versus‐leukaemia effects after allogeneic hematopoietic cell transplantation. Methods Here, we evaluated the kinetics of relapse rate in correlation with GVHD occurrence after UCBT. The kinetics of relapse rate over time in correlation to GVHD occurrence were assessed by calculating the relapse rate per patient‐year within sequential 90‐day intervals. The impact of GVHD on relapse and mortality was further studied in multivariate Cox models handling GVHD as a time‐dependent covariate. Results The study included data from 1068 patients given single (n = 567) or double (n = 501) UCBT. The proportion of patients with grade II, III and IV acute GVHD was 20%, 7% and 4%, respectively. At 2 years, the cumulative incidence of chronic GVHD was 42%, the cumulative incidence of relapse was 32%, and overall survival was 32% as well. Relapse rates declined gradually over time during the first 30 months after transplantation. There was a possible suggestion that grade II–IV acute (HR = 0.8, P = 0.1) and chronic (HR = 0.65, P = 0.1) GVHD decreased relapse risk. However, grade II–IV acute GVHD significantly increased early (the first 18 months after UCBT) mortality (HR = 1.3, P = 0.02), whilst chronic GVHD increased each early (HR = 2.7, P < 0.001) and late (HR = 4.9, P < 0.001) mortality after UCBT. Conclusions The occurrence of grade II–IV acute or chronic GVHD each increases overall mortality after UCBT for AML mitigating the possible graft‐versus‐leukemia effect of GVHD.

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“…Therapy of lower gut disease must not be delayed. Interestingly, a number of analyses have suggested development of acute GVHD is not associated with a decrement in survival 104,105 . Multiple series have reported low incidences of moderate or severe disabling chronic GVHD 4,73,74,103 and increased corticosteroid responsiveness 106 after CBT.…”

Section: Gvhd Diagnosis and Therapymentioning

confidence: 99%

Optimal Practices in Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies

Barker

Kurtzberg

Ballen

et al. 2017

Biology of Blood and Marrow Transplantation

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115

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Unrelated donor cord blood (CB) transplantation (CBT) results in disease-free survival comparable to that of unrelated adult donor transplantation in patients with hematologic malignancies. Extension of allograft access to racial and ethnic minorities, rapid graft availability, flexibility of transplant date, and low risks of disabling chronic graft-versus-host disease (GVHD) and relapse are significant advantages of CBT, and multiple series have reported a low risk of late transplant-related mortality (TRM) post-transplant. Nonetheless, early post-transplant morbidity and TRM and the requirement for intensive early post-transplant management have slowed wide adoption of CBT. Targeted care strategies in CBT recipients can, however, mitigate early transplant complications and reduce transplant costs. Herein, we provide a practical “how to” guide to CBT for hematologic malignancies on behalf of the NMDP and the ASBMT CB Special Interest Group (SIG). It shares the best practices of 6 experienced United States transplant centers with a special interest in the use of CB as a hematopoietic stem cell source. We address donor search and unit selection, unit thaw and infusion, conditioning regimens, immune suppression, management of GVHD, opportunistic infections and other factors in supportive care appropriate for CBT. Meticulous attention to such details has improved CBT outcomes and will facilitate the success of CBT as a platform for future graft manipulations.

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Impact of graft-versus-host disease on outcomes after unrelated cord blood transplantation

Cited by 56 publications

References 26 publications

Development of Grade II Acute Graft-versus-Host Disease Is Associated with Improved Survival after Myeloablative HLA-Matched Bone Marrow Transplantation using Single-Agent Post-Transplant Cyclophosphamide

Development of Grade II Acute Graft-versus-Host Disease Is Associated with Improved Survival after Myeloablative HLA-Matched Bone Marrow Transplantation using Single-Agent Post-Transplant Cyclophosphamide

Occurrence of graft‐versus‐host disease increases mortality after umbilical cord blood transplantation for acute myeloid leukaemia: a report from Eurocord and the ALWP of the EBMT

Optimal Practices in Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies

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