Different effects of HLA disparity on transplant outcomes after single-unit cord blood transplantation between pediatric and adult patients with leukemia

Atsuta, Yoshiko; Kanda, Junya; Takanashi, Minoko; Morishima, Yasuo; Taniguchi, Satoshi; Takahashi, Satoshi; Ogawa, Hiroyasu; Ohashi, Kazuteru; Ohno, Yuju; Onishi, Yasushi; Aotsuka, Nobuyuki; Nagamura‐Inoue, Tokiko; Kato, Koji; Kanda, Yoshinobu

doi:10.3324/haematol.2012.076042

Cited by 78 publications

(66 citation statements)

References 42 publications

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“…The intensity of conditioning regimen was classified as myeloablative or reduced intensity on the basis of the Center for International Blood and Marrow Transplant Research report and the information from the questionnaire, as previously described. [20][21][22][23] We defined the following as standard-risk diseases: AML and ALL in first or second remission; CML in the first or Male to female 398 21 573 26 109 15 Female to male 496 27 389 18 131 18 Missing 0 0 2 0 277 37 Disease AML 799 43 986 45 395 53 0.004 MDS 210 11 276 12 76 10 CML 60 3 73 3 25 3 ALL 385 21 439 20 123 17 ATL 110 6 131 6 29 4 NHL 206 11 214 10 70 9 Other diseases 89 5 96 4 The probability of developing chronic GVHD was estimated on the basis of cumulative incidence curves. 24 Competing events for chronic GVHD were death or relapse without GVHD.…”

Section: Discussionmentioning

confidence: 99%

Risk factors and organ involvement of chronic GVHD in Japan

Kanda

Nakasone

Atsuta

et al. 2013

Bone Marrow Transplant

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on behalf of the GVHD Working Group of the Japan Society for Hematopoietic Cell Transplantation Few studies have evaluated the risk factors for chronic GVHD and organ involvement associated with different graft types, including unrelated cord blood (U-CB). We retrospectively studied 4818 adult patients who received their first allogeneic transplantation and survived for at least 100 days. The incidence of chronic GVHD at 2 years was 37%. The following factors were associated with the development of chronic GVHD: female donor/male recipient, CMV-Ab seropositivity, matched related peripheral blood grafts vs matched related BM grafts, no in vivo T-cell depletion and the occurrence of grade II-IV acute GVHD. Among these factors, the association with acute GVHD occurrence was consistently significant across donor subtypes. The use of U-CB was not associated with chronic GVHD, but was associated with a low incidence of extensive chronic GVHD. Chronic GVHD patients who had received U-CB transplants showed less frequent involvement of the oral cavity (28% vs 55%), eye (12% vs 26%), liver (20% vs 44%), lung (11% vs 25%) and joint (0% vs 6%) than those with matched related BM grafts. In conclusion, we found that U-CB transplants were associated with a low incidence of extensive chronic GVHD and less frequent involvement of the oral cavity, eye, liver, lung and joints.

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Section: Discussionmentioning

confidence: 99%

Risk factors and organ involvement of chronic GVHD in Japan

Kanda

Nakasone

Atsuta

et al. 2013

Bone Marrow Transplant

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“…Included in this retrospective analysis were patients aged 50 years or older with AML, ALL, or MDS who received first allogeneic HSCT using bone marrow (BM) or peripheral blood stem cell (PBSC) from MSDs, or a single HLA 0-2 antigen-mismatched unrelated CB unit between January 2007 and December 2012 in Japan. Because HLA-DR mismatches were previously evaluated at the low-resolution level at CB unit selection in Japan [30], the number of HLA disparities between recipient and MSD or between recipient and CB unit was defined as a low-resolution for HLA-A, HLA-B, and HLA-DR loci in this study. CB units were obtained from the Japan Cord Blood Bank Network.…”

Section: Methodsmentioning

confidence: 99%

Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older

et al. 2016

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Older recipient and donor age were associated with higher incidences of severe graft-versus-host disease (GVHD) and mortality after allogeneic hematopoietic stem cell transplantation from matched sibling donors (MSDs) and matched unrelated donors. Since a lower incidence of severe GVHD is advantageous in unrelated cord blood transplantation (CBT), a higher incidence of GVHD using older MSDs could be overcome using cord blood for older patients. We retrospectively analyzed Japanese registration data of 2,091 patients with acute myeloid leukemia, acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome aged 50 years or older who underwent MSD bone marrow transplantation (BMT) (n 5 319), MSD peripheral blood stem cell transplantation (PBSCT) (n 5 462), or unrelated CBT (n 5 1,310) between 2007 and 2012. Median age of MSD was 56 (range, 38-74) years. Compared with CBT, the risk of developing extensive chronic GVHD was higher after BMT (hazard ratio [HR], 2.00; P 5 0.001) or PBSCT (HR, 2.38; P < 0.001), and transplant-related mortality was lower after BMT (HR, 0.61; P < 0.001) or PBSCT (HR, 0.63; P < 0.001). Relapse rates were not significant difference between three groups. Although overall mortality was lower after BMT (HR, 0.67; P < 0.001) or PBSCT (HR, 0.75; P 5 0.002) compared with CBT, the rates of a composite endpoint of GVHD-free, relapse-free survival (GRFS) were not significant difference between three groups. These data showed that MSDs remain the best donor source for older patients, but CBT led to similar GRFS to BMT and PBSCT.Am. J. Hematol. 91:E284-E292,

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“…There is no robust evidence to support counting of the HLA-DRB1 locus at the allele level. Possibly, an antigen-or allele-level mismatch at the DRB1 locus would not substantially affect clinical outcomes [36,40]. Differences in the effects of antigen and allele mismatch on UCB outcomes will be extensively studied in the near future.…”

Section: Impact Of Hla Mismatch Directionmentioning

confidence: 99%

“…The effect of HLA disparity may differ in adults, as total nucleated cell doses and doses of other cellular components, such as T cells, per recipient weight are much lower compared to those in pediatric patients. To reveal the impact of HLA matching in both pediatric and adult cohorts, Atsuta et al [36] analyzed the impact of HLA mismatch on outcomes of UCBT separately in 498 children and 1,880 adults with leukemia (Table 3). In agreement with the results from the US and European cohorts, the risk of grade 2-4 acute GVHD was significantly increased in pediatric patients receiving HLA mismatched UCB.…”

Section: Effects Of Hla Mismatch In Ucbtmentioning

confidence: 99%

Effect of HLA mismatch on acute graft-versus-host disease

Kanda

2013

Int J Hematol

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HLA matching between donors and recipients is the most important factor associated with acute graftversus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation. With improvements in GVHD prophylaxis and supportive care, transplantations from HLA mismatched donors are performed increasingly frequently, drawing greater attention to the effects of HLA mismatch. In related transplantation, HLA 1-antigen mismatch at the HLA-A, HLA-B, and HLA-DR loci is considered acceptable, but the incidence of severe acute GVHD under standard prophylaxis is higher than that for matched related and unrelated transplantation, highlighting the need for a modification of GVHD prophylaxis. Development of new GVHD prophylaxes has now made HLA 2-3-antigen mismatched related transplantation feasible, and has almost overcome the HLA barrier. In unrelated bone marrow or peripheral blood stem cell transplantation, donors matched for HLA-A, HLA-B, HLA-C, and HLA-DRB1 alleles are the most preferable. The impact of allele or antigen mismatch has been evaluated in a number of studies, but the results of these have not been consistent, partly due to differences in race and HLA distribution. The effects of HLA mismatch may differ depending on the year of transplantation and the form of GVHD prophylaxis administered. In cord blood transplantation, successful transplantation can be achieved with up to two HLA mismatches. In children, compared to the use of HLA mismatched units, the use of HLA-matched units is associated with a lower risk of acute GVHD and mortality, while in adults HLA mismatches may have a lower impact on outcome. Thus, the effect of HLA matching should be evaluated separately for different stem cell sources.

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Different effects of HLA disparity on transplant outcomes after single-unit cord blood transplantation between pediatric and adult patients with leukemia

Cited by 78 publications

References 42 publications

Risk factors and organ involvement of chronic GVHD in Japan

Risk factors and organ involvement of chronic GVHD in Japan

Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older

Effect of HLA mismatch on acute graft-versus-host disease

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